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Exercise‐induced cardioprotection is dependent on enhanced glutathione reductase activity
Author(s) -
Frasier Chad R,
Sloan Ruben C,
Hayes Brian,
Brown David A
Publication year - 2012
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.26.1_supplement.1142.34
Subject(s) - cardioprotection , sed , ex vivo , glutathione , glutathione reductase , reperfusion injury , chemistry , oxidative stress , medicine , pharmacology , ischemia , endocrinology , cardiology , biochemistry , glutathione peroxidase , in vitro , enzyme
Oxidation of myocardial glutathione beyond a critical level collapses mitochondrial energetics and leads to cardiac ischemia‐reperfusion injury. We recently found that exercise‐induced cardioprotection was characterized by improved glutathione replenishment during varying oxidative insults. Since we observed increased glutathione reductase (GR) activity following exercise, we conducted this study to determine if inhibiting GR activity abolished exercise preconditioning. Female rats were either sedentary (Sed) or exercised for 10 consecutive days (Ex). Isolated hearts were exposed to 25 min ischemia and 2 h of reperfusion (I/R). Ex reduced infarct size (41±3% and 52±2% of risk zone for Ex and Sed respectively; P<0.05), protected against arrhythmia (arrhythmia scores were 3.0±0 and 3.7±0.3 for Ex and Sed respectively; P<0.05) and preserved coronary flow during reperfusion (10±1 and 7±1 mL/min/g for Ex and Sed respectively; P<0.05). Perfusion with the GR inhibitor BCNU (150 μM) during I/R abolished the exercise‐induced protection against infarction (57±1% in Ex+BCNU; P<0.05), arrhythmia (arrhythmia score 4.8±0.2 in Ex+BCNU; P<0.05) and coronary reactivity (5±1 mL/min/g in Ex+BCNU; P<0.05). Ex did not protect when animals received anti‐oxidant treatment, suggesting that increased GR activity is triggered by ROS. These data support our hypothesis that maintaining the reduced glutathione pool protects the Ex heart against I/R injury.