Suppression of Reactive Oxygen Species and Neurodegeneration by the Pgc-1 Transcriptional Coactivators.
From: Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Cell
- Publish Date: Oct 2006
- ISSN: 0092-8674
- Volume: 127
- Issue: 2
- Pages: 397-408
- Medium: Print
- Language: English
- Citation (JAMA): St-Pierre Julie, Drori Stavit, Uldry Marc, et al. Suppression of Reactive Oxygen Species and Neurodegeneration by the Pgc-1 Transcriptional Coactivators.. Cell Oct 2006;127:397-408
Abstract
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.
Mesh Headings (Keywords): Animals, Brain, CREB-Binding Protein, Catalase, Cell Line, Transformed, Cell Line, Tumor, Cell Survival, Fibroblasts, Glutathione Peroxidase, Humans, Hydrogen Peroxide, Male, Mice, Mice, Knockout, Neurodegenerative Diseases, Neurons, Oxidants, Oxidative Stress, Promoter Regions (Genetics), Reactive Oxygen Species, Stem Cells, Superoxide Dismutase, Trans-Activators
Check for Full Text / PubMed Unique Identifier (PMID): 17055439
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