Quinolinic acid induces cell apoptosis in PC12 cells through HIF-1-dependent RTP801 activation
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  • 作者:Xiaojia Huang ; Kaiyong Yang ; Yi Zhang ; Qiang Wang ; Yongjin Li
  • 关键词:Quinolinic acid ; Cell apoptosis ; Hypoxia inducible factor ; 1 ; RTP801
  • 刊名:Metabolic Brain Disease
  • 出版年:2016
  • 出版时间:April 2016
  • 年:2016
  • 卷:31
  • 期:2
  • 页码:435-444
  • 全文大小:1,433 KB
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  • 作者单位:Xiaojia Huang (1)
    Kaiyong Yang (1)
    Yi Zhang (1)
    Qiang Wang (2)
    Yongjin Li (1)

    1. Department of Pharmacology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, China
    2. Department of Preventive Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, China
  • 刊物类别:Biomedical and Life Sciences
  • 刊物主题:Biomedicine
    Neurosciences
    Neurology
    Biochemistry
    Oncology
  • 出版者:Springer Netherlands
  • ISSN:1573-7365
文摘
Neurological disease comprises a series of disorders featuring brain dysfunction and neuronal cell death. Among the factors contributing to neuronal death, excitotoxicity induced by excitatory amino acids, such as glutamate, plays a critical role. However, the mechanisms about how the excitatory amino acids induce neuronal death remain elucidated. In this study, we investigated the role of HIF-1α (hypoxia inducible factor-1α) and RTP801 in cell apoptosis induced by quinolinic acid (QUIN), a glutamatergic agonist, in PC12 cells. We found that QUIN at 5 μM increased the expression of HIF-1α significantly with a peak at 24 h. After the treatment with QUIN (5–20 μM) for 24 h, the cells exhibited decreased viability and cell apoptosis with a concomitant increased expression of apoptosis related proteins. QUIN treatment also induced the generation of intracellular reactive oxygen species and RTP801 up-regulation in a HIF-1α-dependent manner that were inhibited by 2-methoxyestradiol, a HIF-1α inhibitor. Importantly, HIF-1 or RTP801 invalidation by siRNA rescued the cell apoptosis induced by QUIN or cobalt chloride, a chemical inducer of HIF-1. Taken together, these findings support the concept that neurotoxicity induced by QUIN is associated with HIF-1-dependent RTP801 activation and provide insight into the potential of RTP801 inhibitor in treatment of neurological disorders.

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