title: Protective effect of clusterin from oxidative stress-induced apoptosis in human retinal pigment epithelial cells.
abstract: OBJECTIVE
  Oxidative stress to retinal pigment epithelial (RPE) cells is thought to play a critical role in the pathogenesis of age-related macular degeneration (AMD). This study was conducted to investigate whether clusterin protects human RPE cells from ROS-induced apoptosis through a PI3K/Akt survival pathway.
  
  
  METHODS
  The preventive effect of clusterin on reactive oxygen species (ROS) production and RPE cell death induced by hydrogen peroxide was determined in ARPE-19 cells. The ability of clusterin to protect RPE cells against ROS-mediated apoptosis was assessed by caspase-3 activity and DAPI staining. Furthermore, the protective effect of clusterin via the PI3K/Akt pathway was determined by Western blot analysis.
  
  
  RESULTS
  Clusterin prevented ARPE-19 cells from H(2)O(2)-induced cell death and ROS production. H(2)O(2)-induced oxidative stress increased caspase-3 activity, which was significantly inhibited by clusterin, as determined by the abrogation of apoptotic bodies. Interestingly, clusterin induced Akt phosphorylation in human RPE cells under oxidative stress, which contributed to cell viability in ARPE-19 cells. This cell survival by clusterin was blocked by a PI3K inhibitor.
  
  
  CONCLUSIONS
  Clusterin may play a protective role in responding to the local redox environment of human RPE cells, which contributes to the cell survival via the PI3K/Akt pathway. Therefore, clusterin could be considered for the preventive approach to AMD.
authors.affiliation: Fight against Angiogenesis-Related Blindness Laboratory, Department of Ophthalmology, Seoul National University College of Medicine and Seoul Artificial Eye Center, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
authors.forename: Jeong Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kim
authors.forename: Hyoung Oh
authors.initials: HO
authors.lastname: Jun
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Yu
authors.forename: Bon Hong
authors.initials: BH
authors.lastname: Min
authors.forename: Kyu Hyung
authors.initials: KH
authors.lastname: Park
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D051152:Clusterin / Q000502:physiology*; D019610:Cytoprotection; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C495242:CLU protein, human; D051152:Clusterin; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3