Regulation of ROMK (Kir 1.1) channel expression in kidney thick ascending limb by hypertonicity: role of TonEBP and MAPK pathways.
Nephron Physiol
; 104(4): 126-35, 2006.
Article
en En
| MEDLINE
| ID: mdl-17003571
ABSTRACT
The present study assessed the mechanisms by which hypertonicity caused by NaCl enhances the renal outer medullary potassium channel (ROMK) mRNA abundance in rat kidney medullary thick ascending limb (MTAL) and in cultured mouse TAL cells. Using the run-off technique, we observed that the ROMK gene transcription rate in nuclei isolated from MTAL fragments was enhanced approximately 40% by a high NaCl medium. In MTAL fragments, hypertonicity (450 mosm) caused by NaCl, not by mannitol or urea, enhanced both ROMK mRNA abundance and tonicity-responsive enhancer binding protein (TonEBP) total abundance and nuclear localization. In an immortalized mouse TAL cell culture in which ROMK is apically expressed, hypertonicity caused by both NaCl and mannitol, not urea, enhanced both ROMK mRNA abundance and TonEBP total abundance and nuclear localization. Confocal microscopy confirmed an increased nuclear translocation of TonEBP in response to NaCl-induced hypertonicity. Finally, inhibition of the p38 MAPK pathway by SB203580 and of the ERK pathway by PD98059 abolished the NaCl-induced stimulation of TonEBP and ROMK. These results establish that mRNA expression of ROMK is augmented in the MTAL by NaCl-induced hypertonicity through stimulation of ROMK gene transcription, and that TonEBP and the p38 MAPK and ERK pathways are involved in this effect.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Transcripción Genética
/
Cloruro de Sodio
/
Sistema de Señalización de MAP Quinasas
/
Canales de Potasio de Rectificación Interna
/
Asa de la Nefrona
Límite:
Animals
Idioma:
En
Revista:
Nephron Physiol
Asunto de la revista:
NEFROLOGIA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Francia