Rac1 prevents cisplatin-induced apoptosis through down-regulation of p38 activation in NIH3T3 cells.
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.
Jeong
Hye-Gwang
HG
Research Center for Proteineous Materials, Chosun University, 375 Seusuk-dong, 501-759, Kwangju, South Korea
Cho
Hyun-Ju
HJ
Chang
In-Youb
IY
Yoon
Sang-Pil
SP
Jeon
Young-Jin
YJ
Chung
Myung-Hee
MH
You
Ho Jin
HJ
D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors*; D017209:Apoptosis; D002945:Cisplatin / Q000037:antagonists & inhibitors*; D003574:Cytochrome c Group / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D009154:Mutation; D048051:p38 Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000502:physiology*
D000970:Antineoplastic Agents; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein; D002945:Cisplatin