title: Green Tea Catechin Prevents Hypoxia/Reperfusion-Evoked Oxidative Stress-Regulated Autophagy-Activated Apoptosis and Cell Death in Microglial Cells.
abstract: Defective activation and proliferation in microglial cells has been suggested to be associated with the increase of cerebral ischemia/reperfusion injury. We investigated the protection and molecular mechanism of green tea catechin on hypoxia/reperfusion-induced microglial cell injury in vitro. Microglial cells were cultured in hypoxia condition (O2 < 1%) and then re-incubated to the complete normal culture medium (reperfusion). Hypoxia/reperfusion obviously decreased cell viability and induced apoptosis in microglial cells, but not in neuronal cells. Catechin significantly inhibited the hypoxia/reperfusion-induced decreased cell viability and increased reactive oxygen species (ROS) and apoptosis in microglia. The administration of both PI3K/Akt inhibitor LY294002 and mTOR inhibitor rapamycin demonstrated that Akt/mTOR-regulated autophagy was involved in the hypoxia/reperfusion-induced microglia apoptosis/death. Catechin up-regulated the Akt and mTOR phosphorylation and inhibited the hypoxia/reperfusion-induced autophagy in microglia. These results suggest that hypoxia/reperfusion can evoke autophagy-activated microglia apoptosis/death via an ROS-regulated Akt/mTOR signaling pathway, which can be reversed by catechin.
authors.affiliation: Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University, College of Medicine , Taipei, Taiwan.
authors.forename: Chang-Mu
authors.initials: CM
authors.lastname: Chen
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University , Taipei, Taiwan.
authors.forename: Cheng-Tien
authors.initials: CT
authors.lastname: Wu
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital , Taipei, Taiwan.
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Yang
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University , Taipei, Taiwan.
authors.forename: Ya-An
authors.initials: YA
authors.lastname: Chang
authors.affiliation: Institute of Biomedical Sciences, College of Life Sciences, National Chung Hsing University , Taichung, Taiwan.
authors.forename: Meei-Ling
authors.initials: ML
authors.lastname: Sheu
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University , Taipei, Taiwan.|Department of Medical Research, China Medical University Hospital, China Medical University , Taichung, Taiwan.
authors.forename: Shing Hwa
authors.initials: SH
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D028241:Camellia sinensis / Q000737:chemistry*; D002392:Catechin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D002392:Catechin; D019869:Phosphatidylinositol 3-Kinases; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D058570:TOR Serine-Threonine Kinases
keywords: apoptosis; autophagy; catechin; hypoxia reperfusion; microglia