Increased expression and activation of serum- and glucocorticoid-inducible kinase-1 (SGK1) by cadmium in HK-2 renal proximal tubular epithelial cells.

In HK-2 cells exposed to cadmium chloride (CdCl2), the level of serum- and glucocorticoid-inducible kinase-1 (SGK1) protein is increased, but the levels of SGK2 and SGK3 proteins are not. Phosphorylation of SGK1 protein is also observed. Treatment with actinomycin D abolished CdCl2-induced elevation of SGK1 mRNA level. Treatment with actinomycin D or cycloheximide suppressed SGK1 protein levels in cells exposed to CdCl2. Treatment with SGK1 inhibitor EMD638683 or knockdown of SGK1 with siRNA suppressed CdCl2-induced phosphorylation of N-Myc downstream-regulated kinase 1 (NDRG1). These results indicate that cadmium induces the transcriptional upregulation of SGK1 expression and regulates NDRG1 in HK-2 cells.