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

FEBS Letters

Yoon, Sang-Pil³  Chang, In-Youb³  Chung, Myung-Hee¹  Jeong, Hye-Gwang²  Cho, Hyun-Ju²  Jeon, Young-Jin²  You, Ho Jin² 

[1] Department of Pharmacology, Seoul National University College of Medicine, 28 Yongon-dong, Seoul 110-799, South Korea;Research Center for Proteineous Materials, Chosun University, 375 Seusuk-dong, Kwangju 501-759, South Korea;Department of Anatomy, Chosun University, 375 Seusuk-dong, Kwangju 501-759, South Korea

关键词: Rac1;    Rho family;    Cisplatin;    Apoptosis;    p38;    Cytochrome c;    JNK;    c-Jun N-terminal kinase;    ERK;    extracellular signal-regulated kinase;    MAPK;    mitogen-activated protein kinase;    MEK;    mitogen-activated protein kinase kinase;   

DOI  :  10.1016/S0014-5793(02)02674-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown