title: Glutathione prevents free fatty acids-induced oxidative stress and apoptosis in human brain vascular endothelial cells through Akt pathway.
abstract: OBJECTIVE
  The damage of human brain vascular endothelial cells (HBVECs) is the key pathogenesis of diabetes-associated cerebral vascular complications. The aim of this study was to elucidate the effects of glutathione (GSH) on free fatty acids (FFAs)-induced HBVECs apoptosis, oxidative stress, and the involved possible signaling pathway.
  
  
  METHODS
  After culturing HBVECs for 72 h with GSH and FFAs, we determined cell proliferation by CCK8, detected apoptosis by caspase-3 and Annexin V-FITC/PI staining, and judged oxygen stress by determining the reactive oxygen species (ROS) and the mitochondrial membrane potential (MMP). We investigated whether the Akt pathway was involved in FFAs-induced signaling pathway alteration and whether GSH influenced the above effects.
  
  
  RESULTS
  After being cultured in 200 μM FFAs for 72 h, the HBVECs proliferation significantly decreased; HBVECs apoptosis increased; the ROS levels increased; and the HBVECs MMP subsequently decreased. FFAs induced a significant decrease in phosphorylated active Akt. These alterations were obviously prevented when 1 mM GSH was added to culture medium containing FFAs, and the above effects of GSH were blocked by Akt inhibitor.
  
  
  CONCLUSIONS
  GSH may prevent FFAs-induced HBVECs damage, oxidative stress, and apoptosis through activating the Akt pathway.
authors.affiliation: Department of Geriatrics Neurology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Hou-Guang
authors.initials: HG
authors.lastname: Zhou
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Huang
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Tao
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhang
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Su
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Tang
authors.forename: Zhuang-Li
authors.initials: ZL
authors.lastname: Guo
authors.forename: Ren-Ming
authors.initials: RM
authors.lastname: Hu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dong
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005978:Glutathione / Q000502:physiology*; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D005230:Fatty Acids, Nonesterified; D051057:Proto-Oncogene Proteins c-akt; D005978:Glutathione