Abstract
α-ENaC expression and activity is regulated by a variety of hormones including β-adrenergic agonists via the second messenger cAMP. We evaluated the early intermediate pathways involved in the up-regulation of SGK1 by DbcAMP and whether SGK1 is a prerequisite for induction of α-ENaC expression. Submandibular gland epithelial (SMG-C6) cells treated with DbcAMP (1 mM) induced both SGK1 mRNA and protein expression. DbcAMP-stimulated SGK1 mRNA expression was decreased by actinomycin D and mRNA and protein expressions were attenuated by PKA inhibitors (H-89 and KT5720). Inhibition of PI3-K with either LY294002 or dominant negative PI3-K reduced DbcAMP-stimulated SGK1 protein and mRNA levels, attenuated the phosphorylation of CREB (a cAMP-activated transcription factor) and decreased α-ENaC protein levels and Na+ transport. In addition, the combination of PKA inhibitors with dominant negative PI3-K synergistically inhibited DbcAMP-induced Na+ transport. Inhibition of SGK1 expression by siRNA decreased but did not obliterate DbcAMP-induced α-ENaC expression. Thus, in a cell line which endogenously exhibits minimal α-ENaC expression, induction of SGK1 by DbcAMP occurs via the PI3-K and PKA pathways. Increased α-ENaC levels and function are partly dependent upon the early induction of SGK1 expression.
Original language | English (US) |
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Pages (from-to) | 632-642 |
Number of pages | 11 |
Journal | Journal of Cellular Physiology |
Volume | 217 |
Issue number | 3 |
DOIs | |
State | Published - Dec 2008 |
ASJC Scopus subject areas
- Physiology
- Clinical Biochemistry
- Cell Biology