title: Peripheral benzodiazepine receptor ligand, PK11195 induces mitochondria cytochrome c release and dissipation of mitochondria potential via induction of mitochondria permeability transition.
abstract: 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.
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital, China Medical University, Shenyang 110001, China. jnyuanli@163.com
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Li
authors.forename: Junke
authors.initials: J
authors.lastname: Wang
authors.forename: Yinming
authors.initials: Y
authors.lastname: Zeng
mesh_terms: 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
chemical_list: D058787:GABA-A Receptor Antagonists; D007546:Isoquinolines; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D045304:Cytochromes c; C037850:PK 11195