Peripheral benzodiazepine receptor ligand, PK11195 induces mitochondria cytochrome c release and dissipation of mitochondria potential via induction of mitochondria permeability transition
- 作者：Jingyuan Li ; Junke Wang ; Yinming Zeng
- 关键词：Peripheral benzodiazepine receptor ; PK11195 ; Mitochondria permeability transition
- 刊名：European Journal of Pharmacology
- 出版年：2007
- 期刊代码：24_00142999
- 类别：neu
- 出版时间：10 April 2007
- 卷：560
- 期：2-3
- 页码：117-122
- 文件大小：1823 K
摘要
Mitochondrial permeability transition pore plays an important role in the processes of cell apoptosis and necrosis. The peripheral benzodiazepine receptor, a mitochondria outer-membrane protein, is involved in the regulation of mitochondrial permeability transition. In the present study, we test if PK11195, a peripheral benzodiazepine receptor ligand, can lead to the opening of mitochondrial permeability transition pores, and subsequently causes mitochondria cytochrome c loss and mitochondria uncoupling. In isolated cardiac mitochondria, PK11195 (50, 100, 200 μM) caused a dose-dependent mitochondrial swelling, cytochrome c loss, and the dissipation of mitochondrial potential. Cyclosporin A (0.2 μM), a specific inhibitor of mitochondrial permeability transition, completely prevented the mitochondrial swelling induced by PK11195, and maintained the cytochrome c content and membrane potential. These data suggest that peripheral benzodiazepine receptor ligand, PK11195 caused mitochondrial uncoupling and cytochrome c loss via induction of mitochondrial permeability transition.