Down-expression of PGC-1alpha partially mediated by JNK/c-Jun through binding to CRE site during apoptotic procedure in cerebellar granule neurons.
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.
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, P.R. China.
Jingyao
J
Liang
Yi
Y
Yang
Xiaonan
X
Zhu
Xuelan
X
Wang
Ruzhu
R
Chen
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011188:Potassium / Q000378:metabolism; D011191:Potassium Deficiency / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D000873:Anthracenes; C469298:CEP-11004; D002227:Carbazoles; D004791:Enzyme Inhibitors; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D011188:Potassium