title: Idebenone prevents human optic nerve head astrocytes from oxidative stress, apoptosis, and senescence by stabilizing BAX/Bcl-2 ratio.
abstract: OBJECTIVE
  Oxidative stress plays an important role in the pathogenesis of several neurodegenerative diseases including glaucoma. Astrocytes are supposed to play a role in glaucoma pathogenesis. This study investigates the antiapoptotic and cytoprotective effects of idebenone on optic nerve head astrocytes (ONHA) under oxidative stress.
  
  
  METHODS
  ONHA were treated with 1 to 150 µM idebenone. Cell viability (MTT assay and live-dead assay), induction of intracellular reactive oxygen species, senescence-associated β-galactosidase activity were investigated. In addition, apoptosis (detection of histone-associated DNA fragmentation), and expression of BAX and Bcl-2, and their mRNA were determined after 48 hours and after hydrogen peroxide (H2O2) treatment.
  
  
  RESULTS
  Idebenone concentrations from 1 to 50 µM showed no effects on ONHA viability. Pretreatment with 10 µM idebenone led to an increase in viability of ONHA after H2O2 treatment. In addition, idebenone pretreatment significantly attenuated the increase of histone-associated DNA fragmentation, induction of senescence-associated β-galactosidase, and intracellular reactive oxygen species after treatment with H2O2. When ONHA cells were treated with idebenone and H2O2, real-time polymerase chain reaction and Western blot analysis yielded an increased expression of Bcl-2 and a decrease of BAX compared with those cells that were treated with H2O2 only.
  
  
  CONCLUSIONS
  Idebenone reduced senescence, oxidative stress, and apoptotic cell death in cultured ONHA in vitro. Our results suggest that idebenone may help to protect ONHA in vivo, and therefore might be helpful in preventing the progression of glaucomatous degeneration.
authors: Department of Ophthalmology, Ludwig Maximilian University, Munich, Germany. marcus.kernt@med.uni-muenchen.de
authors: Marcus
authors: M
authors: Kernt
authors: Nicole
authors: N
authors: Arend
authors: Alexandra
authors: A
authors: Buerger
authors: Thomas
authors: T
authors: Mann
authors: Christos
authors: C
authors: Haritoglou
authors: Michael W
authors: MW
authors: Ulbig
authors: Anselm
authors: A
authors: Kampik
authors: Christoph
authors: C
authors: Hirneiss
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008875:Middle Aged; D009898:Optic Disk / Q000166:cytology; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014019:Tissue Donors; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000975:Antioxidants; C494826:BAX protein, human; 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; D001616:beta-Galactosidase; C036619:idebenone