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Peripheral benzodiazepine receptor ligand, PK11195 induces mitochondria cytochrome c release and dissipation of mitochondria potential via induction of mitochondria permeability transition



Peripheral benzodiazepine receptor ligand, PK11195 induces mitochondria cytochrome c release and dissipation of mitochondria potential via induction of mitochondria permeability transition



European Journal of Pharmacology 560(2-3): 117-122



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 microM) caused a dose-dependent mitochondrial swelling, cytochrome c loss, and the dissipation of mitochondrial potential. Cyclosporin A (0.2 microM), 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.

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Accession: 049893750

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PMID: 17291492

DOI: 10.1016/j.ejphar.2006.12.027


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