title: SOD2 Mediates Amifostine-Induced Protection against Glutamate in PC12 Cells.
abstract: BACKGROUND
  Cytoprotectant amifostine attenuates radiation-induced oxidative injury by increasing intracellular manganese superoxide dismutase (SOD2) in peripheral tissue. However, whether amifostine could protect neuronal cells against oxidative injury has not been reported. The purpose of this study is to explore the protection of amifostine in PC12 cells.
  
  
  METHODS
  PC12 cells exposed to glutamate were used to mimic neuronal oxidative injury. SOD assay kit was taken to evaluate intracellular Cu/Zn SOD (SOD1) and SOD2 activities; western blot analysis and immunofluorescence staining were performed to investigate SOD2 protein expression; MTT, lactate dehydrogenase (LDH), release and cell morphology were used to evaluate cell injury degree, and apoptotic rate and cleaved caspase-3 expression were taken to assess apoptosis; mitochondrial superoxide production, intracellular reactive oxygen species (ROS), and glutathione (GSH) and catalase (CAT) levels were evaluated by reagent kits.
  
  
  RESULTS
  Amifostine increased SOD2 activity and expression, decreased cell injury and apoptosis, reduced mitochondrial superoxide production and intracellular ROS generation, and restored intracellular GSH and CAT levels in PC12 cells exposed to glutamate. SOD2-siRNA, however, significantly reversed the amifostine-induced cytoprotective and antioxidative actions.
  
  
  CONCLUSIONS
  SOD2 mediates amifostine-induced protection in PC12 cells exposed to glutamate.
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of Anesthesiology, Xi'an No. 4 Hospital, Xi'an 710032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Fuzhou General Hospital of Nanjing Military Command, Fuzhou 350025, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Anesthesiology, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070, China.
authors.forename: Mingchun
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Gastrointestinal Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Huo
mesh_terms: D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D018698:Glutamic Acid / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D000066829:Neuroprotection / Q000187:drug effects*; D016716:PC12 Cells; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000099156:Superoxide Dismutase 2
chemical_list: D004999:Amifostine; D002374:Catalase; D018698:Glutamic Acid; D005978:Glutathione; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D013481:Superoxides; D000099156:Superoxide Dismutase 2