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NMDA Receptor Dependent PGC-1α Up-Regulation Protects the Cortical Neuron Against Oxygen-Glucose Deprivation/Reperfusion Injury

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Abstract

The peroxisome proliferator activated receptor coactivator 1 alpha (PGC-1α) is a nuclear transcriptional coactivator that is widely expressed in the brain areas. Over-expression of PGC-1α can protect neuronal cells from oxidant-induced injury. The purpose of the current study is to investigate the role of PGC-1α in the oxygen (anoxia) deprivation (OGD) neurons. The PGC-1α mRNA and protein level between control and OGD neurons were examined by real-time PCR and Western blot. More PGC-1α expression was found in the OGD neurons compared with the normal group. Over-expression of PGC-1α suppressed cell apoptosis while inhibition of the PGC-1α expression induced cell apoptosis in OGD neurons. Furthermore, increase of PGC-1α resulted in activation of N-methyl-d-aspartate (NMDA) receptor, p38, and ERK mitogen-activated protein kinase (MAPK) pathway. The blocking of the NMDA receptor by its antagonists MK-801 reduced PGC-1α mRNA expression in OGD neurons, while NMDA itself can directly induce the expression of PGC-1α in neuronal cells. At the same time, PD98059 (ERK MAPK inhibitor) and SB203580 (P38 MAPK inhibitor) also prevented the up-regulation of PGC-1α in OGD neurons and MK801 can inhibit the expression of P38 and ERK MAPK. These data suggested that the expression of PGC-1α was up-regulated in OGD mice cortical neurons, which protected the neurons against OGD injury. Moreover, this effect was correlated to the NMDA receptor and the ERK and P38 MAPK pathway. The protective effect of PGC-1α on OGD cortical neurons may be useful for stroke therapy.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 30225037, 30400538, 30471991, 30570731, 30670739), the 973 Program of China (No. 2006CB503909, 2004CB518603), the “111” Project, and the Natural Science Foundation of Jiangsu Province (No. BK2004082, BK2006714). We thank doctor Yan Zhang for writing modification.

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Authors and Affiliations

  1. Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China

    Yun Luo, Wenjing Zhu & Yun Xu

  2. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China

    Jia Jia, Chenyu Zhang & Yun Xu

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  1. Yun Luo
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  2. Wenjing Zhu
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  3. Jia Jia
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  4. Chenyu Zhang
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Correspondence to Chenyu Zhang or Yun Xu.

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Wenjing Zhu is co-author who contributes equally to this work.

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Luo, Y., Zhu, W., Jia, J. et al. NMDA Receptor Dependent PGC-1α Up-Regulation Protects the Cortical Neuron Against Oxygen-Glucose Deprivation/Reperfusion Injury. J Mol Neurosci 39, 262–268 (2009). https://doi.org/10.1007/s12031-009-9196-5

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