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

 Jong Wook Song  ;  Hyo Jung Kim  ;  Hyelin Lee  ;  Jae-woo Kim  ;  Young-Lan Kwak 
 Oxidative Medicine and Cellular Longevity, Vol.2016 : 3539649, 2016 
Journal Title
 Oxidative Medicine and Cellular Longevity 
Issue Date
Animals ; Arrhythmias, Cardiac/complications ; Arrhythmias, Cardiac/pathology ; Arrhythmias, Cardiac/physiopathology ; Cardiotonic Agents/metabolism* ; Cell Hypoxia/drug effects ; Cell Line ; Cell Survival/drug effects ; Coronary Occlusion/complications ; Coronary Occlusion/pathology ; Coronary Occlusion/physiopathology ; Coronary Vessels/pathology ; Hemodynamics/drug effects ; Ion Channels/metabolism* ; Male ; Mitochondrial Proteins/metabolism* ; Myocardial Infarction/complications ; Myocardial Infarction/pathology ; Myocardial Infarction/physiopathology ; Myocardial Reperfusion Injury/metabolism* ; Myocardial Reperfusion Injury/pathology* ; Myocardial Reperfusion Injury/physiopathology ; PPAR alpha/metabolism* ; Pyrimidines/pharmacology ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Uncoupling Protein 3 ; Up-Regulation*/drug effects
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%, P<0.05). During reperfusion, the incidence of arrhythmia was higher in the control group compared with the WY-14643 group (9/10 versus 3/10, P<0.05). 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.
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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kwak, Young Lan(곽영란) ORCID logo https://orcid.org/0000-0002-2984-9927
Kim, Jae Woo(김재우) ORCID logo https://orcid.org/0000-0001-5456-9495
Kim, Hyo Jung(김효정) ORCID logo https://orcid.org/0000-0002-3514-1247
Song, Jong Wook(송종욱) ORCID logo https://orcid.org/0000-0001-7518-2070
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