Cardioprotective Intermittent Hypoxia Conditioning Induces Glyoxalase-1 in Rat Left Ventricle

Intermittent, normobaric hypoxia (IH) conditioning provides significant cardioprotection, including dramatically increasing myocardial resistance to ischemia-reperfusion. The cardioprotective mechanisms of IH are unknown. Myocardial ischemia-reperfusion generates methylglyoxal, a potent and toxic glycating agent. Our previous studies1 demonstrated that reactive oxygen species (ROS) generated during IH cycles contribute to cardioprotection. We hypothesize that the generation of ROS during IH cycles induce the transcription factor Nrf2 to activate expression of genes encoding cytoprotective proteins. Here we evaluated IH induction of glyoxylase 1 (GLO-1), a major enzyme responsible for methylglyoxal detoxification. Sprague-Dawley rats were conditioned by a 20 day IH program consisting of 5-8 daily, 5-10 min cycles of hypoxia (9.5-10% inspired O2) with intervening 4 min room air exposures, previously shown to produce robust cardioprotection.1 Control rats were sham-conditioned using 21% O2. After completion of the conditioning protocol, the left ventricle was isolated and extracted for enzyme analysis. The activities of cytoprotective enzymes were analyzed by spectrophotometric assays. GLO-1 activity (U/mg protein) increased threefold in IH conditioned (1.05±0.16) vs. sham (0.35±0.11) rats. Glutathione reductase activity (U/mg protein) was unchanged between IH conditioned (0.015±0.0047) vs. sham rats (0.023±0.016). IH augmentation of the anti-glycation enzyme GLO-1 may contribute to the heart’s increased resistance to ischemic injury.