Rac1 prevents cisplatin-induced apoptosis through down-regulation of p38 activation in NIH3T3 cells

• Published in: FEBS letters 2002-05, Vol.518 (1), p.129-134
• Main Authors: Jeong, Hye-Gwang, Cho, Hyun-Ju, Chang, In-Youb, Yoon, Sang-Pil, Jeon, Young-Jin, Chung, Myung-Hee, You, Ho Jin
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Antineoplastic Agents - antagonists & inhibitors; Apoptosis; Cisplatin; Cisplatin - antagonists & inhibitors; Cytochrome c; Cytochrome c Group - metabolism; Down-Regulation; Enzyme Activation; Enzyme Inhibitors - pharmacology; ERK, extracellular signal-regulated kinase; JNK Mitogen-Activated Protein Kinases; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; MEK, mitogen-activated protein kinase kinase; Mice; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Mitogen-Activated Protein Kinases - physiology; Mutation; p38; p38 Mitogen-Activated Protein Kinases; Rac1; rac1 GTP-Binding Protein - genetics; rac1 GTP-Binding Protein - physiology; Rho family
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(02)02674-1

In this study, the role of V12-Rac1 in the cisplatin-induced apoptosis was investigated. Cisplatin-induced apoptosis is associated with cytochrome c release, which can be inhibited by V12-Rac1 expression. The analysis of mitogen-activated protein kinase activity indicated that V12-Rac1 expression led to a decrease in p38 activity after exposure to cisplatin but not c-jun N-terminal kinase and extracellular signal-regulated kinase. Using pharmacological inhibitors, it was found that only p38 is a critical mediator in the cisplatin-induced apoptosis of NIH3T3 cells. This suggests that V12-Rac1 can stimulate the anti-apoptotic signaling pathway in response to cisplatin, and that decreased p38 activity caused by V12-Rac1 expression in cisplatin-treated NIH3T3 cells is crucial for V12-Rac1-dependent cell survival.