title: Oxidative stress occurs early in Down syndrome pregnancy: A redox proteomics analysis of amniotic fluid.
abstract: OBJECTIVE
  The present study aims to evaluate a set of oxidative stress biomarkers in the amniotic fluid (AF) of women carrying Down syndrome (DS) fetuses that could prove in vivo the early occurrence of oxidative damage in DS.
  
  
  METHODS
  To assess the extent of protein oxidation in DS AF, we measured protein carbonylation and protein-bound HNE by slot-blot analysis, total and oxidized GSH levels by enzymatic assay and heat shock proteins (HSPs) thioredoxin (Trx) induction by Western blot. Further, by a redox proteomics approach specific targets of protein carbonylation were identified.
  
  
  RESULTS
  We found increased levels of oxidative stress, as indexed by increased protein oxidation, lipid peroxidation, reduction of GSH and Trx levels and induction of the HSP response. By a redox proteomics approach, we identified selective proteins which showed increased oxidation in DS fetuses compared with healthy controls. The identified proteins are involved in iron homeostasis (ceruloplasmin and transferin), lipid metabolism (zinc-α2-glycoprotein, retinol-binding protein 4 and apolipoprotein A1) and inflammation (complement C9, α-1B-glycoprotein, collagen α-1V chain) with critical relevance in the clinical outcome of DS.
  
  
  CONCLUSIONS
  Our results indicate that oxidative damage is an early event in the DS pathogenesis and might contribute to the development of deleterious DS phenotypes, including abnormal development and AD-like neuropathology.
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Perluigi
authors.forename: Fabio
authors.initials: F
authors.lastname: di Domenico
authors.forename: Ada
authors.initials: A
authors.lastname: Fiorini
authors.forename: Annalisa
authors.initials: A
authors.lastname: Cocciolo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Giorgi
authors.forename: Cesira
authors.initials: C
authors.lastname: Foppoli
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
authors.forename: Maurizio
authors.initials: M
authors.lastname: Giorlandino
authors.forename: Claudio
authors.initials: C
authors.lastname: Giorlandino
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: Schininà
authors.forename: Raffaella
authors.initials: R
authors.lastname: Coccia
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry*; D004314:Down Syndrome / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D010641:Phenotype; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D011506:Proteins