title: Upregulation of HIF-1α by hypoxia protect neuroblastoma cells from apoptosis by promoting survivin expression.
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-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.
authors.affiliation: Department of Physical Medicine and Rehabilitation, Qi Lu Hospital, Medical School of Shandong University. Jinan, China E-mail : shouweiy@sdu.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Cui-Ping
authors.initials: CP
authors.lastname: Yin
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Shou-Wei
authors.initials: SW
authors.lastname: Yue
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D014407:Tumor Cells, Cultured
chemical_list: C107489:BIRC5 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D000077022:Survivin