Myocardial protection from ischemia/reperfusion injury by exogenous galanin fragment
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Andrei Timotin1,2, Oleg Pisarenko3, Maria Sidorova3, Irina Studneva3, Valentin Shulzhenko3, Marina Palkeeva3, Larisa Serebryakova3, Aleksander Molokoedov3, Oksana Veselova3, Mathieu Cinato1,2, Helene Tronchere1,2, Frederic Boal1,2,*, Oksana Kunduzova1,2,*
1National Institute of Health and Medical Research (INSERM), Toulouse, France
2University of Toulouse, UPS, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France
3Russian Cardiology Research-and-Production Complex, Moscow, Russian Federation, Russia
*These authors have contributed equally to this work
Oksana Kunduzova, email: [email protected]
Keywords: galanin (2-11), heart, ischemia and reperfusion, energy metabolism, ROS production
Received: November 02, 2016 Accepted: January 09, 2017 Published: February 03, 2017
Background and purpose: Galanin is a multifunctional neuropeptide with pleiotropic roles. The present study was designed to evaluate the potential effects of galanin (2-11) (G1) on functional and metabolic abnormalities in response to myocardial ischemia-reperfusion (I/R) injury.
Experimental approach: Peptide G1 was synthesized by the 9-fluorenylmethoxycarbonyl (Fmoc)-based solid-phase method. The chemical structure was identified by 1H-NMR spectroscopy and mass spectrometry. Experiments were conducted using a rat model of I/R injury in vivo, isolated perfused rat hearts ex vivo and cultured rat cardiomyoblast H9C2 cells in vitro. Cardiac function, infarct size, myocardial energy metabolism, hemodynamic parameters, plasma levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) were measured in order to evaluate the effects of G1 on myocardial I/R injury.
Key results: Treatment with G1 increased cell viability in a dose-dependent manner, inhibited cell apoptosis and excessive mitochondrial reactive oxygen species (ROS) production in response to oxidative stress in H9C2 cells. Pre- or postischemic infusion of G1 enhanced functional and metabolic recovery during reperfusion of the ischemic isolated rat heart. Administration of G1 at the onset of reperfusion significantly reduced infarct size and plasma levels of CK-MB and LDH in rats subjected to myocardial I/R injury.
Conclusions and implications: These data provide the first evidence for cardioprotective activity of galanin G1 against myocardial I/R injury. Therefore, peptide G1 may represent a promising treatment strategy for ischemic heart disease.
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