Peripheral benzodiazepine receptor ligand, PK11195 induces mitochondria cytochrome c release and dissipation of mitochondria potential via induction of mitochondria permeability transition.
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.
Li
Jingyuan
J
Department of Anesthesiology, the First Affiliated Hospital, China Medical University, Shenyang 110001, China. jnyuanli@163.com
Wang
Junke
J
Zeng
Yinming
Y
D000818:Animals; D045304:Cytochromes c / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D058787:GABA-A Receptor Antagonists; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects*; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D058787:GABA-A Receptor Antagonists; D007546:Isoquinolines; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D045304:Cytochromes c; C037850:PK 11195