Proteome analysis of differential protein expression in infarcted rat heart after verapamil treatment

Abstract

To explore the protein-level mechanism of action verapamil in acute myocardial infarcted rats, the myocardial proteome was analyzed by two-dimensional electrophoresis (2-DE). Compared with the sham-operated group and the infarcted group, the result shows that 8 protein expressions in the verapamil treated group were up-regulated, and 7 protein expressions in this group were down-regulated significantly. Using MALDI-TOF-MS, 15 proteins with significant changes were identified through a database search. These proteins can be divided into 4 groups by their biological function: (1) Energy metabolism and mitochondrial function related proteins; (2) oxidative stress-induced proteins; (3) cytoskeletal Proteins; (4) other proteins. The findings show that the myocardial protective effects of verapamil in the myocardial damage process are related to the recovery of energy supply as well as anti-oxidative stress property.

Keywords

verapamil / proteomics / two-dimensional electrophoresis (2-DE) / myocardial ischemia

References

[1] Redfearn D P, Skanes A C, Lane J, Stafford P J. Signal-averaged P wave reflects change in atrial electrophysiological substrate afforded by verapamil following cardioversion from atrial fibrillation. Pacing Clin Electrophysiol, 2006, 10: 1089–1095

[2] Cooper-DeHoff R M, Aranda J M, Jr, Gaxiola E, Cangiano J L, Garcia-Barreto D, ContiC R, Hewkin A, Pepine C J. Blood pressure control and cardiovascular outcomes in high-risk Hispanic patients-findings from the International Verapamil SR/Trandolapril Study (INVEST). Am Heart, 2006, 151(5): 1072–1079

[3] Shaheen N, Mahboob T. Antihypertensive and metabolic effects of verapamil: role of Na-K-ATPase and electrolytes homeostasis in male and female rats. Pak J Pharm Sci, 2004, 17(2): 1–11

[4] Hansen J F. Treatment with verapamil after an acute myocardial infarction. Review of the Danish studies on verapamil in myocardial infarction (DAVIT I and II). Drugs, 1991, 42: 43–53

[5] Yoshida M, Loo J A, Lepleya R A. Proteomics as a tool in the pharmaceutical drug design process. Curr Pharm Des, 2001, 7: 291

[6] Grunenfelder B, Rummel G, Vohradsky J, Roder D, Langen H, Jenal U. Proteomic analysis of the bacterial cell cycle. Proc Nat1 Acad Sci U S A, 2001, 98: 468l

[7] Chapal N, Molina L, Molina F, Laplanche M, Pau B, Petit P. Pharmacoproteomic approach to the study of drug mode of action, toxicity, and resistance: applications in diabetes and cancer. Fund & Clin Pharm, 2004, 18: 413–422

[8] Luo G A, Deng B, Ye N S, Wang Y M. Comparative proteome analysis of human squamous lung carcinomas and small cell lung carcinomas. Chem J Chinese Universities, 2005, 9: 1645–1649

[9] Liu N, Li Z J, Liu Z Q, Liu S Y, Han Q D, Zhang Y Y. Proteomic analysis of proteins with altered expression induced by phenylephrine in neonatal rat cardiomyocyte. Chem J Chinese Universities, 2006, 1: 79–81

[10] Yamaguchi F, Sanbe A, Takeo S. Cardiac sarcoplasmic reticular function in rats with chronic heart failure following myocardial infarction. J Mol Cell Cardiol, 1997, 29: 753–763

[11] Wang Y, Liu L, Hu C C, Cheng Y Y. Effects of Salviae Mitiorrhizae and Cortex Moutan extract on the rat heart after myocardial infarction: A proteomic study. Biochem Pharm, 2007, 74: 415–424

[12] Jensen O N, Wilm M, Shevchenko A, Mann M. Sample preparation methods for mass spectrometric peptide mapping directly from 2-DE gels. Methods Mol Biol, 1999, 112: 513–530

[13] FrolovV A, Drozdova G A, Rieger P, Blagonravov M. Changes in myocardial blood supply during experimental hypertension treated with verapamil in rabbits. Bull Exp Biol Med, 2005, 139(3): 277–278

[14] Lesnefsky E J, Slabe T J, Stoll M S, Minkler P E, Hoppel C L. Myocardial ischemia selectively depletes cardiolipin in rabbit heart subsarcolemmal mitochondria. Am J Physiol Heart Circ Physiol, 2001, 280: H2770–H2778

[15] Lepore D A, Knight K R, Anderson R L, Morrison W A. Role of priming stresses and Hsp70 in protection from ischemia-reperfusion injury in cardiac and skeletal muscle. Cell Stress Chap, 2001, 6: 93–96

[16] Vivanco F, Martin-Ventura J L, Duran M C, Barderas M G, Blanco-Colio L, Darde V M, Mas S, Meilhac O, Michel J B, Tunon J, Egido J. Quest for novel cardiovascular biomarkers by proteomic analysis. J Proteome Res, 2005, 4: 1181–1191

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg