Zhang Bo, Yin Cui-Ping, Zhao Qian, Yue Shou-Wei
Department of Physical Medicine and Rehabilitation, Qi Lu Hospital, Medical School of Shandong University. Jinan, China E-mail :
Asian Pac J Cancer Prev. 2014;15(19):8251-7. doi: 10.7314/apjcp.2014.15.19.8251.
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-1α 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-1α in SH-SY5Y cells, and hypoxia-induced survivin upregulation and cell apoptosis were determined. Results demonstrated that the HIF-1α and survivin were significantly promoted in a mouse model of hypoxic-ischemia or in SH-SY5Y cells post hypoxia in vitro. Manually upregulated HIF-1α could promote the hypoxia-induced survivin upregulation and improve the hypoxia-induced SH-SY5Y cell apoptosis. On the other hand, the HIF-1α knockdown by RNAi reduced the hypoxia-induced survivin upregulation and cell apoptosis. Therefore, the present study confirmed the protective role of HIF-1α and survivin in the hypoxia-induced SH- SY5Y cell apoptosis, and the survivin upregulation by hypoxia is HIF-1α-dependent. Promotion of HIF-1α and survivin might be a valuable stragegy for therapeutic intervention for hypoxic-ischemic encephalopathy.
细胞凋亡是神经细胞死亡的主要类型之一，具有可逆性，是治疗干预的主要靶点。然而，详细的凋亡级联反应仍有待明确。在本研究中，我们测定了缺氧缺血小鼠模型脑样本及缺氧处理后的神经母细胞瘤SH-SY5Y细胞中HIF-1α和生存素的表达上调情况。然后采用功能获得和功能丧失策略来调控SH-SY5Y细胞中的HIF-1α，并测定缺氧诱导的生存素上调和细胞凋亡情况。结果表明，在缺氧缺血小鼠模型或体外缺氧处理后的SH-SY5Y细胞中，HIF-1α和生存素均显著上调。人工上调HIF-1α可促进缺氧诱导的生存素上调，并改善缺氧诱导的SH-SY5Y细胞凋亡。另一方面，RNAi敲低HIF-1α可降低缺氧诱导的生存素上调和细胞凋亡。因此，本研究证实了HIF-1α和生存素在缺氧诱导的SH-SY5Y细胞凋亡中的保护作用，且缺氧诱导的生存素上调依赖于HIF-1α。促进HIF-1α和生存素可能是缺氧缺血性脑病治疗干预的一种有价值策略。
