title: SOD1 suppresses maternal hyperglycemia-increased iNOS expression and consequent nitrosative stress in diabetic embryopathy.
abstract: OBJECTIVE
  Hyperglycemia induces oxidative stress and increases inducible nitric oxide synthase (iNOS) expression. We hypothesized that oxidative stress is responsible for hyperglycemia-induced iNOS expression.
  
  
  METHODS
  iNOS-luciferase activities, nitrosylated protein, and lipid peroxidation markers 4-hydroxynonenal and malondialdehyde were determined in parietal yolk sac-2 cells exposed to 5 mmol/L glucose or high glucose (25 mmol/L) with or without copper zinc superoxide dismutase 1 (SOD1) treatment. Levels of iNOS protein and messenger RNA, nitrosylated protein, and cleaved caspase-3 and -8 were assessed in wild-type embryos and SOD1-overexpressing embryos from nondiabetic and diabetic dams.
  
  
  RESULTS
  SOD1 treatment diminished high glucose-induced oxidative stress, as evidenced by 4-hydroxynonenal and malondialdehyde reductions, and it blocked high glucose-increased iNOS expression, iNOS-luciferase activities, and nitrosylated protein. In vivo SOD1 overexpression suppressed hyperglycemia-increased iNOS expression and nitrosylated protein, and it blocked caspase-3 and -8 cleavage.
  
  
  CONCLUSIONS
  We conclude that oxidative stress induces iNOS expression, nitrosative stress, and apoptosis in diabetic embryopathy.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Weng
authors.forename: Xuezheng
authors.initials: X
authors.lastname: Li
authors.forename: E Albert
authors.initials: EA
authors.lastname: Reece
authors.forename: Peixin
authors.initials: P
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D005315:Fetal Diseases / Q000209:etiology* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000378:metabolism* / Q000494:pharmacology; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism* / Q000494:pharmacology; D000072105:Superoxide Dismutase-1; D015017:Yolk Sac / Q000166:cytology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016166:Free Radical Scavengers; D052247:Nitric Oxide Synthase Type II; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1