title: Superoxide dismutase 1 overexpression in mice abolishes maternal diabetes-induced endoplasmic reticulum stress in diabetic embryopathy.
abstract: OBJECTIVE
  Both oxidative stress and endoplasmic reticulum stress (ER stress) are causal events in diabetic embryopathy. We tested whether oxidative stress causes ER stress.
  
  
  METHODS
  Wild-type (WT) and superoxide dismutase 1 (SOD1)-overexpressing day 8.75 embryos from nondiabetic WT control with SOD1 transgenic male and diabetic WT female with SOD1 transgenic male were analyzed for ER stress markers: C/EBP-homologous protein (CHOP), calnexin, eukaryotic initiation factor 2α (eIF2α), protein kinase ribonucleic acid (RNA)-like ER kinase (PERK), binding immunoglobulin protein, protein disulfide isomerase family A member 3, kinases inositol-requiring protein-1α (IRE1α), and the X-box binding protein (XBP1) messenger RNA (mRNA) splicing.
  
  
  RESULTS
  Maternal diabetes significantly increased the levels of CHOP, calnexin, phosphorylated (p)-eIF2α, p-PERK, and p-IRE1α; triggered XBP1 mRNA splicing; and enhanced ER chaperone gene expression in WT embryos. SOD1 overexpression blocked these diabetes-induced ER stress markers.
  
  
  CONCLUSIONS
  Mitigating oxidative stress via SOD1 overexpression blocks maternal diabetes-induced ER stress in vivo.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: E Albert
authors.initials: EA
authors.lastname: Reece
authors.forename: Peixin
authors.initials: P
authors.lastname: Yang
mesh_terms: D000818:Animals; D037281:Calnexin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000378:metabolism / Q000503:physiopathology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D004722:Endoribonucleases / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D005260:Female; D005315:Fetal Diseases / Q000503:physiopathology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000502:physiology; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism / Q000503:physiopathology*; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000071701:Regulatory Factor X Transcription Factors; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology*; D000072105:Superoxide Dismutase-1; D051742:Transcription Factor CHOP / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D000071717:X-Box Binding Protein 1; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D037281:Calnexin; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D004722:Endoribonucleases; D015852:Eukaryotic Initiation Factor-2; D006360:Heat-Shock Proteins; D019704:Protein Disulfide-Isomerases; D017346:Protein Serine-Threonine Kinases; D000071701:Regulatory Factor X Transcription Factors; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D051742:Transcription Factor CHOP; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; D019892:eIF-2 Kinase; C497250:Ddit3 protein, mouse; C000605544:Xbp1 protein, mouse; C000606291:Sod1 protein, mouse; C510185:Ern1 protein, mouse; C513195:Pdia3 protein, mouse
keywords: diabetic embryopathy; endoplasmic reticulum stress; oxidative stress; superoxide dismutase 1 transgenic mice