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Biochem Biophys Res Commun ; 381(3): 301-5, 2009 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-19146830

RESUMO

TonEBP/NFAT5 transcription factor is a master regulator of genes involved in osmoprotection. Cyclooxygenase 2 (COX2) has been reported to be a cytoprotective molecule in the inner renal medulla, where cells are physiologically exposed to the highest osmolality of the body. Our aim was to study whether COX2 expression requires TonEBP/NFAT5. Incubation of MDCK cells in hypertonic NaCl medium (500 mOsm/kg H2O) caused fully translocation of TonEBP/NFAT5 from cytoplasm to nucleoplasm and significantly increased COX2 mRNA, protein and activity levels. TonEBP/NFAT5-siRNA prevented hypertonic induction of COX2 mRNA and protein, leading to a depressed-prostaglandin synthesis and to a decreased cell survival. By using COX2-siRNA and COX2 specific inhibitor NS398, we found that cell survival does not depend on endogenous COX2-induced prostaglandin synthesis, but that cytoprotection strongly correlates with COX2 protein levels. These results demonstrate a new function for TonEBP/NFAT5, i.e., to mediate hypertonic-induced COX2 expression, and suggest that osmoprotection strongly depends on COX2 protein levels.


Assuntos
Ciclo-Oxigenase 2/biossíntese , Rim/efeitos dos fármacos , Fatores de Transcrição NFATC/metabolismo , Pressão Osmótica , Cloreto de Sódio/farmacologia , Animais , Sobrevivência Celular , Cães , Indução Enzimática , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/enzimologia , Rim/enzimologia , Solução Salina Hipertônica/farmacologia
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