title: Extracellular signal-regulated kinase 1/2 activation is involved in intermedin1-53 attenuating myocardial oxidative stress injury induced by ischemia/reperfusion.
abstract: Intermedin (IMD)(1-53) is a novel member of the calcitonin gene-related peptide superfamily and has potent cardioprotective effects against myocardial injury induced by ischemia-reperfusion (I/R). To explore the mechanism of the IMD(1-53) cardioprotective effect, we studied the anti-oxidant effects of IMD(1-53) on myocardial injury induced by I/R in vivo in rat and H(2)O(2) treatment in vitro in rat cardiomyocytes. Compared with sham treatment, I/R treatment induced severe lipid peroxidation injury in rat myocardium: plasma malondialdehyde (MDA) content and myocardial LDH activity was increased by 34% and 85% (all P<0.01); Mn-superoxide dismutase (Mn-SOD) and catalase (CAT) activity was reduced 80% and 86% (all P<0.01), respectively, and the protein levels of the NADPH oxidase complex subunits gp91(phox) and p47(phox) were markedly increased, by 86% (P<0.05) and 95% (P<0.01), respectively; IMD(1-53) treatment ameliorated lipid peroxidation injury: plasma MDA content and myocardial LDH activity was decreased by 30% (P<0.05) and 36% (P<0.01); Mn-SOD and CAT activity was elevated 1.0- and 4.3-fold (all P<0.01), respectively; and the protein levels of gp91(phox) and p47(phox) were reduced, by 28% and 36% (both P<0.05), respectively. Concurrently, IMD(1-53) treatment markedly promoted cell viability and inhibited apoptosis in cardiomyocytes as compared with H(2)O(2) treatment alone. Furthermore, IMD(1-53) increased the ratio of p-ERK to ERK by 66% (P<0.05) as compared with I/R alone, and the protective effect of IMD(1-53) on H(2)O(2)-induced apoptosis was abolished by preincubation with PD98059, a MEK inhibitor. IMD(1-53) may improve the oxidative stress injury induced by I/R via inhibiting the production of reactive oxygen species and enhancing ERK phosphorylation.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Ding-Qiong
authors.initials: DQ
authors.lastname: Peng
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Jun-Qiu
authors.initials: JQ
authors.lastname: Song
authors.forename: Xu
authors.initials: X
authors.lastname: Teng
authors.forename: Yan-Rong
authors.initials: YR
authors.lastname: Yu
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
authors.forename: Yong-Fen
authors.initials: YF
authors.lastname: Qi
mesh_terms: D053607:Adrenomedullin / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D019610:Cytoprotection; D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008562:Membrane Glycoproteins / Q000378:metabolism; D017202:Myocardial Ischemia / Q000201:enzymology / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism / Q000502:physiology*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000502:physiology; D020033:Protein Isoforms / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: C499411:Adm2 protein, rat; D000975:Antioxidants; D008562:Membrane Glycoproteins; D009479:Neuropeptides; D016877:Oxidants; D010446:Peptide Fragments; D020033:Protein Isoforms; D053607:Adrenomedullin; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; C505410:Casp3 protein, rat; D053148:Caspase 3