| Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. | |
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MedLine Citation:
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PMID: 17055439 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PPARgamma coactivator 1alpha (PGC-1alpha) is a potent stimulator of mitochondrial biogenesis and respiration. Since the mitochondrial electron transport chain is the main producer of reactive oxygen species (ROS) in most cells, we examined the effect of PGC-1alpha on the metabolism of ROS. PGC-1alpha is coinduced with several key ROS-detoxifying enzymes upon treatment of cells with an oxidative stressor; studies with RNAi or null cells indicate that PGC-1alpha is required for the induction of many ROS-detoxifying enzymes, including GPx1 and SOD2. PGC-1alpha null mice are much more sensitive to the neurodegenerative effects of MPTP and kainic acid, oxidative stressors affecting the substantia nigra and hippocampus, respectively. Increasing PGC-1alpha levels dramatically protects neural cells in culture from oxidative-stressor-mediated death. These studies reveal that PGC-1alpha is a broad and powerful regulator of ROS metabolism, providing a potential target for the therapeutic manipulation of these important endogenous toxins. |
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Authors:
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Julie St-Pierre; Stavit Drori; Marc Uldry; Jessica M Silvaggi; James Rhee; Sibylle Jäger; Christoph Handschin; Kangni Zheng; Jiandie Lin; Wenli Yang; David K Simon; Robert Bachoo; Bruce M Spiegelman |
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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 |
Journal Detail:
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Title: Cell Volume: 127 ISSN: 0092-8674 ISO Abbreviation: Cell Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-10-23 Completed Date: 2006-12-04 Revised Date: 2011-10-12 |
Medline Journal Info:
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Nlm Unique ID: 0413066 Medline TA: Cell Country: United States |
Other Details:
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Languages: eng Pagination: 397-408 Citation Subset: IM |
Affiliation:
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Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain / metabolism, pathology CREB-Binding Protein / metabolism Catalase / metabolism Cell Line, Transformed Cell Line, Tumor Cell Survival / drug effects Fibroblasts / drug effects, metabolism Glutathione Peroxidase / metabolism Humans Hydrogen Peroxide / pharmacology Male Mice Mice, Knockout Neurodegenerative Diseases / metabolism*, pathology Neurons / drug effects, metabolism Oxidants / pharmacology Oxidative Stress / drug effects Promoter Regions, Genetic / drug effects Reactive Oxygen Species / metabolism* Stem Cells / drug effects, metabolism Superoxide Dismutase / metabolism Trans-Activators / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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DK54477/DK/NIDDK NIH HHS; K02 NS4311/NS/NINDS NIH HHS; P30 DK040561-11/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Oxidants; 0/Ppargc1a protein, mouse; 0/Reactive Oxygen Species; 0/Trans-Activators; 7722-84-1/Hydrogen Peroxide; EC 1.11.1.6/Catalase; EC 1.11.1.9/Glutathione Peroxidase; EC 1.15.1.1/Superoxide Dismutase; EC 2.3.1.48/CREB-Binding Protein |
| Comments/Corrections | |
Comment In:
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Cell. 2006 Nov 3;127(3):465-8
[PMID:
17081970
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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