title: CGRP inhibits norepinephrine induced apoptosis with restoration of Bcl-2/Bax in cultured cardiomyocytes of rat.
abstract: Calcitonin gene related peptide (CGRP) and norepinephrine (NE) may interact in acute myocardial ischemia, protecting cardiomyocytes but the underlying mechanism is unclear. Here we investigated the correlation of the anti-apoptotic effect of CGRP with the change of Bcl-2/Bax. Cultured cardiomyocytes were divided into four groups: (1) control group (no treatment with any test agent), (2) NE group (treated with 10(-5)mol/L of NE), (3) CGRP+NE group (treated with 10(-8)mol/L of CGRP and NE at 10(-5)mol/L) and (4) CGRP8-37+CGRP+NE group (treated with 10(-7)mol/L of CGRP8-37, a specific antagonist of CGRP receptor, CGRP at 10(-8)mol/L and NE at 10(-5)mol/L). Apoptosis ratio was analyzed by flow cytometry. Bcl-2 and Bax and the coding mRNA were examined. It was found that the apoptosis ratio in NE group (29.4 ± 1.8%) was significantly greater (P<0.05) than that of the control group (10.1 ± 1.7%). The effect of NE was attenuated by CGRP (18.7 ± 2.1%), which was reversed by CGRP8-37 (24.9 ± 2.9%). NE treatment resulted in reductions in the ratio of Bcl-2/Bax (by 33%) and their mRNA (by 53%). CGRP restored the level of Bcl-2/Bax, which was abolished by CGRP8-37. Current study suggests that norepinephrine inhibits synthesis of Bcl-2 and increases Bax and apoptosis of cardiomyocytes. CGRP restores the ratio of Bcl-2/Bax and attenuates the apoptosis induced by NE, via specific CGRP receptor.
authors.affiliation: Department of Anesthesiology, Shanxi Medical University, 56 Xinjian Nan Road, Taiyuan 030001, Shanxi, China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Ma
authors.forename: Zheng
authors.initials: Z
authors.lastname: Guo
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002478:Cells, Cultured; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger; D051381:Rats; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D015740:Calcitonin Gene-Related Peptide; D009638:Norepinephrine
keywords: Apoptosis; Bcl-2/Bax; CGRP; Calcitonin gene related peptide; Cardiomyocytes; NE; Norepinephrine