Calcitonin Gene-Related Peptide Inhibits Cardiomyocyte Injury Induced by Hypoxia/Reoxygenation via Restoration of Cytosolic and Mitochondrial Calcium

Abstract

Background: Calcium overload plays an important role in myocardial ischemia and reperfusion injury. Calcitonin gene-related peptide (CGRP) presents a property of cardioprotection, underlying which the mechanism is still elusive. In this study, we investigated the association of CGRP in attenuation of myocyte injury induced by hypoxia/reoxygenation (H/R) with modulation of cytosolic and mitochondrial calcium.Methods: Cultured cardiomyocytes were assigned to four groups, 1) control group, without any treatment with any test agent, 2) H/R group, cells exposed to H/R, 3) H/R+CGRP group, cells treated with CGRP (at 10-8 mol/L) at the beginning of reoxygenation, and 4) H/R+CGRP+CGRP8-37 group, cells treated with CGRP (10-8 mol/l) and CGRP8-37, a special antagonist of CGRP receptor (at 10-7 mol/l), 1 hour before start of the hypoxia. The changes in calcium concentration, cell apoptosis, lactate dehydrogenase (LDH) and caspase-3 were analyzed using immunocytochemical, terminal deoxyuridine triphosphate (dUTP) deoxynucleotidyltransferase nick end-labeling (TUNEL) staining and enzyme-linked immunosorbent assay (ELISA) respectively.Results: The greater levels of the apoptosis ratio, LDH, caspase-3, the cytosolic and mitochondrial calcium in H/R group were detected (all P<0.05), compared to those in the control group, respectively. CGRP significantly attenuated the increases of the LDH, caspase-3 and myocyte apoptosis, with reduction of cytosolic and mitochondrial calcium in the myocytes treated with H/R. The effect of CGRP was reversed by CGRP8-37.Conclusions: The findings in this study suggested that CGRP prevents myocyte injury induced by H/R in cultured cardiomyocytes, which may be associated with homeostasis of cytosolic and mitochondrial calcium. Citation: Mu-Rong Li, Zheng Guo, Lu Chen. Calcitonin gene-related peptide inhibits cardiomyocyte injury induced by hypoxia/reoxygenation via restoration of cytosolic and mitochondrial calcium. J Anesth Perioper Med 2016; 3: 125-131. doi: 10.24015/JAPM.2016.0017This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.