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Upregulation of HIF-1α by Hypoxia Protect Neuroblastoma Cells from Apoptosis by Promoting Survivin Expression

  • Zhang, Bo (Department of Physical Medicine and Rehabilitation, Qi Lu Hospital, Medical School of Shandong University) ;
  • Yin, Cui-Ping (Department of Physical Medicine and Rehabilitation, Qi Lu Hospital, Medical School of Shandong University) ;
  • Zhao, Qian (Department of Ultrasound in Medicine, Dongying People's Hospital) ;
  • Yue, Shou-Wei (Department of Physical Medicine and Rehabilitation, Qi Lu Hospital, Medical School of Shandong University)
  • Published : 2014.10.23

Abstract

Apoptosis is one of main types of neural cell death and is reversible and is a major target of therapeutic interventions. However, detailed apoptotic cascades still need to be recognized. In present study, we determined the promotion of HIF-$1{\alpha}$ and survivin in brain samples of a mouse model of hypoxic-ischemia and in neuroblastoma SH-SY5Y cells post hypoxia treatment. Then gain-of-function and loss-of-function strategies were adopted to manipulate the HIF-$1{\alpha}$ in SH-SY5Y cells, and hypoxia-induced survivin upregulation and cell apoptosis were determined. Results demonstrated that the HIF-$1{\alpha}$ and survivin were significantly promoted in a mouse model of hypoxic-ischemia or in SH-SY5Y cells post hypoxia in vitro. Manually upregulated HIF-$1{\alpha}$ could promote the hypoxia-induced survivin upregulation and improve the hypoxia-induced SH-SY5Y cell apoptosis. On the other hand, the HIF-$1{\alpha}$ knockdown by RNAi reduced the hypoxia-induced survivin upregulation and cell apoptosis. Therefore, the present study confirmed the protective role of HIF-$1{\alpha}$ and survivin in the hypoxia-induced SH-SY5Y cell apoptosis, and the survivin upregulation by hypoxia is HIF-$1{\alpha}$-dependent. Promotion of HIF-$1{\alpha}$ and survivin might be a valuable stragegy for therapeutic intervention for hypoxic-ischemic encephalopathy.

Keywords

Hypoxic-ischemic encephalopathy;HIF-$1{\alpha}$;survivin;apoptosis

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