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Oxidative Medicine and Cellular Longevity
Volume 2016, Article ID 3539649, 11 pages
http://dx.doi.org/10.1155/2016/3539649
Research Article

Protective Effect of Peroxisome Proliferator-Activated Receptor α Activation against Cardiac Ischemia-Reperfusion Injury Is Related to Upregulation of Uncoupling Protein-3

1Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
2Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
3Department of Biochemistry and Molecular Biology, Integrated Genomic Research Center for Metabolic Regulation, Institute of Genetic Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
4Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Republic of Korea
5Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea

Received 14 May 2015; Revised 17 August 2015; Accepted 25 August 2015

Academic Editor: Massimo Collino

Copyright © 2016 Jong Wook Song et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Activation of peroxisome proliferator-activated receptor α (PPARα) confers cardioprotection, while its mechanism remains elusive. We investigated the protective effect of PPARα activation against cardiac ischemia-reperfusion injury in terms of the expression of uncoupling protein (UCP). Myocardial infarct size and UCP expression were measured in rats treated with WY-14643 20 mg/kg, a PPARα ligand, or vehicle. WY-14643 increased UCP3 expression in vivo. Myocardial infarct size was decreased in the WY-14643 group (76 ± 8% versus 42 ± 12%, ). During reperfusion, the incidence of arrhythmia was higher in the control group compared with the WY-14643 group (9/10 versus 3/10, ). H9c2 cells were incubated for 24 h with WY-14643 or vehicle. WY-14643 increased UCP3 expression in H9c2 cells. WY-14643 decreased hypoxia-stimulated ROS production. Cells treated with WY-14643 were more resistant to hypoxia-reoxygenation than the untreated cells. Knocking-down UCP3 by siRNA prevented WY-14643 from attenuating the production of ROS. UCP3 siRNA abolished the effect of WY-14643 on cell viability against hypoxia-reoxygenation. In summary, administration of PPARα agonist WY-14643 mitigated the extent of myocardial infarction and incidence of reperfusion-induced arrhythmia. PPARα activation conferred cytoprotective effect against hypoxia-reoxygenation. Associated mechanisms involved increased UCP3 expression and resultant attenuation of ROS production.