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  • Title: Calcitonin gene related peptide (CGRP) inhibits norepinephrine induced apoptosis in cultured rat cardiomyocytes not via PKA or PKC pathways.
    Author: Zhao FP, Guo Z, Wang PF.
    Journal: Neurosci Lett; 2010 Sep 27; 482(2):163-6. PubMed ID: 20650306.
    Abstract:
    Evidence showed overrelease of norepinephrine can induce apoptosis in ventricle myocytes. Calcitonin gene related peptide and norepinephrine could be simultaneously up-regulated in early time of acute myocardial ischemia, suggesting a co-participation of calcitonin gene related peptide and norepinephrine in the pathology. In this study, we investigated a potential anti-apoptotic effect of calcitonin gene related peptide on myocardial apoptosis induced by norepinephrine and its link with the protein kinase A (PKA) or protein kinase C (PKC) pathway in cultured neonatal rat cardiomyocytes. Cultured cardiomyocytes were exposed to one of the treatments, separately: (1) 3 ml DMEM culture medium, (2) norepinephrine (10(-5)mol/l), (3) H89 (3 x 10(-5)mol/l), a specific PKA inhibitor, with norepinephrine (10(-5)mol/l), (4) calcitonin gene related peptide at a range of concentrations (10(-9)mol/l, 10(-8)mol/l and 10(-7)mol/l) with norepinephrine (10(-5)mol/l) and (5) calcitonin gene related peptide (10(-8)mol/l) with norepinephrine (10(-5)mol/l)+CGRP(8-7) (10(-7)mol/l), a specific antagonist of calcitonin gene related peptide receptor. Then, apoptosis rate and the activity of PKA and PKC were examined. The dose of norepinephrine induced a marked increase in apoptosis of the myocytes (31+/-2%), compared to the control (17+/-4%, p<0.05). The pro-apoptotic effect of norepinephrine was attenuated by H89 (3 x 10(-5)mol/l) or by calcitonin gene related peptide which could be completely reversed by CGRP(8-37). The activities of PKA and PKC were increased by norepinephrine but no difference in the activities of PKA and PKC was detected in the presence and absence of co-treatment with calcitonin gene related peptide (10(-8)mol/l). Calcitonin gene related peptide inhibits norepinephrine induced apoptosis in cultured cardiomyocytes, which is mediated by CGRP receptor but unlikely to be mediated by PKA or PKC pathway.
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