Mitochondrial involvement in IGF-1 induced protection of cardiomyocytes against hypoxia/reoxygenation injury

• Published in: Molecular and cellular biochemistry 2007-07, Vol.301 (1-2), p.181-189
• Main Authors: Pi, YeQing, Goldenthal, Michael J, Marín-García, José
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Cardiomyocyte; Cardiomyocytes; Cardioprotection; Cardiotonic Agents - metabolism; Cells, Cultured; Citrate synthase; Citric Acid Cycle; Enzymatic activity; Enzymes; Evaluation; Growth factors; Hypoxia; IFG-1; Injury prevention; Insulin; Insulin-like growth factor I; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factors; Ischemia; Krebs cycle; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Lipid Peroxidation; Lipids; Male; Membrane potential; Membrane Potentials - physiology; Mitochondria; Mitochondria - metabolism; Myocardial ischemia; Myocardial Reperfusion Injury - prevention & control; Myocytes; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Oxidative phosphorylation; Oxygen - metabolism; Peroxidation; Phosphorylation; Rats; Rats, Sprague-Dawley; Reperfusion; Respiratory complex; Rodents; Signal Transduction - physiology; Tricarboxylic acid cycle
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-007-9410-0

Studies in animal models of myocardial ischemia-reperfusion revealed that the administration of insulin-like growth factor (IGF-1) can provide substantial cardioprotective effect. However, the mechanisms by which IGF-1 prevents myocardial ischemia-reperfusion injury are not fully understood. This study addresses whether mitochondrial bioenergetic pathways are involved in the cardioprotective effects of IGF-1. Single cardiomyocytes from adult rats were incubated in the absence or presence of IGF-1 for 60 min and subjected to 60 min hypoxia followed by 30 min reoxygenation at 37°C. Mitochondrial function was evaluated by assessment of enzyme activities of oxidative phosphorylation and Krebs cycle pathways. Hypoxia/reoxygenation (HR) caused significant inhibition of mitochondrial respiratory complex IV and V activities and of the Krebs cycle enzyme citrate synthase, whereas pretreatment with IGF-1 maintained enzyme activities in myocytes at or near control levels. Mitochondrial membrane potential, evaluated with JC-1 staining, was significantly higher in IGF-1 + HR- treated myocytes than in HR alone, with levels similar to those found in normal control cardiomyocytes. In addition, IGF-1 reduced both HR-induced lactate dehydrogenase (LDH) release and malondialdehyde production (an indicator of lipid peroxidation) in cardiomyocytes. These results suggest that IGF-1 protects cardiomyocytes from HR injury via stabilizing mitochondria and reducing reactive oxidative species (ROS) damage.