title: Cadmium activates extracellular signal-regulated kinase 5 in HK-2 human renal proximal tubular cells.
abstract: We examined the effects of cadmium chloride (CdCl(2)) exposure on the phosphorylation and functionality of extracellular signal-regulated kinase 5 (ERK5), a recently identified member of the mitogen-activated protein kinase (MAPK) family, in HK-2 human renal proximal tubular cells. Following exposure to CdCl(2), ERK5 phosphorylation increased markedly, but the level of total ERK5 was unchanged. ERK5 phosphorylation following CdCl(2) exposure was rapid and transient, similar to the time course of ERK1/2 phosphorylation. Treatment of HK-2 cells with the MAPK/ERK kinase 5 inhibitor, BIX02189, suppressed CdCl(2)-induced ERK5 but not ERK1/2 phosphorylation. The CdCl(2)-induced increase of phosphorylated cAMP response element-binding protein (CREB) and activating transcription factor-1 (ATF-1), as well as the accumulation of mobility-shifted c-Fos protein, were suppressed by BIX02189 treatment. Furthermore, BIX02189 treatment enhanced cleavage of poly(ADP-ribose) polymerase and increased the level of cytoplasmic nucleosomes in HK-2 cells exposed to CdCl(2). These findings suggest that ERK5 pathway activation by CdCl(2) exposure might induce the phosphorylation of cell survival-transcription factors, such as CREB, ATF-1, and c-Fos, and may exert a partial anti-apoptotic role 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: Mio
authors.initials: M
authors.lastname: Kondo
authors.forename: Hisako
authors.initials: H
authors.lastname: Inamura
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Matsumura
authors.forename: Masato
authors.initials: M
authors.lastname: Matsuoka
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000814:Aniline Compounds / Q000494:pharmacology; D002104:Cadmium / Q000633:toxicity*; D019256:Cadmium Chloride / Q000633:toxicity; D002460:Cell Line; D003593:Cytoplasm / Q000201:enzymology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology; D020935:MAP Kinase Signaling System; D048054:Mitogen-Activated Protein Kinase 7 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D009707:Nucleosomes / Q000201:enzymology; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
chemical_list: D000393:Air Pollutants; D000814:Aniline Compounds; C533207:BIX 02189; D007211:Indoles; D009707:Nucleosomes; D047428:Protein Kinase Inhibitors; D002104:Cadmium; D011065:Poly(ADP-ribose) Polymerases; D048054:Mitogen-Activated Protein Kinase 7; D019256:Cadmium Chloride