title: Mitochondrial energy metabolism plays a critical role in the cardioprotection afforded by intermittent hypobaric hypoxia.
abstract: Intermittent hypobaric hypoxia (IHH) is an effective protective strategy against myocardial ischaemia-reperfusion (I/R) injury, but the precise mechanisms are far from clear. To understand the overall effects of IHH on the myocardial proteins during I/R, we analysed functional performance and the protein expression profile in isolated hearts from normoxic rats and from rats adapted to IHH (5000 m, 4 h day(-1), 4 weeks) following I/R injury (30 min/45 min). Intermittent hypobaric hypoxia significantly improved the postischaemic recovery of left ventricular function compared with the recovery in time-matched normoxic control hearts. Two-dimensional electrophoresis with matrix-assisted laser desorption/ionization and time-of-flight mass spectrometric analysis was then used to assess protein alterations in left ventricles from normoxic and IHH groups, with or without I/R. The expressions of 16 proteins changed by over fivefold; nine of these proteins are involved in energy metabolism. Immunoblot and real-time PCR analysis confirmed the IHH-increased expressions of the ATP synthase subunit β, mitochondrial aldehyde dehydrogenase and heat shock protein 27 in left ventricles. Furthermore, IHH significantly attenuated the reduction of myocardial ATP content, mitochondrial ATP synthase activity, membrane potential and respiratory control ratios due to I/R. In addition, inhibition of mitochondrial ATP synthase by oligomycin (1 μmol l(-1)) abolished the IHH-induced improvements in three parameters: postischaemic recovery of left ventricular function, mitochondrial membrane potential and respiratory control ratios. These results suggest that an improvement in mitochondrial energy metabolism makes an important contribution to the cardioprotection afforded by IHH against postischaemic myocardial dysfunction.
authors.affiliation: Key Laboratory of Stem Cell Biology and Laboratory of Molecular Cardiology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Wang
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Cai
authors.forename: Lan
authors.initials: L
authors.lastname: Wu
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yu
authors.forename: Jin-Long
authors.initials: JL
authors.lastname: Liu
authors.forename: Zhao-Nian
authors.initials: ZN
authors.lastname: Zhou
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
authors.forename: Huang-Tian
authors.initials: HT
authors.lastname: Yang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008929:Mitochondria, Heart / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D055551:HSP27 Heat-Shock Proteins; D020543:Proteome; D000255:Adenosine Triphosphate; D000444:Aldehyde Dehydrogenase; D025261:Mitochondrial Proton-Translocating ATPases