title: Cardioprotection and altered mitochondrial adenine nucleotide transport.
abstract: It is becoming increasingly clear that mitochondrial dysfunction is critically important in myocardial ischemic injury, and that cardioprotective mechanisms must ultimately prevent or attenuate mitochondrial damage. Mitochondria are also essential for energy production, and therefore prevention of mitochondrial injury must not compromise oxidative phosphorylation during reperfusion. This review will focus on one mitochondrial mechanism of cardioprotection involving inhibition of adenine nucleotide transport across the outer mitochondria membrane under de-energized conditions. This slows ATP hydrolysis by the mitochondria, and would be expected to lower mitochondrial membrane potential during ischemia, to inhibit calcium uptake during ischemia, and potentially to reduce free radical generation during early reperfusion. Two interventions that similarly inhibit mitochondrial adenine nucleotide transport are Bcl-2 overexpression and GSK inhibition. A possible final common mechanism shared by both of these interventions is discussed.
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA. csteenb1@jhmi.edu
authors.forename: Charles
authors.initials: C
authors.lastname: Steenbergen
authors.forename: Samarjit
authors.initials: S
authors.lastname: Das
authors.forename: Jason
authors.initials: J
authors.lastname: Su
authors.forename: Renee
authors.initials: R
authors.lastname: Wong
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Murphy
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008929:Mitochondria, Heart / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000227:Adenine Nucleotides; D000255:Adenosine Triphosphate