PKCα contributes to high NaCl-induced activation of NFAT5 (TonEBP/OREBP) through MAP kinase ERK1/2.

PKCα contributes to high NaCl-induced activation of NFAT5 (TonEBP/OREBP) through MAP kinase ERK1/2. Am J Physiol Renal Physiol. 2014 Nov 12;:ajprenal.00471.2014 Authors: Wang H, Ferraris JD, Klein JD, Sands JM, Burg MB, Zhou X Abstract High NaCl in the renal medullary interstitial fluid powers concentration of the urine, but can damage cells. The transcription factor NFAT5 activates expression of osmoprotective genes. We studied whether PKCα contributes to activation of NFAT5. PKCα protein abundance is greater in the renal medulla than in the cortex. Knockout of PKCα reduces NFAT5 protein abundance and expression of its target genes in the inner medulla. In HEK293 cells, high NaCl increases PKCα activity and siRNA-mediated knockdown of PKCα attenuates high NaCl-induced NFAT5 transcriptional activity. Expression of ERK1/2 protein and phosphorylation of ERK1/2 is higher in the renal inner medulla than in the cortex. Knockout of PKCα decreases ERK1/2 phosphorylation in the inner medulla, as does knockdown of PKCα in HEK293 cells. Also, knockdown of ERK2 reduces high NaCl-dependent NFAT5 transcriptional activity in HEK293 cells. Combined knockdown of PKCα and ERK2 has no greater effect than knocking down either alone. Knockdown of either PKCα or ERK2 reduces the high NaCl-induced increase of NFAT5 transactivating activity. We previously found that the high NaCl-induced increase of phosphorylation of...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

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Source: Revista da Escola de Enfermagem da USP - Category: Nursing Source Type: research
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