title: Idebenone Prevents Oxidative Stress, Cell Death and Senescence of Retinal Pigment Epithelium Cells by Stabilizing BAX/Bcl-2 Ratio.
abstract: OBJECTIVE
  Age-related macular degeneration (AMD) is one of the leading causes of blindness. Degeneration of the retinal pigment epithelium (RPE) is pathognomonic for the disease, and oxidative stress plays an important role in the pathogenesis of this disease. This study investigates potential antiapoptotic and cytoprotective effects of idebenone on cultured RPE cells (ARPE-19) under conditions of oxidative stress.
  
  
  METHODS
  ARPE-19 cells were treated with 1-100 µ<smlcap>M</smlcap> idebenone. Cell viability (MTT assay), induction of intracellular reactive oxygen species (ROS) and histone-associated DNA fragments in mono- and oligonucleosomes, expression of proapoptotic BAX and antiapoptotic Bcl-2 as well as senescence-associated β-galactosidase (SA-β-Gal) activity were investigated under exposure to hydrogen peroxide (H2O2).
  
  
  RESULTS
  Idebenone concentrations from 1 to 20 µ<smlcap>M</smlcap> showed no toxic effects on ARPE-19 cells. When cells were treated with H2O2, pretreatment with 5, 7.5, 10, and 20 µ<smlcap>M</smlcap> idebenone led to a significant increase in the viability of ARPE-19 cells. In addition, idebenone pretreatment significantly attenuated the induction of SA-β-Gal and intracellular ROS as well as the amount of histone-associated DNA fragments after treatment with H2O2. The reduction of proapoptotic BAX and the elevation of antiapoptotic Bcl-2 under idebenone show that this process is rather mediated by inhibiting H2O2-induced apoptosis, not necrosis.
  
  
  CONCLUSIONS
  In this study, idebenone increased survival of ARPE-19 cells and reduced cell death, senescence, and oxidative stress by stabilizing the BAX/Bcl-2 ratio.
authors.affiliation: Department of Ophthalmology, Ludwig Maximilian University, Munich, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Arend
authors.forename: Christian
authors.initials: C
authors.lastname: Wertheimer
authors.forename: Peter
authors.initials: P
authors.lastname: Laubichler
authors.forename: Armin
authors.initials: A
authors.lastname: Wolf
authors.forename: Anselm
authors.initials: A
authors.lastname: Kampik
authors.forename: Marcus
authors.initials: M
authors.lastname: Kernt
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000975:Antioxidants; C494826:BAX protein, human; C000595707:BCL2 protein, human; D016877:Oxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D014451:Ubiquinone; D006861:Hydrogen Peroxide; C036619:idebenone