title: Increased expression and activation of serum- and glucocorticoid-inducible kinase-1 (SGK1) by cadmium in HK-2 renal proximal tubular epithelial cells.
abstract: 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.
authors.affiliation: Department of Hygiene and Public Health I, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Miyayama
authors.affiliation: Department of Hygiene and Public Health I, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. Electronic address: matsuoka@research.twmu.ac.jp.
authors.forename: Masato
authors.initials: M
authors.lastname: Matsuoka
mesh_terms: D001549:Benzamides / Q000494:pharmacology; D019256:Cadmium Chloride / Q000633:toxicity*; D002460:Cell Line; D004785:Environmental Pollutants / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D001549:Benzamides; D019256:Cadmium Chloride; D004785:Environmental Pollutants; D006834:Hydrazines; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases; C569030:EMD 638683
keywords: Cadmium; EMD638683; HK-2 cells; NDRG1; SGK1