Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Antineoplastic Agents / antagonists & inhibitors*
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Apoptosis*
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Cisplatin / antagonists & inhibitors*
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Cytochrome c Group / metabolism
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Down-Regulation
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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JNK Mitogen-Activated Protein Kinases
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Mice
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism*
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Mitogen-Activated Protein Kinases / physiology
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Mutation
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p38 Mitogen-Activated Protein Kinases
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rac1 GTP-Binding Protein / genetics
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rac1 GTP-Binding Protein / physiology*
Substances
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Antineoplastic Agents
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Cytochrome c Group
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Enzyme Inhibitors
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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rac1 GTP-Binding Protein
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Cisplatin