A viral vector expressing hypoxia-inducible factor 1 alpha inhibits hippocampal neuronal apoptosis

被引：29

作者：

Chai, Xiqing ^{[1
]}

Kong, Weina ^{[1
]}

Liu, Lingyun ^{[2
]}

Yu, Wenguo ^{[1
]}

Zhang, Zhenqing ^{[3
]}

Sun, Yimin ^{[1
]}

机构：

[1] Hebei Univ, Bioreactor & Prot Drug Res & Dev Ctr, Hebei Chem & Pharmaceut Coll, Shijiazhuang 050026, Hebei Province, Peoples R China

[2] Shanghai Yangpu Dist Cent Hosp, Dept Neurol, Shanghai, Peoples R China

[3] Hebei Med Univ, Dept Neurol, Hosp 1, Shijiazhuang, Hebei Province, Peoples R China

来源：

NEURAL REGENERATION RESEARCH | 2014年 / 9卷 / 11期

基金：

中国国家自然科学基金;

关键词：

nerve regeneration; Alzheimer's disease; adeno-associated virus; hypoxia-inducible factor 1 alpha; apoptosis; gene therapy; calcium concentration; transduction; intracerebroventricular injection; NSFC grant; neural regeneration; AMYLOID-BETA-PEPTIDE; ADENOASSOCIATED VIRUS VECTOR; ALZHEIMERS-DISEASE; CORTICAL-NEURONS; RAT HIPPOCAMPUS; GROWTH-FACTOR; GENE-THERAPY; TARGET GENES; CELLS; IMPAIRMENTS;

D O I：

10.4103/1673-5374.135317

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Hypoxia-inducible factor 1 (HIF-1) attenuates amyloid-beta protein neurotoxicity and decreases apoptosis induced by oxidative stress or hypoxia in cortical neurons. In this study, we constructed a recombinant adeno-associated virus (rAAV) vector expressing the human HIP-1 alpha gene (rAAV-HIF-1 alpha), and tested the assumption that rAAV-HIF-1 alpha represses hippocampal neuronal apoptosis induced by amyloid-beta protein. Our results confirmed that rAAV-HIF-1 alpha significantly reduces apoptosis induced by amyloid-beta protein in primary cultured hippocampal neurons. Direct intracerebral rAAV-HIF-1 alpha administration also induced robust and prolonged HIF-1 alpha production in rat hippocampus. Single rAAV-HIF-1 alpha administration resulted in decreased apoptosis of hippocampal neurons in an Alzheimer's disease rat model established by intracerebroventricular injection of aggregated amyloid-beta protein (25-35). Our in vitro and in vivo findings demonstrate that HIF-1 has potential for attenuating hippocampal neuronal apoptosis induced by amyloid-beta protein, and provides experimental support for treatment of neurodegenerative diseases using gene therapy.

引用

页码：1145 / 1153

页数：9

共 41 条

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