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Down-expression of PGC-1alpha partially mediated by JNK/c-Jun through binding to CRE site during apoptotic procedure

Jingyao Liang1, Yi Yang, Xiaonan Zhu

  • 1Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, P.R. China.

Journal of Neuroscience Research
|February 10, 2010
PubMed

Insights

Peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) is down-regulated in neurons during apoptosis. This down-regulation, mediated by JNK/c-Jun signaling, contributes to neuronal cell death.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Mitochondria are vital for cellular energy and apoptosis.
  • Peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) regulates mitochondrial biogenesis and function.
  • The role of PGC-1alpha in neuronal apoptosis and its regulation by apoptotic pathways remain unclear.

Purpose of the Study:

  • To investigate the role of PGC-1alpha in neuronal apoptosis.
  • To determine if the JNK/c-Jun pathway regulates PGC-1alpha expression during apoptosis.

Main Methods:

  • Potassium deprivation was used to induce apoptosis in cerebellar granule neurons (CGNs).
  • Overexpression of PGC-1alpha and JNK-specific inhibitors (SP600125, CEP11004) were employed.
  • Chromatin immunoprecipitation (ChIP) assays were performed to assess c-Jun binding to the PGC-1alpha promoter.

Main Results:

  • PGC-1alpha expression was reduced in CGNs following JNK/c-Jun pathway activation induced by potassium deprivation.
  • Overexpressing PGC-1alpha offered partial protection against apoptosis.
  • JNK inhibitors partially reversed the inhibitory effects of JNK on PGC-1alpha expression and promoter activity.
  • c-Jun was found to bind to the CRE site on the PGC-1alpha promoter.

Conclusions:

  • Down-regulation of PGC-1alpha, partly mediated by JNK/c-Jun pathway activation through c-Jun binding to the PGC-1alpha promoter, is implicated in potassium deprivation-induced apoptosis in CGNs.
  • PGC-1alpha plays a protective role in neuronal apoptosis.

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