title: Blockade of electron transport during ischemia preserves bcl-2 and inhibits opening of the mitochondrial permeability transition pore.
abstract: Myocardial ischemia damages the electron transport chain and augments cardiomyocyte death during reperfusion. To understand the relationship between ischemic mitochondrial damage and mitochondrial-driven cell death, the isolated perfused heart underwent global stop-flow ischemia with and without mitochondrial protection by reversible blockade of electron transport. Ischemic damage to electron transport depleted bcl-2 content and favored mitochondrial permeability transition (MPT). Reversible blockade of electron transport preserved bcl-2 content and attenuated calcium-stimulated mitochondrial swelling. Thus, the damaged electron transport chain leads to bcl-2 depletion and MPT opening. Chemical inhibition of bcl-2 with HA14-1 also dramatically increased mitochondrial swelling, augmented by exogenous H(2)O(2) stress, indicating that bcl-2 depleted mitochondria are poised to undergo MPT during the enhanced oxidative stress of reperfusion.
authors.affiliation: Department of Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Qun
authors.initials: Q
authors.lastname: Chen
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Lesnefsky
mesh_terms: D000654:Amobarbital / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004579:Electron Transport / Q000502:physiology; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D015151:Immunoblotting; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D009570:Nitriles / Q000494:pharmacology; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001578:Benzopyrans; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009570:Nitriles; D016877:Oxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C456800:ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D000654:Amobarbital