title: Increased response to oxidative stress challenge in Graves' ophthalmopathy orbital fibroblasts.
abstract: OBJECTIVE
  To investigate whether orbital fibroblasts from patients with Graves' ophthalmopathy (GO) are more responsive to oxidative stress.
  
  
  METHODS
  Lipid peroxidation, oxidative DNA damage, reactive oxygen species (ROS) contents and activities of antioxidant enzymes were measured in cultured orbital fibroblasts from GO patients and age-matched normal controls in response to 200 μM hydrogen peroxide (H(2)O(2)).
  
  
  RESULTS
  GO fibroblasts had increased basal levels of malondialdehyde (MDA), 8-hydroxy 2'-deoxyguanosine, superoxide anions, H(2)O(2), and manganese-dependent superoxide dismutase (Mn-SOD) activity, as well as decreased glutathione peroxidase (GPx) activity and the ratio between reduced (GSH) and oxidized glutathione (GSSG) compared with the orbital fibroblasts from normal subjects. After treatment of the cells with 200 μM H(2)O(2), the amplitude of increase in the intracellular levels of MDA (63% versus 26%), H(2)O(2) (24% versus 13%) and Mn-SOD activity (48% versus 23%) was exaggerated in GO fibroblasts compared with normal controls, respectively. In addition, treatment of GO fibroblasts with 200 μM H(2)O(2) led to a dramatic reduction of catalase activity (-59% versus -29%), GPx activity (-56% versus -13%), and GSH/GSSG ratio (-49% versus -21%), respectively.
  
  
  CONCLUSIONS
  Elevated ROS and redox imbalance in GO orbital fibroblasts were exacerbated by H(2)O(2) as a result of exhaustion of GSH and compromise of antioxidant enzymes. Hypersensitivity to oxidative stress of GO orbital fibroblasts may play a role in the pathogenesis of GO.
authors: Department of Ophthalmology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan.
authors: Chieh-Chih
authors: CC
authors: Tsai
authors: Shi-Bei
authors: SB
authors: Wu
authors: Ching-Yu
authors: CY
authors: Cheng
authors: Shu-Ching
authors: SC
authors: Kao
authors: Hui-Chuan
authors: HC
authors: Kau
authors: Shui-Mei
authors: SM
authors: Lee
authors: Yau-Huei
authors: YH
authors: Wei
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000975:Antioxidants / Q000378:metabolism*; D016022:Case-Control Studies; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D049970:Graves Ophthalmopathy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects* / Q000032:analysis; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000032:analysis; D009915:Orbit / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D003849:Deoxyguanosine; D005978:Glutathione; D019803:Glutathione Disulfide