Premium
Down‐expression of PGC‐1α partially mediated by JNK/c‐Jun through binding to CRE site during apoptotic procedure in cerebellar granule neurons
Author(s) -
Liang Jingyao,
Yang Yi,
Zhu Xiaonan,
Wang Xuelan,
Chen Ruzhu
Publication year - 2010
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22354
Subject(s) - coactivator , mitochondrial biogenesis , microbiology and biotechnology , apoptosis , regulator , c jun , mitochondrion , biology , chemistry , transcription factor , gene , biochemistry
In eukaryotes, mitochondria are critical for cellular bioenergetics and mediating apoptosis. The transcriptional coactivator peroxisome proliferator‐activated receptor gamma coactivator 1alpha (PGC‐1α) is an important regulator of mitochondrial biogenesis and function. However, the role of PGC‐1α in neuronal apoptosis and its regulation by apoptotic pathway are still unknown. We demonstrated that PGC‐1α expression was down‐regulated in cerebellar granule neurons(CGNs) after activation of the JNK/c‐Jun pathway by potassium deprivation. Overexpression of PGC‐1α partially protected CGNs from potassium deprivation‐induced apoptosis. JNK‐specific inhibitors, SP600125 and CEP11004, partially blocked the inhibitory effects of JNK on PGC‐1α 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‐1α promoter. In conclusion, these results suggest that down‐expression of PGC‐1α partially mediated by activation of JNK/c‐Jun may be through the binding of c‐Jun to the CRE site in the PGC‐1α promoter, and it might be involved in potassium deprivation‐induced apoptosis in CGNs. © 2010 Wiley‐Liss, Inc.