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

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.