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.
Copyright © 2011. Published by Elsevier B.V.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Amobarbital / pharmacology
-
Animals
-
Benzopyrans / pharmacology
-
Cytochromes c / metabolism
-
Electron Transport / physiology
-
Hydrogen Peroxide / metabolism
-
Hydrogen Peroxide / pharmacology
-
Immunoblotting
-
In Vitro Techniques
-
Mitochondria, Heart / drug effects
-
Mitochondria, Heart / metabolism*
-
Mitochondrial Membrane Transport Proteins / metabolism*
-
Mitochondrial Permeability Transition Pore
-
Mitochondrial Swelling / drug effects
-
Myocardial Reperfusion Injury / metabolism
-
Myocardial Reperfusion Injury / physiopathology*
-
Nitriles / pharmacology
-
Oxidants / metabolism
-
Oxidants / pharmacology
-
Oxidative Phosphorylation / drug effects
-
Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
-
Proto-Oncogene Proteins c-bcl-2 / metabolism*
-
Rabbits
-
Reactive Oxygen Species / metabolism
Substances
-
Benzopyrans
-
Mitochondrial Membrane Transport Proteins
-
Mitochondrial Permeability Transition Pore
-
Nitriles
-
Oxidants
-
Proto-Oncogene Proteins c-bcl-2
-
Reactive Oxygen Species
-
ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate
-
Cytochromes c
-
Hydrogen Peroxide
-
Amobarbital