Quantitative proteomic analysis of amniocytes reveals potentially dysregulated molecular networks in down syndrome 英文参考文献.docVIP

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Quantitative proteomic analysis of amniocytes reveals potentially dysregulated molecular networks in down syndrome 英文参考文献.doc

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Quantitative proteomic analysis of amniocytes reveals potentially dysregulated molecular networks in down syndrome 英文参考文献

Choetal.ClinicalProteomics2013,10:2 /content/10/1/2 CLINICAL PROTEOMICS RESEARCH OpenAccess Quantitativeproteomicanalysisofamniocytes revealspotentiallydysregulatedmolecular networksinDownsyndrome Chan-KyungJCho1,AndreiPDrabovich2,GeorgeSKaragiannis1,2,EduardoMartínez-Morillo2,ShawnDason1, ApostolosDimitromanolakis2andEleftheriosPDiamandis1,2,3,4* Abstract Background:Downsyndrome(DS),causedbyanextracopyofchromosome21,affects1in750livebirthsandis characterizedbycognitiveimpairmentandaconstellationofcongenitaldefects.Currently,littleisknownaboutthe molecularpathogenesisandnodirectgenotype-phenotyperelationshiphasyetbeenconfirmed.SinceDS amniocytesareexpectedtohaveadistinctbiologicalbehaviourcomparedtonormalamniocytes,wehypothesize thatrelativequantificationofproteinsproducedfromtrisomyandeuploid(chromosomallynormal)amniocyteswill revealdysregulatedmolecularpathways. Results:Chromosomallynormal-andTrisomy21-amniocyteswerequantitativelyanalyzedbyusingStableIsotope LabelingofAminoacidsinCellcultureandtandemmassspectrometry.Atotalof4919uniqueproteinswere identifiedfromthesupernatantandcelllysateproteome.Morespecifically,4548uniqueproteinswereidentified fromthelysate,and91%oftheseproteinswerequantifiedbasedonMS/MSspectraratiosofpeptidescontaining isotope-labeledaminoacids.Atotalof904proteinsshowedsignificantdifferentialexpressionandwereinvolvedin 25molecularpathways,eachcontainingaminimumof16proteins.Sixtyoftheseproteinsconsistentlyshowed aberrantexpressionfromtrisomy21affectedamniocytes,indicatingtheirpotentialroleinDSpathogenesis.Nine proteinswereanalyzedwithamultiplexselectedreactionmonitoringassayinanindependentsetofTrisomy 21-amniocytesamplesandtwoofthem(SOD1andNES)showedaconsistentdifferentialexpression. Conclusions:Themostextensiveproteomeofamniocytesandamnioticfluidhasbeengeneratedanddifferentially expressedproteinsfromamniocyteswithTrisomy21revealedmolecularpathwaysthatseemtobemost significantlyaffectedbythepresenceofanextracopyofchromosome21. Keywords:Downsyndr