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: Lei Zhao, Ding-Qiong Peng, Jing Zhang, Jun-Qiu Song, Xu Teng, Yan-Rong Yu, Chao-Shu Tang, Yong-Fen Qi
• Journal: Peptides (Peptides) Vol. 33 Issue 2 Pg. 329-35 (Feb 2012) ISSN: 1873-5169 [Electronic] United States
• PMID: 22244813 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Adm2 protein, rat
• Antioxidants
• Membrane Glycoproteins
• Neuropeptides
• Oxidants
• Peptide Fragments
• Protein Isoforms
• Adrenomedullin
• Malondialdehyde
• Hydrogen Peroxide
• L-Lactate Dehydrogenase
• Catalase
• Superoxide Dismutase
• Cybb protein, rat
• NADPH Oxidase 2
• NADPH Oxidases
• neutrophil cytosolic factor 1
• Casp3 protein, rat
• Caspase 3

Topics

• Adrenomedullin (metabolism, physiology)
• Animals
• Antioxidants (metabolism, physiology)
• Caspase 3 (metabolism)
• Catalase (metabolism)
• Cell Survival
• Cells, Cultured
• Cytoprotection
• Enzyme Activation
• Hydrogen Peroxide (pharmacology)
• L-Lactate Dehydrogenase (metabolism)
• MAP Kinase Signaling System
• Male
• Malondialdehyde (blood)
• Membrane Glycoproteins (metabolism)
• Myocardial Ischemia (enzymology, metabolism)
• Myocardial Reperfusion Injury (enzymology, metabolism)
• Myocardium (enzymology, metabolism, pathology)
• Myocytes, Cardiac (drug effects, metabolism, physiology)
• NADPH Oxidase 2
• NADPH Oxidases (metabolism)
• Neuropeptides (metabolism, physiology)
• Oxidants (pharmacology)
• Oxidative Stress
• Peptide Fragments (physiology)
• Protein Isoforms (physiology)
• Rats
• Rats, Sprague-Dawley
• Superoxide Dismutase (metabolism)