IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
artículos
Título:
Hypertonic induction of COX2 expression requires TonEBP/NFAT5 in renal epithelial cells
Autor/es:
N.O. FAVALE,; C.I. CASALI; L.G. LEPERA,; L.G. PESCIO; M.C. FERNÁNDEZ-TOME
Revista:
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Editorial:
Elsevier
Referencias:
Lugar: nehetlands ; Año: 2008
ISSN:
0006-291X
Resumen:
TonEBP/NFAT5 transcription factor is a master regulator of genes involved in osmoprotection. Cyclooxygenase2 (COX2) has been reported to be a cytoprotective molecule in the inner renal medulla, wherecells are physiologically exposed to the highest osmolality of the body. Our aim was to study whetherCOX2 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 significantlyincreased COX2 mRNA, protein and activity levels. TonEBP/NFAT5-siRNA prevented hypertonicinduction of COX2 mRNA and protein, leading to a depressed-prostaglandin synthesis and to a decreasedcell survival. By using COX2-siRNA and COX2 specific inhibitor NS398, we found that cell survival doesnot depend on endogenous COX2-induced prostaglandin synthesis, but that cytoprotection strongly correlateswith COX2 protein levels. These results demonstrate a new function for TonEBP/NFAT5, i.e., tomediate hypertonic-induced COX2 expression, and suggest that osmoprotection strongly depends onCOX2 protein levels.