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Role of ERK activation in cisplatin‐induced apoptosis in OK renal epithelial cells
Author(s) -
Kim Yong Keun,
Kim Hyun Ju,
Kwon Chae Hwa,
Kim Jae Ho,
Woo Jae Suk,
Jung Jin Sup,
Kim Jong Min
Publication year - 2005
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1081
Subject(s) - apoptosis , cisplatin , mapk/erk pathway , microbiology and biotechnology , signal transduction , kinase , cytochrome c , p38 mitogen activated protein kinases , biology , chemistry , mitochondrion , cancer research , biochemistry , genetics , chemotherapy
Cisplatin induces apoptosis in a variety of cell types. However, the signaling pathway of cisplatin‐induced apoptosis in renal epithelial cells is poorly understood. The present study was undertaken to determine the role of the extracellular signal‐regulated kinase (ERK) in cisplatin‐induced apoptosis of renal epithelial cells using opossum kidney cells. Cisplatin at 50 µ m induced apoptosis in a time‐dependent manner. Cisplatin treatment caused sustained activation of ERK1/2, which was prevented by PD98059 and U0126, inhibitors of ERK1/2 upstream kinase MEK1/2. Transient transfection of cells with constitutive active MEK1 increased the cisplatin‐induced apoptosis, whereas that with a dominant‐negative mutant of MEK1 decreased it. Cisplatin induced an increase in Bax expression, mitochondrial membrane depolarization, mitochondrial cytochrome c release and caspase‐3 activation, and these changes were prevented by the MEK inhibitor. These results suggested that (1) the ERK1/2 activation is required for the cisplatin‐induced apoptosis of renal epithelial cells; and (2) ERK1/2 mediates the mitochondria‐dependent apoptotic signaling by acting upstream of Bax expression. Copyright © 2005 John Wiley & Sons, Ltd.