title: A viral vector expressing hypoxia-inducible factor 1 alpha inhibits hippocampal neuronal apoptosis.
abstract: 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 HIF-1α gene (rAAV-HIF-1α), and tested the assumption that rAAV-HIF-1α represses hippocampal neuronal apoptosis induced by amyloid-beta protein. Our results confirmed that rAAV-HIF-1α significantly reduces apoptosis induced by amyloid-beta protein in primary cultured hippocampal neurons. Direct intracerebral rAAV-HIF-1α administration also induced robust and prolonged HIF-1α production in rat hippocampus. Single rAAV-HIF-1α 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.
authors.affiliation: Bioreactor and Protein Drug Research and Development Center of Hebei Universities, Hebei Chemical and Pharmaceutical College, Shijiazhuang, Hebei Province, China.
authors.forename: Xiqing
authors.initials: X
authors.lastname: Chai
authors.affiliation: Bioreactor and Protein Drug Research and Development Center of Hebei Universities, Hebei Chemical and Pharmaceutical College, Shijiazhuang, Hebei Province, China.
authors.forename: Weina
authors.initials: W
authors.lastname: Kong
authors.affiliation: Department of Neurology, Shanghai Yangpu District Central Hospital, Shanghai, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Liu
authors.affiliation: Bioreactor and Protein Drug Research and Development Center of Hebei Universities, Hebei Chemical and Pharmaceutical College, Shijiazhuang, Hebei Province, China.
authors.forename: Wenguo
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Neurology, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Bioreactor and Protein Drug Research and Development Center of Hebei Universities, Hebei Chemical and Pharmaceutical College, Shijiazhuang, Hebei Province, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Sun
keywords: Alzheimer's disease; NSFC grant; adeno-associated virus; apoptosis; calcium concentration; gene therapy; hypoxia-inducible factor 1α; intracerebroventricular injection; nerve regeneration; neural regeneration; transduction