title: Hypoxia Induces autophagic cell death through hypoxia-inducible factor 1α in microglia.
abstract: As phagocytic cells of central nervous system, excessive activation or cell death of microglia is involved in a lot of nervous system injury and degenerative disease, such as stroke, epilepsy, Parkinson's disease, Alzheimer's disease. Accumulating evidence indicates that hypoxia upregulates HIF-1α expression leading to cell death of microglia. However, the exact mechanism of cell death induced by hypoxia in microglia is not clear. In the current study, we showed that hypoxia induced cell death and autophagy in microglia. The suppression of autophagy using either pharmacologic inhibitors (3-methyladenine, bafilomycin A1) or RNA interference in essential autophagy genes (BECN1 and ATG5) decreased the cell death induced by hypoxia in microglia cells. Moreover, the suppression of HIF-1α using either pharmacologic inhibitors (3-MA, Baf A1) or RNA interference decreased the microglia death and autophagy in vitro. Taken together, these data indicate that hypoxia contributes to autophagic cell death of microglia through HIF-1α, and provide novel therapeutic interventions for cerebral hypoxic diseases associated with microglia activation.
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Tian-Zhi
authors.initials: TZ
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Zou
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D017628:Microglia / Q000166:cytology* / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C025946:3-methyladenine; D000225:Adenine