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

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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°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.

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  1. The Molecular Cardiology and Neuromuscular Institute, 75 Raritan Avenue, Highland Park, NJ, USA

    YeQing Pi, Michael J. Goldenthal & José Marín-García

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  1. YeQing Pi
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  2. Michael J. Goldenthal
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Correspondence to José Marín-García.

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Pi, Y., Goldenthal, M.J. & Marín-García, J. Mitochondrial involvement in IGF-1 induced protection of cardiomyocytes against hypoxia/reoxygenation injury. Mol Cell Biochem 301, 181–189 (2007). https://doi.org/10.1007/s11010-007-9410-0

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