Role of ERK activation in cisplatin-induced apoptosis in OK renal epithelial cells

✍ Scribed by Yong Keun Kim; Hyun Ju Kim; Chae Hwa Kwon; Jae Ho Kim; Jae Suk Woo; Jin Sup Jung; Jong Min Kim

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 311 KB
• Volume: 25
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.1081

✦ Synopsis

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 microM 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.