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Cardioprotective Intermittent Hypoxia Conditioning Induces Glyoxalase‐1 in Rat Left Ventricle
Author(s) -
Ramani Azaan,
Scott Gary F.,
Williams Arthur G.,
Ryou MyoungGwi,
Mallet Robert T.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.759.3
Subject(s) - cardioprotection , ischemia , intermittent hypoxia , methylglyoxal , hypoxia (environmental) , medicine , ventricle , chemistry , endocrinology , reperfusion injury , pharmacology , cardiology , enzyme , biochemistry , oxygen , organic chemistry , obstructive sleep apnea
Background Intermittent, normobaric hypoxia (IH) conditioning increases myocardial resistance to subsequent ischemia‐reperfusion, resulting in near‐prevention of myocardial infarct and ventricular tachyarrhythmias after coronary artery occlusion and reperfusion. The cardioprotective mechanisms of IH are unknown. Myocardial ischemia‐reperfusion triggers overproduction of the powerful dicarbonyl glycating agent, methylglyoxal (MG), which injures cells by modifying arginyl and lysyl residues and, thus, inactivating enzymes and other proteins. The glyoxalase system detoxifies the modest amounts of MG normally generated by glycolysis, but this system may be insufficient to manage the excessive MG production induced by ischemia‐reperfusion. The enzyme components of this system are expressed and synthesized in response to reactive oxygen species, which are generated in myocardium by cyclic hypoxia‐reoxygenation. Purpose This study evaluated IH induction of glyoxalase‐1 (GLO‐1), the rate‐controlling enzyme in the MG‐detoxifying glyoxalase cycle. Methods Sprague‐Dawley rats (n=10) were conditioned by a 20 day IH program consisting of 5–8 daily, 5–10 min cycles of hypoxia (9.5–10% inspired O 2 ) with intervening 4 min room air exposures, previously shown to produce robust cardioprotection [ Exp Biol Med 2004; 229: 806–812; Basic Res Cardiol 2006; 101: 436–446]. Control rats (n=10) completed sham‐conditioning with 21% O 2 . 24 h after the last IH or sham session, left ventricles were harvested, flash‐frozen in liquid N 2 and extracted for enzyme analyses. Results GLO‐1 activity (U/mg protein) was increased threefold in myocardium of IH (0.53±0.08) vs. sham (0.17±0.06) rats (P<0.01), while activity of the antioxidant enzyme glutathione reductase was unchanged (IH: 0.0154±0.0057; sham: 0.023274±0.0043). Conclusion IH augments the heart's anti‐glycation defenses, which may contribute to IH‐induced cardioprotection against ischemia‐reperfusion. Support or Funding Information Funding: NINDS NS076975; NCCAM AT003598