title: Mitochondrial involvement in IGF-1 induced protection of cardiomyocytes against hypoxia/reoxygenation injury.
abstract: 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 degrees 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.
authors.affiliation: The Molecular Cardiology and Neuromuscular Institute, Highland Park, NJ, USA.
authors.forename: YeQing
authors.initials: Y
authors.lastname: Pi
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Goldenthal
authors.forename: José
authors.initials: J
authors.lastname: Marín-García
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000378:metabolism*; D002478:Cells, Cultured; D002952:Citric Acid Cycle; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
chemical_list: D002316:Cardiotonic Agents; D007334:Insulin-Like Growth Factor I; D010100:Oxygen