Document Detail

Down-expression of PGC-1alpha partially mediated by JNK/c-Jun through binding to CRE site during apoptotic procedure in cerebellar granule neurons.
MedLine Citation:
PMID:  20143420     Owner:  NLM     Status:  MEDLINE    
In eukaryotes, mitochondria are critical for cellular bioenergetics and mediating apoptosis. The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) is an important regulator of mitochondrial biogenesis and function. However, the role of PGC-1alpha in neuronal apoptosis and its regulation by apoptotic pathway are still unknown. We demonstrated that PGC-1alpha expression was down-regulated in cerebellar granule neurons(CGNs) after activation of the JNK/c-Jun pathway by potassium deprivation. Overexpression of PGC-1alpha partially protected CGNs from potassium deprivation-induced apoptosis. JNK-specific inhibitors, SP600125 and CEP11004, partially blocked the inhibitory effects of JNK on PGC-1alpha expression and its promoter activity. Furthermore, ChIP assays revealed that c-Jun was able to bind to the CRE site (-188 to -180) in the PGC-1alpha promoter. In conclusion, these results suggest that down-expression of PGC-1alpha partially mediated by activation of JNK/c-Jun may be through the binding of c-Jun to the CRE site in the PGC-1alpha promoter, and it might be involved in potassium deprivation-induced apoptosis in CGNs.
Jingyao Liang; Yi Yang; Xiaonan Zhu; Xuelan Wang; Ruzhu Chen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  88     ISSN:  1097-4547     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-05-17     Completed Date:  2010-09-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1918-25     Citation Subset:  IM    
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, P.R. China.
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MeSH Terms
Anthracenes / pharmacology
Apoptosis / drug effects,  physiology*
Carbazoles / pharmacology
Cells, Cultured
Cerebellum / drug effects,  enzymology,  physiology*
Down-Regulation / drug effects,  physiology
Enzyme Inhibitors / pharmacology
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism*
Neurons / drug effects,  enzymology,  physiology*
Potassium / metabolism
Potassium Deficiency / metabolism
Promoter Regions, Genetic
Protein Binding
RNA-Binding Proteins / genetics,  metabolism*
Rats, Sprague-Dawley
Transcription Factors / genetics,  metabolism*
Reg. No./Substance:
0/Anthracenes; 0/CEP-11004; 0/Carbazoles; 0/Enzyme Inhibitors; 0/Ppargc1a protein, rat; 0/RNA-Binding Proteins; 0/Transcription Factors; 0/anthra(1,9-cd)pyrazol-6(2H)-one; 7440-09-7/Potassium; EC Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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