Abstract:
: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.
journal_name
J Neurosci Resjournal_title
Journal of neuroscience researchauthors
Liang J,Yang Y,Zhu X,Wang X,Chen Rdoi
10.1002/jnr.22354subject
Has Abstractpub_date
2010-07-01 00:00:00pages
1918-25issue
9eissn
0360-4012issn
1097-4547journal_volume
88pub_type
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