Cadmium activates extracellular signal-regulated kinase 5 in HK-2 human renal proximal tubular cells

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• 作者：Mio Kondo ; Hisako Inamura ; Ken-ichi Matsumura ; Masato Matsuoka ; ^{matsuoka@research.twmu.ac.jp}
• 关键词：ATF-1 ; activating transcription factor-1 ; CdCl2 ; cadmium chloride ; CREB ; cAMP response element-binding protein ; DMSO ; dimethyl sulfoxide ; ERK ; extracellular signal-regulated kinase ; JNK ; c-Jun NH2-terminal kinase ; MAPK ; mitogen-activated protein kinase ; M
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：11 May, 2012
• 卷：421
• 期：3
• 页码：490-493
• 文件大小：376 K

摘要

We examined the effects of cadmium chloride (CdCl₂) 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 CdCl₂, ERK5 phosphorylation increased markedly, but the level of total ERK5 was unchanged. ERK5 phosphorylation following CdCl₂ 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 CdCl₂-induced ERK5 but not ERK1/2 phosphorylation. The CdCl₂-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 CdCl₂. These findings suggest that ERK5 pathway activation by CdCl₂ 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.