title: Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha overexpression prevents endothelial apoptosis by increasing ATP/ADP translocase activity.
abstract: OBJECTIVE
  Fatty acids increase reactive oxygen species generation and cell apoptosis in endothelial cells. The peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1alpha) is a transcriptional coactivator that increases mitochondrial biogenesis and fatty acid oxidation in various cells. This study was undertaken to investigate the possible preventive effect of PGC-1alpha on endothelial apoptosis and its molecular mechanism.
  
  
  RESULTS
  Treatment with linoleic acid in cultured human aortic endothelial cells increased reactive oxygen species generation and cell apoptosis. These effects appeared to be mediated by increases in cytosolic fat metabolites, ie, fatty acyl CoA, diacylglycerol, and ceramide, and consequent decreases in ATP/ADP translocase activity of adenine nucleotide translocator. Adenoviral overexpression of PGC-1alpha prevented linoleic acid-induced increases in reactive oxygen species generation and cell apoptosis in human aortic endothelial cells by increasing fatty acid oxidation, decreasing diacylglycerol and ceramide, and increasing ATP/ADP translocase activity. In isolated aorta, PGC-1alpha overexpression prevented linoleic acid-induced decrease in endothelium-dependent vasorelaxation, and this effect was abolished by adenine nucleotide translocator1 shRNA.
  
  
  CONCLUSIONS
  PGC-1alpha regulates reactive oxygen species generation and apoptosis in endothelial cells by increasing fatty acid oxidation and enhancing ATP/ADP translocase activity. Measures to increase PGC-1alpha expression or ATP/ADP translocase activity in vascular cells may aid in the prevention or treatment of atherosclerosis.
authors: Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea.
authors: Jong Chul
authors: JC
authors: Won
authors: Joong-Yeol
authors: JY
authors: Park
authors: Yun Mi
authors: YM
authors: Kim
authors: Eun Hee
authors: EH
authors: Koh
authors: Somi
authors: S
authors: Seol
authors: Byeong Hwan
authors: BH
authors: Jeon
authors: Jin
authors: J
authors: Han
authors: Jung Ran
authors: JR
authors: Kim
authors: Tae-Sik
authors: TS
authors: Park
authors: Cheol Soo
authors: CS
authors: Choi
authors: Woo Je
authors: WJ
authors: Lee
authors: Min-Seon
authors: MS
authors: Kim
authors: In-Kyu
authors: IK
authors: Lee
authors: Jang Hyun
authors: JH
authors: Youn
authors: Ki-Up
authors: KU
authors: Lee
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D033741:Adenine Nucleotide Translocator 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology; D005227:Fatty Acids / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019787:Linoleic Acid / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000201:enzymology* / Q000473:pathology; D010084:Oxidation-Reduction; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation; D014664:Vasodilation
chemical_list: D000214:Acyl Coenzyme A; D033741:Adenine Nucleotide Translocator 1; D002518:Ceramides; D004075:Diglycerides; D005227:Fatty Acids; D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D019787:Linoleic Acid