Extracellular signal-regulated kinase 1/2 activation is involved in intermedin1-53 attenuating myocardial oxidative stress injury induced by ischemia/reperfusion

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 IMD1-53 cardioprotective effect, we studied the anti-oxidant effects of IMD1-53 on myocardial injury induced by I/R in vivo in rat and H2O2 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; IMD1-53 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, IMD1-53 treatment markedly promoted cell viability and inhibited apoptosis in cardiomyocytes as compared with H2O2 treatment alone. Furthermore, IMD1-53 increased the ratio of p-ERK to ERK by 66% (P < 0.05) as compared with I/R alone, and the protective effect of IMD1-53 on H2O2-induced apoptosis was abolished by preincubation with PD98059. a MEK inhibitor. IMD1-53 may improve the oxidative stress injury induced by I/R via inhibiting the production of reactive oxygen species and enhancing ERK phosphorylation. (C) 2012 Elsevier Inc. All rights reserved.