Authors: Vu Thi Thu Hyoung Kyu Kim Seung Hee Ha JiYoung Yoo Won Sun Park Nari Kim Goo Taeg Oh Jin Han
Publish Date: 2010/03/20
Volume: 460, Issue: 1, Pages: 55-68
Abstract
Glutathione peroxidase 1 GPx1 plays an important role in preventing cardiac dysfunction following ischemiareperfusion injury However its role in protecting cardiac mitochondria against reoxygenationinduced reactive oxygen species ROS generation in vivo is unclear We examined the role of GPx1 in protecting cardiac mitochondria against hypoxia–reoxygenation HR damage by testing for alterations in cardiac mitochondrial function We used a twodimensional gel electrophoresis proteomics analysis to examine the effects of reoxygenation on cardiac protein in wildtype GPx1+/+ and GPx1 knockout GPx1−/− mouse hearts We identified 42 protein spots showing differential expression in the two groups Sixteen of the proteins identified were located in mitochondria and were involved in a number of key metabolic pathways To verify our proteomics findings functionally we performed NADH autofluorescence measurements and ATP production assays The reduced expression of oxidative phosphorylation proteins in GPx1−/− mice following HR treatment resulted in loss of the mitochondrial membrane potential and decreased mitochondrial respiration Mitochondrial ROS production and oxidative mtDNA damage were increased markedly during reoxygenation in GPx1−/− hearts We also found morphological abnormalities in cardiac mitochondria and myocytes in HRtreated GPx1−/− This is the first report of the role of GPx1 in protecting cardiac mitochondria against reoxygenation damage in vivo These findings will help clarify the mechanisms of HR injury and will aid in the development of antioxidant therapies to prevent cardiac mitochondrial dysfunction associated with reoxygenation
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