Glutathione peroxidase 1 protects mitochondria against hypoxia/ reoxygenation damage in mouse hearts

Vu Thi Thu, Hyoung Kyu Kim, Seung Hee Ha, Ji Young Yoo, Won Sun Park, Nari Kim, Goo Taeg Oh, Jin Han

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Glutathione peroxidase 1 (GPx1) plays an important role in preventing cardiac dysfunction following ischemia-reperfusion injury. However, its role in protecting cardiac mitochondria against reoxygenation-induced 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 two-dimensional gel electrophoresis proteomics analysis to examine the effects of reoxygenation on cardiac protein in wild-type (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 HR-treated 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.

Original languageEnglish
Pages (from-to)55-68
Number of pages14
JournalPflugers Archiv European Journal of Physiology
Volume460
Issue number1
DOIs
StatePublished - Jun 2010

Bibliographical note

Funding Information:
This research was supported by Basic Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (R0A-2007-000-20085-0, R15-2006-020 and R13-2007-023-00000-0).

Keywords

  • Glutathione peroxidase 1 (GPx1)
  • Hypoxia-reoxygenation
  • Mitochondria
  • Reactive oxygen species

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