| Mitochondria-specific transgenic overexpression of phospholipid hydroperoxide glutathione peroxidase (GPx4) attenuates ischemia/reperfusion-associated cardiac dysfunction. | |
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MedLine Citation:
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PMID: 18638546 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ischemia/reperfusion (I/R) injury elicits damage to mitochondria. Antioxidants provide protection from I/R-induced mitochondrial damage. The goal of this study was to determine the impact of mitochondria-specific overexpression of GPx4 (PHGPx) on cardiac function following I/R. Transgenic mice were created in which PHGPx was overexpressed solely in the mitochondrion (mPHGPx). MPHGPx and littermate control hearts were subjected to global no-flow ischemia (20 min) followed by reflow reperfusion (30, 60, and 90 min). Following I/R, mPHGPx hearts possessed significantly better rates of contraction, developed pressures, and peak-systolic pressures as compared to controls (P<0.05). No differences were observed in rates of relaxation or end-diastolic pressures. Lipid peroxidation was significantly lower in mitochondria from mPHGPx hearts as compared to controls, following I/R (P<0.05). Electron transport chain (ETC) complex I, III, and IV activities were significantly higher in mPHGPx hearts as compared to controls, following I/R (P<0.05). MPHGPx overexpression enhanced ETC complex I, III, and IV activities in subsarcolemmal mitochondria (SSM; P<0.05), and ETC complex I and III activities in interfibrillar mitochondria (IFM; P<0.05) following I/R. These results indicate that mitochondria-specific GPx4 overexpression protects cardiac contractile function and preserves ETC complex activities following I/R. These results provide further rationale for the use of mPHGPx as a therapeutic protectant. |
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Authors:
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Erinne R Dabkowski; Courtney L Williamson; John M Hollander |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-06-30 |
Journal Detail:
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Title: Free radical biology & medicine Volume: 45 ISSN: 0891-5849 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2008 Sep |
Date Detail:
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Created Date: 2008-10-17 Completed Date: 2008-11-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: United States |
Other Details:
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Languages: eng Pagination: 855-65 Citation Subset: IM |
Affiliation:
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West Virginia University School of Medicine, Division of Exercise Physiology, and Center for Interdisciplinary Research in Cardiovascular Sciences, 1 Medical Center Drive, Morgantown, WV 26506, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Glutathione Peroxidase / genetics, metabolism* Heart Failure / complications*, pathology Lipid Peroxidation Mice Mice, Transgenic Mitochondria / enzymology* Necrosis Reperfusion Injury / complications, prevention & control* |
| Grant Support | |
ID/Acronym/Agency:
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RR015574/RR/NCRR NIH HHS; RR016440/RR/NCRR NIH HHS; RR020866/RR/NCRR NIH HHS; RR16440/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 1.11.1.12/phospholipid-hydroperoxide glutathione peroxidase; EC 1.11.1.9/Glutathione Peroxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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