We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Induction of serum- and glucocorticoid-induced kinase-1 (SGK1) by cAMP regulates increases in alpha-ENaC.
- Authors
Vasquez, Margarita M; Castro, Robert; Seidner, Steven R; Henson, Barbara M; Ashton, Daniel J; Mustafa, Shamimunisa B
- Abstract
Alpha-ENaC expression and activity is regulated by a variety of hormones including beta-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 alpha-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 alpha-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 alpha-ENaC expression. Thus, in a cell line which endogenously exhibits minimal alpha-ENaC expression, induction of SGK1 by DbcAMP occurs via the PI3-K and PKA pathways. Increased alpha-ENaC levels and function are partly dependent upon the early induction of SGK1 expression.
- Publication
Journal of cellular physiology, 2008, Vol 217, Issue 3, p632
- ISSN
1097-4652
- Publication type
Journal Article
- DOI
10.1002/jcp.21534