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Oxidative stress occurs early in Down syndrome pregnancy: A redox proteomics analysis of amniotic fluid

Purpose: 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. Experimental design: To assess the extent of protein oxidation in DS AF, w...

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Published in:Proteomics. Clinical applications 2011-04, Vol.5 (3-4), p.167-178
Main Authors: Perluigi, Marzia, di Domenico, Fabio, Fiorini, Ada, Cocciolo, Annalisa, Giorgi, Alessandra, Foppoli, Cesira, Butterfield, D. Allan, Giorlandino, Maurizio, Giorlandino, Claudio, Eugenia Schininà, M., Coccia, Raffaella
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cited_by cdi_FETCH-LOGICAL-c5041-fe4cc1b97c1da4dae86beaf8866eaaaeef2f376e6160e6e3f8aa67c1573dd6e53
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container_title Proteomics. Clinical applications
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creator Perluigi, Marzia
di Domenico, Fabio
Fiorini, Ada
Cocciolo, Annalisa
Giorgi, Alessandra
Foppoli, Cesira
Butterfield, D. Allan
Giorlandino, Maurizio
Giorlandino, Claudio
Eugenia Schininà, M.
Coccia, Raffaella
description Purpose: 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. Experimental design: 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 and clinical relevance: 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.
doi_str_mv 10.1002/prca.201000121
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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. 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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 and clinical relevance: 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.</abstract><cop>Weinheim</cop><pub>WILEY-VCH Verlag</pub><pmid>21360684</pmid><doi>10.1002/prca.201000121</doi><tpages>12</tpages></addata></record>
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source Wiley-Blackwell Read & Publish Collection
subjects Adult
Amniotic fluid
Amniotic Fluid - chemistry
Biological and medical sciences
Chromosome aberrations
Diverse techniques
Down syndrome
Down Syndrome - diagnosis
Down Syndrome - genetics
Down Syndrome - metabolism
Female
Fetuses
Fundamental and applied biological sciences. Psychology
Humans
Medical genetics
Medical sciences
Molecular and cellular biology
Oxidation-Reduction
Oxidative stress
Oxidative Stress - genetics
Phenotype
Pregnancy
Pregnancy Trimester, First - genetics
Pregnancy Trimester, First - metabolism
Protein oxidation
Proteins
Proteins - analysis
Proteins - genetics
Proteins - metabolism
Proteomics
Redox proteomics
Retrospective Studies
Sensitivity and Specificity
title Oxidative stress occurs early in Down syndrome pregnancy: A redox proteomics analysis of amniotic fluid
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