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Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators

St-Pierre, J. and Drori, S. and Uldry, M. and Silvaggi, J. M. and Rhee, J. and Jager, S. and Handschin, C. and Zheng, K. and Lin, J. and Yang, W. and Simon, D. K. and Bachoo, R. and Spiegelman, B. M.. (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell, Vol. 127, H. 2. pp. 397-408.

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Official URL: http://edoc.unibas.ch/dok/A5258719

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Abstract

PPARγ coactivator 1α (PGC-1α) 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-1α on the metabolism of ROS. PGC-1α 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-1α is required for the induction of many ROS-detoxifying enzymes, including GPx1 and SOD2. PGC-1α 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-1α levels dramatically protects neural cells in culture from oxidative-stressor-mediated death. These studies reveal that PGC-1α is a broad and powerful regulator of ROS metabolism, providing a potential target for the therapeutic manipulation of these important endogenous toxins.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Associated Research Groups > Pharmakologie (Handschin)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Growth & Development (Handschin)
UniBasel Contributors:Handschin, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Cell Press
ISSN:0092-8674
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:21 Mar 2019 14:01
Deposited On:22 Mar 2012 13:20

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