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artículos
Título:
Hypertonic induction of COX2 expression requires TonEBP/NFAT5 in renal epithelial cells
Autor/es:
NICOLAS O. FAVALE; CECILIA I CASALI; LEANDRO G LEPERA; LUCILA G PESCIO; MARIA C. FERNÁNDEZ TOME
Revista:
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Editorial:
Elsevier
Referencias:
Año: 2009 vol. 381 p. 301 - 305
ISSN:
0006-291X
Resumen:
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.
2O) 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.
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.
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.