Down-expression of PGC-1 alpha Partially Mediated by JNK/c-Jun Through Binding to CRE Site During Apoptotic Procedure in Cerebellar Granule Neurons

作者：Liang, Jingyao; Yang, Yi; Zhu, Xiaonan; Wang, Xuelan; Chen, Ruzhu^*

来源：Journal of Neuroscience Research, 2010, 88(9): 1918-1925.

DOI：10.1002/jnr.22354

• PGC-l alpha
• JNK
• c-Jun
• apoptosis

In eukaryotes, mitochondria are critical for cellular bio-energetics and mediating apoptosis. The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1 alpha) is an important regulator of mitochondrial biogenesis and function. However, the role of PGC-1 alpha in neuronal apoptosis and its regulation by apoptotic pathway are still unknown. We demonstrated that PGC-1 alpha expression was down-regulated in cerebellar granule neurons(CGNs) after activation of the JNK/c-Jun pathway by potassium deprivation. Overexpression of PGC-1 alpha partially protected CGNs from potassium deprivation-induced apoptosis. JNK-specific inhibitors, SP600125 and CEP11004, partially blocked the inhibitory effects of JNK on PGC-1 alpha 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-1 alpha promoter. In conclusion, these results suggest that down-expression of PGC-1 alpha partially mediated by activation of JNK/cJun may be through the binding of c-Jun to the CRE site in the PGC-1 alpha promoter, and it might be involved in potassium deprivation-induced apoptosis in CGNs.

• 出版日期2010-7
• 单位中山大学