Quantitative proteomic analysis of amniocytes reveals potentially dysregulated molecular networks in Down syndrome.
Quantitative proteomic analysis of amniocytes reveals potentially dysregulated molecular networks in Down syndrome.
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DOI：
10.1186/1559-0275-10-2
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发表时间：
2013-02-08
影响因子：
3.8
通讯作者：
Diamandis EP
中科院分区：
文献类型：
--
作者：
Cho CK;Drabovich AP;Karagiannis GS;Martínez-Morillo E;Dason S;Dimitromanolakis A;Diamandis EP
唐氏综合症（DS）是由21号染色体的额外拷贝引起的，每750例活产婴儿中就有1例患病，其特征是认知障碍和一系列先天性缺陷。目前对其分子发病机制知之甚少，基因型与表型之间的直接关系尚未得到证实。由于DS羊膜细胞与正常羊膜细胞相比具有不同的生物学行为，我们假设三体和整倍体（染色体正常）羊膜细胞产生的蛋白质的相对定量将揭示失调的分子途径。采用细胞培养氨基酸稳定同位素标记和串联质谱法对染色体正常和21-三体羊膜细胞进行定量分析。从上清和细胞裂解液蛋白质组中共鉴定出4919个独特的蛋白质。更具体地说，从裂解物中鉴定出4548种独特的蛋白质，其中91%的蛋白质是基于含有同位素标记氨基酸的肽的MS/MS谱比进行定量的。共有904个蛋白表现出显著的差异表达，涉及25个分子途径，每个分子途径至少包含16个蛋白。这些蛋白中的60个在21三体受影响的羊膜细胞中一致表现出异常表达，表明它们在DS发病机制中的潜在作用。在独立的21-三体羊膜细胞样本中，用多重选择反应监测法分析了9种蛋白，其中两种（SOD1和NES）表现出一致的差异表达。羊膜细胞和羊水中最广泛的蛋白质组已经产生，来自21三体羊膜细胞的差异表达蛋白揭示了分子途径，这些途径似乎最显著地受到21号染色体额外拷贝的影响。
Down syndrome (DS), caused by an extra copy of chromosome 21, affects 1 in 750 live births and is characterized by cognitive impairment and a constellation of congenital defects. Currently, little is known about the molecular pathogenesis and no direct genotype-phenotype relationship has yet been confirmed. Since DS amniocytes are expected to have a distinct biological behaviour compared to normal amniocytes, we hypothesize that relative quantification of proteins produced from trisomy and euploid (chromosomally normal) amniocytes will reveal dysregulated molecular pathways. Chromosomally normal- and Trisomy 21-amniocytes were quantitatively analyzed by using Stable Isotope Labeling of Amino acids in Cell culture and tandem mass spectrometry. A total of 4919 unique proteins were identified from the supernatant and cell lysate proteome. More specifically, 4548 unique proteins were identified from the lysate, and 91% of these proteins were quantified based on MS/MS spectra ratios of peptides containing isotope-labeled amino acids. A total of 904 proteins showed significant differential expression and were involved in 25 molecular pathways, each containing a minimum of 16 proteins. Sixty of these proteins consistently showed aberrant expression from trisomy 21 affected amniocytes, indicating their potential role in DS pathogenesis. Nine proteins were analyzed with a multiplex selected reaction monitoring assay in an independent set of Trisomy 21-amniocyte samples and two of them (SOD1 and NES) showed a consistent differential expression. The most extensive proteome of amniocytes and amniotic fluid has been generated and differentially expressed proteins from amniocytes with Trisomy 21 revealed molecular pathways that seem to be most significantly affected by the presence of an extra copy of chromosome 21.
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影响因子：
64.8
作者：
Arron, Joseph R.;Winslow, Monte M.;Crabtree, Gerald R.
通讯作者：
Crabtree, Gerald R.
DOI：
10.1111/j.1471-0528.2004.00340.x
发表时间：
2005-02-01
影响因子：
5.8
作者：
Buhimschi, IA;Christner, R;Buhimschi, CS
通讯作者：
Buhimschi, CS
影响因子：
4.4
作者：
Drabovich, Andrei P.;Diamandis, Eleftherios P.
通讯作者：
Diamandis, Eleftherios P.
影响因子：
4.4
作者：
Lockstone, H. E.;Harris, L. W.;Bahn, S.
通讯作者：
Bahn, S.
影响因子：
7
作者：
Cho, Chan-Kyung J.;Shan, Shannon J.;Diamandis, Eleftherios P.
通讯作者：
Diamandis, Eleftherios P.