Na, K-ΠΠ’Π Π°Π·Π° ΠΊΠ°ΠΊ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΡΡ Π³Π»ΠΈΠΊΠΎΠ·ΠΈΠ΄ΠΎΠ²: ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΊΠ°ΡΠΊΠ°Π΄Π°, Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΠΎΠ³ΠΎ ΠΎΡ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΉ Na+ ΠΈ K+
![ΠΠΈΡΡΠ΅ΡΡΠ°ΡΠΈΡ: Na, K-ΠΠ’Π Π°Π·Π° ΠΊΠ°ΠΊ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΡΡ
Π³Π»ΠΈΠΊΠΎΠ·ΠΈΠ΄ΠΎΠ²: ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΊΠ°ΡΠΊΠ°Π΄Π°, Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΠΎΠ³ΠΎ ΠΎΡ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΉ Na+ ΠΈ K+](https://niscu.ru/work/5151132/cover.png)
Π Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΠ΅ ΠΌΡ ΠΏΠΎΡΡΠ°ΡΠ°Π»ΠΈΡΡ Π²ΡΡΡΠ½ΠΈΡΡ, ΠΊΠ°ΠΊΠΈΠ΅ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΠ΅ ΠΏΡΡΠΈ ΠΊΠ»Π΅ΡΠΊΠΈ ΡΡΠ°ΡΡΠ²ΡΡΡ Π² ΠΏΠ΅ΡΠ΅Π΄Π°ΡΠ΅ Π²ΡΠ·Π²Π°Π½Π½ΠΎΠ³ΠΎ ΡΠ°Π±Π°ΠΈΠ½ΠΎΠΌ ΡΠΈΠ³Π½Π°Π»Π° ΡΠΌΠ΅ΡΡΠΈ. ΠΡ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ, ΡΡΠΎ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ Π‘Π°2+, ΡΡΠΎΠ²Π½Ρ Π°ΠΊΡΠΈΠ²Π½ΡΡ ΡΠΎΡΠΌ ΠΊΠΈΡΠ»ΠΎΡΠΎΠ΄Π° Π½Π΅ ΠΈΠ³ΡΠ°Π΅Ρ ΠΊΠ»ΡΡΠ΅Π²ΠΎΠΉ ΡΠΎΠ»ΠΈ Π² ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΡΠΌΠ΅ΡΡΠΈ ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΡΠ°Π±Π°ΠΈΠ½Π°. Π‘ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ Π°ΠΊΡΠΈΠ²Π°ΡΠΎΡΠΎΠ² ΠΈ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠΎΠ² ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΡ ΠΏΡΡΠ΅ΠΉ ΠΌΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π»ΠΈ, Π½Π΅ ΡΡΠ°ΡΡΠ²ΡΡΡ Π»ΠΈ… Π§ΠΈΡΠ°ΡΡ Π΅ΡΡ >
- Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅
- ΠΡΠ΄Π΅ΡΠΆΠΊΠ°
- ΠΠΈΡΠ΅ΡΠ°ΡΡΡΠ°
- ΠΡΡΠ³ΠΈΠ΅ ΡΠ°Π±ΠΎΡΡ
- ΠΠΎΠΌΠΎΡΡ Π² Π½Π°ΠΏΠΈΡΠ°Π½ΠΈΠΈ
Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅
- 1. ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅
- 2. ΠΠ±Π·ΠΎΡ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ
- 2. 1. ΠΠ°, Π-ΠΠ’Π Π°Π·Π°: ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½Π°Ρ ΡΡΡΡΠΊΡΡΡΠ°, ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌ 8 ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈ ΡΠ΅Π³ΡΠ»ΡΡΠΈΡ
- 2. 1. 1. Π‘ΡΡΡΠΊΡΡΡΠ½Π°Ρ ΠΎΡΠ³Π°Π½ΠΈΠ·Π°ΡΠΈΡ β, Π-ΠΠ’Π Π°Π·Ρ
- 2. 1. 2. ΠΠ΅Ρ Π°Π½ΠΈΠ·ΠΌ ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π«Π°Π-ΠΠ’Π Π°Π·Ρ
- 2. 1. 3. ΠΠ·ΠΎΡΠ΅ΡΠΌΠ΅Π½ΡΡ Π«Π°Π-ΠΠ’Π Π°Π·Ρ ΠΈ ΠΈΡ ΡΠ²ΠΎΠΉΡΡΠ²Π°
- 2. 1. 4. Π ΠΎΠ»Ρ Π¨, Π-ΠΠ’Π Π°Π·Ρ Π² ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ 19 ΡΠΊΠ°Π½Π΅ΠΉ
- 2. 1. 5. ΠΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΡ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ β, Π-ΠΠ’Π Π°Π·Ρ
- 2. 1. 5. 1. Π€ΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ β, Π-ΠΠ’Π Π°Π·Ρ ΠΏΡΠΎΡΠ΅Π½ΠΊΠΈΠ½Π°Π·Π°ΠΌΠΈ
- 2. 1. 5. 2. ΠΠ·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ β, Π-ΠΠ’Π Π°Π·Ρ Ρ Π΄ΡΡΠ³ΠΈΠΌΠΈ Π±Π΅Π»ΠΊΠ°ΠΌΠΈ
- 2. 1. ΠΠ°, Π-ΠΠ’Π Π°Π·Π°: ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½Π°Ρ ΡΡΡΡΠΊΡΡΡΠ°, ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌ 8 ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈ ΡΠ΅Π³ΡΠ»ΡΡΠΈΡ
- 2. 2. ΠΠ°ΡΠ΄ΠΈΠΎΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΡΠ΅ΡΠΎΠΈΠ΄Ρ ΠΊΠ°ΠΊ ΠΌΠΎΠ΄ΡΠ»ΡΡΠΎΡΡ 31 Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π«Π°Π-ΠΠ’Π Π°Π·Ρ
- 2. 2. 1. Π£ΡΠ°ΡΡΠΊΠΈ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ ΠΠ’Π‘ Π½Π° ΠΌΠΎΠ»Π΅ΠΊΡΠ»Π΅ Π°-ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΡ 32 Π¨, Π-ΠΠ’Π Π°Π·Ρ
- 2. 2. 2. ΠΠ½Π΄ΠΎΠ³Π΅Π½Π½ΡΠ΅ ΠΠ’Π‘
- 2. 3. Π‘ΠΈΠ³Π½Π°Π»ΡΠ½ΡΠ΅ ΠΊΠ°ΡΠΊΠ°Π΄Ρ, Π°ΠΊΡΠΈΠ²ΠΈΡΡΠ΅ΠΌΡΠ΅ ΠΠ’Π‘
- 2. 3. 1. Π‘ΠΈΠ³Π½Π°Π»ΡΠ½ΡΠΉ ΠΊΠ°ΡΠΊΠ°Π΄, ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΡΠΉ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅ΠΌ 38 Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΉ Π‘Π°2+ ΠΈ Π«Π°+
- 2. 3. 2. Π‘ΠΈΠ³Π½Π°Π»ΡΠ½ΡΠΉ ΠΊΠ°ΡΠΊΠ°Π΄, Π½Π΅Π·Π°Π²ΠΈΡΡΡΠΈΠΉ ΠΎΡ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ 39 Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ Π‘Π°2+ ΠΈ ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΡΠΉ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ΠΌ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΠΠ°+
- 2. 3. 3. Π‘ΠΈΠ³Π½Π°Π»ΡΠ½ΡΠ΅ ΠΊΠ°ΡΠΊΠ°Π΄Ρ, Π½Π΅Π·Π°Π²ΠΈΡΡΡΠΈΠ΅ ΠΎΡ ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΡ 43 Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΉ Π«Π°+ ΠΈ Π+
- 2. 3. 3. 1. Π£ΡΠΈΠ»Π΅Π½ΠΈΠ΅ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ 43 Π½ΠΈΠ·ΠΊΠΈΡ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ ΠΠ’Π‘
- 2. 3. 3. 2. Π‘ΠΌΠ΅ΡΡΡ ΡΠΏΠΈΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΡΡ ΠΈ ΡΠ½Π΄ΠΎΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΠΎΠ΄ 46 Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΠΠ’Π‘
- 3. 1. ΠΡΠ»ΡΡΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ
- 3. 1. 1. ΠΠΏΠΈΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΡΠ΅ ΠΊΠ»Π΅ΡΠΊΠΈ Π»ΠΈΠ½ΠΈΠΈ Π‘7-ΠΠΠ‘Π
- 3. 1. 2. ΠΠΏΠΈΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΡΠ΅ ΠΊΠ»Π΅ΡΠΊΠΈ Π»ΠΈΠ½ΠΈΠΈ Π‘Π°ΡΠΎ
- 3. 2. ΠΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈ Π±ΠΈΠΎΡ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ ΠΎΡΠ΅Π½ΠΊΠΈ 53 ΡΠΈΠΏΠ° ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΡΠΌΠ΅ΡΡΠΈ
- 3. 2. 1. Π€Π°Π·ΠΎΠ²ΠΎ-ΠΊΠΎΠ½ΡΡΠ°ΡΡΠ½Π°Ρ ΠΌΠΈΠΊΡΠΎΡΠΊΠΎΠΏΠΈΡ
- 3. 2. 2. Π€Π»ΡΠΎΡΠ΅ΡΡΠ΅Π½ΡΠ½Π°Ρ ΠΌΠΈΠΊΡΠΎΡΠΊΠΎΠΏΠΈΡ
- 3. 2. 3. ΠΠ°ΡΡΡΠ΅Π½ΠΈΠ΅ ΡΠ²ΡΠ·ΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ Ρ ΠΏΠΎΠ΄Π»ΠΎΠΆΠΊΠΎΠΉ
- 3. 2. 4. ΠΠΊΡΠ°ΡΠΈΠ²Π°Π½ΠΈΠ΅ ΠΠ’Π’
- 3. 2. 5. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΊΠ°ΡΠΏΠ°Π·Ρ
- 3. 3. ΠΠ΅ΡΠΎΠ΄Ρ ΠΈΠ·ΡΡΠ΅Π½ΠΈΡ ΠΈΠΎΠ½Π½ΠΎΠ³ΠΎ Π³ΠΎΠΌΠ΅ΠΎΡΡΠ°Π·Π° ΠΊΠ»Π΅ΡΠΎΠΊ
- 3. 3. 1. ΠΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π«Π°Π-Π½Π°ΡΠΎΡΠ°
- 3. 3. 2. Π‘Π²ΡΠ·ΡΠ²Π°Π½ΠΈΠ΅ [3Π]-ΡΠ°Π±Π°ΠΈΠ½Π°
- 3. 3. 3. Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅ ΠΎΠ±ΠΌΠ΅Π½ΠΈΠ²Π°Π΅ΠΌΠΎΠ³ΠΎ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ Π½Π°ΡΡΠΈΡ
- 3. 3. 4. ΠΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΠ΅ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ
- 3. 4. ΠΠΈΠΎΡ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ
- 3. 4. 1. ΠΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΠ΅ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΡ ΠΠΠΠ/Π«ΠΠΠ Π ΠΈ Π ΠΠΠ2 Π² 59 ΠΊΠ»Π΅ΡΠΊΠ΅
- 3. 4. 2. ΠΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΠ΅ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΡ Π°ΠΊΡΠΈΠ²Π½ΡΡ ΡΠΎΡΠΌ ΠΊΠΈΡΠ»ΠΎΡΠΎΠ΄Π° Π² 60 ΠΊΠ»Π΅ΡΠΊΠ΅
- 3. 4. 3. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΡΠΈΠ½ΡΠ΅Π·Π° Π ΠΠ ΠΈ Π±Π΅Π»ΠΊΠ°
- 3. 4. 4. ΠΠΌΠΌΡΠ½ΠΎΠΏΡΠ΅ΡΠΈΠΏΠΈΡΠ°ΡΠΈΡ Π±Π΅Π»ΠΊΠΎΠ² Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ 62 Π°Π½ΡΠΈΡΠ΅Π» Π½Π° β, Π-ΠΠ’Π Π°Π·Ρ
- 3. 4. 5. ΠΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΠ΅ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ Π±Π΅Π»ΠΊΠ° ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΡΡΠ΄ΡΠΎΡΠ΄Π°
- 3. 4. 6. ΠΠ΄Π½ΠΎΠΌΠ΅ΡΠ½ΡΠΉ ΡΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅Π· Π² ΠΏΠΎΠ»ΠΈΠ°ΠΊΡΠΈΠ»Π°ΠΌΠΈΠ΄Π½ΠΎΠΌ Π³Π΅Π»Π΅ 64 ΠΏΠΎ ΠΌΠ΅ΡΠΎΠ΄Ρ ΠΡΠΌΠΌΠ»ΠΈ
- 3. 4. 7. ΠΠ²ΡΠΌΠ΅ΡΠ½ΡΠΉ ΡΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅Π· Π² ΠΏΠΎΠ»ΠΈΠ°ΠΊΡΠΈΠ»Π°ΠΌΠΈΠ΄Π½ΠΎΠΌ Π³Π΅Π»Π΅
- 3. 4. 8. ΠΠ΅ΡΡΠ΅ΡΠ½-Π±Π»ΠΎΡ
- 3. 4. 9. ΠΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ Π±Π΅Π»ΠΊΠΎΠ² ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΌΠ°ΡΡ-ΡΠΏΠ΅ΠΊΠ³ΡΠΎΠΌΠ΅ΡΡΠΈΠΈ
- 3. 5. Π Π΅Π°ΠΊΡΠΈΠ²Ρ
- 4. 1. Π‘ΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· Π΄Π΅ΠΉΡΡΠ²ΠΈΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ 69 ΠΊΠ°ΡΠ΄ΠΈΠΎΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ ΡΡΠ΅ΡΠΎΠΈΠ΄ΠΎΠ² (ΠΠ’Π‘) ΠΊΠ°ΠΊ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠΎΠ²
- 4. 2. ΠΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΊΠ°ΡΠΊΠ°Π΄Π°, Π²ΠΎΠ²Π»Π΅ΡΠ΅Π½Π½ΠΎΠ³ΠΎ Π² ΡΠ°Π·Π²ΠΈΡΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΡΠΌΠ΅ΡΡΠΈ, Π²ΡΠ·Π²Π°Π½Π½ΠΎΠΉ ΠΠ’Π‘
- 4. 2. 1. Π ΠΎΠ»Ρ ΠΊΠ°Π»ΡΡΠΈΡ Π² ΡΠ°Π·Π²ΠΈΡΠΈΠΈ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ 88 ΡΠ°Π±Π°ΠΈΠ½Π°
- 4. 2. 2. Π ΠΎΠ»Ρ Ras, PI3K ΠΈ ΠΏΡΠΎΡΠ΅ΠΈΠ½ΠΊΠΈΠ½Π°Π· Π² ΡΠ°Π·Π²ΠΈΡΠΈΠΈ ΡΠΌΠ΅ΡΡΠΈ 89 ΠΊΠ»Π΅ΡΠΎΠΊ, Π²ΡΠ·Π²Π°Π½Π½ΠΎΠΉ ΡΠ°Π±Π°ΠΈΠ½ΠΎΠΌ
- 4. 2. 3. Π ΠΎΠ»Ρ Π°ΠΊΡΠΈΠ²Π½ΡΡ ΡΠΎΡΠΌ ΠΊΠΈΡΠ»ΠΎΡΠΎΠ΄Π° (ΠΠ€Π) Π² ΠΈΠ½Π΄ΡΠΊΡΠΈΠΈ 92 ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΡΠ°Π±Π°ΠΈΠ½Π°
- 4. 2. 4. Π ΠΎΠ»Ρ Π±Π΅Π»ΠΊΠΎΠ² ΡΠΈΡΠΎΡΠΊΠ΅Π»Π΅ΡΠ° Π² ΠΈΠ½Π΄ΡΠΊΡΠΈΠΈ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΠΎΠ΄ 95 Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΡΠ°Π±Π°ΠΈΠ½Π°
- 4. 2. 5. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΈΠ΅ ΡΠΎΠ»ΠΈ ΠΊΠ°Π²Π΅ΠΎΠ» Π² ΠΈΠ½Π΄ΡΠΊΡΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ 95 ΡΠΌΠ΅ΡΡΠΈ ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΡΠ°Π±Π°ΠΈΠ½Π°
- 4. 2. 6. Π ΠΎΠ»Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π³Π΅Π½ΠΎΠ² de novo Π² ΠΈΠ½Π΄ΡΠΊΡΠΈΠΈ ΡΠΌΠ΅ΡΡΠΈ 97 ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΡΠ°Π±Π°ΠΈΠ½Π°
- 4. 2. 7. Π ΠΎΠ»Ρ ΡΠ Π² ΡΠ°Π·Π²ΠΈΡΠΈΠΈ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ 100 ΡΠ°Π±Π°ΠΈΠ½Π°
- 4. 3. ΠΡΡΠ²Π»Π΅Π½ΠΈΠ΅ Π±Π΅Π»ΠΊΠΎΠ², Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΡΡΡΠΈΡ Ρ Na, Π- 114 ΠΠ’Π Π°Π·ΠΎΠΉ
- 4. 4. ΠΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ Π±Π΅Π»ΠΊΠΎΠ², Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΡΡΡΠΈΡ Ρ 145 Π°-ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ΅ΠΉ Na, K-ATPa3bi Π² ΠΎΡΠ²Π΅Ρ Π½Π° ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΠ΅ ΡΠ°Π±Π°ΠΈΠ½Π°
- 5. 1. Π‘ΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· Π΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΠ’Π‘
- 5. 2. ΠΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ ^^Π^-Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΠΎΠ³ΠΎ 155 ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΊΠ°ΡΠΊΠ°Π΄Π°, Π·Π°ΠΏΡΡΠΊΠ°Π΅ΠΌΠΎΠ³ΠΎ ΠΠ’Π‘ ΠΈ ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΠ΅Π³ΠΎ ΠΊ ΡΠΌΠ΅ΡΡΠΈ ΡΠΏΠΈΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ
- 5. 2. 1. Π ΠΎΠ»Ρ ΠΈΠ·Π²Π΅ΡΡΠ½ΡΡ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΡ ΠΊΠ°ΡΠΊΠ°Π΄ΠΎΠ², Π·Π°ΠΏΡΡΠΊΠ°Π΅ΠΌΡΡ 155 ΠΠ’Π‘
- 5. 2. 2. Π ΠΎΠ»Ρ ΡΠ 160 5.3. ΠΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ Π±Π΅Π»ΠΊΠΎΠ², Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΡΡΡΠΈΡ Ρ 162 Π°-ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ΅ΠΉ Na, K-ATPa3b
Na, K-ΠΠ’Π Π°Π·Π° ΠΊΠ°ΠΊ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΡΡ Π³Π»ΠΈΠΊΠΎΠ·ΠΈΠ΄ΠΎΠ²: ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΊΠ°ΡΠΊΠ°Π΄Π°, Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΠΎΠ³ΠΎ ΠΎΡ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΉ Na+ ΠΈ K+ (ΡΠ΅ΡΠ΅ΡΠ°Ρ, ΠΊΡΡΡΠΎΠ²Π°Ρ, Π΄ΠΈΠΏΠ»ΠΎΠΌ, ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½Π°Ρ)
Na, K-ATPa3a (β, Π-Π°ΠΊΡΠΈΠ²ΠΈΡΡΠ΅ΠΌΠ°Ρ, Mg-Π·Π°Π²ΠΈΡΠΈΠΌΠ°Ρ Π°Π΄Π΅Π½ΠΎΠ·ΠΈΠ½ΡΡΠΈΡΠΎΡΡΠΎΠ³ΠΈΠ΄ΡΠΎΠ»Π°Π·Π°, ΠΠ€ 3.6.1.3) Π±ΡΠ»Π° Π²ΠΏΠ΅ΡΠ²ΡΠ΅ ΠΎΠΏΠΈΡΠ°Π½Π° ΠΠ΅Π½ΡΠΎΠΌ Π‘ΠΊΠΎΡ Π² 1957 Π³ΠΎΠ΄Ρ (Skou, 1957). Π€Π΅ΡΠΌΠ΅Π½Ρ ΠΏΡΠΈΡΡΡΡΡΠ²ΡΠ΅Ρ Π² ΠΏΠ»Π°Π·ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Π΅ Π²ΡΠ΅Ρ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ ΠΈ ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΠ΅Ρ ΡΠ»Π΅ΠΊΡΡΠΎΠ³Π΅Π½Π½ΡΠΉ ΠΎΠ±ΠΌΠ΅Π½ ΡΡΠ΅Ρ ΠΈΠΎΠ½ΠΎΠ² Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ Na+ Π½Π° Π΄Π²Π° ΠΈΠΎΠ½Π° Π²Π½Π΅ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ Π+, ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΡ Π΄Π»Ρ ΡΡΠ°Π½ΡΠΏΠΎΡΡΠ° ΠΈΠΎΠ½ΠΎΠ² ΡΠ½Π΅ΡΠ³ΠΈΡ, Π²ΡΡΠ²ΠΎΠ±ΠΎΠΆΠ΄Π°ΡΡΡΡΡΡ ΠΏΡΠΈ Π³ΠΈΠ΄ΡΠΎΠ»ΠΈΠ·Π΅ ΠΠ’Π .
Na, K-ATPa3a ΡΠΎΡΡΠΎΠΈΡ ΠΈΠ· ΠΏΠΎΠ»ΠΈΠΏΠ΅ΠΏΡΠΈΠ΄Π½ΡΡ ΡΠ΅ΠΏΠ΅ΠΉ Π΄Π²ΡΡ ΡΠΈΠΏΠΎΠ², Π½Π°Π·Π²Π°Π½Π½ΡΡ Π°ΠΈ Π -ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ°ΠΌΠΈ. Π°-Π‘ΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ° ΠΈΠΌΠ΅Π΅Ρ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΡ ΠΌΠ°ΡΡΡ ΠΎΠΊΠΎΠ»ΠΎ 110 ΠΊΠΠ°, Π° Ρ-ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ° ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅Ρ ΡΠΎΠ±ΠΎΠΉ Π³Π»ΠΈΠΊΠΎΠΏΡΠΎΡΠ΅ΠΈΠ΄, ΠΈ Π² Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ Π³Π»ΠΈΠΊΠΎΠ·ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π΅Ρ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½Π°Ρ ΠΌΠ°ΡΡΠ° Π² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ ΡΠΊΠ°Π½ΡΡ ΡΠΎΡΡΠ°Π²Π»ΡΠ΅Ρ ΠΎΡ 40 Π΄ΠΎ 60 ΠΊΠΠ°. Π°-Π‘ΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ° Na, K-ATPa3bi, ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠ°Ρ ΡΡΠ°ΡΡΠΊΠΈ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ ΠΠ’Π , Π½Π°ΡΡΠΈΡ ΠΈ ΠΊΠ°Π»ΠΈΡ, ΡΠΏΠΎΡΠΎΠ±Π½Π° ΠΏΠΎΠ»Π½ΠΎΡΡΡΡ Π²ΡΠΏΠΎΠ»Π½ΡΡΡ ΠΊΠ°ΡΠ°Π»ΠΈΡΠΈΡΠ΅ΡΠΊΡΡ ΡΡΠ½ΠΊΡΠΈΡ ΠΈ Π² ΠΏΡΠΎΡΠ΅ΡΡΠ΅ ΠΊΠ°ΡΠ°Π»ΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΈΠΊΠ»Π° ΠΏΠΎΠ΄Π²Π΅ΡΠ³Π°Π΅ΡΡΡ ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ-Π΄Π΅ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ. Π -Π‘ΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ° ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΠΌ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠΎΠΌ Na, K-ΠΠ’Π Π°Π·Ρ, Ρ ΠΎΡΡ Π½Π΅ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ ΡΡΠ°ΡΡΠΈΡ Π² ΠΊΠ°ΡΠ°Π»ΠΈΠ·Π΅ ΡΡΠ° ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ° Π½Π΅ ΠΏΡΠΈΠ½ΠΈΠΌΠ°Π΅Ρ, Π½ΠΎ Π²Π»ΠΈΡΠ΅Ρ Π½Π° ΡΡΠ°Π½ΡΠΏΠΎΡΡΠ½ΡΠ΅ ΡΡΠ½ΠΊΡΠΈΠΈ ΡΠ΅ΡΠΌΠ΅Π½ΡΠ°, ΠΈΠ·ΠΌΠ΅Π½ΡΡ ΡΡΠΎΠ΄ΡΡΠ²ΠΎ ΠΊ ΠΈΠΎΠ½Π°ΠΌ Π+. Π -ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ° ΠΈΠ³ΡΠ°Π΅Ρ Π²Π°ΠΆΠ½ΡΡ ΡΠΎΠ»Ρ Π² ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠ°Π½ΠΈΠΈ Π½Π°ΡΠΈΠ²Π½ΠΎΠΉ ΡΡΡΡΠΊΡΡΡΡ ΠΊΠ°ΡΠ°Π»ΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΡ β, Π-ΠΠ’Π Π°Π·Ρ. Π ΡΠΎΡΡΠ°Π²Π΅ ΠΎΡΠΈΡΠ΅Π½Π½ΡΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² Na, K-ATPa3bi ΠΏΠΎΡΠ΅ΠΊ ΠΊΡΠΎΠΌΠ΅ Π°ΠΈ Ρ-ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡ ΠΏΡΠΈΡΡΡΡΡΠ²ΡΠ΅Ρ Π±Π΅Π»ΠΊΠΎΠ²ΡΠΉ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½Ρ, Π°ΡΡΠΎΡΠΈΠΈΡΠΎΠ²Π°Π½Π½ΡΠΉ Ρ Na-Π½Π°ΡΠΎΡΠΎΠΌ, ΠΈ ΠΊΠΎΡΠΎΡΡΠΉ Π±ΡΠ» Π½Π°Π·Π²Π°Π½ Ρ-ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ΅ΠΉ (Forbush et al., 1978). Π ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°Ρ ΡΠ΅ΡΠΌΠ΅Π½ΡΠ°, ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ ΠΈΠ· Π΄ΡΡΠ³ΠΈΡ ΠΈΡΡΠΎΡΠ½ΠΈΠΊΠΎΠ², Ρ-ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ° Π½Π΅ Π²ΡΡΠ²Π»Π΅Π½Π°, ΠΈ, ΠΏΠΎ-Π²ΠΈΠ΄ΠΈΠΌΠΎΠΌΡ, Π΅Ρ ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠ΅ Π½Π΅ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΎΠ±ΡΠ·Π°ΡΠ΅Π»ΡΠ½ΡΠΌ. Π ΡΠ²ΡΠ·ΠΈ Ρ ΡΡΠΈΠΌ ΠΏΡΠΈΠ½ΡΡΠΎ ΡΡΠΈΡΠ°ΡΡ, ΡΡΠΎ Na, K-ATPa3a ΡΠΎΡΡΠΎΠΈΡ ΡΠΎΠ»ΡΠΊΠΎ ΠΈΠ· Π΄Π²ΡΡ ΡΠΈΠΏΠΎΠ² ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡ.
ΠΠ·Π²Π΅ΡΡΠ½ΠΎ, ΡΡΠΎ β, Π-ΠΠ’Π Π°Π·Π° ΠΈΠ³ΡΠ°Π΅Ρ ΠΊΠ»ΡΡΠ΅Π²ΡΡ ΡΠΎΠ»Ρ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ ΠΎΠ΄Π½ΠΎΠ²Π°Π»Π΅Π½ΡΠ½ΡΡ ΠΊΠ°ΡΠΈΠΎΠ½ΠΎΠ², Π² ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠ°Π½ΠΈΠΈ ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Π½ΠΎΠ³ΠΎ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»Π°, ΠΎΠ±ΡΠ΅ΠΌΠ° ΠΊΠ»Π΅ΡΠΊΠΈ, ΡΠΎΠΏΡΡΠΆΠ΅Π½Π½ΠΎΠ³ΠΎ ΡΡΠ°Π½ΡΠΏΠΎΡΡΠ° Na+ ΠΈ.
2+ + Π°ΠΌΠΈΠ½ΠΎΠΊΠΈΡΠ»ΠΎΡ, Π³Π»ΡΠΊΠΎΠ·Ρ, Π½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄ΠΎΠ² ΠΈ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ ΠΈΠΎΠ½ΠΎΠ² (Π½Π°ΠΏΡΠΈΠΌΠ΅Ρ, Π‘Π°, Π) ΡΠ΅ΡΠ΅Π· ΠΏΠ»Π°Π·ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΡΡ ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Ρ (Lang et al., 2000; Mongin, Orlov, 2001; Blanco, Mercer, 1998). ΠΠ΅ΡΠ΄ΠΈΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎ, ΡΡΠΎ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π΄Π°Π½Π½ΠΎΠ³ΠΎ ΡΠ΅ΡΠΌΠ΅Π½ΡΠ° Π²Π»ΠΈΡΠ΅Ρ Π½Π° ΡΠ΅Π»ΡΠΉ ΡΡΠ΄ ΠΏΡΠΎΡΠ΅ΡΡΠΎΠ² Π² ΠΊΠ»Π΅ΡΠΊΠ΅. Π’Π°ΠΊ, Π½Π°ΠΏΡΠΈΠΌΠ΅Ρ, ΡΠ°Π±Π°ΠΈΠ½ ΠΈ Π΄ΡΡΠ³ΠΈΠ΅ ΠΊΠ°ΡΠ΄ΠΈΠΎΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΡΠ΅ΡΠΎΠΈΠ΄Ρ (ΠΠ’Π‘), ΠΈΠ½Π³ΠΈΠ±ΠΈΡΡΡΡΠΈΠ΅ Π«Π°, Π-ΠΠ’Π Π°Π·Ρ ΠΏΡΡΠ΅ΠΌ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ Ρ Π΅Ρ Π°-ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ΅ΠΉ, ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡ ΠΊ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΡ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ Na+, ΡΡΠΎ Π² ΡΠ²ΠΎΡ ΠΎΡΠ΅ΡΠ΅Π΄Ρ Π°ΠΊΡΠΈΠ²ΠΈΡΡΠ΅Ρ ΠΠ°+/Π‘Π°2±ΠΎΠ±ΠΌΠ΅Π½Π½ΠΈΠΊ ΠΈ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»-Π°ΠΊΡΠΈΠ²ΠΈΡΡΠ΅ΠΌΡΠ΅ Π‘Π°2+ ΠΊΠ°Π½Π°Π»Ρ (Lang et al.,.
Π I.
1998; Lang et al., 1992). ΠΡΠΈ ΡΡΠΎΠΌ Π²ΠΎΠ·ΡΠ°ΡΡΠ°Π΅Ρ ΡΡΠΎΠ²Π΅Π½Ρ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ Π‘Π°, ΡΡΠΎ Π²Π΅Π΄Π΅Ρ ΠΊ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΡ ΡΠΎΠΊΡΠ°ΡΠ΅Π½ΠΈΡ ΠΊΠ°ΡΠ΄ΠΈΠΎΠΌΠΈΠΎΡΠΈΡΠΎΠ² (Blastein, Lederer, 1999).
ΠΠ° ΠΏΠΎΡΠ»Π΅Π΄Π½Π΅Π΅ Π²ΡΠ΅ΠΌΡ ΠΏΠΎΡΠ²ΠΈΠ»ΠΎΡΡ Π±ΠΎΠ»ΡΡΠΎΠ΅ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΡΠ°Π±ΠΎΡ, ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡΠΈΡ ΠΎ ΡΠΎΠΌ, ΡΡΠΎ ΠΏΠΎΠΌΠΈΠΌΠΎ ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠΉ ΡΡΠ½ΠΊΡΠΈΠΈ Na, K-ATPa3bi, ΡΠ²ΡΠ·Π°Π½Π½ΠΎΠΉ Ρ ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅ΠΌ Π½Π΅ΡΠ°Π²Π½ΠΎΠ²Π΅ΡΠ½ΠΎΠ³ΠΎ ΡΠ°ΡΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ Na+ ΠΈ Π+, ΡΡΠΎΡ ΡΠ΅ΡΠΌΠ΅Π½Ρ Π²ΡΡΡΡΠΏΠ°Π΅Ρ Π² ΡΠΎΠ»ΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ΠΊΠ°ΡΠ΄ΠΈΠΎΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ ΡΡΠ΅ΡΠΎΠΈΠ΄ΠΎΠ², ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΠ³ΠΎ Π²ΡΠ·ΡΠ²Π°ΡΡ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠΎΡΡΠΎΡΠ½ΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ. Π Π½Π°ΡΡΠΎΡΡΠ΅Π΅ Π²ΡΠ΅ΠΌΡ ΠΏΠΎΠ»ΡΡΠ΅Π½Ρ ΠΌΠ½ΠΎΠ³ΠΎΡΠΈΡΠ»Π΅Π½Π½ΡΠ΅ Π΄Π°Π½Π½ΡΠ΅, ΠΏΠΎΠΊΠ°Π·ΡΠ²Π°ΡΡΠΈΠ΅, ΡΡΠΎ ΠΊΠ°ΡΠ΄ΠΈΠΎΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΡΠ΅ΡΠΎΠΈΠ΄Ρ, ΠΈΠ½Π³ΠΈΠ±ΠΈΡΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Na, K-ATPa3bi, Π²ΡΠ·ΡΠ²Π°ΡΡ ΡΠ°ΠΊΠΆΠ΅ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΡ ΠΊΠ°ΡΠΊΠ°Π΄ΠΎΠ² ΠΊΠ»Π΅ΡΠΊΠΈ. Π‘ΡΠ΅Π΄ΠΈ Π½ΠΈΡ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΠ΅ ΠΊΠ°ΡΠΊΠ°Π΄Ρ Ρ ΡΡΠ°ΡΡΠΈΠ΅ΠΌ ΠΏΡΠΎΡΠ΅ΠΈΠ½ΠΊΠΈΠ½Π°Π· Ras/Raf/MEK/Erk 1 /2 (Ρ42/44 ΠΠΠ Π) (Kometiani et al., 1998) ΠΈ Π°ΠΊΡΠΈΠ²Π½ΡΡ ΡΠΎΡΠΌ ΠΊΠΈΡΠ»ΠΎΡΠΎΠ΄Π° (Xie et al., 1999), Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ ΠΊΠΎΡΠΎΡΡΡ Π² ΡΠ²ΠΎΡ ΠΎΡΠ΅ΡΠ΅Π΄Ρ Π²Π»ΠΈΡΠ΅Ρ Π½Π° ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΡΡΠ΄Π° Π³Π΅Π½ΠΎΠ² (Xie et al., 2002; Taurin et al., 2003), Π²ΠΊΠ»ΡΡΠ°Ρ Π³Π΅Π½Ρ, Π²ΠΎΠ²Π»Π΅ΡΠ΅Π½Π½ΡΠ΅ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΡ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΈ ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΌΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΡΠΌΠ΅ΡΡΠΈ (Π°ΠΏΠΎΠΏΡΠΎΠ·Π°) (Orlov et al., 2005; Taurin et al., 2003). ΠΠ»Ρ ΠΊΠ»Π΅ΡΠΎΠΊ Π³Π»Π°Π΄ΠΊΠΎΠΉ ΠΌΡΡΠΊΡΠ»Π°ΡΡΡΡ ΡΠΎΡΡΠ΄ΠΎΠ² (VSMC) Π±ΡΠ» ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ Π·Π°ΡΠΈΡΠ½ΡΠΉ ΡΡΡΠ΅ΠΊΡ ΡΠ°Π±Π°ΠΈΠ½Π°, ΠΏΡΠ΅Π΄ΠΎΡΠ²ΡΠ°ΡΠ°ΡΡΠΈΠΉ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ Π°ΠΏΠΎΠΏΡΠΎΠ·Π° ΠΊΠ»Π΅ΡΠΎΠΊ, Π²ΡΠ·Π²Π°Π½Π½ΠΎΠ³ΠΎ ΠΎΡΡΡΡΡΡΠ²ΠΈΠ΅ΠΌ ΡΠΎΡΡΠΎΠ²ΡΡ ΡΠ°ΠΊΡΠΎΡΠΎΠ² (Orlov et al., 1999). ΠΡΠ»ΠΎ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ Π²Π°ΠΆΠ½ΡΡ ΡΠΎΠ»Ρ Π² Π°Π½ΡΠΈΠ°ΠΏΠΎΠΏΡΠΎΡΠΈΡΠ΅ΡΠΊΠΎΠΌ Π΄Π΅ΠΉΡΡΠ²ΠΈΠΈ ΡΠ°Π±Π°ΠΈΠ½Π° ΠΈΠ³ΡΠ°Π΅Ρ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΡ [Na+]b ΡΡΠΎ Π²Π΅Π΄Π΅Ρ ΠΊ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π°Π½ΡΠΈΠ°ΠΏΠΎΠΏΡΠΎΡΠΈΡΠ΅ΡΠΊΠΈΡ Π³Π΅Π½ΠΎΠ² (Taurin et al., 2002Π°Taurin et al., 2002b).
ΠΠ΅Π΄Π°Π²Π½ΠΎ Π² Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠΈΠΈ ΠΡΠ»ΠΎΠ²Π° Π‘. Π. Π±ΡΠ»ΠΎ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ, Π² ΠΎΡΠ»ΠΈΡΠΈΠ΅ ΠΎΡ VSMC, Π² ΡΠΏΠΈΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΡΡ ΠΊΠ»Π΅ΡΠΊΠ°Ρ ΠΏΠΎΡΠ΅ΠΊ ΡΠΎΠ±Π°ΠΊΠΈ (C7-MDCK) ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΡΠ°Π±Π°ΠΈΠ½Π° Π½Π°Π±Π»ΡΠ΄Π°Π΅ΡΡΡ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΊΠ°ΡΠΊΠ°Π΄Π°, ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΠ΅Π³ΠΎ ΠΊ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΠΎ ΠΎΡ Π²ΠΎΠ·ΡΠ°ΡΡΠ°Π½ΠΈΡ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΡ [ΠΠ°+]/[Π+^ (Π ΡΠ¬Π΅]Π΅1Π·1ΠΈ Π΅1 Π°1., 2003). ΠΡΠΎ ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΠ»ΠΎ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠΈΡΡ, ΡΡΠΎ ΠΌΠΎΠ³ΡΡ ΡΡΡΠ΅ΡΡΠ²ΠΎΠ²Π°ΡΡ ΡΠ°ΠΊΠΈΠ΅ ΠΠ’Π‘, ΠΊΠΎΡΠΎΡΡΠ΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΡΡΡ Π«Π°, Π-ΠΠ’Π Π°Π·Ρ, Π½Π΅ Π²Π»ΠΈΡΡ Π½Π° ΠΆΠΈΠ·Π½Π΅ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ, ΠΈ Π½Π°ΠΎΠ±ΠΎΡΠΎΡ. ΠΠΎΠΌΠΈΠΌΠΎ ΠΊΠ»Π΅ΡΠΎΠΊ Π»ΠΈΠ½ΠΈΠΈ Π‘7-ΠΠΠ‘Π, Π΄Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΡΠ°Π±Π°ΠΈΠ½Π° ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ Π³ΠΈΠ±Π΅Π»ΠΈ ΡΡΠ΄Π° Π΄ΡΡΠ³ΠΈΡ ΡΠΈΠΏΠΎΠ² ΠΊΠ»Π΅ΡΠΎΠΊ, Π²ΠΊΠ»ΡΡΠ°Ρ ΡΠ½Π΄ΠΎΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΡΠ΅ ΠΊΠ»Π΅ΡΠΊΠΈ Π°ΠΎΡΡΡ ΡΠ²ΠΈΠ½ΡΠΈ (Π ΠΠΠ‘) ΠΈ ΡΠΏΠΈΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΡΠ΅ ΠΊΠ»Π΅ΡΠΊΠΈ ΠΊΠΈΡΠ΅ΡΠ½ΠΈΠΊΠ° ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° (Π‘Π°ΡΠΎ-2) (ΠΠ³1ΠΎΡ Π΅1 Π°1., 2005). ΠΠ°ΠΊ ΠΈ Π² ΡΠ»ΡΡΠ°Π΅ Π‘7-ΠΠΠ‘Π ΠΊΠ»Π΅ΡΠΎΠΊ, ΡΠΌΠ΅ΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ Π»ΠΈΠ½ΠΈΠΈ Π ΠΠΠ ΠΈ Π‘Π°ΡΠΎ-2 Π½Π΅ Π·Π°Π²ΠΈΡΠΈΡ ΠΎΡ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ ΡΠ°Π±Π°ΠΈΠ½Π° Π½Π° Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ΅ ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠ΅ |ΠͺΠΠ°+]/[Π+]-. ΠΠΎ Π½Π°ΡΡΠΎΡΡΠ΅Π³ΠΎ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ, ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠΉ ΡΠ°Π±Π°ΠΈΠ½ΠΎΠΌ, ΠΎΡΡΠ°Π΅ΡΡΡ ΠΌΠ°Π»ΠΎ ΠΈΠ·ΡΡΠ΅Π½Π½ΡΠΌ. Π ΠΏΠ΅ΡΠ²ΠΎΠΉ ΡΠ°ΡΡΠΈ ΡΠ°Π±ΠΎΡΡ ΠΌΡ ΡΡΠ°Π²Π½ΠΈΠ»ΠΈ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΡ ΡΡΠ΄Π° ΠΊΠ°ΡΠ΄ΠΈΠΎΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ ΡΡΠ΅ΡΠΎΠΈΠ΄ΠΎΠ² ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°ΡΡ ΠΠ°, Π-Π½Π°ΡΠΎΡ, ΠΈΠ·ΠΌΠ΅Π½ΡΡΡ ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠ΅ ΠΈ [Π+]- ΠΈ Π²ΠΊΠ»ΡΡΠ°ΡΡ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΠΉ ΠΊΠ°ΡΠΊΠ°Π΄, ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΠΈΠΉ ΠΊ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ Π»ΠΈΠ½ΠΈΠΈ Π‘7-ΠΠΠ‘Π. ΠΠΎ Π²ΡΠΎΡΠΎΠΉ ΡΠ°ΡΡΠΈ ΡΠ°Π±ΠΎΡΡ ΠΌΡ ΠΏΡΠ΅Π΄ΠΏΡΠΈΠ½ΡΠ»ΠΈ ΠΏΠΎΠΏΡΡΠΊΡ ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°ΡΡ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠΉ ΠΊΠ°ΡΠΊΠ°Π΄, Π·Π°ΠΏΡΡΠΊΠ°Π΅ΠΌΡΠΉ ΠΠ’Π‘ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π»ΠΈΠ½ΠΈΠΈ Π‘7-ΠΠΠ‘Π ΠΈ Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΡΠΉ ΠΎΡ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΡ [ΠΠ°+]-/[Π+]]. Π‘ ΡΠ΅Π»ΡΡ ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ Π½Π°ΡΠ°Π»ΡΠ½ΡΡ Π·Π²Π΅Π½ΡΠ΅Π² ΡΡΠΎΠ³ΠΎ ΠΊΠ°ΡΠΊΠ°Π΄Π°, ΠΌΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π»ΠΈ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ΠΠ’Π‘ Π½Π° Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ Π°-ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΡ β, Π-ΠΠ’Π Π°Π·Ρ Ρ Π΄ΡΡΠ³ΠΈΠΌΠΈ Π±Π΅Π»ΠΊΠ°ΠΌΠΈ, ΠΏΡΠΈΠΌΠ΅Π½ΠΈΠ² ΠΌΠ΅ΡΠΎΠ΄ ΠΈΠΌΠΌΡΠ½ΠΎΠΏΡΠ΅ΡΠΈΠΏΠΈΡΠ°ΡΠΈΠΈ, Π΄Π²ΡΠΌΠ΅ΡΠ½ΠΎΠ³ΠΎ ΡΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅Π·Π° ΠΈ ΠΌΠ°ΡΡ-ΡΠΏΠ΅ΠΊΡΡΠΎΠΌΠ΅ΡΡΠΈΠΈ. ΠΡΠΈ Π΄Π°Π½Π½ΡΠ΅ ΡΡΠΌΠΌΠΈΡΠΎΠ²Π°Π½Ρ Π² Π·Π°ΠΊΠ»ΡΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠΉ ΡΠ°ΡΡΠΈ Π½Π°ΡΠ΅ΠΉ ΡΠ°Π±ΠΎΡΡ.
2. ΠΠ±Π·ΠΎΡ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ.
2.1. Na, K-ATPa3a: ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½Π°Ρ ΡΡΡΡΠΊΡΡΡΠ°, ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌ ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈ ΡΠ΅Π³ΡΠ»ΡΡΠΈΡ.
6.
ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅
.
ΠΠ°ΡΠΈΠ½Π°Ρ Ρ 60-Ρ Π³ΠΎΠ΄ΠΎΠ² ΠΏΡΠΎΡΠ»ΠΎΠ³ΠΎ ΡΡΠΎΠ»Π΅ΡΠΈΡ, ΡΠ°Π±Π°ΠΈΠ½ ΠΈ ΡΠΎΠ΄ΡΡΠ²Π΅Π½Π½ΡΠ΅ Π΅ΠΌΡ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΈΠ·Π²Π΅ΡΡΠ½Ρ ΠΊΠ°ΠΊ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΡ Na, K-ATPa3bi (Na-Hacoca). ΠΠ° ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΠ΅ Π΄Π²Π° Π΄Π΅ΡΡΡΠΈΠ»Π΅ΡΠΈΡ ΠΏΠΎΡΠ²ΠΈΠ»ΠΎΡΡ Π±ΠΎΠ»ΡΡΠΎΠ΅ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΡΠ°Π±ΠΎΡ, ΠΏΠΎΠΊΠ°Π·ΡΠ²Π°ΡΡΠΈΡ , ΡΡΠΎ ΡΠ°Π±Π°ΠΈΠ½ Π²ΡΠ·ΡΠ²Π°Π΅Ρ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΡ ΠΊΠ°ΡΠΊΠ°Π΄ΠΎΠ² ΠΊΠ»Π΅ΡΠΊΠΈ, Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ ΠΏΡΠΎΡΠ΅ΠΈΠ½ΠΊΠΈΠ½Π°Π· Ras/Raf/MEK/Erkl/2 (Ρ42/44 ΠΠΠ Π) (Kometiani et al., 1998), ΠΏΡΠΎΠ΄ΡΠΊΡΠΈΡ Π°ΠΊΡΠΈΠ²Π½ΡΡ ΡΠΎΡΠΌ ΠΊΠΈΡΠ»ΠΎΡΠΎΠ΄Π° (Xie et al., 1999; Liu et al., 2000; Valente et al., 2003), ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΡΡΠ΄Π° Π³Π΅Π½ΠΎΠ² (Peng et al., 1996; Huang et al., 1997; Qin et al., 1994), Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ Π³Π΅Π½ΠΎΠ², Π²ΠΎΠ²Π»Π΅ΡΠ΅Π½Π½ΡΡ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΡΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ. ΠΡΠΈ ΡΡΠΎΠΌ Π² ΠΊΠ°ΡΠ΄ΠΈΠΎΠΌΠΈΠΎΡΠΈΡΠ°Ρ , Π³Π΄Π΅ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΎ Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²ΠΎ ΡΡΠΈΡ ΡΡΡΠ΅ΠΊΡΠΎΠ², Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΡΠ°Π±Π°ΠΈΠ½Π° ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½ΠΎ ΠΊΠ°ΠΊ ΠΌΠΈΠ½ΠΈΠΌΡΠΌ Π΄Π²ΡΠΌΡ ΠΏΡΠΈΡΠΈΠ½Π°ΠΌΠΈ: 1) ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ΠΌ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ Na+ (ΡΡΠΎ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ Π‘Π°2+ ΠΈ Π²ΠΊΠ»ΡΡΠ΅Π½ΠΈΡ ΡΡΠ΄Π° Π‘Π°2±Π·Π°Π²ΠΈΡΠΈΠΌΡΡ ΠΊΠ°ΡΠΊΠ°Π΄ΠΎΠ²) — 2) ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΠ΅ΠΌ Ρ Π«Π°, Π-ΠΠ’Π Π°Π·ΠΎΠΉ Src-ΠΊΠΈΠ½Π°Π·Ρ, ΠΊΠΎΡΠΎΡΠ°Ρ Π²ΡΠ»Π΅Π΄ΡΡΠ²ΠΈΠ΅ ΡΡΠΎΠ³ΠΎ Π°ΠΊΡΠΈΠ²ΠΈΡΡΠ΅ΡΡΡ ΠΈ ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΡΠ΅Ρ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ ΡΠΏΠΈΠ΄Π΅ΡΠΌΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ°ΠΊΡΠΎΡΠ° ΡΠΎΡΡΠ°, ΡΡΠΎ Π°ΠΊΡΠΈΠ²ΠΈΡΡΠ΅Ρ Π΄ΡΡΠ³ΠΈΠ΅ ΠΊΠ°ΡΠΊΠ°Π΄Ρ. ΠΠ° ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π³Π»Π°Π΄ΠΊΠΎΠΉ ΠΌΡΡΠΊΡΠ»Π°ΡΡΡΡ ΡΠΎΡΡΠ΄ΠΎΠ² (VSMC) Π±ΡΠ»ΠΎ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ ΡΠ°Π±Π°ΠΈΠ½ Π·Π°ΡΠΈΡΠ°Π΅Ρ ΠΊΠ»Π΅ΡΠΊΠΈ ΠΎΡ ΡΠ°Π·Π²ΠΈΡΠΈΡ Π°ΠΏΠΎΠΏΡΠΎΠ·Π°, Π²ΡΠ·Π²Π°Π½Π½ΠΎΠ³ΠΎ ΡΠ΄Π°Π»Π΅Π½ΠΈΠ΅ΠΌ ΡΠΎΡΡΠΎΠ²ΡΡ ΡΠ°ΠΊΡΠΎΡΠΎΠ² (Orlov et al., 1999). Π ΡΡΠΎΠΌ ΡΠ»ΡΡΠ°Π΅ ΡΡΡΠ΅ΠΊΡ ΡΠ°Π±Π°ΠΈΠ½Π° ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½ ΠΈΡΠΊΠ»ΡΡΠΈΡΠ΅Π»ΡΠ½ΠΎ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅ΠΌ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ Na+, ΡΡΠΎ ΠΈΠ½Π΄ΡΡΠΈΡΡΠ΅Ρ ΡΠΈΠ½ΡΠ΅Π· Π±Π΅Π»ΠΊΠΎΠ² de novo (ΡΡΡΠ»ΠΊΠ°). Π ΠΎΡΠ»ΠΈΡΠΈΠ΅ ΠΎΡ VSMC, Π΄Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΡΠ°Π±Π°ΠΈΠ½Π° ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ Π³ΠΈΠ±Π΅Π»ΠΈ ΡΠΏΠΈΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΠΎΡΠ΅ΠΊ Π»ΠΈΠ½ΠΈΠΈ C7-MDCK, ΠΏΡΠΈΡΠ΅ΠΌ Π² ΠΎΡΠ»ΠΈΡΠΈΠ΅ ΠΎΡ ΠΏΠ΅ΡΠ²ΡΡ Π΄Π²ΡΡ ΡΠΈΠΏΠΎΠ² ΠΊΠ»Π΅ΡΠΎΠΊ ΡΡΠΎΡ ΡΡΡΠ΅ΠΊΡ ΡΠ°Π·Π²ΠΈΠ²Π°Π΅ΡΡΡ Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΠΎ ΠΎΡ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΡ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ [Na+]j/[K+]j (Pchejetski et al., 2003).
ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ, ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π½ΡΠ΅ Π² 80−90 Π³ΠΎΠ΄Ρ ΠΏΡΠΎΡΠ»ΠΎΠ³ΠΎ ΡΡΠΎΠ»Π΅ΡΠΈΡ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ, ΡΡΠΎ ΡΠ°Π±Π°ΠΈΠ½ ΠΈ Π΅Π³ΠΎ Π°Π½Π°Π»ΠΎΠ³ΠΈ, ΠΏΡΠΈΡΡΡΡΡΠ²ΡΡΡ Π½Π΅ ΡΠΎΠ»ΡΠΊΠΎ Ρ ΡΠ°ΡΡΠ΅Π½ΠΈΠΉ (ΠΊΠ°ΡΠ΄Π΅Π½Π΅Π»ΠΈΠ΄Ρ) ΠΈ Π² ΡΠ»ΠΈΠ·ΠΈ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ Π±Π΅ΡΠΏΠΎΠ·Π²ΠΎΠ½ΠΎΡΠ½ΡΡ (Π±ΡΡΠ°Π΄ΠΈΠ΅Π½ΠΎΠ»ΠΈΠ΄Ρ), Π½ΠΎ ΠΈ ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΡΡΡΡΡ Ρ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ Π² Π½Π°Π΄ΠΏΠΎΡΠ΅ΡΠ½ΠΈΠΊΠ°Ρ ΠΈ Π³ΠΈΠΏΠΎΡΠ°Π»Π°ΠΌΡΡΠ΅ ΠΈ, ΠΏΠΎ-Π²ΠΈΠ΄ΠΈΠΌΠΎΠΌΡ, ΡΡΠ½ΠΊΡΡΠΎΠ½ΠΈΡΡΡΡ ΠΊΠ°ΠΊ Π³ΠΎΡΠΌΠΎΠ½Ρ. ΠΡΠΈΡΡΡΡΡΠ²ΠΈΠ΅ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ Π²ΠΈΠ΄ΠΎΠ² ΠΊΠ°ΡΠ΄ΠΈΠΎΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ ΡΡΠ΅ΡΠΎΠΈΠ΄ΠΎΠ² Π² ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ°Ρ ΠΌΠ»Π΅ΠΊΠΎΠΏΠΈΡΠ°ΡΡΠΈΡ ΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠ΅ ΡΡΡΠ΅ΠΊΡΡ ΡΠ°Π±Π°ΠΈΠ½Π° Π½Π° ΡΠ°Π·Π½ΡΠ΅ ΡΠΈΠΏΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΠ»ΠΈ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠΈΡΡ, ΡΡΠΎ ΠΌΠΎΠ³ΡΡ ΡΡΡΠ΅ΡΡΠ²ΠΎΠ²Π°ΡΡ ΠΊΠ°ΡΠ΄ΠΈΠΎΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΡΠ΅ΡΠΎΠΈΠ΄Ρ, ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎ.
ΠΈΠ½Π³ΠΈΠ±ΠΈΡΡΡΡΠΈΠ΅ Na, K-ATPa3y, Π½Π΅ Π²Π»ΠΈΡΡ Π½Π° ΠΆΠΈΠ·Π½Π΅ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ, ΠΈ Π½Π°ΠΎΠ±ΠΎΡΠΎΡ. ΠΠΎΠ΄ΠΎΠ±Π½ΠΎ ΡΠ°Π±Π°ΠΈΠ½Ρ, Π΄ΡΡΠ³ΠΈΠ΅ ΠΊΠ°ΡΠ΄Π΅Π½ΠΎΠ»ΠΈΠ΄Ρ, Π° ΡΠ°ΠΊΠΆΠ΅ Π±ΡΡΠ°Π΄ΠΈΠ΅Π½ΠΎΠ»ΠΈΠ΄Ρ (Π±ΡΡΠ°Π»ΠΈΠ½, ΡΠΈΠ½ΠΎΠ±ΡΡΠ°ΡΠ°Π»ΠΈΠ½, ΡΠΈΠ½ΠΎΠ±ΡΡΠ°Π³ΠΈΠΈΠ½ ΠΈ ΡΠ΅Π»ΠΎΠ±ΡΡΠ°ΡΠΎΠΊΡΠΈΠ½), Π΄ΠΎΠ±Π°Π²Π»Π΅Π½Π½ΡΠ΅ ΠΊ ΠΊΠ»Π΅ΡΠΊΠ°ΠΌ MDCK, ΡΠ½ΠΈΠΆΠ°ΡΡ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎΡΡΡ ΠΎΠΊΡΠ°ΡΠΈΠ²Π°Π½ΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΠ’Π’ ΠΈ ΡΠΌΠ΅Π½ΡΡΠ°ΡΡ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΠΊΠ»Π΅ΡΠΎΠΊ, ΡΠΎΡ ΡΠ°Π½ΠΈΠ²ΡΠΈΡ ΡΠ²ΡΠ·Ρ Ρ ΠΏΠΎΠ΄Π»ΠΎΠΆΠΊΠΎΠΉ. Π‘ΠΌΠ΅ΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ Π»ΠΈΠ½ΠΈΠΈ C7-MDCK, Π²ΡΠ·Π²Π°Π½Π½Π°Ρ ΠΠ’Π‘, Π½Π΅ Π·Π°Π²ΠΈΡΠΈΡ ΠΎΡ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π«Π°, Π-ΠΠ’Π Π°Π·Ρ ΠΈ ΠΏΠΎΡΠ»Π΅Π΄ΡΡΡΠ΅Π³ΠΎ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΡ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΡ [Na+]?/[K+]?. ΠΡ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ, ΡΡΠΎ Π΄Π²Π° Π±ΡΡΠ°Π΄Π΅Π½ΠΎΠ»ΠΈΠ΄Π°: ΠΌΠ°ΡΠΈΠ½ΠΎΠ±ΡΡΠ°Π³Π΅Π½ΠΈΠ½ ΠΈ ΠΌΠ°ΡΠΈΠ½ΠΎΠ±ΡΡΠ°ΡΠΎΠΊΡΠΈΠ½ — ΡΠ²Π»ΡΡΡΡΡ ΡΠΈΠ»ΡΠ½ΡΠΌΠΈ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ°ΠΌΠΈ Na, K-ATPa3bi, Π½ΠΎ ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ Π΄ΡΡΠ³ΠΈΠΌΠΈ ΠΠ’Π‘ ΠΎΠ±Π»Π°Π΄Π°ΡΡ Π±ΠΎΠ»Π΅Π΅ ΡΠ»Π°Π±ΠΎΠΉ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΡΡ ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°ΡΡ ΡΠΌΠ΅ΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ, Π½Π΅Π·Π°Π²ΠΈΡΡΡΡΡ ΠΎΡ ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΡ [Na+]?/[K+]i.
Π Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΠ΅ ΠΌΡ ΠΏΠΎΡΡΠ°ΡΠ°Π»ΠΈΡΡ Π²ΡΡΡΠ½ΠΈΡΡ, ΠΊΠ°ΠΊΠΈΠ΅ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΠ΅ ΠΏΡΡΠΈ ΠΊΠ»Π΅ΡΠΊΠΈ ΡΡΠ°ΡΡΠ²ΡΡΡ Π² ΠΏΠ΅ΡΠ΅Π΄Π°ΡΠ΅ Π²ΡΠ·Π²Π°Π½Π½ΠΎΠ³ΠΎ ΡΠ°Π±Π°ΠΈΠ½ΠΎΠΌ ΡΠΈΠ³Π½Π°Π»Π° ΡΠΌΠ΅ΡΡΠΈ. ΠΡ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ, ΡΡΠΎ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ Π‘Π°2+, ΡΡΠΎΠ²Π½Ρ Π°ΠΊΡΠΈΠ²Π½ΡΡ ΡΠΎΡΠΌ ΠΊΠΈΡΠ»ΠΎΡΠΎΠ΄Π° Π½Π΅ ΠΈΠ³ΡΠ°Π΅Ρ ΠΊΠ»ΡΡΠ΅Π²ΠΎΠΉ ΡΠΎΠ»ΠΈ Π² ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΡΠΌΠ΅ΡΡΠΈ ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΡΠ°Π±Π°ΠΈΠ½Π°. Π‘ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ Π°ΠΊΡΠΈΠ²Π°ΡΠΎΡΠΎΠ² ΠΈ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠΎΠ² ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΡ ΠΏΡΡΠ΅ΠΉ ΠΌΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π»ΠΈ, Π½Π΅ ΡΡΠ°ΡΡΠ²ΡΡΡ Π»ΠΈ Π² ΠΏΠ΅ΡΠ΅Π΄Π°ΡΠ΅ ΡΠΈΠ³Π½Π°Π»Π° ΠΌΠ°Π»ΡΠΉ G-Π±Π΅Π»ΠΎΠΊ Ras, ΠΏΡΠΎΡΠ΅ΠΈΠ½ΠΊΠΈΠ½Π°Π·Ρ Erk, PI3K, Π° ΡΠ°ΠΊΠΆΠ΅ ΡΠ΅ΡΠΈΠ½-ΡΡΠ΅ΠΎΠ½ΠΈΠ½ΠΎΠ²ΡΠ΅ ΠΏΡΠΎΡΠ΅ΠΈΠ½ΠΊΠΈΠ·Ρ. ΠΠ΄Π½Π°ΠΊΠΎ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΡΡΠΎΠ³ΠΎ ΠΏΠΎΠ΄Ρ ΠΎΠ΄Π° ΠΌΡ Π½Π΅ ΠΎΠ±Π½Π°ΡΡΠΆΠΈΠ»ΠΈ ΠΊΠ°ΠΊΠΎΠ³ΠΎ-Π»ΠΈΠ±ΠΎ ΡΡΠ°ΡΡΠΈΡ Π½Π°Π·Π²Π°Π½Π½ΡΡ ΡΠΈΡΡΠ΅ΠΌ Π² ΠΏΠ΅ΡΠ΅Π΄Π°ΡΠ΅ ΡΠΈΠ³Π½Π°Π»Π°, Π²ΡΠ·Π²Π°Π½Π½ΠΎΠ³ΠΎ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΠ΅ΠΌ ΡΠ°Π±Π°ΠΈΠ½Π° Ρ Π«Π°, Π-ΠΠ’Π€Π°Π·ΠΎΠΉ ΠΈ ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΠ΅Π³ΠΎ ΠΊ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ. ΠΡΠΈ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠΈ ΡΠΎΠ»ΠΈ ΡΠ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΡΡΠ΅Π΄Ρ Π² ΡΠ°Π·Π²ΠΈΡΠΈΠΈ ΡΠΈΠ³Π½Π°Π»Π° ΡΠΌΠ΅ΡΡΠΈ ΠΌΡ ΠΎΠ±Π½Π°ΡΡΠΆΠΈΠ»ΠΈ, ΡΡΠΎ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ ΡΠ Ρ 7,36 Π΄ΠΎ 7,03 ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΠΏΠΎΠ»Π½ΠΎΠΌΡ ΠΏΠΎΠ΄Π°Π²Π»Π΅Π½ΠΈΡ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ, ΠΎΠ±ΡΠ°Π±ΠΎΡΠ°Π½Π½ΡΡ ΡΠ°Π±Π°ΠΈΠ½ΠΎΠΌ. ΠΠ°ΡΠΈ Π΄Π°Π½Π½ΡΠ΅ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠΈΡΡ, ΡΡΠΎ ΡΡΠΎΡ ΡΡΡΠ΅ΠΊΡ ΡΠ²ΡΠ·Π°Π½ Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠ΅ΠΉ de novo pH¡—ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΡΡ Π³Π΅Π½ΠΎΠ², Π²ΠΎΠ²Π»Π΅ΡΠ΅Π½Π½ΡΡ Π² Π·Π°ΡΠΈΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΎΡ ΠΎΠ½ΠΊΠΎΠ·Π°.
ΠΠΎΡΠΊΠΎΠ»ΡΠΊΡ ΠΏΠΎΠ΄Ρ ΠΎΠ΄ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠΎΠ² ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΡ ΠΊΠ°ΡΠΊΠ°Π΄ΠΎΠ² Π½Π΅ Π΄Π°Π» ΠΈΠ½ΡΠΎΡΠΌΠ°ΡΠΈΠΈ ΠΎ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΠ΅ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΠΈΠ³Π½Π°Π»Π°, ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠΈΠ²Π°ΡΡΠ΅Π³ΠΎ ΡΠΌΠ΅ΡΡΡ ΡΠΏΠΈΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ, Π° ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ ΡΠΈΠ³Π½Π°Π»Π° ΠΌΠΎΠΆΠ΅Ρ Π±ΡΡΡ Π²ΡΠ·Π²Π°Π½ΠΎ Π»ΠΈΡΡ Ρ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ Ρ ΠΠ°, Π-ΠΠ’Π€Π°Π·ΠΎΠΉ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ Π±Π΅Π»ΠΊΠΎΠ² Π² ΠΎΡΠ²Π΅Ρ Π½Π° ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΠ΅ Ρ Π½Π΅ΠΉ ΡΠ°Π±Π°ΠΈΠ½Π°, ΠΌΡ ΡΠ΅ΡΠΈΠ»ΠΈ Π½Π°ΠΉΡΠΈ ΠΈ ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°ΡΡ ΡΡΠΈ Π±Π΅Π»ΠΊΠΈ. ΠΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΈΠΌΠΌΡΠ½ΠΎΠΏΡΠ΅ΡΠΈΠΏΠΈΡΠ°ΡΠΈΠΈ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π΄Π²ΡΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ Π΄Π΅ΡΠ΅ΡΠ³Π΅Π½ΡΠΎΠ² Π±ΡΠ»ΠΎ.
Π²ΡΡΠ²Π»Π΅Π½ΠΎ Π΄Π²Π° Π½Π°Π±ΠΎΡΠ° Π±Π΅Π»ΠΎΠ², ΠΏΠΎΡΠ²Π»Π΅Π½ΠΈΠ΅ ΠΊΠΎΡΠΎΡΡΡ Π² ΠΈΠΌΠΌΡΠ½ΠΎΠΏΡΠ΅ΡΠΈΠΏΠΈΡΠ°ΡΠ°Ρ ΠΈΠ½Π΄ΡΡΠΈΡΡΠ΅ΡΡΡ ΡΠ°Π±Π°ΠΈΠ½ΠΎΠΌ. ΠΡΠΈ ΠΎΠ±ΡΠ°Π±ΠΎΡΠΊΠ΅ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΠΎΠ½ΠΈΠ΄Π΅ΡΠΎΠΌ Π -40 ΠΌΡ ΠΎΠ±Π½Π°ΡΡΠΆΠΈΠ»ΠΈ Π±Π΅Π»ΠΊΠΈ Ρ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΠΌΠΈ ΠΌΠ°ΡΡΠ°ΠΌΠΈ 70, 64, 55, 40, ΠΈ 35−34 ΠΊΠΠ°, ΡΠΎΠ³Π΄Π° ΠΊΠ°ΠΊ Π² ΡΠ»ΡΡΠ°Π΅ Π’ΡΠΈΡΠΎΠ½Π° Π₯-100 — 96−93, 73−70, 48, 40, 39−35 ΠΈ 35−34 ΠΊΠΠ°. ΠΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΌΠ°ΡΡ-ΡΠΏΠ΅ΠΊΠ³ΡΠΎΠΌΠ΅ΡΡΠΈΠΈ Π±ΡΠ»ΠΎ ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½ΠΎ 18 Π±Π΅Π»ΠΊΠΎΠ², ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΈΠΌΠΌΡΠ½ΠΎΠΏΡΠ΅ΡΠΈΠΏΠΈΡΠ°ΡΠΈΠΈ ΠΈΠ· ΡΡΠΈΡΠΎΠ½ΠΎΠ²ΠΎΠ³ΠΎ Π»ΠΈΠ·Π°ΡΠ°, ΡΡΠ΅Π΄ΠΈ ΠΊΠΎΡΠΎΡΡΡ Π³Π»ΡΠΊΠΎΠΊΠΎΡΡΠΈΠΊΠΎΠΈΠ΄Π½ΡΠΉ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ, ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΡΠΉ Π±Π΅Π»ΠΎΠΊ ΡΠΎΡΡΠ°ΡΠ°Π·Ρ ΡΠΈΠΏΠ° 2Π‘, ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΡΠΉ Π±Π΅Π»ΠΎΠΊ 1 ΠΈΠ· ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° Src, Π°ΠΊΡΠΈΠ²Π°ΡΠΎΡ 1 Π±Π΅Π»ΠΊΠ° Rae GTPa3bi, Π±Π΅Π»ΠΊΠΈ Π‘ΠΠΠ’Π1 ΠΈ ΠΠ‘Π15 775 NID, ΠΈ, Π½Π°ΠΊΠΎΠ½Π΅Ρ, ΡΠ΅Π³ΡΠ»ΠΈΡΡΠ΅ΠΌΠ°Ρ ΡΡΠ²ΠΎΡΠΎΡΠΊΠΎΠΉ/Π³Π»ΡΠΊΠΎΠΊΠΎΡΡΠΈΠΊΠΎΠΈΠ΄Π°ΠΌΠΈ ΠΊΠΈΠ½Π°Π·Π° 2. ΠΠΎΠΆΠ½ΠΎ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠΈΡΡ, ΡΡΠΎ, ΠΏΠΎ ΠΊΡΠ°ΠΉΠ½Π΅ΠΉ ΠΌΠ΅ΡΠ΅, ΡΠ°ΡΡΡ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½Π½ΡΡ Π½Π°ΠΌΠΈ Π±Π΅Π»ΠΊΠΎΠ² ΡΠ²Π»ΡΡΡΡΡ ΡΡΠ°ΡΡΠ½ΠΈΠΊΠ°ΠΌΠΈ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΊΠ°ΡΠΊΠ°Π΄Π°, Π²Π΅Π΄ΡΡΠ΅Π³ΠΎ ΠΊ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΡΠ°Π±Π°ΠΈΠ½Π°. ΠΡ ΠΏΠ»Π°Π½ΠΈΡΡΠ΅ΠΌ ΠΏΡΠΎΠ²Π΅ΡΠΈΡΡ ΡΡΠΎ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΠ΅ Π² Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠ΅ΠΌ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎΠΉ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΠΈ ΠΈ ΠΏΡΠΎΡΠ΅ΠΎΠΌΠΈΠΊΠΈ.
Π ΡΠΎΠ²ΠΎΠΊΡΠΏΠ½ΠΎΡΡΠΈ ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ Π½Π°ΠΌΠΈ Π΄Π°Π½Π½ΡΠ΅ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠΈΡΡ ΡΠ»Π΅Π΄ΡΡΡΡΡ ΠΌΠΎΠ΄Π΅Π»Ρ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΊΠ°ΡΠ΄ΠΈΠΎΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ ΡΡΠ΅ΡΠΎΠΈΠ΄ΠΎΠ² ΠΈ pH ΡΡΠ΅Π΄Ρ Π½Π° ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ Π»ΠΈΠ½ΠΈΠΈ C7-MDCK (ΡΠΈΡ. 56). Π‘ΠΎΠ³Π»Π°ΡΠ½ΠΎ ΡΡΠΎΠΉ ΠΌΠΎΠ΄Π΅Π»ΠΈ ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΡΠ°Π±Π°ΠΈΠ½Π° ΠΈ ΠΌΠ°ΡΠΈΠ½ΠΎΠ±ΡΡΠ°Π³Π΅Π½ΠΈΠ½Π° ΠΏΡΠΎΠΈΡΡ ΠΎΠ΄ΠΈΡ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΠΊΠΎΠ½ΡΠΎΡΠΌΠ°ΡΠΈΠΈ Na, K-ATPa3bi, ΡΡΠΎ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΡΠ΅Π·ΠΊΠΎΠΌΡ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠ΅ΡΠΌΠ΅Π½ΡΠ°. Π ΠΎΡΠ»ΠΈΡΠΈΠ΅ ΠΎΡ ΡΠ°Π±Π°ΠΈΠ½Π°, ΠΌΠ°ΡΠΈΠ½ΠΎΠ±ΡΡΠ°Π³Π΅Π½ΠΈΠ½ Π½Π΅ ΠΎΠΊΠ°Π·ΡΠ²Π°Π΅Ρ ΡΠΎΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΡΡΠ΅ΠΊΡΠ° Π½Π° ΠΊΠ»Π΅ΡΠΊΠΈ ΠΈ Π² Π΅Π³ΠΎ ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ Π½Π΅ Π½Π°Π±Π»ΡΠ΄Π°Π΅ΡΡΡ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ Π»ΠΈΠ½ΠΈΠΈ C7-MDCK. ΠΠ΄Π½Π° ΠΈΠ· Π³ΠΈΠΏΠΎΡΠ΅Π·, ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡΠ°Ρ ΠΎΠ±ΡΡΡΠ½ΠΈΡΡ Π΄Π°Π½Π½ΠΎΠ΅ ΡΠ°Π·Π»ΠΈΡΠΈΠ΅ Π² Π΄Π΅ΠΉΡΡΠ²ΠΈΠΈ Π΄Π²ΡΡ ΠΊΠ°ΡΠ΄ΠΈΠΎΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ ΡΡΠ΅ΡΠΎΠΈΠ΄ΠΎΠ² Π½Π° ΠΆΠΈΠ·Π½Π΅ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ Π·Π°ΠΊΠ»ΡΡΠ°Π΅ΡΡΡ Π² ΡΡΡΠ΅ΡΡΠ²ΠΎΠ²Π°Π½ΠΈΠΈ Π΄Π²ΡΡ ΡΠ°Π·Π½ΡΡ ΠΊΠΎΠ½ΡΠΎΡΠΌΠ°ΡΠΈΠΎΠ½Π½ΡΡ ΡΠΎΡΡΠΎΡΠ½ΠΈΠΉ Na, K-ATPa3bi, ΠΎΠ΄Π½ΠΎ ΠΈΠ· ΠΊΠΎΡΠΎΡΡΡ Π² ΡΠ»ΡΡΠ°Π΅ ΡΠ°Π±Π°ΠΈΠ½Π° Π²Π΅Π΄Π΅Ρ ΠΊ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠΈ ΡΠΈΠ³Π½Π°Π»Π° ΡΠΌΠ΅ΡΡΠΈ, ΡΠΎΠ³Π΄Π° ΠΊΠ°ΠΊ ΠΏΠ΅ΡΠ΅Ρ ΠΎΠ΄ Π² Π΄ΡΡΠ³ΠΎΠ΅ ΡΠΎΡΡΠΎΡΠ½ΠΈΠ΅ ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΠΌΠ°ΡΠΈΠ½ΠΎΠ±ΡΡΠ°Π³Π΅Π½ΠΈΠ½Π° Π½Π΅ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ. Π Π°Π·Π½ΡΠΌΠΈ Π³ΡΡΠΏΠΏΠ°ΠΌΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»Π΅ΠΉ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ Na, K-ATPa3bi Ρ ΡΠ΅Π»ΡΠΌ ΡΡΠ΄ΠΎΠΌ Π±Π΅Π»ΠΊΠΎΠ². ΠΠ·Π²Π΅ΡΡΠ½Ρ ΡΠ°ΠΊΠΆΠ΅ Π΄Π°Π½Π½ΡΠ΅ ΠΎ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ΡΠ°Π±Π°ΠΈΠ½Π° Π½Π° Π½Π΅ΠΊΠΎΡΠΎΡΡΠ΅ Π±Π΅Π»ΠΎΠΊ-Π±Π΅Π»ΠΊΠΎΠ²ΡΠ΅.
Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ ΡΠ΅ΡΠΌΠ΅Π½ΡΠ°. ΠΡΠΎ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠΈΡΡ, ΡΡΠΎ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ Na, K-ATPa3bi Ρ.
ΡΠ ΡΡΠ΅Π΄Ρ.
Π±Π΅Π»ΠΊΠΎΠΌ-ΠΏΠ°ΡΡΠ½Π΅ΡΠΎΠΌ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ΅ΡΡΡ ΠΊΠΎΠ½ΡΠΎΡΠΌΠ°ΡΠΈΠΎΠ½Π½ΡΠΌ ΡΠΎΡΡΠΎΡΠ½ΠΈΠ΅ΠΌ Na-Hacoca. ΠΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΈΠΌΠΌΡΠ½ΠΎΠΏΡΠ΅ΡΠΈΠΏΠΈΡΠ°ΡΠΈΠΈ ΠΌΡ Π²ΡΡΠ²ΠΈΠ»ΠΈ Π½Π°Π±ΠΎΡ Π±Π΅Π»ΠΊΠΎΠ² Ρ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΠΌΠΈ ΠΌΠ°ΡΡΠ°ΠΌΠΈ 96−93, 73−70, 70, 64, 55, 48, 40, 39−35 ΠΈ 35−34 ΠΊΠΠ°, ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠ΅ ΠΊΠΎΡΠΎΡΡΡ Π² ΠΈΠΌΠΌΡΠ½ΠΎΠΏΡΠ΅ΡΠΈΠΏΠΈΡΠ°ΡΠ°Ρ ΠΈΠ½Π΄ΡΡΠΈΡΡΠ΅ΡΡΡ ΡΠ°Π±Π°ΠΈΠ½ΠΎΠΌ, ΡΡΠ΅Π΄ΠΈ ΠΊΠΎΡΠΎΡΡΡ Π±ΡΠ»ΠΈ ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½Ρ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ Π³Π»ΡΠΊΠΎΠΊΠΎΡΡΠΈΠΊΠΎΠΈΠ΄ΠΎΠ², ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½Π°Ρ ΡΠΎΡΡΠ°ΡΠ°Π·Ρ ΡΠΈΠΏΠ° 2Π‘, ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΡΠΉ Π±Π΅Π»ΠΎΠΊ 1 ΠΈΠ· ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° Src, Π°ΠΊΡΠΈΠ²Π°ΡΠΎΡ 1 Π±Π΅Π»ΠΊΠ° Rac Π²Π’Π Π°Π·Ρ, Π±Π΅Π»ΠΊΠΈ Π‘ΠΠΠ’Π1 ΠΈ ΠΠ‘15 775 NID, ΠΈ, Π½Π°ΠΊΠΎΠ½Π΅Ρ, ΠΊΠΈΠ½Π°Π·Π° 2, ΡΠ΅Π³ΡΠ»ΠΈΡΡΠ΅ΠΌΠ°Ρ.
ΡΡΠ²ΠΎΡΠΎΡΠΊΠΎΠΉ/Π³Π»ΡΠΊΠΎΠΊΠΎΡΡΠΈΠΊΠΎΠΈΠ΄Π°ΠΌΠΈ. ΠΠ°ΠΊΡΡ ΡΠΎΠ»Ρ ΠΈΠ³ΡΠ°ΡΡ Π½Π°ΠΉΠ΄Π΅Π½Π½ΡΠ΅ Π±Π΅Π»ΠΊΠΈ Π² ΡΠ°Π·Π²ΠΈΡΠΈΠΈ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ, Π²ΡΠ·Π²Π°Π½Π½ΠΎΠΉ ΡΠ°Π±Π°ΠΈΠ½ΠΎΠΌ, ΠΎΡΡΠ°Π΅ΡΡΡ Π½Π΅ΡΡΠ½ΡΠΌ. ΠΡΡΠ°Π΅ΡΡΡ ΡΠ°ΠΊΠΆΠ΅ Π½Π΅ΡΡΠ½ΡΠΌ ΠΈ ΡΠΎ, ΡΠΎΡ ΡΠ°Π½ΡΡΡΡΡ Π»ΠΈ ΠΏΠΎΠ΄ΠΎΠ±Π½ΡΠ΅ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ ΠΌΠ°ΡΠΈΠ½ΠΎΠ±ΡΡΠ°Π³Π΅Π½ΠΈΠ½Π° ΠΈΠ»ΠΈ ΡΡΡΠ΅ΡΡΠ²ΡΠ΅Ρ Π΄ΡΡΠ³ΠΎΠΉ Π½Π°Π±ΠΎΡ Π±Π΅Π»ΠΊΠΎΠ², Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΡΡΡΠΈΡ Ρ Π«Π°, Π-ΠΠ’Π Π°Π·ΠΎΠΉ ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ Π΄Π°Π½Π½ΠΎΠ³ΠΎ Π±Π°ΡΠ°Π΄ΠΈΠ΅Π½ΠΎΠ»ΠΈΠ΄Π°. ΠΡ Π½Π°Π΄Π΅Π΅ΠΌΡΡ, ΡΡΠΎ ΡΡΠΈ Π²ΠΎΠΏΡΠΎΡΡ ΡΡΠ°Π½ΡΡ ΠΏΡΠ΅Π΄ΠΌΠ΅ΡΠΎΠΌ Π±ΡΠ΄ΡΡΠΈΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ.
Π, Π½Π°ΠΊΠΎΠ½Π΅Ρ, ΠΌΡ ΠΏΠΎΠ»ΡΡΠΈΠ»ΠΈ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ, ΡΠΊΠ°Π·ΡΠ²Π°ΡΡΠΈΠ΅ Π½Π° ΡΡΡΠ΅ΡΡΠ²ΠΎΠ²Π°Π½ΠΈΠ΅ Π·Π°ΡΠΈΡΠ½ΠΎΠ³ΠΎ ΡΡΡΠ΅ΠΊΡΠ° Π·Π°ΠΊΠΈΡΠ»Π΅Π½ΠΈΡ ΡΡΠ΅Π΄Ρ Π² Π΄ΠΈΠ°ΠΏΠ°Π·ΠΎΠ½Π΅ ΡΠ ΠΎΡ 7,36 Π΄ΠΎ 7,03, ΠΎΡ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ Π»ΠΈΠ½ΠΈΠΈ Π‘7-ΠΠΠ‘Π ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΡΠ°Π±Π°ΠΈΠ½Π°. ΠΠΎ-Π²ΠΈΠ΄ΠΈΠΌΠΎΠΌΡ, ΠΏΠΎΠ΄Π°Π²Π»Π΅Π½ΠΈΠ΅ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠ²ΡΠ·Π°Π½ΠΎ Ρ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΠΏΡΠΎΡΠΎΠ½ΠΎΠ² (Π+) Ρ Π½Π΅ΠΈΠ·Π²Π΅ΡΡΠ½ΡΠΌ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠΌ ΡΠ΅Π½ΡΠΎΡΠΎΠΌ. Π ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠΎΠ² ΡΠΈΠ½ΡΠ΅Π·Π° Π ΠΠ (Π°ΠΊΡΠΈΠ½ΠΎΠΌΠΈΡΠΈΠ½Π° Π) ΠΈ Π±Π΅Π»ΠΊΠ° (ΡΠΈΠΊΠ»ΠΎΠ³Π΅ΠΊΡΠ°ΠΌΠΈΠ΄Π°) Π·Π°ΡΠΈΡΠ½ΡΠΉ ΡΡΡΠ΅ΠΊΡ ΡΡΠ΅Π΄Ρ Ρ Π·Π°ΠΊΠΈΡΠ»Π΅Π½Π½ΡΠΌ ΡΠ ΡΠ°ΡΡΠΈΡΠ½ΠΎ ΡΠΌΠ΅Π½ΡΡΠ°Π΅ΡΡΡ (ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΡΠΈΠΊΠ»ΠΎΠ³Π΅ΠΊΡΠΈΠΌΠΈΠ΄Π°) ΠΈΠ»ΠΈ ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΈ ΠΏΠΎΠ»Π½ΠΎΡΡΡΡ ΠΈΡΡΠ΅Π·Π°Π΅Ρ (Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ Π°ΠΊΡΠΈΠ½ΠΎΠΌΠΈΡΠΈΠ½Π° Π). ΠΡΠΎ ΡΠΊΠ°Π·ΡΠ²Π°Π΅Ρ, ΡΡΠΎ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌ Π·Π°ΡΠΈΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΎΡ ΡΠΌΠ΅ΡΡΠΈ, Π²ΡΠ·Π²Π°Π½Π½ΠΎΠΉ ΡΠ°Π±Π°ΠΈΠ½ΠΎΠΌ, ΡΠ²ΡΠ·Π°Π½ Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠ΅ΠΉ Π±Π΅Π»ΠΊΠΎΠ², ΡΡΠ°ΡΡΠ²ΡΡΡΠΈΡ Π² ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΡΠΈΠ³Π½Π°Π»Π° ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΡΠΌΠ΅ΡΡΠΈ. ΠΠ΄Π½Π°ΠΊΠΎ Π΄Π»Ρ Π±ΠΎΠ»Π΅Π΅ Π΄Π΅ΡΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΏΠΎΠ½ΠΈΠΌΠ°Π½ΠΈΡ Π΄Π°Π½Π½ΠΎΠ³ΠΎ Π·Π°ΡΠΈΡΠ½ΠΎΠ³ΠΎ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΠ° ΠΏΡΠ΅Π΄ΡΡΠΎΠΈΡ ΠΎΡΠ²Π΅ΡΠΈΡΡ Π΅ΡΠ΅ Π½Π° ΡΡΠ΄ Π²ΠΎΠΏΡΠΎΡΠΎΠ², Π½Π°ΠΏΡΠΈΠΌΠ΅Ρ, ΠΊΠ°ΠΊΠΎΠ²Π° ΠΏΡΠΈΡΠΎΠ΄Π° Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ-ΡΠ΅Π½ΡΠΎΡΠ°? ΠΠ°ΠΊΠΈΠ΅ Π±Π΅Π»ΠΊΠΈ ΠΊΠ»Π΅ΡΠΊΠΈ ΡΡΠ°ΡΡΠ²ΡΡΡ Π² Π΄Π°Π½Π½ΠΎΠΌ Π·Π°ΡΠΈΡΠ½ΠΎΠΌ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΠ΅? ΠΡ Π½Π°Π΄Π΅Π΅ΠΌΡΡ, ΡΡΠΎ ΠΎΡΠ²Π΅ΡΡ Π½Π° ΡΡΠΈ Π²ΠΎΠΏΡΠΎΡΡ Π±ΡΠ΄ΡΡ ΠΏΠΎΠ»ΡΡΠ΅Π½Ρ Π² Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠΈΡ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Ρ .
7. ΠΡΠ²ΠΎΠ΄Ρ.
1. 24-Ρ ΠΈΠ½ΠΊΡΠ±Π°ΡΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠΏΠΈΡΠ΅Π»ΠΈΡ ΠΏΠΎΡΠ΅ΠΊ ΡΠΎΠ±Π°ΠΊΠΈ (Π»ΠΈΠ½ΠΈΡ C7-MDCK) Ρ ΠΊΠ°ΡΠ΄ΠΈΠΎΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΡΡΠ΅ΡΠΎΠΈΠ΄Π°ΠΌΠΈ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ Π·Π° ΡΡΠ΅Ρ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ ΡΡΠ΅ΡΠΎΠΈΠ΄ΠΎΠ² Ρ Π°-ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ΅ΠΉ Na, K-ATPa3bi, Π½ΠΎ Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΠΎ ΠΎΡ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠΎΠ½Π½ΡΡ ΠΏΠΎΡΠΎΠΊΠΎΠ², ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΠ΅ΠΌΡΡ ΡΡΠΈΠΌ ΡΠ΅ΡΠΌΠ΅Π½ΡΠΎΠΌ.
2. 50% ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Na, K-ATPa3bi Π½Π°Π±Π»ΡΠ΄Π°Π΅ΡΡΡ ΠΏΡΠΈ ΠΎΠ΄ΠΈΠ½Π°ΠΊΠΎΠ²ΠΎΠΉ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ ΠΌΠ°ΡΠΈΠ½ΠΎΠ±ΡΡΠ°Π³Π΅Π½ΠΈΠ½Π° ΠΈ ΡΠ°Π±Π°ΠΈΠ½Π° (1 ΠΌΠΊΠ) Π² ΡΠΎ Π²ΡΠ΅ΠΌΡ ΠΊΠ°ΠΊ ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°Π½Π½Π°Ρ ΠΌΠ°ΡΠΈΠ½ΠΎΠ±ΡΡΠ°Π³Π΅Π½ΠΈΠ½ΠΎΠΌ ΡΠΌΠ΅ΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ Π½Π°Π±Π»ΡΠ΄Π°Π΅ΡΡΡ ΠΏΡΠΈ Π±ΠΎΠ»Π΅Π΅ Π²ΡΡΠΎΠΊΠΎΠΉ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ Π΄ΡΡΠ³ΠΈΠΌΠΈ ΠΊΠ°ΡΠ΄ΠΈΠΎΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΡΡΠ΅ΡΠΎΠΈΠ΄Π°ΠΌΠΈ (ID50 0,2 ΠΈ > 10 ΠΌΠΊΠ Π΄Π»Ρ ΡΠ°Π±Π°ΠΈΠ½Π° ΠΈ ΠΌΠ°ΡΠΈΠ½ΠΎΠ±ΡΡΠ°Π³Π΅Π½ΠΈΠ½Π° ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ).
3. ΠΠΎΠ±Π°Π²Π»Π΅Π½ΠΈΠ΅ ΠΊ ΠΊΠ»Π΅ΡΠΊΠ°ΠΌ Π»ΠΈΠ½ΠΈΠΈ C7-MDCK ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠΎΠ² ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΡ ΠΊΠ°ΡΠΊΠ°Π΄ΠΎΠ²,.
Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΡΡΡΠΈΡ Π½Π° Π±Π΅Π»ΠΎΠΊ Ras, ΡΠΈΡΠΎΠ·ΠΈΠ½ΠΎΠ²ΡΠ΅ ΠΏΡΠΎΡΠ΅ΠΈΠ½ΠΊΠΈΠ½Π°Π·Ρ, ΠΏΡΠΎΡΠ΅ΠΈΠ½ΠΊΠΈΠ½Π°Π·Ρ Erk,.
ΠΏΡΠΎΡΠ΅ΠΈΠ½ΠΊΠΈΠ½Π°Π·Ρ Π‘, ΡΠΎΡΡΠΎΡΠΈΠ΄ΠΈΠ»ΠΈΠ½ΠΎΠ·ΠΈΡΠΈΠ΄-3-ΠΊΠΈΠ½Π°Π·Ρ, Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡ Π‘Π° Π°ΠΊΡΠΈΠ²Π½ΡΠ΅ ΡΠΎΡΠΌΡ ΠΊΠΈΡΠ»ΠΎΡΠΎΠ΄Π°, Π±Π΅Π»ΠΊΠΈ ΡΠΈΡΠΎΡΠΊΠ΅Π»Π΅ΡΠ° Π½Π΅ Π²Π»ΠΈΡΠ΅Ρ Π½Π° ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΡΠΌΠ΅ΡΡΠΈ, Π²ΡΠ·Π²Π°Π½Π½ΠΎΠΉ ΡΠ°Π±Π°ΠΈΠ½ΠΎΠΌ.
4. Π‘Π½ΠΈΠΆΠ΅Π½ΠΈΠ΅ ΡΠ ΡΠΈΡΠΎΠΏΠ»Π°Π·ΠΌΡ ΠΊΠ»Π΅ΡΠΎΠΊ Π»ΠΈΠ½ΠΈΠΈ C7-MDCK Ρ 7,2 Π΄ΠΎ 6,9 ΠΏΠΎΠ»Π½ΠΎΡΡΡΡ ΠΏΡΠ΅Π΄ΠΎΡΠ²ΡΠ°ΡΠ°Π΅Ρ ΡΠΌΠ΅ΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ, Π²ΡΠ·Π²Π°Π½Π½ΡΡ ΡΠ°Π±Π°ΠΈΠ½ΠΎΠΌ. ΠΠ°ΡΠΈΡΠ½ΠΎΠ΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΠΊΠΈΡΠ»ΡΡ ΡΠ ΡΡΡΡΠ°Π½ΡΠ΅ΡΡΡ Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠΎΠ² ΡΠΈΠ½ΡΠ΅Π·Π° Π ΠΠ ΠΈ Π±Π΅Π»ΠΊΠ°.
5. Π‘ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π΄Π²ΡΠΌΠ΅ΡΠ½ΠΎΠ³ΠΎ ΡΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅Π·Π° ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ ΠΎΠ±ΡΠ°Π±ΠΎΡΠΊΠ° ΠΊΠ»Π΅ΡΠΎΠΊ Π»ΠΈΠ½ΠΈΠΈ Π‘Π°ΡΠΎ-2 ΡΠ°Π±Π°ΠΈΠ½ΠΎΠΌ, ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΠ°Ρ ΠΊ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΠΎ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΡ, Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠ½ΠΎΠΌΡ Π΄Π»Ρ ΠΊΠ»Π΅ΡΠΎΠΊ Π»ΠΈΠ½ΠΈΠΈ C7-MDCK, ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΠΏΠΎΡΠ²Π»Π΅Π½ΠΈΡ Π² ΠΈΠΌΠΌΡΠ½ΠΎΠΏΡΠ΅ΡΠΈΠΏΠΈΡΠ°ΡΠ°Ρ , ΠΎΡΠ°ΠΆΠ΄Π°Π΅ΠΌΡΡ Π°Π½ΡΠΈΡΠ΅Π»Π°ΠΌΠΈ ΠΏΡΠΎΡΠΈΠ² al-ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΡ Na, K-ATPa3bi, 29 Π½ΠΎΠ²ΡΡ Π±Π΅Π»ΠΊΠΎΠ².
6. ΠΠ»Ρ 18 Π±Π΅Π»ΠΊΠΎΠ², ΠΏΡΠ΅ΡΠΈΠΏΠΈΡΠΈΡΡΡΡΠΈΡ ΡΠΎΠ²ΠΌΠ΅ΡΡΠ½ΠΎ Ρ Π«Π°, Π-ΠΠ’Π Π°Π·ΠΎΠΉ ΠΈΠ· Π»ΠΈΠ·Π°ΡΠ° ΠΊΠ»Π΅ΡΠΎΠΊ Π»ΠΈΠ½ΠΈΠΈ Π‘Π°ΡΠΎ-2 ΠΏΠΎΡΠ»Π΅ ΠΎΠ±ΡΠ°Π±ΠΎΡΠΊΠΈ ΡΠ°Π±Π°ΠΈΠ½ΠΎΠΌ, ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ ΠΌΠ°ΡΡ-ΡΠΏΠ΅ΠΊΡΡΠΎΠΌΠ΅ΡΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΏΡΠΎΠ΄ΡΠΊΡΠΎΠ² ΡΡΠΈΠΏΡΠΈΠ½ΠΎΠ»ΠΈΠ·Π°. Π‘ Π±ΠΎΠ»ΡΡΠΎΠΉ Π΄ΠΎΠ»Π΅ΠΉ Π²Π΅ΡΠΎΡΡΠ½ΠΎΡΡΠΈ 5 ΠΈΠ· ΡΡΠΈΡ 18 Π±Π΅Π»ΠΊΠΎΠ² ΡΠ²Π»ΡΡΡΡΡ: ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠΌ Π³Π»ΡΠΊΠΎΠΊΠΎΡΡΠΈΠΊΠΎΠΈΠ΄ΠΎΠ², ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΠΎΡΡΠ°ΡΠ°Π·ΠΎΠΉ ΡΠΈΠΏΠ° 2Π‘, ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΡΠΌ Π±Π΅Π»ΠΊΠΎΠΌ 1 ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° Src, Π°ΠΊΡΠΈΠ²Π°ΡΠΎΡΠΎΠΌ 1 Π±Π΅Π»ΠΊΠ° Rac-GTPa3a, Π±Π΅Π»ΠΊΠΎΠΌ Π‘ΠΠΠ’Π1, ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΠΌ Π°Π½ΠΊΠΈΡΠΈΠ½ΠΎΠ²ΡΠ΅ ΠΏΠΎΠ²ΡΠΎΡΡ. ΠΡΠΎΠΌΠ΅ ΡΠΎΠ³ΠΎ, Π΄Π²Π° Π±Π΅Π»ΠΊΠ° ΠΈΠ· 18 ΡΠΎΠ΄Π΅ΡΠΆΠ°Ρ Π΄ΠΎΠΌΠ΅Π½Ρ, ΠΏΡΠΈΡΡΡΡΡΠ²ΡΡΡΠΈΠ΅ Ρ ΡΠ΅ΡΠΈΠ½ΠΎΠ²ΡΡ (ΡΡΠ΅ΠΎΠ½ΠΈΠ½ΠΎΠ²ΡΡ ) ΠΏΡΠΎΡΠ΅ΠΈΠ½ΠΊΠΈΠ½Π°Π·.
8.
Π‘ΠΏΠΈΡΠΎΠΊ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ
.
1. ΠΠ°ΡΡΡΠΊΠΎΠ²Π° Π. Π., ΠΠ΅ΡΠΈΠ½ Π. Π., Π ΡΠ±ΡΠΎΠ² A.M., ΠΠΎΠΏΠΈΠ½Π° Π. Π. (2000) ΠΠ½ΠΊΠΈΡΠΈΠ½: ΡΡΡΠΎΠ΅Π½ΠΈΠ΅, ΡΠ²ΠΎΠΉΡΡΠ²Π° ΠΈ ΡΡΠ½ΠΊΡΠΈΠΈ. ΠΠΈΠΎΡ ΠΈΠΌΠΈΡ, 65,469−484.
2. ΠΠ°ΡΡΡΠΊΠΎΠ²Π° Π. Π., ΠΠ΅ΡΠΈΠ½ Π. Π., Π ΡΠ±ΡΠΎΠ² A.M., ΠΠΎΠΏΠΈΠ½Π° Π. Π. (2000) ΠΠ½ΠΊΠΈΡΠΈΠ½: ΡΡΡΠΎΠ΅Π½ΠΈΠ΅, ΡΠ²ΠΎΠΉΡΡΠ²Π° ΠΈ ΡΡΠ½ΠΊΡΠΈΠΈ. ΠΠΈΠΎΡ ΠΈΠΌΠΈΡ, 65,469−484.
3. ΠΠ»Π°Π΄ΠΈΠΌΠΈΡΠΎΠ²Π° Π. Π., Π‘Π°ΡΡΠΊΠΈΠ½Π° Π. Π., ΠΠ²ΡΠΈΠ½Π½ΠΈΠΊΠΎΠ²Π° Π’. Π., ΠΠ°ΡΠ°ΠΏΠ΅Π½ΠΊΠΎ Π. Π. (2002) ΠΠ·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΡΡΠ±ΡΠ»ΡΠΈΠ½Π° ΠΈ Na, K-ATPa3bi Π² Π½Π΅ΠΉΡΠΎΠ½Π°Ρ ΡΡΠ²ΠΎΠ»Π° ΠΌΠΎΠ·Π³Π°. ΠΠΈΠΎΡ ΠΈΠΌΠΈΡ, 67, 601−608.
4. ΠΠΎΠ»Π³ΠΎΠ²Π° Π. Π. ΠΠ°Π½Π΄ΠΈΠ΄Π°ΡΡΠΊΠ°Ρ Π΄ΠΈΡΡΠ΅ΡΡΠ°ΡΠΈΡ, 2005.
5. ΠΠΎΠΏΠΈΠ½Π° Π. Π. (1998) ΠΠ°, Π-Π·Π°Π²ΠΈΡΠΈΠΌΠ°Ρ Π°Π΄Π΅Π½ΠΎΠ·ΠΈΠ½ΡΡΠΈΡΠΎΡΡΠΎΡΠ°Π·Π°: ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΠ΅ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΡ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ. Π., (Π΄ΠΎΠΊΡΠΎΡΡΠΊΠ°Ρ Π΄ΠΈΡΡΠ΅ΡΡΠ°ΡΠΈΡ).
6. ΠΠΎΠΏΠΈΠ½Π° Π. Π. (1999) Na, K-ATPa3a: ΡΡΡΡΠΊΡΡΡΠ°, ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌ ΠΈ ΡΠ΅Π³ΡΠ»ΡΡΠΈΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ. ΠΠΈΠΎΠ». ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Ρ, 16, 584−603.
7. ΠΡΠ°ΠΊΡΠΈΠΊΡΠΌ ΠΏΠΎ Π±ΠΈΠΎΡ ΠΈΠΌΠΈΠΈ: ΡΡΠ΅Π±Π½ΠΎΠ΅ ΠΏΠΎΡΠΎΠ±ΠΈΠ΅ ΠΏΠΎΠ΄ ΡΠ΅Π΄Π°ΠΊΡΠΈΠ΅ΠΉ. Π‘Π΅Π²Π΅ΡΠΈΠ½Π° Π‘. Π, Π‘ΠΎΠ»ΠΎΠ²ΡΠ΅Π²ΠΎΠΉ Π. Π. (1989). Π., ΠΠ·Π΄. ΠΠΠ£, 84.
8. Abramowitz, J., Dai, Π‘., Hirschi, Π.Π., Dmitrieva, R.I., Doris, P.A., Liu, L. et al. (2003) Ouabainand marinobufagenin-induced proliferation of human umbilical vein smooth muscle cells and a rat vascular smooth muscle cell line, A7r5. Circulation, 108, 1049−1054.
9. Aizman, O., Uhlen, P., Lai, M., Brismar, H., Aperia, A. (2001) Ouabain, a steroid hormone that signals with slow calcium oscillations. Proc Natl Acad Sci USA, 98, 13 420−13 424.
10. Akera, Π’., Ng, Y.-C., Shien, I.-S., Bero, E., Brody, Π’. M., and Braselton, W. E. (1985) Effects of K+ on the interaction between cardiac glycosides and Na, K-ATPase. Eur.J.Pharmacol 111, 147−157.
11.Albers R.W., Fahn S., Koval G.J. (1963) The role of sodium ions in the activation of Electrophorus electric organ adenosine triphosphatase. Proc. Natl. Acad. Sci. USA, 50,474−481.
12. Anderson, R.G. (1998) The caveolae membrane system. Annu Rev Biochem, 67, 199 225.
13. Andrawis, N.S. and Abernethy, D.R. (1993) Effect of calcium antogonistis on RNA synthesis of NIH 3T3 cells. Am. J. Med. Sci., 306, 137 — 40.
14. Arguello J.M., Peluffo R.D., Feng J., Lingrel J.B., Berlin J.R. (1996) Substitution of glutamic 779 with alanine in the Na, K-ATPase alpha subunit removes voltage dependence of ion transport. J. Biol. Chem., 271,24 611−24 616.
15. Arguello, J.M., and Lingrel, J.B. (1995) Substitutions of Serine 775 in the a subunit of the Na, K-ATPase selectively disrupt K+ high affinity activation without affecting Na+ interaction. J. Biol. Chem., 270, 22 764−22 771.
16.Arystarkhova E., Sweadner K. J. (1997) Tissue-specific expression of the Na, K-ATPase P-subunit. The presence of P3 in lung and liver addresses the problem of the missing subunit. J. Biol. Chem., 272, 22 405−22 408.
17. Arystarkhova, E., Gasparian, M., Modyanov, N.N., and Sweadner, K.J. (1992) Na, K-ATPase extracellular surface probed with a monoclonal antibody that enchances ouabain binding. J. Biol. Chem., 267, 13 694−13 701.
18. Arystarkhova, E., Wetzel, R.K., Asinovski, N.K., and Sweadner, K.J. (1999) The y subunit modulates Na+ and K+ affinity of renal Na, K-ATPase. J. Biol. Chem., 274, 33 183−33 185.
19.Askari, A. (2000) Significance of protein-protein interactions to Na+ /K+ -ATPase functions. In: Ncf-iC-ATPase and Related ATPase K. Taniguchi and S. Kaya, Eds., Excerpta Medica Internat. Congress Series 1207, Elsevier, Amsterdam.
20.Aydemir-Koksoy, A., Abramowitz, J., and Allen, J.C. (2001) Ouabain induced signaling and vascular smooth muscle cell proliferation. J. Biol. Chem. 276: 4 660 546 611.
21.Bagrov AY, Fedorova OV, Dmitrieva RI, Howald WN, Hunter AP, Kuznetsova EA et al. (1998) Characterization of a urinary bufodielnolide Na, K-ATPase inhibitor in patients after acute myocardial infarction. Hypertension, 31, 1097−1103.
22.Bagrov, A. Y., Roukoyatkina, N. I., Dmitrieva, R. I., Pinaev, A. G., and Fedorova, O. V. (1995) Effects of two endogenous Na+, K (+)-ATPase inhibitors, marinobufagenin and ouabain, on isolated rat aorta. Eur.J.Pharmacol. 274, 151−158.
23.Bagrov, A.Y., Fedorova, O.V. (1998) Effects of two putative endogenous digitalislike factors, marinobufagenin and ouabain, on the Na+, K±pump in human mesenteric arteries. J Hypertens, 16, 1953;1958.
24.Beauge L.A., and Glynn I.M. (1979) Occlusion of K ions in the unphosphorylated sodium pump. Nature., 280, 510−2.
25.Beggah A.T., Beguin P., Jaunin P., Peitsch M.C., Geering K. (1993) Hydrophobic C-terminal amino acids in the beta-subunit are involved in assambly with the alpha-subunit of Na, K-ATPase. Biochemistry, 32, 14 117−14 124.
26.Beggah, A.T., Jaunin, P., and Geering, K. (1997) Role of glycosylation and disulfide bond formation in the P subunit in the folding and functional expression of Na, K-ATPase. J. Biol Chem., 272, 10 318−10 326.
27. Beguin P., Wang X., Firsov D., Puoti A., Clayes D., Horisberger J.D., Geering K. (1997) The gamma subunit is a specific component of Na, K-ATPase and modulates its transport function. EMBOJ., 16,4250−4260.
28. Beguin, P., Beggah, A.T., Chibalin, A.V., Burgener-Kairuz, P., Jassier, F. Methews, P.M., Rossier, B.C. Cottecchia, S., Geering, K. (1994) Phosphorylation of the Na, K-ATPase a-subunit by protein kinase A and C in vitro and in intact cells. J. Biol. Chem. 269,24 437−24 445.
29. Bennett MR, Evan GI, Schwartz SM. (1995) Apoptosis of rat vascular smooth muscle cells is regulated by p53-dependent andindependent pathways. Circ Res., 77, 266 273.
30. Bennett MR, Macdonald K, Chan S-W, Luzio JP, Simari R, Weissberg P. (1998) Cell surface trafficking of Fas: a rapid mechanism of p53-mediated apoptosis. Science, 282,290−293.
31.Berridge, M. V. and Tan, A. S. (1993) Characterization of the cellular reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT): subcellular.
localization, substrate dependence, and involvement of mitochondrial electron transport in MTT reduction. Arch.Biochem.Biophys. 303,474−482.
32.Bertorello, A.M., Aperia, A., Walaas, S.I., Nairn, A.C., Greengard, P. (1991) Phosphorylation of the catalytic subunit of Na+, K (+)-ATPase inhibits the activity of the enzyme. Proc. Natl. Acad. Sci. USA 88, 11 359−11 362.
33. Blanco G., Koster J., Sanchez G., Mercer R.W. (1995) Kinetic properties of the a2pl and a2p2 isozymes of the Na, K-ATPase. Biochemistry, 34,319−325.
34. Blanco G., Mercer R.W. (1998) Izozymes of Na, K-ATPase: heterogeneity in structure, diversity in function. Am. J. Physiol., 275, F633−650.
35.Blaustein M.P., and Lederer W.J. (1999) Sodium/calcium exchange: its physiological implications. Physiol Rev., 79,763−854.
36.Blostein, R., Zhang, R., Gottardi, C.J., and Caplan, M.J. (1993) Functional properties of an H, K-ATPase/Na, K-ATPase chimera. J. Biol. Chem., 268, 10 654−10 658.
37.Bortner C.D., Cidlowski J.A. (1998) A necessary role for cell shrinkage in apoptosis. Biochem Pharmacol, 56:1549−1559.
38.Bortner CD, Cidlowski JA. (1996) Absence of volume regulatory mechanisms contributes to the rapid activation of apoptosis in thymocytes. Am J Physiol, 271, C950-C961.
39.Bourcier N., Grygorczyk R., Gekle M., Berthiaume Y., Orlov S.N. (2002) Purinergic-induced ion current in monolayers of C7-MDCK cells: role of basolateral and apical ion transporters. JMembr Biol., 186, 131−43.
40.Canessa, C.M., Horisberger, J.D., Louvard, D., and Rossier, B.C. (1992) Mutation of cysteine in the first transmembrane segment of Na, K-ATPase alpha subunit confers ouabain resistance. EMBOJ., 11, 1681−1687.
41.Cantiello HF. (1995) Actin filaments stimulate the Na±K±ATPase. Am J Physiol, 269, F637-F643.
42. Carini R, Autelli R, Bellomo G, Albono E. (1999) Alteration of cell volume regulation in the development of hepatocyte necrosis. Exp Cell Res, 248,280−293.
43.Cayanis E., Russo J.J., Wu Y.S., Edelman I.S. (1992) Serum independence of low K+ induction of Na, K-ATPase: possible role of c-fos. J Membr Biol., 125, 163−70.
44. Champagne, M.-J., Dumas, P., Orlov, S. N., Bennett, M. R., Hamet, P., and Tremblay, J. (1999) Protection against necrosis but not apoptosis by heat-stress proteins in vascular smooth muscle cells: evidence for distinct modes of cell death. Hypertension 33, 906−913.
45.Chibalin A.V., Ogimoto G., Pedemonte C.H., Pressley T.A., Katz A.I., feraille E., Berggren P.O., Bertorello A.M. (1999) Dopamine-induced endocytosis of Na+, K±ATPase is initiated by phosphorylation of Ser-18 in the rat alpha subunit and Is responsible for the decreased activity in epithelial cells. J Biol Chem., 21 A, 1920;7.
46. Chibalin, A.V., Vasilets, L.A., Hennekes, H., Pralong, D., Geering, K. (1992) Phosphorylation of Na, K-ATPase a-subunits in microsomes and in homogenate of Xenopus oocytes resulting from the stimulation protein kinase A and protein kinase C. J. Biol. Chem. 267,22 378−22 384.
47. Chow, D.C., and Forte, J.G. (1995) Functional significance of the psubunit for heterodimeric P-type of ATPase. J. Exp. Biol., 198, 1−17.
48. Chueh, S-C., Guh, J-H., Chen, J., Lai, M-K., Teng, C-M. (2001) Dual effect of ouabain on the regulation of proliferation and apoptosis in human prostatic smooth muscle cells. J Urol, 166,47−353.
49. Cohen G.M., Sun X.M., Snowden R.T., Dinsdale D., Skilleter D.N. (1992) Key morphological features of apoptosis may occur in the absence of internucleosomal DNA fragmentation. Biochem J., 286, 331−4.
50. Contreras, R.G., Lazaro, A., Mujica, A., Gonzalez-Mariscal, L., Valdes, J., Garcia-Villegas, M.R. et al. (1995) Ouabain resistance of the epithelial cell line (Ma 104) is not due to lack of affinity of its pumps for the drug. J Membr Biol, 145,295−300.
51. Contreras, R.G., Shoshani, L., Flores-Maldonado, C., Lazaro, A., Cereijido, M. (1999) Relationship between Na+, K±ATPase and cell attachment. J Cell Sci, 112, 4223−4232.
52. Cornelius, F., Logvinenko, N. (1996) Functional regulation of reconstituted Na, K-ATPase by protein kinase A phosphorylation. FEBS lett., 380, 277−280.
53.Cranbert G., Beguin P., Uidry M., Monnet-Tschudi F., Horisberger J.D., Garty H., Geering K. (2003) FXYD7, the first brainand isoform-specific regulator of Na, K;
ATPase: biosynthesis and function of its posttranslational modifications. Ann N Y AcadSci., 986, 444−8.
54. Daniel, D., Susal, C., Kopp, B., Opelz, G., and Terness, P. (2003) Apoptosis-mediated selective killing of malignant cells by cardiac steroids: maintenance of cytotoxicity and loss of cardiac activity of chemically modified derivatives. Int.Immunopharmacol. 3, 1791−1801.
55.Devarajan, P., Scaramuzzino, D.A., Morrow, J.S. (1994) Ankyrin binds to two distinct cytoplasmic domains of Na, K-ATPase a subunit. Proc Natl Acad Sci USA, 91,2965−2969.
56.Dmitrieva RI, Doris PA. (2004) Ouabain is a potent promoter of growth and activator of ERK½ in ouabain-resistant rat renal epithelial cells. J Biol Chem, 278, 2 816 028 166.
57.Efwndiev R., Bertorello A.M., Pressley T.A., Rousselot M., Feraille E., Pedemonte C.H. (2000) Simultaneous phosphorylation of Serll and Serl8 in the alpha-subunit promotes the recruitment of Na (+), K (+)-ATPase molecules to the plasma membrane. Biochemistry., 39, 9884−92.
58.Elsasser A., Suzuki K., Schaper J. (2000) Unresolved issues regarding the role of apoptosis in the pathogenesis of ischemic injury and heart failure. J Mol Cell Cardiol., 32, 711−24.
59. Evan GI, Zornig M (1996) Cell cycle: on target with myc. Curr Biol, 6, 1553−1556.
60. Evan GI, Zornig M (1996) Cell cycle: on target with myc. Curr Biol, 6,1553−1556.
61.Ewart H.S., and Klip A. (1995) Hormonal regulation of the Na (+)-K (+)-ATPase: mechanisms underlying rapid and sustained changes in pump activity. Am J Physiol., 269,295−311.
62.FaIciola, J., Volet, B., Anner, R.M., Moosmayer, M., Lacotte, D., Anner, B.M. (1994) Role of cell membrane Na, K-ATPase for survival of human lymphocytes in vivo. BiosciRep, 14, 189−204.
63.Fedorova, O.V., Talan, M.I., Agalkova, N.I., Lakatta, E.G., Bagrov, A.Y. (2002) Endogenous ligand of aj sodium pump, marinobufagenin, is a novel mediator of sodium chloride-dependent hypertension. Circulation, 105, 1122−1127.
64.Feng, J., and Lingrel, J.B. (1994) Analysis of amino acid residues in the H5-H6 transmembrane and extracellular domains of Na, K-ATPase alpha subunit identifies threonine 797 as a determinant of ouabain sensitivity. Biochemistry, 33,4218−4224.
65.Feng, J., Orlowski, J., Lingrel, J.B. (1993) Identification of a functional thyroid hormone response elements in upstream flanking region of the human Na, K-ATPase pl gen. Nucleic. Acids Res., 21,2619−2626.
66.Feraille E., and Doucet A. (2001) Sodium-potassium-adenosinetriphosphatase-dependent sodium transport in the kidney: hormonal control. Physiol Rev., 81, 345 418.
67.Feraille E., Carranza M.L., Gonin S., Beguin P., Pedemonte C., Rousselot M., Caverzasio J., Geering K., martin P.Y., Favre H. (1999) Insulin-induced stimulation of Na+, K (+)-ATPase activity in kidney proximal tubule cells depends on phosphorylation of the alpha-subunit at Tyr-10. MolBiol Cell., 10, 2847−59.
68.Feraille E., Carranza M.L., Rousselot M., Favre H. (1997) Modulation of Na+, K (+)-ATPase activity by a tyrosine phosphorylation process in rat proximal convoluted tubule. J Physiol., 498,99−108.
69.Ferrandi, M., Salardi, S., Tripodi, G. et al. (1999) Evidence for an interaction between adducin and Na+ K+ - ATPase: Relation to genetic hypertension. Am. J. Physiol. 277: H1338-H1349.
70. Feschenko, M.S., Sweadner, K.J. (1994) Conformation-dependent phosphorylation of Na, K-ATPase by protein kinase A and protein kinase C. J. Biol.Chem., 269, 3 043 630 444.
71.Fisone, G., Cheng, S., Nairn, A., Czernik, A., Bergman, T., Jornvall, H., Aperia, A., Greengard, P. (1994) Identification of the phosphorylation site for cAMP-dependent protein kinase on Na, K-ATPase and effects of site directed mutagenesis. J. Biol. Chem. 269,9368−9373.
72.Forbush B., Kaplan J.H., Hoffman J.F. (1978) Characterization of a new photoaffinity derivative of ouabain: labeling of the large polypeptide and of a proteolipid component of the Na, K-ATPase. Biochemistry, 17, 3667−3676.
73.Fozzard, H.A., Sheets, M.F. (1985) Cellular mechanism of action of cardiac glycosides. J Am Coll Cardiol. 5:1 OA-15 A.
74.Fukasawa K, Rulong S, Resau J, Pinta da Silva P, Woude GF (1995) Overexpression of mos oncogene product in Swiss 3T3 cells induces apoptosis preferentually during S-phase. Oncogene, 10, 1−8.
75.Fukasawa K, Rulong S, Resau J, Pinta da Silva P, Woude GF (1995) Overexpression of mos oncogene product in Swiss 3T3 cells induces apoptosis preferentually during S-phase. Oncogene, 10, 1−8.
76. Gagnon, F., Dulin, N.O., Tremblay, J., Hamet, P., Orlov, S.N. (1999) ATP-induced inhibition of Na+, K+, CIcotransport in Madin-Darby canine kidney cells: lack of involvement of known purinoceptor-coupled signaling pathways. J Membr Biol. 167: 193−204.
77. Geering K" Beggah A., Good P., Girardet S., Roy S., Schaer D., Jaunin P. (1996) Oligomerization and maturation of Na, K-ATPase: functional interaction of the cytoplasmic NH2 terminus of the beta subunit with the alpha subunit. J. Cell Biol., 133, 1193−1204.
78. Gekle, M., Wunsch, S., Oberleithner, H., and Silbernagl, S. (1994) Characterization of two MDCK-cell subtypes as a model system to study principal cell and intercalated cell properties. Pfluegers Arch., 428, 157−162.
79.Giasson, E., Servant, M.J. and Meloche, S. (1997) Cyclic AMP-mediated inhibition of angiotensin II — induced protein synthesis is associated with suppression of tyrosine phosphorylation signalin in vascular smooth muscle cells. J. Biol. Chem., 272, 26 879 -86.
80. Gloor S., Antonicek H., Sweadner K.J., Pagliusi S., Frank R., Moos M., Schachner M. (1990) The adhesion molecule on glia (AMOG) is a homologue of the P-subunit of the Na, K-ATPase. J. Cell. Biol., 110, 165−174.
81. Gomez-Sanchez, E.P., Gomez-Sanches, C.E., Fort, C. (1994) Immunization of Dahl SS/jr rats with an ouabain conjugate mitigates hypertension. Am J Hyper tens, 7, 591 596.
82.Gorina S., Pavletich N.P. (1996) Structure of the p53 tumor suppressor bound to the ankyrin and SH3 domains of 53BP2. Science, 274, N5289, 1001−1005.
83. Goto, A., Ishiguro, T., Yamada, K., Ishii, M., Yoshioka, M., Eguchi, C. et al. (1990) Isolation of an urinary digitalis-like factor indistinguishable from digoxin. Biochem Biophys Res Commun, 173, 1093−1101.
84. Goto, A., Yamada, K. (1998) Ouabain-like factor. Curr Opin Nephrol Hypert, 7,189 196.
85.Grinstein S, Rotin D, Mason MJ (1989) Na+/H+ exchange and growth factor-induced cytosolic pH changes. Role in cellular proliferation. Biochim Biophys Acta, 988, 7397.
86.Gruber, K.A., Whitaker, J.M., Buckalew, V.M. (1980) Endogenous digitalis-like substance in plasma of volume-expanded dogs. Nature, 287, 743−745.
87. Haas, M., Askari, A., and Xie, Z. (2000) Involvement of Src and epidermal growth factor receptor in the signal transducing function of Na+ /K+ -ATPase. J. Biol. Chem. 275: 27 832−27 837.
88. Haas, M., Wang, H., Tian, J., and Xie, Z. (2002) Src-mediated interceptor cross-talk between the Na+ -K+ -ATPase and the EGF receptor relays the signal from ouabain to mitogen-activated protein kinases. J. Biol. Chem. 277: 18 694−18 702.
89.Hamlyn J.M., Lu Z.R., Manunta P., Ludens J.H., Kimura K., Shah J.R., Laredo J., Hamilton J.P., Hamilton M.J. Hamilton B.P. (1998) Observations on the nature, biosynthesis, secretion and significance of endogenous ouabain. Clin Exp Hypertens., 20, 523−33.
90.Hamlyn, J.M., Ringel, R., Schueffer, J., Levinson, P.D., Hamilton, B.P., Kowarski, A.A. et al. (1982) A circulating inhibitor of (Na++K+)ATPase associated with essential hypertension. Nature, 300, 650−652.
91.Harris, C. and Fliegel, L. (1999) Amiloride and the Na (+)/H (+) exchanger protein: mechanism and significance of inhibition of the Na (+)/H (+) exchanger (review). Int.J.Mol.Med. 3,315−321.
92. Harris, R.C., Savin, V.J., Lechene, C. (1987) Rat renal proximal tubular cells (RPTC) increase net ionic content following return to isotonicity from hypotonisity. Kidney. Int. 31,435a.
93.Hartee, E. I. (1972) Determination of protein: A modification of the Lowry method that gives a linear photometric response. Anal. Biochem., 48,422−427.
94.Hasler U., Wang X., Crambert G., Beguin P., Jassier F., Horisberger J-D., Geering K. (1998) Role of f3-subunit domains in the assembly, stable expression, intracellular routing, and functional properties of Na, K-ATPase. J. Biol. Chem., 273, 3 082 630 835.
95. Huang L., Li H., Xie Z. (1997) Ouabain-induced hypertrophy in cultured cardiac myocytes is accompanied by changes in expression of several late response genes. J Mol Cell Cardiol, 29,429−37.
96.Huang, B.S., Huang, X., Harmsen, E., Leenen, F.H. (1994) Chronic central versus peripheral ouabain, blood pressure, and sympathetic activity in rats. Hypertension, 23, 1087−1090.
97.1saev NK, Stelmashook EV, Halle A, Harms C, Lautenschlager M, Weih M et al. (2000) Inhibition of Na+, K±ATPase activity in cultured cerebellar granule cells prevents the onset of apoptosis induced by low potassium. Neurosci Lett, 283, 41−44.
98.Isobe, I., Yanagisawa, K., Michikawa, M. (2001) 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) causes Akt phosphorylation and morphological changes in intracellular organellae in cultured rat astrocytes. J Neurochem. 77, 27 480.
99. Joannidis M, Cantley LG, Spokes K, Stuart-Tilley AK, Alper SL, Epstein FH. (1997) Modulation of c-fos and egr-1 expression in the isolated perfused kidney by agents that alter tubular work. Kidney Int, 52, 130−139.
100. Joannidis M., Cantley L.G., Spokes K., Stuart-Tilley A.K., Alper S.L., Epstein F.H. (1997) Modulation of c-fos and egr-1 expression in the isolated perfused kidney by agents that alter tubular work. Kidney Int., 52,130−9.
101. Jorgensen, P.L. (1982) Mechanism of the (Na++K+)-ATPase. Protein structure and conformation of the pure (Na++K+)-ATPase. Biochim. Biophys. Acta, 694,27−68.
102. Kaul SC, Reddel RR, Mitsui Y, Wadhwa R. (2001) An N-terminal region of mot-2 binds to p53 in vitro. Neoplasia, 3, 110−114.
103. Kawamura, A., Guo, J., Itagaki, Y., Bell, C., Wang, Y., Haupert, J. et al. (1999) On the structure of endogenous ouabain. Proc Natl Acad Sci USA, 96, 6654−6659.
104. Kawazoe, N., Watabe, M., Masuda, Y., Nakajo, S., and Nakaya, K. (1999) Tiaml is involved in the regulation of bufalin-induced apoptosis in human leukemia cells. Oncogene 18,2413−2421.
105. Kerr J.K., Wyllie A.H., Currie A.R. (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer., 26, 23 957.
106. Khand, F.D., Gordge, M.P., Robertson, W.G., Noronha-Dutra, A.A., and Hothersall J.S. (2002) Mitochondrial superoxide production during oxalate-mediated oxidative stress in renal epithelial cells. Free Radical Biology & Medicine, 32, 1339 -1350.
107. Kimura, K., Manunta, P., Hamilton, B.P., Hamlyn, J.M. (2000) Diferent effects of in vivo ouabain and digoxin on renal artery function and blood pressure in the rat. Hypertens Res, 23, S67-S76.
108. Kirley T.L. (1989) Determination of three disulfide bonds and one free sulfhydryl in the beta subunit of (Na, K)-ATPase. J. Biol. Chem., 264, N13, 7185−7192.
109. Kometiani, P., Li, J., Gnudi, L., Kahn, B.B., Askari, A., Xie, Z. (1998) Multiple signal transduction pathways link Na+/K±ATPase to growth-related genes in cardiac myocytes: the roles of ras and mitogen-activated protein kinases. J Biol Chem, 273, 15 249−15 256.
110. Komiyama, Y., Dong, X.H., Nishimura, N., Masaki, H., Yoshika, M., Masuda, M., Takahashi, H. (2005) A novel endogenous digitalis, telocinobufagin, exhibits elevated plasma levels in patients with terminal renal failure. Cliri Biochem. 38, 3645.
111. Koob R, Kraemer D, Trippe G, Aebi U, Drenckhahn D. (1990) Association of kidney and parotid Na+, K±ATPase with actin and analogs of spectrin and ankyrin. Eur J Cell Biol, 53, 93−100.
112. Koster, J.C., Blanco, G., Mercer, R.W. (1995) A cytoplasmic region of the Na, K-ATPase alpha-subunit is necessary for specific alpha/alpha association. J. Biol. Chem., 270,14 332−14 339.
113. Kraemer DM, Strizek B, Meyer HE, Marcus K, Drenckhahn D. (2003) Kidney Na+, K±ATPase is associated with moesin. Eur J Cell Biol, 82, 87−92.
114. Kraemer, D., Koob, R., Friedrichs, B., Drenckhahn, D. (1990) Two novel peripheral membrane proteins, pasin 1 and pasin 2, associated with Na+, K±ATPase in various cells and tissues. J Cell Biol, 111, 2375−2383.
115. Krenn L, Kopp B. (1998) Bufadienolides from animal and plant sources. Phytochemistry, 48, 1−29.
116. Kroemer G, El-Deiry WS, Golstein P, Peter ME, Vaux D, Vandenabeele P, Zhivolovsky B, Blagosklonny MV, Malorni W, Knight RA, Piacentini M, Nagata S, and Melino G. (2005) Classification of cell death: recommendations of the nomenclature committee on cell death. Cell Death and Differentiation, 12, 14 631 467.
117. Kurihara K., Nakanishi N., Ueha T. (2000) Regulation of Na (+)-K (+)-ATPase by cAMP-dependent protein kinase anchored on membrane via its anchoring protein. Am J Physiol Cell Physiol., 279, C1516−27.
118. Kuster B., Shainskaya A., Pu H.X., Goldshleger R., Blostein R., Mann M., Karlish S.J. (2000) A new variant of the gamma subunit of renal Na, K-ATPase. Identification by mass spectrometry, antibody binding, and expression in cultured cells. J. Biol. Chem., 275, N24, 18 441−18 446.
119. Kutzweiler, T.A., Arguello, J.M., and Lingrel, J.B. (1996) Asp804 and Asp808 in the transmembrane domain of the Na, K-ATPase a subunit are cation coordinating residues. J. Biol. Chem., 271, 29 682−29 687.
120. Laemmli U.K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227, N259, 680−685.
121. Lang F., Busch G.L., Ritter M., Volkl H. (1998) Functional significance of cell volume regulatory mechanisms. Physiol /?ev., 78(l), 247−306.
122. Lang F., Ritter M., Gamper N., Huber S., Fillon S., Tanneur V., Lepple-Wienhues A., Szabo I., and Gulbins E. (2000) Cell volume in the regulation of cell proliferation and apoptotic cell death. Cell Physiol Biochem., lQ, 417−28.
123. Lang F., Ritter M., Woll E., Bichler I., Haussinger D., Offner F., and Grunicke H.
(1992) Altered cell volume regulation in ras oncogene expressing NIH fibroblasts. Pflugers Arch, 420,424−7.
124. Lavoie L., Levenson R., Martin-Vasallo P., Klip A. (1997) The molar ratios of a and p subunits of the Na±K±ATPase differ in distinct subcellular membranes from rat skeletal muscle. Biochemistry, 36, 7726−7732.
125. Ledbetter, M.L., Young, G.J., Wright, E.R. (1986) Cooperation between epithelial cells demonstrated by potassium transfer. Am J Physiol, 250, C306-C313.
126. Lee, K., Jung, J., Kim, M., Guidotti, G. (2001) Interaction of the a subunit of Na, K-ATPase with cofilin. Biochem J, 353,377−385.
127. Lemas, M.V., Hamrick, M., Takeyasu, K., Fambrough, D.M. (1994) 26 Amino acids of an extracellular domain of Na, K-ATPase a-subunit are sufficient for assembly with the Na, K-ATPase p-subunit. J. Biol. Chem., 269, 8255−8259.
128. Li K.X., and Sperelakis N. (1993) Isoproterenoland insulin-induced hyperpolarization in rat skeletal muscle. J Cell Physiol., 157, 631−6.
129. Li, Y., Zhu, H., Kuppusamy, P., Roubaud, V., Zweier, J.L., and Trush, M.A. (1998) Validation of lucigenin (Bis-N-methylacridinium) as a chemilumigenic probe for detecting anion radical production by enzymatic and cellular systems. J. Biol. Chem., 273, 2015;2023.
130. Lichtstein, D., Gati, I., Samuelov, S., Berson, D., Rozenman, Y., Landau, L. et al.
(1993) Identification of digitalis-like compounds in human cataractous lenses. Eur J Biochem, 216, 261−268.
131. Lingrel J.B. (1992) Na, K-ATPase: isoform structure, function and expression. J. Bioenerg. Biomembr., 24, 263−270.
132. Lingrel, J.B., Croyle, M.L., Woo, A.L., Arguello, J.M. (1998) Ligand binding sites of Na, K-ATPase. Acta. Physiol. Scand. Suppl., 643, 69−77.
133. Liu J, Kesiry R, Periyasamy SM, Malhotra D, Xie Z, Shapiro JI. (2004) Ouabain-induced endocytosis of plasmalemmal Na/K-ATPase in LLC-PK1 cells by clathrin-dependent mechanism. Kidney Int, 66,227−241.
134. Liu, J., Tian, J., Haas, M., Shapiro, J.I., Askari, A., Xie, Z.(2000) Ouabain interaction with cardiac Na+/K±ATPase initiates signal cascade independent of changes in intracellular Na+ and Ca2+ concentrations. J Biol Chem, 275,27 838−27 844.
135. Liu, L., Mohammadi, K., Aynafshar, B., Wang, H., Li, D., Liu, J., Ivanov, A.V., Xie, Z., Askari. A. (2003) Role of caveolae in signal-transducting function of cardiac Na+/K±ATPase. Am J Physiol, 284, C1550-C1560.
136. Liu, P., Rudick, M., and Anderson, R.G. (2002) Multiple functions of caveolin-1. J. Biol. Chem. 277:41 295−41 298.
137. Liu, Y., Peterson, D.A., Kimura, H., Schubert, D. (1997) Mechanism of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. J Neurochem. 69, 581−93.
138. Lutsenko, S., Anderko, R., Kaplan, J.H. (1995) Membrane disposition of the M5-M6 hairpin of Na+, K (+)-ATPase alpha subunit is ligand dependent. Proc. Natl. Acad. Sci. USA, 92,7936−7940.
139. Lux S. E, John K. M, Bennett V. (1990) Analysis of cDNA for human erythrocyte ankyrin indicates a repeated structure with homology to tissue-differentiation and cell-cycle control proteins. Nature, 344, N6261,36−42.
140. Mahmmoud Y.A., Vorum H., Cornelius F. (2000) Identification of a phospholemman-like protein from shark rectal glands. Evidence for indirect regulation of Na, K-ATPase by protein kinase c via a novel member of the FXYDY family. J. Biol. Chem., 275, N46, 35 969−35 977.
141. Maingret F, Patel AJ, Lesage F, Lazdunski M, Honore E (1999) Mechanoand acid stimulation, two interactive modes of activation of the TREK-1 potassium channels. J Biol Chem., 274,26 691−26 696.
142. Majno, G., Joris, I. (1995) Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol, 146, 3−15.
143. Malik N" Canfield V.A., Beckers M-C., Gros P., Levenson R (1996) Identification of the mammalian Na, K-ATPase p3-subunit. J. Biol. Chem., 271,22 754−22 758.
144. Manunta, P., Barlassina, C., and Bianchi, G. (1998) Adducin in essential hypertension. FEBS Lett. 430: 41−44.
145. Martin-Vasallo P., Dackowski W., Emanuel J.R., Levenson R. (1989) Identification of putative isoform of the Na, K-ATPase P-subunit. J. Biol. Chem., 264, 4613−4618.
146. Matsui, H., and Schwartz, A. (1968) Mechanism of cardiac glycoside inhibition of the (Na±K+)-dependent ATPase from cardiac tissue. Biochim. Biophys. Acta., 151, 655−663.
147. Maxient, J.-M., Lelievre, L., and Berrebi-Betrand, I. (1998) Mechanism underlying the strong positive inotropic effects ofLND-623: specific inhibition ofNa, K-ATPase isoforms and exclusion of cellular sites of contractile control. Cardiovasc. Drugs Ther. 12,585−594.
148. McDonough A.A. and farley R.A. (1993) Regulation of Na, K-ATPase activity. Curr Opin Nephrol Hypertens., 2, 725−34.
149. Mercer R.W. (1993) The structure of Na, K-ATPase. Int. Rev. Cytol., 13, 7C, 139 168.
150. Miakawa-Naito A, Uhlen P, Lai M, Aizman O, Mikoshiba K, Brismar H et al. (2003) Cell signaling microdomain with Na, K-ATPase and inositol 1,4,5-triphosphate receptor generates calcium oscillations. J Biol Chem, 278, 50 355−50 361.
151. Miller R.P., Farley R.A. (1990) Beta-subunit of (Na+ + K+)-ATPase contains three disulfide bonds. Biochemistry, 29, 1524−1532.
152. Mobasheri A., Avila J., Cozar-Castellano I., Brownleader M.D., Trevan M., Francis M.J., Lamb J.F., Martin-Vasallo P. (2000) Na+, K±ATPase isozyme diversitycomparative biochemistry and physiological implications of novel functional interactions. Biosci Rep., 20, N2, 51−91.
153. Mohammadi, K., Kometiani, P., Xie, Z., Askari, A.(2001) Role of protein kinase C in the signal pathways that link Na+/K±ATPase to ERK½. J Biol Chem, 276, 42 050;42056.
154. Mongin A.A., Orlov S.N. (2001) Mechanisms of cell volume regulation and possible nature of the cell volume sensor. Pathophysiology, 8(2):77−88.
155. Morrow JS, Cianci CD, Ardito T, Mann AS, Kashgarin M. (1989) Ankyrin links to the alpha subunit of Na, K-ATPase in MadinDarby canine kidney cells and in intact renal tubule cells. J Cell Biol, 108,455−465.
156. Muller-Ehmsen J., Juwadi P., Thompson C.B., Tumyan L., Croyle M., Lingrel J.B., Schwinger R.H., McDonouogh A.A., Farley R.A. (2001) Ouabain and substrate affinities of human Na (+)-K (+)-ATPase alpha (l)beta (l), alpha (2)beta (l), and alpha (3)beta (l) when expressed separately in yeast cells. Am J Physiol Cell Physiol., 281, 1355−64.
157. Munzer, J.S., Daly, S.E. Jewell-Motz, E.A., Lingrel, J.B., and Blostein, R. (1994) Tissueand isoform-specific kinetic behavior of the Na, K-ATPase. J. Biol. Chem., 269, 16 668−16 676.
158. Murtazina D.A. Petukhov S.P., Rubtsov A.M., Storey K.B., Lopina O.D. (2001) Phosphorylation of the alpha-subunit of Na, K-ATPase from duck salt glands by cAMP-dependent protein kinase inhibits the enzyme activity. Biochemistry (Mosc)., 66, 865−74.
159. Nakagawa Y, Petricoin EF, Akai H, Grimley PM, Rupp B, Larner AC.(1992a) Interferon-alpha-induced gene expression: evidence for a selective effect on activation of the ISGF3 transcription complex. Virology, 190, 210−220.
160. Nakagawa Y, Rivera V, Larner AC. (1992b) A role for Na/K-ATPase in the control of human c-fos and c-jun transcription. J Biol Chem, 267, 8785−8788.
161. Nelson, W.J., Veshnock, P. (1987) Ankyrin binding to (Na+K)-ATPase and implications for the organization of membrane domains in polarized cells. Nature 328, 533−537.
162. Numazawa S, Inoue N, Nakuta H, Sugiyama T, Fujino E, Shinoki M et al. (1996) A cardiac steroid bufalin-induced differentiation of THPcells. Involvement of Na+, K±ATPase inhibition in the early changes on proto-oncogene expression. Biochem Pharmacol, 52, 321−329.
163. Orlov S.N., Akimova O.A., Hamet P. (2005). Cardiotonic steroids: novel mechanisms of Na±mediated andindependent signaling involved in regulation of gene expression, proliferation and cell death. Current Hypertension Reviews. In press.
164. Orlov S.N., Dam T.V., Tremblay. J., Hamet. P. (1996) Apoptosis in cultured vascular smooth muscle cells. Role of cell volume decrease. Biochem Biophys Res Commun-, 221:708−715.
165. Orlov S.N., Taurin S., Thorin-Trescases N., Dulin N.O., Tremblay J., Hamet P. (2000) Inversion of the intracellular Na+/K+ ratio blocks apoptosis in vascular smooth muscle cells by induction ofRNA synthesis. Hypertension- 35:1062−1068.
166. Orlov S.N., Taurin S., Tremblay J., Hamet P. (2001) Inhibition of Na+, K+ pump affects nucleic acid synthesis and smooth muscle cell proliferation via elevation of the [Na+]-/[K+]i ratio: possible implication in vascular remodeling. J Hyper tens', 19:15 591 565.
167. Orlov S.N., Thorin-Trescases N., Kotelevtsev S.V., Tremblay J., Hamet P. (1999) Inversion of the intracellular Na+/K+ ratio blocks apoptosis in vascular smooth muscle at a site upstream of caspase-3. J Biol Chem- 274:16 545−16 552.
168. Orlov, S. N., Pchejetski, D., Taurin, S., Thorin-Trescases, N., Maximov, G. V., Pshezhetsky, A. V., Rubin, A. B., and Hamet, P. (2004) Apoptosis in serum-deprived vascular smooth muscle cells: evidence for cell volume-independent mechanism. Apoptosis 9,55−66.
169. Orlov, S.N., Adarichev, V.A., Devlin, A.M., Maximova, N.V., Sun, Y.L., Tremblay, J., Dominiczak, A.F., Postnov, Y.V., and Hamet P. (2000) Increased Na+/H+ exchanger isoform 1 activity in spontaneously hypertensive rats: lack of mutations within the coding region of NHE1. Biochim. Biophys. Acta, 1500, 169 -180.
170. Orlov, S.N., Dulin, N.O., Gagnon, F., Gekle, M., Douglas, J.G., Schwartz, J.H., Hamet, P. (1999) Purinergic modulation of Na (+), K (+), C1(-) cotransport and MAP kinases is limited to Cll-MDCK cells resembling intercalated cells from collecting ducts.JMembrBiol. 172,225−34.
171. Orlov, S.N., Taurin, S., Tremblay, J., Hamet, P. (2001) Inhibition of Na+, K+ pump affects nucleic acid synthesis and smooth muscle cell proliferation via elevation of the [Na+]/[K+]i ratio: possible implication in vascular remodeling. JHypertens, 19, 15 591 565.
172. Orlov, S.N., Thorin-Trescases, N., Kotelevtsev, S.V., Tremblay, J., Hamet, P. (1999) Inversion of the intracellular Na+/K+ ratio blocks apoptosis in vascular smooth muscle at a site upstream of caspase-3. J Biol Chem, 274, 6545−16 552.
173. Orlov, S.N., Thorin-Trescases, N., Pchejetski, D., Taurin, S., Farhat, N., Tremblay, J., Thorin, E., and Hamet, P. (2004) Na/K-pump and endothelial cell survival: [Na+]i/[K+]i-independent necrosis triggered by ouabain, and protection against apoptosis mediated by elevation of [Na+]i. PJluegers Arch., 448, 335 — 345.
174. Orlov, S.N., Tremblay, J., and Hamet, P. (1996) Bumethanide-sensitive ion fluxes in vascular smooth muscle cells: lack of functional Na+, K+, 2C1- cotransport. J. Membr. Biol., 153,125 — 135.
175. Orlov, S.N., Tremblay, J., Hamet, P. (1995) Altered beta-adrenergic regulation of Na-K-Cl cotransport in cultured smooth muscle cells from the aorta of spontaneously hypertensive rats. Role of the cytoskeleton network. Am J Hypertens, 8, 739−747.
176. Otto E., Kunimoto M., McLaughlin T., Bennett V. (1991) Isolation and characterization of cDNAs encoding human brain ankyrins reveal a family of alternatively spliced genes. J. Cell. Biol., 114, N2,241−253.
177. Palasis, M., Kuntzweiler, T.A., Arguello, J.M., and Lingrel, J.B. (1996) Ouabain interactions with the H6-H6 hairpin of the Na, K-ATPase reveal a possible inhibition mechanism via the cation binding domain. J. Biol. Chem., 271, 14 176−14 182.
178. Pamnani, M., Huot, S., Buggy, J., Clough, D., Haddy, F. (1981) Demonstration of a humoral inhibitor of the Na±K+ pump in some models of experimental hypertension. Hypertension, 3, 96−101.
179. Pchejetski, D., Taurin, S., der Sarkissian, S., Lopina, O.D., Pchezhetsky, A.V., Tremblay, J., DeBlois, D., Hamet, P., and Orlov, S.N. (2003) Inhibition of Na, K-ATPase by ouabain triggers epithelial cell death independently of inversion of the [Na+]i/[K+]i ratio. Biochem. Biophys. Res. Commun, 301, 735 — 744.
180. Pedemonte C.H., Pressley T.A., Lokhandwala M.F., Cinelli A.R. (1997) Regulation of Na, K-ATPase transport activity by protein kinase C. J Membr Biol., 155, 219−27.
181. Pedersen, P.A., Nielsen, J.M., Rasmussen, J.H., and Jorgensen, P.L. (1998) Contribution to Ti+, K+, and Na+ binding of Asn776, Ser775, Thr774, Thr772, and.
Thr771 in cytoplasmic part of fifth transmembrane segment in alpha-subunit of renal Na, K-ATPase. Biochemestry, 37, 17 818−17 827.
182. Peng L., Martin-Vasallo P., Sweadner K.J. (1997) Isoforms of Na,.K-ATPAse a and P subunits in the rat cerebellum and in granule cell cultures. J. Membr. Biol., 155, 219−227.
183. Peng, M., Huang, L., Xie, Z., Huang, W-H., Askari, A.(1996) Partial inhibition of Na+/K±ATPase by ouabain induces the Ca2±dependent expression of early-response genes in cardiac myocytes. J Biol Chem, 271, 10 372−10 378.
184. Pontiggia L., Winterhalter K., Gloor S.M. (1998) Inhibition of Na, K-ATPase activity by cGMP is isoform-specific in brain endothelial cells. FEBS Lett., 436, 46 670.
185. Post R.L., Sen A.K., Rosenthal A.S. (1965) A phosphorylated intermediate in adenosine triphosphate dependent sodium and potassium transport across kidney membranes. J. Biol. Chem., 240, 1437−1445.
186. Post, R.L., Hegyvary, C., and Kume, S. (1972) Activation by adenosine triphosphate in the phosphorylation kinetics of sodium and potassium ion transport adenosine triphosphatase. J. Biol. Chem., 247, 6530−6540.
187. Price, E.M., and Lingrel, J.B. (1988) Structure-function relationships in the Na, K-ATPase alpha-subunit: site-directed mutagenesis of glutamine-111 to arginine and asparagine-122 to aspartic acid generates a ouabain-resistence enzyme. Biochemistry, 27, 8400−8408.
188. Price, E.M., Rice, D.A., and Lingrel, J.B. (1989) Site-directed mutagenesis of a conserved, extracellular aspartic acid residue affects the ouabain sensitivity of sheep Na, K-ATPase. J. Biol. Chem., 264,21 902;21906.
189. Qiu, L.Y., Koenderink, J.B., Swarts, H.G.P., Willems, P.H.G.M., Pont, J.J.H.H.M. (2003) Phe783, Thr797, and Asp804 in transmembrane hairpin M5-M6 of Na, K-ATPase play a key role in ouabain binding. J. Biol. Chem., 278,47 240−47 244.
190. Rajan S, Wischmeter E, Liu GX, Preisig-Muller R, Daut J, Karschin A, Derst C (2000) TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histidine as pH sensor. J Biol Chem, 275, 16 650−16 657.
191. Rajasekaran, S.A., Gopal, J., Wills, D., Espineda, C., Twiss, J.K., Rajasekaran, A.K. (2004) Na, K-ATPase betal-subunit increases the translation efficiency of the alpha 1-subunit in MSV-MDCK cells. Mol Biol Cell., 15(7), 3224−32.
192. Raymond, M.-A., Mollica, L., Vigneault, N., Desormeaux, A., Chan, J. S. D., Filep, J. G., and Hebert, M.-J. (2003) Blockade of the apoptotic machinery by cyclosporin A redirects cell death toward necrosis in arterial endothelial cells: regulation by reactive oxygen species and cathepsin D. FASEB J. 17, 515−517.
193. Razani, B., Woodman, S.E. and Lisanti, M.P. (2002) Caveolae: From cell biology to animal physiology. Pharmacol. Rev. 54: 431−467.
194. Reichert M, Steinbach JP, Supra P, Weller M (2002) Modulation of growth and radiochemosensitivity of human malignant glioma cells by acidosis. Cancer, 95, 1113−1119.
195. Renner, E.L., Lake, J.R., Persico, M., Scharschmidt, B.F. (1989) Na±H+ exchange activity in rat hepatocytes: role in regulation of intracellular pH. Am J Physiol. 256, G44−52.
196. Reshkin SJ, Bellizzi A, Caldeira S, Albarini V, Malanchi I, Poignee M, Alluni-Fabbroni M, Casavola V, Tommasino M (2000) Na exchanger-dependent intracellular alkalinization is an early event in malignant transformation and plays an essential role in the development of subsequent transformation-associated phenotypes. FASEB J, 14,2185−2197.
197. Sarvazyan, N.A., Modynov, N. N., Askari, A. (1995) Intersubunit and intrasubunit contact regions of Na+/K±ATPase revealed by controlled proteolysis and chemical cross-linking. J. Biol. Chem. 270,26 528−26 532.
198. Saunders, R., Scheiner-Bobis, G. (2004) Ouabain stimulates endothelin release and expression in human endothelial cells without inhibiting the sodium pump. Eur J Biochem, 111, 1054−1062.
199. Schatzmann HJ. (1953) Herzglykoside ais Hennstoffe fur den aktiven Kaliumund Natriumtransport durch die erythrocytenmembran. Helv Physiol Pharmacol Acta, 11, 346−354.
200. Schneider, R., Wray, V., Nimtz, M., Lehmann, W-D., Kirch, U., Antoloic, R. et al. (1998) Bovine adrenals contain, in addition to ouabain, a second inhibitor of the sodium pump. J Biol Chem, 273,784−792.
201. Schoner, W. (2002) Endogenous cardiac glycosides, a new class of steroid hormones. Eur JBiochem, 269, 2440−2448.
202. Schultheis, P.J., and Lingrel, J.B. (1993) Substitution of transmembrane residues with hydrogen-bonding potential in the alpha subunit of Na, K-ATPase reveals alteration in ouabain sensitivity. Biochemistry, 32, 544−550.
203. Schultheis, P.J., Wallick, E.T., and Lingrell, J.B. (1993) Kinetic analysis of ouabain binding to native and mutated forms of Na, K-ATPase and identification of a new region involved in cardiac glycoside interactions. J. Biol. Chem., 268, 2 268 622 694.
204. Schwartz, A. (1976) Is the cell membrane Na+, K+ -ATPase enzyme system the pharmacological receptor for digitalis? Circ Res., 39:1−7.
205. Shamraj, O.I., and Lingrel, J.B. (1994) A putative fourth Na, K-ATPase a subunit gene is expressed in testis. Proc. Natl. Acad. Sci. USA, 91, 12 952−12 956. r.
206. Shan X., Luo H., Chen H., Daloze P., St-Louis G., Wu J. (1993) The effect of rapamycin on c-jun expression in human lymphocytes. Clin Immunol Immunopathoi, 69,314−7.
207. Shevchenko, A., Wilm, M., Vorm, O. and Mann, M. Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal. Chem., 68, 850−858, 1996.
208. Shull G.E., Greeb J., Lingrel J.B. (1986) Molecular cloning of three distinct forms of the (Na+K)-ATPase a-subunit from rat brain. Biochemistry, 25, 8125−8132.
209. Shull G.E., Schwarts A., Lingrel J.B. (1985) Amino-acid sequence of the catalytic subunit of the (Na++K+)ATPase deduced from a complementary DNA. Nature, 316, 691−695.
210. Skou J. C (1957) The influence of some cations on an adenosine triphosphatase from priferal nerves. Biochim. Biophys. Acta, 23, 394−401.
211. Skou J.C., and Esmann M. (1992) The Na, K-ATPase. J Bioenerg Biomembr., 24, 249−61.
212. Skou JC. (1960) Further investigation on a Mg 2+ + Na±activated adenosinetriphosphatase possibly related to the active transport of Na+ and K+ across the nerve cell membrane. Biochim Biophys Acta, 42, 6−23.
213. Stewart D.J., and Sen A.K. (1981) Role of cyclic GMP in cholinergic activation of Na-K pump in duck salt gland. Am J Physiol., 240, 207−14.
214. Sun X.M., MacFarlane M., Zhuang J, m Wolf B.B., Green D.R., Cohen G.M. (1999) Distinct caspase cascades are initiated in receptor-mediated and chemical-induced apoptosis. J Biol Chem., 274, 5053−60.
215. Sweadner K.J., Real E. (2000) The FXYD gene family of small ion transport regulators or channels: cDNA sequence, protein signature sequence, and expression. Genomics., 68, 41−56.
216. Szent-Gyorgyi A. (1953) Chemical physiology of contraction in body and heart. New York, Academic Press. 86−91.
217. Taurin S, Dulin NO, Pchejetski D, Grygorczyk R, Tremblay J, Hamet P et al. (2002) c-Fos expression in ouabain-treated vascular smooth muscle cells from rat aorta: evidence for an intracellular-sodium-mediated, calcium-independent mechanism. J Physiol, 543, 835−847.
218. Taurin S, Hamet P, Orlov SN. (2003) Na/K pump and intracellular monovalent cations: novel mechanism of excitation-transcription coupling involved in inhibition of apoptosis. Mo I Biol, 37, 371−381.
219. Taurin, S., Seyrantepe, V., Orlov, S.N., Tremblay, T.L., Thibault, P., Bennett, M.R., Hamet, P., Pshezhetsky, A.V. (2002) Proteome analysis and functional expression identify mortalin as an antiapoptotic gene induced by elevation of [Na+]i/[K+]i ratio in cultured vascular smooth muscle cells. Circ Res., 91, 915−22.
220. Therien A.G., and Blostein R. (2000) Mexanisms of sodium pump regulation. Am J Physiol Cell Physiol., 279, C541−66.
221. Thevananther S., Kolli A.H., Devarajan P. (1998) Identification of a novel ankyrin isoform (AnkG190) in kidney and lung that associates with the plasma membrane and binds alpha-Na, K-ATPase J. Biol. Chem., 273, 23 952−23 958.
222. Thomas, J.A., Buchsbaum, R.N., Zimniak, A., Racker, E. (1979) Intracellular pH measurements in Ehrlich ascites tumor cells utilizing spectroscopic probes generated in situ. Biochemistry, 18, 2210−8.
223. Thomas, S.M. and Brugge, J.S. (1997) Cellular functions regulated by Src family kinases. Annu. Rev. Cell. Dev. Biol. 13: 513−609.
224. Trevisi L, Visentin B, Cusinato F, Pighin I, Luciani S. (2004) Antiapoptotic effect of ouabain on human umbilical endothelial cells. Biochem Biophys Res Commun, 321, 716−721.
225. Vachon, P.H., Beaulieu, J.F. (1992) Transient mosaic patterns of morphological and functional differentiation in the Caco-2 cell line. Gastroenterology. 103, 414−23.
226. Valente, R.C., Capella, L.S., Monteiro, R.Q., Rumjanek, V.M., Lopes, A.G., Capella, M.A. (2003) Mechanisms of ouabain toxicity. FASEB J., 17, 1700−2.
227. Wadhwa R, Yaguchi T, Hasan MK, Mitsui Y, Reddel RR, Kaul SC. (2002) Hsp70 family member, mot-2/mthsp7-/GSP75, binds to the cytoplasmic sequestration domain of the p53 protein. Exp Cell Res, 274, 246−253.
228. Wallick, E. T. and Schwartz, A. (1988) Interaction of cardiac glycosides with Na+, K±ATPase. Methods Enzymol. 156,201−213.
229. Wang S.G., and Farley R.A. (1998) Valine 904, tyrosine 898, and cysteine 908 in Na, K-ATPase alpha subunits are important for assembly with beta subunits. J Biol Chem., 273, 29 400−5.
230. Wang, H., Haas, M., Liang, M., Cai, T., Tian, J., Li, S., Xie, Z. (2004) Ouabain assembles signaling cascade through the caveolar Na+, K±ATPase. J Biol Chem, 279, 17 250−17 259.
231. Wood EH, Moe GK. (1938) Studies on the effect of digitalis glycosides on potassium ion loss from the heart of the heart lung preparation. Am J Physiol, 123, 219−220.
232. Xie Z, Askari A. (2002) Na+/K±ATPase as a signal transducer. Eur J Biochem, 269,2434−2439.
233. Xie, Z., Cai, T. (2003) Na±K±ATPase-mediated signal transduction: from protein interaction to cellular function. Mol Intervent, 3, 157−168.
234. Xie, Z., Kometiani, P., Liu, J., Li, J., Shapiro, J.I., Askari, A. (1999) Intracellular reactive oxygen species mediate the linkage of Na+/K±ATPase to hypertrophy and its marker genes in cardiac myocytes. J Biol Chem., 274, 19 323−8.
235. Xiong Z-G, Zhu X-M, Chu X-P, Minami M, Hey J, Wei W-L, MacDonald JF, Wemmie JA, Price MP, Welsh MJ, Simon RP (2004) Neuroprotection in ishemia: blocking calcium-permeable acid-sensitive ion channels. Cell, 118,687−698.
236. Xu, W., Harrison, S.C., and Eck, M.J. (1997) Three-dimensional structure of the tyrosine kinase c-Src. Nature 385: 595−602.
237. Young, M.A., Gonfloni, S., Superti-Furga, G., Roux, B., and Kuriyan, J. (2001) Dynamic coupling between the SH2 and SH3 domains of c-Src and Hck underlies their inactivation by C-terminal tyrosine phosphorylation. Cell 105: 115−126.
238. Yudowski G.A., Efendiev R., Pedemonte R., Katz A.I., Berggren P.O., Bertorello A.M. (2000) Phosphoinositide-3 kinase binds to a proline-rich motif in the Na+, K±ATPase alpha subunit and regulates its trafficking. Proc Natl Acad Sci USA., 97, 6556−61.
239. Zhang, Z., Devarajan, P., Dorfman, A.L., Morrow, J.S. (1998) Structure of the ankyrin-binding domain of a-Na-K-ATPase. J Biol Chem, 273, 18 681−18 684.
240. Zhou X, Jiang G, Zhao A, Bondeva T, Hirzel P, Balla T. (2001) Inhibition of Na, K-ATPase activates PI3 kinase and inhibits apoptosis in LLC-PK1 cells. Biochem Biophys Res Commun, 285, 46−51.
Π Π·Π°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠΈ Ρ Ρ ΠΎΡΠ΅Π»Π° Π±Ρ ΠΈΡΠΊΡΠ΅Π½Π½Π΅ ΠΏΠΎΠ±Π»Π°Π³ΠΎΠ΄Π°ΡΠΈΡΡ ΡΠ²ΠΎΠΈΡ Π½Π°ΡΡΠ½ΡΡ ΡΡΠΊΠΎΠ²ΠΎΠ΄ΠΈΡΠ΅Π»Π΅ΠΉ Π‘Π΅ΡΠ³Π΅Ρ ΠΠΈΠΊΠΎΠ»Π°Π΅Π²ΠΈΡΠ° ΠΡΠ»ΠΎΠ²Π° ΠΈ ΠΠ»ΡΠ³Ρ ΠΠΌΠΈΡΡΠΈΠ΅Π²Π½Ρ ΠΠΎΠΏΠΈΠ½Ρ Π·Π° Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΡΠ°Π±ΠΎΡΠ°ΡΡ Π² ΠΈΡ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠΈΡΡ , Π·Π° Π½Π΅ΠΎΡΠ΅Π½ΠΈΠΌΡΡ ΠΏΠΎΠΌΠΎΡΡ Π² ΡΠ°Π±ΠΎΡΠ΅, Π·Π° ΠΏΡΠΈΠΎΠ±ΡΠ΅ΡΠ΅Π½Π½ΡΠ΅ Π·Π½Π°Π½ΠΈΡ, ΠΊΠΎΡΠΎΡΡΠΌ Ρ Π½Π°ΡΡΠΈΠ»Π°ΡΡ Π·Π° Π²ΡΠ΅ΠΌΡ ΡΠΎΠ²ΠΌΠ΅ΡΡΠ½ΠΎΠΉ ΡΠ°Π±ΠΎΡΡ, ΠΈ ΡΠ΅ΠΏΠ»ΠΎΠ΅ ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠ΅ ΠΊΠΎ ΠΌΠ½Π΅.
Π― Π±Π»Π°Π³ΠΎΠ΄Π°ΡΠ½Π° ΠΠ°ΡΠ°Π»ΡΠΈ ΠΠ»Π°Π΄ΠΈΠΌΠΈΡΠΎΠ²Π½Π΅ ΠΠ°Π΅Ρ, ΠΠ°ΡΠ°Π»ΡΠΈ ΠΠ°Π»Π΅ΡΡΠ΅Π²Π½Π΅ ΠΠΎΠ»Π³ΠΎΠ²ΠΎΠΉ ΠΈ Π‘Π΅Π±Π°ΡΡΡΡΠ½Ρ Π’ΠΎΡΠ°Π½ Π·Π° ΡΠ΅ ΡΠ΅Π½Π½ΡΠ΅ ΡΠΎΠ²Π΅ΡΡ ΠΈ ΠΏΠΎΠΌΠΎΡΡ Π² ΠΎΠ±ΡΡΠΆΠ΄Π΅Π½ΠΈΠΈ ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠΎΠ².
Π― ΡΠ°ΠΊΠΆΠ΅ Ρ ΠΎΡΠ΅Π»Π° Π±Ρ ΠΏΠΎΠ±Π»Π°Π³ΠΎΠ΄Π°ΡΠΈΡΡ ΡΠ²ΠΎΠΈΡ ΡΠΎΠ΄ΠΈΡΠ΅Π»Π΅ΠΉ, ΠΊΠΎΡΠΎΡΡΠ΅ ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠΈΠ²Π°Π»ΠΈ ΠΌΠ΅Π½Ρ Π²ΡΠ΅ ΡΡΠΎ Π²ΡΠ΅ΠΌΡ, ΠΈ Π±Π΅Π· ΠΏΠΎΠΌΠΎΡΠΈ ΠΊΠΎΡΠΎΡΡΡ Π΄Π°Π½Π½Π°Ρ ΡΠ°Π±ΠΎΡΠ° Π½Π΅ Π±ΡΠ»Π° Π±Ρ Π·Π°Π²Π΅ΡΡΠ΅Π½Π°.
Π‘ΠΏΠΈΡΠΎΠΊ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ
- Π‘Π½ΠΈΠΆΠ΅Π½ΠΈΠ΅ ΡΠ ΡΠΈΡΠΎΠΏΠ»Π°Π·ΠΌΡ ΠΊΠ»Π΅ΡΠΎΠΊ Π»ΠΈΠ½ΠΈΠΈ C7-MDCK Ρ 7,2 Π΄ΠΎ 6,9 ΠΏΠΎΠ»Π½ΠΎΡΡΡΡ ΠΏΡΠ΅Π΄ΠΎΡΠ²ΡΠ°ΡΠ°Π΅Ρ ΡΠΌΠ΅ΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ, Π²ΡΠ·Π²Π°Π½Π½ΡΡ ΡΠ°Π±Π°ΠΈΠ½ΠΎΠΌ. ΠΠ°ΡΠΈΡΠ½ΠΎΠ΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΠΊΠΈΡΠ»ΡΡ ΡΠ ΡΡΡΡΠ°Π½ΡΠ΅ΡΡΡ Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠΎΠ² ΡΠΈΠ½ΡΠ΅Π·Π° Π ΠΠ ΠΈ Π±Π΅Π»ΠΊΠ°.
- ΠΠ°ΡΡΡΠΊΠΎΠ²Π° Π.Π., ΠΠ΅ΡΠΈΠ½ Π. Π., Π ΡΠ±ΡΠΎΠ² A.M., ΠΠΎΠΏΠΈΠ½Π° Π. Π. (2000) ΠΠ½ΠΊΠΈΡΠΈΠ½: ΡΡΡΠΎΠ΅Π½ΠΈΠ΅, ΡΠ²ΠΎΠΉΡΡΠ²Π° ΠΈ ΡΡΠ½ΠΊΡΠΈΠΈ. ΠΠΈΠΎΡ ΠΈΠΌΠΈΡ, 65,469−484.
- ΠΠ°ΡΡΡΠΊΠΎΠ²Π° Π.Π., ΠΠ΅ΡΠΈΠ½ Π. Π., Π ΡΠ±ΡΠΎΠ² A.M., ΠΠΎΠΏΠΈΠ½Π° Π. Π. (2000) ΠΠ½ΠΊΠΈΡΠΈΠ½: ΡΡΡΠΎΠ΅Π½ΠΈΠ΅, ΡΠ²ΠΎΠΉΡΡΠ²Π° ΠΈ ΡΡΠ½ΠΊΡΠΈΠΈ. ΠΠΈΠΎΡ ΠΈΠΌΠΈΡ, 65,469−484.
- ΠΠ»Π°Π΄ΠΈΠΌΠΈΡΠΎΠ²Π° Π.Π., Π‘Π°ΡΡΠΊΠΈΠ½Π° Π. Π., ΠΠ²ΡΠΈΠ½Π½ΠΈΠΊΠΎΠ²Π° Π’. Π., ΠΠ°ΡΠ°ΠΏΠ΅Π½ΠΊΠΎ Π. Π. (2002) ΠΠ·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΡΡΠ±ΡΠ»ΡΠΈΠ½Π° ΠΈ Na, K-ATPa3bi Π² Π½Π΅ΠΉΡΠΎΠ½Π°Ρ ΡΡΠ²ΠΎΠ»Π° ΠΌΠΎΠ·Π³Π°. ΠΠΈΠΎΡ ΠΈΠΌΠΈΡ, 67, 601−608.
- ΠΠΎΠ»Π³ΠΎΠ²Π° Π.Π. ΠΠ°Π½Π΄ΠΈΠ΄Π°ΡΡΠΊΠ°Ρ Π΄ΠΈΡΡΠ΅ΡΡΠ°ΡΠΈΡ, 2005.
- ΠΠΎΠΏΠΈΠ½Π° Π.Π. (1998) ΠΠ°, Π-Π·Π°Π²ΠΈΡΠΈΠΌΠ°Ρ Π°Π΄Π΅Π½ΠΎΠ·ΠΈΠ½ΡΡΠΈΡΠΎΡΡΠΎΡΠ°Π·Π°: ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΠ΅ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΡ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ. Π., (Π΄ΠΎΠΊΡΠΎΡΡΠΊΠ°Ρ Π΄ΠΈΡΡΠ΅ΡΡΠ°ΡΠΈΡ).
- ΠΠΎΠΏΠΈΠ½Π° Π.Π. (1999) Na, K-ATPa3a: ΡΡΡΡΠΊΡΡΡΠ°, ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌ ΠΈ ΡΠ΅Π³ΡΠ»ΡΡΠΈΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ. ΠΠΈΠΎΠ». ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Ρ, 16, 584−603.
- ΠΡΠ°ΠΊΡΠΈΠΊΡΠΌ ΠΏΠΎ Π±ΠΈΠΎΡ ΠΈΠΌΠΈΠΈ: ΡΡΠ΅Π±Π½ΠΎΠ΅ ΠΏΠΎΡΠΎΠ±ΠΈΠ΅ ΠΏΠΎΠ΄ ΡΠ΅Π΄Π°ΠΊΡΠΈΠ΅ΠΉ. Π‘Π΅Π²Π΅ΡΠΈΠ½Π° Π‘. Π, Π‘ΠΎΠ»ΠΎΠ²ΡΠ΅Π²ΠΎΠΉ Π. Π. (1989). Π., ΠΠ·Π΄. ΠΠΠ£, 84.
- Aizman, O., Uhlen, P., Lai, M., Brismar, H., Aperia, A. (2001) Ouabain, a steroid hormone that signals with slow calcium oscillations. Proc Natl Acad Sci USA, 98, 13 420−13 424.
- Akera, Π’., Ng, Y.-C., Shien, I.-S., Bero, E., Brody, Π’. M., and Braselton, W. E. (1985) Effects of K+ on the interaction between cardiac glycosides and Na, K-ATPase. Eur.J.Pharmacol 111, 147−157.
- Albers R.W., Fahn S., Koval G.J. (1963) The role of sodium ions in the activation of Electrophorus electric organ adenosine triphosphatase. Proc. Natl. Acad. Sci. USA, 50,474−481.
- Anderson, R.G. (1998) The caveolae membrane system. Annu Rev Biochem, 67, 199 225.
- Andrawis, N.S. and Abernethy, D.R. (1993) Effect of calcium antogonistis on RNA synthesis of NIH 3T3 cells. Am. J. Med. Sci., 306, 137 40.
- Arguello J.M., Peluffo R.D., Feng J., Lingrel J.B., Berlin J.R. (1996) Substitution of glutamic 779 with alanine in the Na, K-ATPase alpha subunit removes voltage dependence of ion transport. J. Biol. Chem., 271,24 611−24 616.
- Arguello, J.M., and Lingrel, J.B. (1995) Substitutions of Serine 775 in the a subunit of the Na, K-ATPase selectively disrupt K+ high affinity activation without affecting Na+ interaction. J. Biol. Chem., 270, 22 764−22 771.
- Arystarkhova E., Sweadner K. J. (1997) Tissue-specific expression of the Na, K-ATPase P-subunit. The presence of P3 in lung and liver addresses the problem of the missing subunit. J. Biol. Chem., 272, 22 405−22 408.
- Arystarkhova, E., Gasparian, M., Modyanov, N.N., and Sweadner, K.J. (1992) Na, K-ATPase extracellular surface probed with a monoclonal antibody that enchances ouabain binding. J. Biol. Chem., 267, 13 694−13 701.
- Arystarkhova, E., Wetzel, R.K., Asinovski, N.K., and Sweadner, K.J. (1999) The y subunit modulates Na+ and K+ affinity of renal Na, K-ATPase. J. Biol. Chem., 274, 33 183−33 185.
- Askari, A. (2000) Significance of protein-protein interactions to Na+ /K+ -ATPase functions. In: Ncf-iC-ATPase and Related ATPase, K. Taniguchi and S. Kaya, Eds., Excerpta Medica Internat. Congress Series 1207, Elsevier, Amsterdam.
- Aydemir-Koksoy, A., Abramowitz, J., and Allen, J.C. (2001) Ouabain induced signaling and vascular smooth muscle cell proliferation. J. Biol. Chem. 276: 4 660 546 611.
- Bagrov AY, Fedorova OV, Dmitrieva RI, Howald WN, Hunter AP, Kuznetsova EA et al. (1998) Characterization of a urinary bufodielnolide Na, K-ATPase inhibitor in patients after acute myocardial infarction. Hypertension, 31, 1097−1103.
- Bagrov, A. Y., Roukoyatkina, N. I., Dmitrieva, R. I., Pinaev, A. G., and Fedorova, O. V. (1995) Effects of two endogenous Na+, K (+)-ATPase inhibitors, marinobufagenin and ouabain, on isolated rat aorta. Eur.J.Pharmacol. 274, 151−158
- Bagrov, A.Y., Fedorova, O.V. (1998) Effects of two putative endogenous digitalislike factors, marinobufagenin and ouabain, on the Na+, K±pump in human mesenteric arteries. J Hypertens, 16, 1953−1958.
- Beauge L.A., and Glynn I.M. (1979) Occlusion of K ions in the unphosphorylated sodium pump. Nature., 280, 510−2.
- Beggah A.T., Beguin P., Jaunin P., Peitsch M.C., Geering K. (1993) Hydrophobic C-terminal amino acids in the beta-subunit are involved in assambly with the alpha-subunit of Na, K-ATPase. Biochemistry, 32, 14 117−14 124.
- Beggah, A.T., Jaunin, P., and Geering, K. (1997) Role of glycosylation and disulfide bond formation in the P subunit in the folding and functional expression of Na, K-ATPase. J. Biol Chem., 272, 10 318−10 326.
- Beguin P., Wang X., Firsov D., Puoti A., Clayes D., Horisberger J.D., Geering K. (1997) The gamma subunit is a specific component of Na, K-ATPase and modulates its transport function. EMBOJ., 16,4250−4260.
- Bennett MR, Evan GI, Schwartz SM. (1995) Apoptosis of rat vascular smooth muscle cells is regulated by p53-dependent and -independent pathways. Circ Res., 77, 266 273.
- Bennett MR, Macdonald K, Chan S-W, Luzio JP, Simari R, Weissberg P. (1998) Cell surface trafficking of Fas: a rapid mechanism of p53-mediated apoptosis. Science, 282,290−293.
- Bertorello, A.M., Aperia, A., Walaas, S.I., Nairn, A.C., Greengard, P. (1991) Phosphorylation of the catalytic subunit of Na+, K (+)-ATPase inhibits the activity of the enzyme. Proc. Natl. Acad. Sci. USA 88, 11 359−11 362.
- Blanco G., Koster J., Sanchez G., Mercer R.W. (1995) Kinetic properties of the a2pl and a2p2 isozymes of the Na, K-ATPase. Biochemistry, 34,319−325.
- Blanco G., Mercer R.W. (1998) Izozymes of Na, K-ATPase: heterogeneity in structure, diversity in function. Am. J. Physiol., 275, F633−650.
- Blaustein M.P., and Lederer W.J. (1999) Sodium/calcium exchange: its physiological implications. Physiol Rev., 79,763−854.
- Blostein, R., Zhang, R., Gottardi, C.J., and Caplan, M.J. (1993) Functional properties of an H, K-ATPase/Na, K-ATPase chimera. J. Biol. Chem., 268, 10 654−10 658.
- Bortner C.D., Cidlowski J.A. (1998) A necessary role for cell shrinkage in apoptosis. Biochem Pharmacol, 56:1549−1559.
- Bortner CD, Cidlowski JA. (1996) Absence of volume regulatory mechanisms contributes to the rapid activation of apoptosis in thymocytes. Am J Physiol, 271, C950-C961.
- Bourcier N., Grygorczyk R., Gekle M., Berthiaume Y., Orlov S.N. (2002) Purinergic-induced ion current in monolayers of C7-MDCK cells: role of basolateral and apical ion transporters. JMembr Biol., 186, 131−43.
- Canessa, C.M., Horisberger, J.D., Louvard, D., and Rossier, B.C. (1992) Mutation of cysteine in the first transmembrane segment of Na, K-ATPase alpha subunit confers ouabain resistance. EMBOJ., 11, 1681−1687.
- Cantiello HF. (1995) Actin filaments stimulate the Na±K±ATPase. Am J Physiol, 269, F637-F643.
- Carini R, Autelli R, Bellomo G, Albono E. (1999) Alteration of cell volume regulation in the development of hepatocyte necrosis. Exp Cell Res, 248,280−293.
- Cayanis E., Russo J.J., Wu Y.S., Edelman I.S. (1992) Serum independence of low K+ induction of Na, K-ATPase: possible role of c-fos. J Membr Biol., 125, 163−70.
- Chow, D.C., and Forte, J.G. (1995) Functional significance of the psubunit for heterodimeric P-type of ATPase. J. Exp. Biol., 198, 1−17.
- Chueh, S-C., Guh, J-H., Chen, J., Lai, M-K., Teng, C-M. (2001) Dual effect of ouabain on the regulation of proliferation and apoptosis in human prostatic smooth muscle cells. J Urol, 166,47−353.
- Cohen G.M., Sun X.M., Snowden R.T., Dinsdale D., Skilleter D.N. (1992) Key morphological features of apoptosis may occur in the absence of internucleosomal DNA fragmentation. Biochem J., 286, 331−4.
- Contreras, R.G., Lazaro, A., Mujica, A., Gonzalez-Mariscal, L., Valdes, J., Garcia-Villegas, M.R. et al. (1995) Ouabain resistance of the epithelial cell line (Ma 104) is not due to lack of affinity of its pumps for the drug. J Membr Biol, 145,295−300.
- Contreras, R.G., Shoshani, L., Flores-Maldonado, C., Lazaro, A., Cereijido, M. (1999) Relationship between Na+, K±ATPase and cell attachment. J Cell Sci, 112, 4223−4232.
- Cornelius, F., Logvinenko, N. (1996) Functional regulation of reconstituted Na, K-ATPase by protein kinase A phosphorylation. FEBS lett., 380, 277−280.
- Devarajan, P., Scaramuzzino, D.A., Morrow, J.S. (1994) Ankyrin binds to two distinct cytoplasmic domains of Na, K-ATPase a subunit. Proc Natl Acad Sci USA, 91,2965−2969.
- Dmitrieva RI, Doris PA. (2004) Ouabain is a potent promoter of growth and activator of ERK½ in ouabain-resistant rat renal epithelial cells. J Biol Chem, 278, 2 816 028 166.
- Elsasser A., Suzuki K., Schaper J. (2000) Unresolved issues regarding the role of apoptosis in the pathogenesis of ischemic injury and heart failure. J Mol Cell Cardiol., 32, 711−24.
- Evan GI, Zornig M (1996) Cell cycle: on target with myc. Curr Biol, 6, 1553−1556.
- Evan GI, Zornig M (1996) Cell cycle: on target with myc. Curr Biol, 6,1553−1556.
- Ewart H.S., and Klip A. (1995) Hormonal regulation of the Na (+)-K (+)-ATPase: mechanisms underlying rapid and sustained changes in pump activity. Am J Physiol., 269,295−311.
- FaIciola, J., Volet, B., Anner, R.M., Moosmayer, M., Lacotte, D., Anner, B.M. (1994) Role of cell membrane Na, K-ATPase for survival of human lymphocytes in vivo. BiosciRep, 14, 189−204.
- Fedorova, O.V., Talan, M.I., Agalkova, N.I., Lakatta, E.G., Bagrov, A.Y. (2002) Endogenous ligand of aj sodium pump, marinobufagenin, is a novel mediator of sodium chloride-dependent hypertension. Circulation, 105, 1122−1127.
- Feng, J., and Lingrel, J.B. (1994) Analysis of amino acid residues in the H5-H6 transmembrane and extracellular domains of Na, K-ATPase alpha subunit identifies threonine 797 as a determinant of ouabain sensitivity. Biochemistry, 33,4218−4224.
- Feng, J., Orlowski, J., Lingrel, J.B. (1993) Identification of a functional thyroid hormone response elements in upstream flanking region of the human Na, K-ATPase pl gen. Nucleic. Acids Res., 21,2619−2626.
- Feraille E., and Doucet A. (2001) Sodium-potassium-adenosinetriphosphatase-dependent sodium transport in the kidney: hormonal control. Physiol Rev., 81, 345 418.
- Feraille E., Carranza M.L., Rousselot M., Favre H. (1997) Modulation of Na+, K(+)-ATPase activity by a tyrosine phosphorylation process in rat proximal convoluted tubule. J Physiol., 498,99−108.
- Ferrandi, M., Salardi, S., Tripodi, G. et al. (1999) Evidence for an interaction between adducin and Na+, K+ ATPase: Relation to genetic hypertension. Am. J. Physiol. 277: H1338-H1349.
- Feschenko, M.S., Sweadner, K.J. (1994) Conformation-dependent phosphorylation of Na, K-ATPase by protein kinase A and protein kinase C. J. Biol.Chem., 269, 3 043 630 444.
- Forbush B., Kaplan J.H., Hoffman J.F. (1978) Characterization of a new photoaffinity derivative of ouabain: labeling of the large polypeptide and of a proteolipid component of the Na, K-ATPase. Biochemistry, 17, 3667−3676.
- Fozzard, H.A., Sheets, M.F. (1985) Cellular mechanism of action of cardiac glycosides. J Am Coll Cardiol. 5:1 OA-15 A.
- Fukasawa K, Rulong S, Resau J, Pinta da Silva P, Woude GF (1995) Overexpression of mos oncogene product in Swiss 3T3 cells induces apoptosis preferentually during S-phase. Oncogene, 10, 1−8.
- Fukasawa K, Rulong S, Resau J, Pinta da Silva P, Woude GF (1995) Overexpression of mos oncogene product in Swiss 3T3 cells induces apoptosis preferentually during S-phase. Oncogene, 10, 1−8.
- Gekle, M., Wunsch, S., Oberleithner, H., and Silbernagl, S. (1994) Characterization of two MDCK-cell subtypes as a model system to study principal cell and intercalated cell properties. Pfluegers Arch., 428, 157−162.
- Gloor S., Antonicek H., Sweadner K.J., Pagliusi S., Frank R., Moos M., Schachner M. (1990) The adhesion molecule on glia (AMOG) is a homologue of the P-subunit of the Na, K-ATPase. J. Cell. Biol., 110, 165−174.
- Gomez-Sanchez, E.P., Gomez-Sanches, C.E., Fort, C. (1994) Immunization of Dahl SS/jr rats with an ouabain conjugate mitigates hypertension. Am J Hyper tens, 7, 591 596.
- Gorina S., Pavletich N.P. (1996) Structure of the p53 tumor suppressor bound to the ankyrin and SH3 domains of 53BP2. Science, 274, N5289, 1001−1005.
- Goto, A., Ishiguro, T., Yamada, K., Ishii, M., Yoshioka, M., Eguchi, C. et al. (1990) Isolation of an urinary digitalis-like factor indistinguishable from digoxin. Biochem Biophys Res Commun, 173, 1093−1101.
- Goto, A., Yamada, K. (1998) Ouabain-like factor. Curr Opin Nephrol Hypert, 7,189 196.
- Grinstein S, Rotin D, Mason MJ (1989) Na+/H+ exchange and growth factor-induced cytosolic pH changes. Role in cellular proliferation. Biochim Biophys Acta, 988, 7397.
- Gruber, K.A., Whitaker, J.M., Buckalew, V.M. (1980) Endogenous digitalis-like substance in plasma of volume-expanded dogs. Nature, 287, 743−745.
- Haas, M., Askari, A., and Xie, Z. (2000) Involvement of Src and epidermal growth factor receptor in the signal transducing function of Na+ /K+ -ATPase. J. Biol. Chem. 275: 27 832−27 837.
- Haas, M., Wang, H., Tian, J., and Xie, Z. (2002) Src-mediated interceptor cross-talk between the Na+ -K+ -ATPase and the EGF receptor relays the signal from ouabain to mitogen-activated protein kinases. J. Biol. Chem. 277: 18 694−18 702.
- Hamlyn, J.M., Ringel, R., Schueffer, J., Levinson, P.D., Hamilton, B.P., Kowarski, A.A. et al. (1982) A circulating inhibitor of (Na++K+)ATPase associated with essential hypertension. Nature, 300, 650−652.
- Harris, C. and Fliegel, L. (1999) Amiloride and the Na (+)/H (+) exchanger protein: mechanism and significance of inhibition of the Na (+)/H (+) exchanger (review). Int.J.Mol.Med. 3,315−321.
- Harris, R.C., Savin, V.J., Lechene, C. (1987) Rat renal proximal tubular cells (RPTC) increase net ionic content following return to isotonicity from hypotonisity. Kidney. Int. 31,435a.
- Hartee, E. I. (1972) Determination of protein: A modification of the Lowry method that gives a linear photometric response. Anal. Biochem., 48,422−427.
- Hasler U., Wang X., Crambert G., Beguin P., Jassier F., Horisberger J-D., Geering K. (1998) Role of f3-subunit domains in the assembly, stable expression, intracellular routing, and functional properties of Na, K-ATPase. J. Biol. Chem., 273, 3 082 630 835.
- Huang L., Li H., Xie Z. (1997) Ouabain-induced hypertrophy in cultured cardiac myocytes is accompanied by changes in expression of several late response genes. J Mol Cell Cardiol, 29,429−37.
- Isobe, I., Yanagisawa, K., Michikawa, M. (2001) 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) causes Akt phosphorylation and morphological changes in intracellular organellae in cultured rat astrocytes. J Neurochem. 77, 27 480.
- Joannidis M, Cantley LG, Spokes K, Stuart-Tilley AK, Alper SL, Epstein FH. (1997) Modulation of c-fos and egr-1 expression in the isolated perfused kidney by agents that alter tubular work. Kidney Int, 52, 130−139.
- Joannidis M., Cantley L.G., Spokes K., Stuart-Tilley A.K., Alper S.L., Epstein F.H. (1997) Modulation of c-fos and egr-1 expression in the isolated perfused kidney by agents that alter tubular work. Kidney Int., 52,130−9.
- Jorgensen, P.L. (1982) Mechanism of the (Na++K+)-ATPase. Protein structure and conformation of the pure (Na++K+)-ATPase. Biochim. Biophys. Acta, 694,27−68.
- Kaul SC, Reddel RR, Mitsui Y, Wadhwa R. (2001) An N-terminal region of mot-2 binds to p53 in vitro. Neoplasia, 3, 110−114.
- Kawamura, A., Guo, J., Itagaki, Y., Bell, C., Wang, Y., Haupert, J. et al. (1999) On the structure of endogenous ouabain. Proc Natl Acad Sci USA, 96, 6654−6659.
- Kawazoe, N., Watabe, M., Masuda, Y., Nakajo, S., and Nakaya, K. (1999) Tiaml is involved in the regulation of bufalin-induced apoptosis in human leukemia cells. Oncogene 18,2413−2421.
- Kerr J.K., Wyllie A.H., Currie A.R. (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer., 26, 23 957.
- Khand, F.D., Gordge, M.P., Robertson, W.G., Noronha-Dutra, A.A., and Hothersall J.S. (2002) Mitochondrial superoxide production during oxalate-mediated oxidative stress in renal epithelial cells. Free Radical Biology & Medicine, 32, 1339 -1350.
- Kimura, K., Manunta, P., Hamilton, B.P., Hamlyn, J.M. (2000) Diferent effects of in vivo ouabain and digoxin on renal artery function and blood pressure in the rat. Hypertens Res, 23, S67-S76.
- Kirley T.L. (1989) Determination of three disulfide bonds and one free sulfhydryl in the beta subunit of (Na, K)-ATPase. J. Biol. Chem., 264, N13, 7185−7192.
- Komiyama, Y., Dong, X.H., Nishimura, N., Masaki, H., Yoshika, M., Masuda, M., Takahashi, H. (2005) A novel endogenous digitalis, telocinobufagin, exhibits elevated plasma levels in patients with terminal renal failure. Cliri Biochem. 38, 3645.
- Koob R, Kraemer D, Trippe G, Aebi U, Drenckhahn D. (1990) Association of kidney and parotid Na+, K±ATPase with actin and analogs of spectrin and ankyrin. Eur J Cell Biol, 53, 93−100.
- Koster, J.C., Blanco, G., Mercer, R.W. (1995) A cytoplasmic region of the Na, K-ATPase alpha-subunit is necessary for specific alpha/alpha association. J. Biol. Chem., 270,14 332−14 339.
- Kraemer DM, Strizek B, Meyer HE, Marcus K, Drenckhahn D. (2003) Kidney Na+, K±ATPase is associated with moesin. Eur J Cell Biol, 82, 87−92.
- Kraemer, D., Koob, R., Friedrichs, B., Drenckhahn, D. (1990) Two novel peripheral membrane proteins, pasin 1 and pasin 2, associated with Na+, K±ATPase in various cells and tissues. J Cell Biol, 111, 2375−2383.
- Krenn L, Kopp B. (1998) Bufadienolides from animal and plant sources. Phytochemistry, 48, 1−29.
- Kurihara K., Nakanishi N., Ueha T. (2000) Regulation of Na(+)-K (+)-ATPase by cAMP-dependent protein kinase anchored on membrane via its anchoring protein. Am J Physiol Cell Physiol., 279, C1516−27.
- Kutzweiler, T.A., Arguello, J.M., and Lingrel, J.B. (1996) Asp804 and Asp808 in the transmembrane domain of the Na, K-ATPase a subunit are cation coordinating residues. J. Biol. Chem., 271, 29 682−29 687.
- Laemmli U.K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227, N259, 680−685.
- Lang F., Busch G.L., Ritter M., Volkl H. (1998) Functional significance of cell volume regulatory mechanisms. Physiol /?ev., 78(l), 247−306.
- Lang F., Ritter M., Gamper N., Huber S., Fillon S., Tanneur V., Lepple-Wienhues A., Szabo I., and Gulbins E. (2000) Cell volume in the regulation of cell proliferation and apoptotic cell death. Cell Physiol Biochem., lQ, 417−28.
- Lang F., Ritter M., Woll E., Bichler I., Haussinger D., Offner F., and Grunicke H.1992) Altered cell volume regulation in ras oncogene expressing NIH fibroblasts. Pflugers Arch, 420,424−7.
- Lavoie L., Levenson R., Martin-Vasallo P., Klip A. (1997) The molar ratios of a and p subunits of the Na±K±ATPase differ in distinct subcellular membranes from rat skeletal muscle. Biochemistry, 36, 7726−7732.
- Ledbetter, M.L., Young, G.J., Wright, E.R. (1986) Cooperation between epithelial cells demonstrated by potassium transfer. Am J Physiol, 250, C306-C313.
- Lee, K., Jung, J., Kim, M., Guidotti, G. (2001) Interaction of the a subunit of Na, K-ATPase with cofilin. Biochem J, 353,377−385.
- Lemas, M.V., Hamrick, M., Takeyasu, K., Fambrough, D.M. (1994) 26 Amino acids of an extracellular domain of Na, K-ATPase a-subunit are sufficient for assembly with the Na, K-ATPase p-subunit. J. Biol. Chem., 269, 8255−8259.
- Li K.X., and Sperelakis N. (1993) Isoproterenol- and insulin-induced hyperpolarization in rat skeletal muscle. J Cell Physiol., 157, 631−6.
- Lichtstein, D., Gati, I., Samuelov, S., Berson, D., Rozenman, Y., Landau, L. et al.1993) Identification of digitalis-like compounds in human cataractous lenses. Eur J Biochem, 216, 261−268.
- Lingrel J.B. (1992) Na, K-ATPase: isoform structure, function and expression. J. Bioenerg. Biomembr., 24, 263−270.
- Lingrel, J.B., Croyle, M.L., Woo, A.L., Arguello, J.M. (1998) Ligand binding sites of Na, K-ATPase. Acta. Physiol. Scand. Suppl., 643, 69−77.
- Liu J, Kesiry R, Periyasamy SM, Malhotra D, Xie Z, Shapiro JI. (2004) Ouabain-induced endocytosis of plasmalemmal Na/K-ATPase in LLC-PK1 cells by clathrin-dependent mechanism. Kidney Int, 66,227−241.
- Liu, J., Tian, J., Haas, M., Shapiro, J.I., Askari, A., Xie, Z.(2000) Ouabain interaction with cardiac Na+/K±ATPase initiates signal cascade independent of changes in intracellular Na+ and Ca2+ concentrations. J Biol Chem, 275,27 838−27 844.
- Liu, L., Mohammadi, K., Aynafshar, B., Wang, H., Li, D., Liu, J., Ivanov, A.V., Xie, Z., Askari. A. (2003) Role of caveolae in signal-transducting function of cardiac Na+/K±ATPase. Am J Physiol, 284, C1550-C1560.
- Liu, P., Rudick, M., and Anderson, R.G. (2002) Multiple functions of caveolin-1. J. Biol. Chem. 277:41 295−41 298.
- Liu, Y., Peterson, D.A., Kimura, H., Schubert, D. (1997) Mechanism of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. J Neurochem. 69, 581−93.
- Lutsenko, S., Anderko, R., Kaplan, J.H. (1995) Membrane disposition of the M5-M6 hairpin of Na+, K (+)-ATPase alpha subunit is ligand dependent. Proc. Natl. Acad. Sci. USA, 92,7936−7940.
- Lux S. E, John K. M, Bennett V. (1990) Analysis of cDNA for human erythrocyte ankyrin indicates a repeated structure with homology to tissue-differentiation and cell-cycle control proteins. Nature, 344, N6261,36−42.
- Maingret F, Patel AJ, Lesage F, Lazdunski M, Honore E (1999) Mechano- and acid stimulation, two interactive modes of activation of the TREK-1 potassium channels. J Biol Chem., 274,26 691−26 696.
- Majno, G., Joris, I. (1995) Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol, 146, 3−15.
- Malik N" Canfield V.A., Beckers M-C., Gros P., Levenson R (1996) Identification of the mammalian Na, K-ATPase p3-subunit. J. Biol. Chem., 271,22 754−22 758.
- Manunta, P., Barlassina, C., and Bianchi, G. (1998) Adducin in essential hypertension. FEBS Lett. 430: 41−44.
- Martin-Vasallo P., Dackowski W., Emanuel J.R., Levenson R. (1989) Identification of putative isoform of the Na, K-ATPase P-subunit. J. Biol. Chem., 264, 4613−4618.
- Matsui, H., and Schwartz, A. (1968) Mechanism of cardiac glycoside inhibition of the (Na±K+)-dependent ATPase from cardiac tissue. Biochim. Biophys. Acta., 151, 655−663.
- McDonough A.A. and farley R.A. (1993) Regulation of Na, K-ATPase activity. Curr Opin Nephrol Hypertens., 2, 725−34.
- Mercer R.W. (1993) The structure of Na, K-ATPase. Int. Rev. Cytol., 13, 7C, 139 168.
- Miakawa-Naito A, Uhlen P, Lai M, Aizman O, Mikoshiba K, Brismar H et al. (2003) Cell signaling microdomain with Na, K-ATPase and inositol 1,4,5-triphosphate receptor generates calcium oscillations. J Biol Chem, 278, 50 355−50 361.
- Miller R.P., Farley R.A. (1990) Beta-subunit of (Na+ + K+)-ATPase contains three disulfide bonds. Biochemistry, 29, 1524−1532.
- Mohammadi, K., Kometiani, P., Xie, Z., Askari, A.(2001) Role of protein kinase C in the signal pathways that link Na+/K±ATPase to ERK½. J Biol Chem, 276, 42 050−42 056.
- Mongin A.A., Orlov S.N. (2001) Mechanisms of cell volume regulation and possible nature of the cell volume sensor. Pathophysiology, 8(2):77−88.
- Morrow JS, Cianci CD, Ardito T, Mann AS, Kashgarin M. (1989) Ankyrin links to the alpha subunit of Na, K-ATPase in Madin -Darby canine kidney cells and in intact renal tubule cells. J Cell Biol, 108,455−465.
- Munzer, J.S., Daly, S.E. Jewell-Motz, E.A., Lingrel, J.B., and Blostein, R. (1994) Tissue- and isoform-specific kinetic behavior of the Na, K-ATPase. J. Biol. Chem., 269, 16 668−16 676.
- Murtazina D.A. Petukhov S.P., Rubtsov A.M., Storey K.B., Lopina O.D. (2001) Phosphorylation of the alpha-subunit of Na, K-ATPase from duck salt glands by cAMP-dependent protein kinase inhibits the enzyme activity. Biochemistry (Mosc)., 66, 865−74.
- Nakagawa Y, Petricoin EF, Akai H, Grimley PM, Rupp B, Larner AC.(1992a), Interferon-alpha-induced gene expression: evidence for a selective effect on activation of the ISGF3 transcription complex. Virology, 190, 210−220.
- Nakagawa Y, Rivera V, Larner AC. (1992b) A role for Na/K-ATPase in the control of human c-fos and c-jun transcription. J Biol Chem, 267, 8785−8788.
- Nelson, W.J., Veshnock, P. (1987) Ankyrin binding to (Na+K)-ATPase and implications for the organization of membrane domains in polarized cells. Nature 328, 533−537.
- Orlov S.N., Akimova O.A., Hamet P. (2005). Cardiotonic steroids: novel mechanisms of Na±mediated and -independent signaling involved in regulation of gene expression, proliferation and cell death. Current Hypertension Reviews. In press.
- Orlov S.N., Dam T.V., Tremblay. J., Hamet. P. (1996) Apoptosis in cultured vascular smooth muscle cells. Role of cell volume decrease. Biochem Biophys Res Commun-, 221:708−715.
- Orlov S.N., Taurin S., Thorin-Trescases N., Dulin N.O., Tremblay J., Hamet P. (2000) Inversion of the intracellular Na+/K+ ratio blocks apoptosis in vascular smooth muscle cells by induction ofRNA synthesis. Hypertension- 35:1062−1068.
- Orlov S.N., Thorin-Trescases N., Kotelevtsev S.V., Tremblay J., Hamet P. (1999) Inversion of the intracellular Na+/K+ ratio blocks apoptosis in vascular smooth muscle at a site upstream of caspase-3. J Biol Chem- 274:16 545−16 552.
- Orlov, S.N., Thorin-Trescases, N., Kotelevtsev, S.V., Tremblay, J., Hamet, P. (1999) Inversion of the intracellular Na+/K+ ratio blocks apoptosis in vascular smooth muscle at a site upstream of caspase-3. J Biol Chem, 274, 6545−16 552.
- Orlov, S.N., Tremblay, J., and Hamet, P. (1996) Bumethanide-sensitive ion fluxes in vascular smooth muscle cells: lack of functional Na+, K+, 2C1- cotransport. J. Membr. Biol., 153,125 135.
- Orlov, S.N., Tremblay, J., Hamet, P. (1995) Altered beta-adrenergic regulation of Na-K-Cl cotransport in cultured smooth muscle cells from the aorta of spontaneously hypertensive rats. Role of the cytoskeleton network. Am J Hypertens, 8, 739−747.
- Otto E., Kunimoto M., McLaughlin T., Bennett V. (1991) Isolation and characterization of cDNAs encoding human brain ankyrins reveal a family of alternatively spliced genes. J. Cell. Biol., 114, N2,241−253.
- Palasis, M., Kuntzweiler, T.A., Arguello, J.M., and Lingrel, J.B. (1996) Ouabain interactions with the H6-H6 hairpin of the Na, K-ATPase reveal a possible inhibition mechanism via the cation binding domain. J. Biol. Chem., 271, 14 176−14 182.
- Pamnani, M., Huot, S., Buggy, J., Clough, D., Haddy, F. (1981) Demonstration of a humoral inhibitor of the Na±K+ pump in some models of experimental hypertension. Hypertension, 3, 96−101.
- Pedemonte C.H., Pressley T.A., Lokhandwala M.F., Cinelli A.R. (1997) Regulation of Na, K-ATPase transport activity by protein kinase C. J Membr Biol., 155, 219−27.
- Peng L., Martin-Vasallo P., Sweadner K.J. (1997) Isoforms of Na,.K-ATPAse a and P subunits in the rat cerebellum and in granule cell cultures. J. Membr. Biol., 155, 219−227.
- Peng, M., Huang, L., Xie, Z., Huang, W-H., Askari, A.(1996) Partial inhibition of Na+/K±ATPase by ouabain induces the Ca2±dependent expression of early-response genes in cardiac myocytes. J Biol Chem, 271, 10 372−10 378.
- Pontiggia L., Winterhalter K., Gloor S.M. (1998) Inhibition of Na, K-ATPase activity by cGMP is isoform-specific in brain endothelial cells. FEBS Lett., 436, 46 670.
- Post R.L., Sen A.K., Rosenthal A.S. (1965) A phosphorylated intermediate in adenosine triphosphate dependent sodium and potassium transport across kidney membranes. J. Biol. Chem., 240, 1437−1445.
- Post, R.L., Hegyvary, C., and Kume, S. (1972) Activation by adenosine triphosphate in the phosphorylation kinetics of sodium and potassium ion transport adenosine triphosphatase. J. Biol. Chem., 247, 6530−6540.
- Price, E.M., Rice, D.A., and Lingrel, J.B. (1989) Site-directed mutagenesis of a conserved, extracellular aspartic acid residue affects the ouabain sensitivity of sheep Na, K-ATPase. J. Biol. Chem., 264,21 902−21 906.
- Qiu, L.Y., Koenderink, J.B., Swarts, H.G.P., Willems, P.H.G.M., Pont, J.J.H.H.M. (2003) Phe783, Thr797, and Asp804 in transmembrane hairpin M5-M6 of Na, K-ATPase play a key role in ouabain binding. J. Biol. Chem., 278,47 240−47 244.
- Rajan S, Wischmeter E, Liu GX, Preisig-Muller R, Daut J, Karschin A, Derst C (2000) TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histidine as pH sensor. J Biol Chem, 275, 16 650−16 657.
- Rajasekaran, S.A., Gopal, J., Wills, D., Espineda, C., Twiss, J.K., Rajasekaran, A.K. (2004) Na, K-ATPase betal-subunit increases the translation efficiency of the alpha 1-subunit in MSV-MDCK cells. Mol Biol Cell., 15(7), 3224−32.
- Razani, B., Woodman, S.E. and Lisanti, M.P. (2002) Caveolae: From cell biology to animal physiology. Pharmacol. Rev. 54: 431−467.
- Reichert M, Steinbach JP, Supra P, Weller M (2002) Modulation of growth and radiochemosensitivity of human malignant glioma cells by acidosis. Cancer, 95, 1113−1119.
- Renner, E.L., Lake, J.R., Persico, M., Scharschmidt, B.F. (1989) Na±H+ exchange activity in rat hepatocytes: role in regulation of intracellular pH. Am J Physiol. 256, G44−52.
- Sarvazyan, N.A., Modynov, N. N., Askari, A. (1995) Intersubunit and intrasubunit contact regions of Na+/K±ATPase revealed by controlled proteolysis and chemical cross-linking. J. Biol. Chem. 270,26 528−26 532.
- Saunders, R., Scheiner-Bobis, G. (2004) Ouabain stimulates endothelin release and expression in human endothelial cells without inhibiting the sodium pump. Eur J Biochem, 111, 1054−1062.
- Schatzmann HJ. (1953) Herzglykoside ais Hennstoffe fur den aktiven Kalium- und Natriumtransport durch die erythrocytenmembran. Helv Physiol Pharmacol Acta, 11, 346−354.
- Schneider, R., Wray, V., Nimtz, M., Lehmann, W-D., Kirch, U., Antoloic, R. et al. (1998) Bovine adrenals contain, in addition to ouabain, a second inhibitor of the sodium pump. J Biol Chem, 273,784−792.
- Schoner, W. (2002) Endogenous cardiac glycosides, a new class of steroid hormones. Eur JBiochem, 269, 2440−2448.
- Schultheis, P.J., and Lingrel, J.B. (1993) Substitution of transmembrane residues with hydrogen-bonding potential in the alpha subunit of Na, K-ATPase reveals alteration in ouabain sensitivity. Biochemistry, 32, 544−550.
- Schultheis, P.J., Wallick, E.T., and Lingrell, J.B. (1993) Kinetic analysis of ouabain binding to native and mutated forms of Na, K-ATPase and identification of a new region involved in cardiac glycoside interactions. J. Biol. Chem., 268, 2 268 622 694.
- Schwartz, A. (1976) Is the cell membrane Na+, K+ -ATPase enzyme system the pharmacological receptor for digitalis? Circ Res., 39:1−7.
- Shamraj, O.I., and Lingrel, J.B. (1994) A putative fourth Na, K-ATPase a subunit gene is expressed in testis. Proc. Natl. Acad. Sci. USA, 91, 12 952−12 956. r
- Shan X., Luo H., Chen H., Daloze P., St-Louis G., Wu J. (1993) The effect of rapamycin on c-jun expression in human lymphocytes. Clin Immunol Immunopathoi, 69,314−7.
- Shevchenko, A., Wilm, M., Vorm, O. and Mann, M. Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal. Chem., 68, 850−858, 1996.
- Shull G.E., Greeb J., Lingrel J.B. (1986) Molecular cloning of three distinct forms of the (Na+K)-ATPase a-subunit from rat brain. Biochemistry, 25, 8125−8132.
- Shull G.E., Schwarts A., Lingrel J.B. (1985) Amino-acid sequence of the catalytic subunit of the (Na++K+)ATPase deduced from a complementary DNA. Nature, 316, 691−695.
- Skou J. C (1957) The influence of some cations on an adenosine triphosphatase from priferal nerves. Biochim. Biophys. Acta, 23, 394−401.
- Skou J.C., and Esmann M. (1992) The Na, K-ATPase. J Bioenerg Biomembr., 24, 249−61.
- Skou JC. (1960) Further investigation on a Mg 2+ + Na±activated adenosinetriphosphatase possibly related to the active transport of Na+ and K+ across the nerve cell membrane. Biochim Biophys Acta, 42, 6−23.
- Stewart D.J., and Sen A.K. (1981) Role of cyclic GMP in cholinergic activation of Na-K pump in duck salt gland. Am J Physiol., 240, 207−14.
- Sun X.M., MacFarlane M., Zhuang J, m Wolf B.B., Green D.R., Cohen G.M. (1999) Distinct caspase cascades are initiated in receptor-mediated and chemical-induced apoptosis. J Biol Chem., 274, 5053−60.
- Sweadner K.J., Real E. (2000) The FXYD gene family of small ion transport regulators or channels: cDNA sequence, protein signature sequence, and expression. Genomics., 68, 41−56.
- Szent-Gyorgyi A. (1953) Chemical physiology of contraction in body and heart. New York, Academic Press. 86−91
- Taurin S, Hamet P, Orlov SN. (2003) Na/K pump and intracellular monovalent cations: novel mechanism of excitation-transcription coupling involved in inhibition of apoptosis. Mo I Biol, 37, 371−381.
- Therien A.G., and Blostein R. (2000) Mexanisms of sodium pump regulation. Am J Physiol Cell Physiol., 279, C541−66.
- Thevananther S., Kolli A.H., Devarajan P. (1998) Identification of a novel ankyrin isoform (AnkG190) in kidney and lung that associates with the plasma membrane and binds alpha-Na, K-ATPase J. Biol. Chem., 273, 23 952−23 958.
- Thomas, J.A., Buchsbaum, R.N., Zimniak, A., Racker, E. (1979) Intracellular pH measurements in Ehrlich ascites tumor cells utilizing spectroscopic probes generated in situ. Biochemistry, 18, 2210−8.
- Thomas, S.M. and Brugge, J.S. (1997) Cellular functions regulated by Src family kinases. Annu. Rev. Cell. Dev. Biol. 13: 513−609.
- Trevisi L, Visentin B, Cusinato F, Pighin I, Luciani S. (2004) Antiapoptotic effect of ouabain on human umbilical endothelial cells. Biochem Biophys Res Commun, 321, 716−721.
- Vachon, P.H., Beaulieu, J.F. (1992) Transient mosaic patterns of morphological and functional differentiation in the Caco-2 cell line. Gastroenterology. 103, 414−23.
- Valente, R.C., Capella, L.S., Monteiro, R.Q., Rumjanek, V.M., Lopes, A.G., Capella, M.A. (2003) Mechanisms of ouabain toxicity. FASEB J., 17, 1700−2.
- Wadhwa R, Yaguchi T, Hasan MK, Mitsui Y, Reddel RR, Kaul SC. (2002) Hsp70 family member, mot-2/mthsp7-/GSP75, binds to the cytoplasmic sequestration domain of the p53 protein. Exp Cell Res, 274, 246−253.
- Wallick, E. T. and Schwartz, A. (1988) Interaction of cardiac glycosides with Na+, K±ATPase. Methods Enzymol. 156,201−213.
- Wang S.G., and Farley R.A. (1998) Valine 904, tyrosine 898, and cysteine 908 in Na, K-ATPase alpha subunits are important for assembly with beta subunits. J Biol Chem., 273, 29 400−5.
- Wang, H., Haas, M., Liang, M., Cai, T., Tian, J., Li, S., Xie, Z. (2004) Ouabain assembles signaling cascade through the caveolar Na+, K±ATPase. J Biol Chem, 279, 17 250−17 259.
- Wood EH, Moe GK. (1938) Studies on the effect of digitalis glycosides on potassium ion loss from the heart of the heart lung preparation. Am J Physiol, 123, 219−220.
- Xie Z, Askari A. (2002) Na+/K±ATPase as a signal transducer. Eur J Biochem, 269,2434−2439.
- Xie, Z., Cai, T. (2003) Na±K±ATPase-mediated signal transduction: from protein interaction to cellular function. Mol Intervent, 3, 157−168.
- Xie, Z., Kometiani, P., Liu, J., Li, J., Shapiro, J.I., Askari, A. (1999) Intracellular reactive oxygen species mediate the linkage of Na+/K±ATPase to hypertrophy and its marker genes in cardiac myocytes. J Biol Chem., 274, 19 323−8.
- Xiong Z-G, Zhu X-M, Chu X-P, Minami M, Hey J, Wei W-L, MacDonald JF, Wemmie JA, Price MP, Welsh MJ, Simon RP (2004) Neuroprotection in ishemia: blocking calcium-permeable acid-sensitive ion channels. Cell, 118,687−698.
- Xu, W., Harrison, S.C., and Eck, M.J. (1997) Three-dimensional structure of the tyrosine kinase c-Src. Nature 385: 595−602.
- Young, M.A., Gonfloni, S., Superti-Furga, G., Roux, B., and Kuriyan, J. (2001) Dynamic coupling between the SH2 and SH3 domains of c-Src and Hck underlies their inactivation by C-terminal tyrosine phosphorylation. Cell 105: 115−126.
- Yudowski G.A., Efendiev R., Pedemonte R., Katz A.I., Berggren P.O., Bertorello A.M. (2000) Phosphoinositide-3 kinase binds to a proline-rich motif in the Na+, K±ATPase alpha subunit and regulates its trafficking. Proc Natl Acad Sci USA., 97, 6556−61.
- Zhang, Z., Devarajan, P., Dorfman, A.L., Morrow, J.S. (1998) Structure of the ankyrin-binding domain of a-Na-K-ATPase. J Biol Chem, 273, 18 681−18 684.