Submitted on February 22, 2007
Accepted on August 5, 2007
Down-regulation of SGK1 by nucleotides in renal tubular epithelial cells
Liuzhe Li1, Charles S Wingo1, and Shen-Ling Xia1*
1 North Florida/South Georgia Veterans Health System, Gainesville, Florida, United States; Department of Medicine, University of Florida, Gainesville, Florida, United States
* To whom correspondence should be addressed. E-mail: xiasl{at}medicine.ufl.edu.
This study determined whether nucleotides that bind to purinergic receptors (P2R) regulate the expression or function of SGK1 in mouse renal IMCD cells (mIMCD-3). The SGK1 protein was detected by Western blotting. A significant reduction of cytosolic SGK1 expression was observed in the cells pretreated with P2R agonist ATP
S, and the reduction could be reversed by P2R antagonists. This reduction was also observed in cells that were pretreated with agonists for P2R subtypes. Using ELISA, a reduced SGK1 kinase activity was observed in ATPS-pretreated cells. This effect was reversed by P2R antagonists. Furthermore, an increase of SGK1 kinase activity in aldosterone-pretreated cells was suppressed by ATPS. These studies have demonstrated for the first time that SGK1 can be down-regulated by nucleotides in renal collecting duct epithelial cells, likely via the activation of P2R, and suggest that activation of renal purinergic signaling regulates a SGK1-dependent pathway that is known to modulate ion transport in the renal collecting duct.
