title: Effect of advanced glycation end products on oxidative stress and senescence of trabecular meshwork cells.
abstract: OBJECTIVE
  To investigate the effect of advanced glycation end products (AGE) on oxidative stress and cellular senescence in cultured human trabecular meshwork cells (HTMC).
  
  
  METHODS
  Primarily cultured HTMC were exposed to 0, 10, 50, 100, 200 µg/mL of glycated bovine serum albumin (G-BSA) for 5 days. Also co-exposed were L-arginine, sepiapterin, and antioxidant N-acetylcysteine (NAC). Cellular survival and production of nitric oxide (NO), superoxide, and reactive oxygen species were assessed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assay, Griess assay, cytochrome c assay, and dichlorofluorescin diacetate assay, respectively. Senescence-associated β-galactosidase staining was performed to quantify the degree of cellular senescence.
  
  
  RESULTS
  G-BSA decreased cellular survival, NO production, and increased superoxide production significantly in a dose-dependent manner. The effects of G-BSA were abolished with co-exposure of L-arginine, sepiapterin, and NAC. G-BSA enhanced cellular senescence accompanied by increased production of reactive oxygen species. G-BSA-induced cellular senescence was suppressed by application of L-arginine, sepiapterin, and NAC.
  
  
  CONCLUSIONS
  AGE enhances cellular senescence of HTMC accompanied with increased oxidative stress. AGE-induced oxidative stress and cellular senescence could be delayed by application of anti-oxidants.
authors.affiliation: Department of Ophthalmology, Catholic University of Daegu School of Medicine, Daegu, Korea.
authors.forename: Cheul Ho
authors.initials: CH
authors.lastname: Park
authors.forename: Jae Woo
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001120:Arginine / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D017127:Glycation End Products, Advanced / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D011622:Pterins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism / Q000633:toxicity; D014129:Trabecular Meshwork / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*
chemical_list: D017127:Glycation End Products, Advanced; D011622:Pterins; D017382:Reactive Oxygen Species; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; D001120:Arginine; C016727:sepiapterin; D000111:Acetylcysteine