Marked defects in the expression and glycosylation of α2-HS glycoprotein/fetuin-A in plasma from neonates with intrauterine growth restriction -: Proteomics screening and potential clinical implications
Marked defects in the expression and glycosylation of α2-HS glycoprotein/fetuin-A in plasma from neonates with intrauterine growth restriction -: Proteomics screening and potential clinical implications
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DOI：
10.1074/mcp.m700422-mcp200
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发表时间：
2008-03-01
影响因子：
7
通讯作者：
Chrousos, George
中科院分区：
文献类型：
--
作者：
Karamessinis, Panagiotis M.;Malamitsi-Puchner, Ariadne;Chrousos, George
宫内生长受限（IUGR）与围产期发病率和死亡率的增加以及生命后期发病率和代谢异常的增加有关。IUGR的特征是胎儿在子宫内未能实现其遗传生长潜力。与IUGR相关的蛋白表达谱的改变可能为这种疾病的病理机制提供信息，并可能揭示产后并发症的潜在标志物。本研究的目的是比较IUGR和适合胎龄足月新生儿脐带血浆的蛋白质谱。对10例IUGR和10例适龄足月新生儿分娩时双夹脐带血样进行双向电泳和质谱分析，发现IUGR患儿α (2)-HS糖蛋白/胎蛋白a明显变化。具体来说，我们发现这些变化主要发生在蛋白质翻译后修饰的水平上。结合质谱分析和经典生化分析，发现IUGR新生儿中单链和重链形式的胎儿蛋白a缺乏正常存在的o链唾液酸。胎儿蛋白A是一种糖蛋白，与促进体外细胞复制、胎儿生长和成骨以及保护胎儿免受革兰氏阴性细菌内毒素的侵害有关。我们的研究显示胎儿蛋白a糖基化/唾液化的显著缺陷可能是导致胎儿蛋白a功能受损的原因，导致胎儿生长缺陷，特别是成骨，和/或IUGR新生儿生命后期常见的并发症的发展。
Intrauterine growth restriction (IUGR) has been associated with increased perinatal morbidity and mortality and increased morbidity and metabolic abnormalities later in life. IUGR is characterized as the failure of a fetus to achieve his or her genetic growth potential in utero. Altered protein expression profiles associated with IUGR may be informative on the pathologic mechanisms of this condition and might reveal potential markers for postnatal complications. The aim of this study was to compare protein profiles of umbilical cord plasma from IUGR and appropriate for gestational age full-term neonates. Blood samples from doubly clamped umbilical cord at delivery from 10 IUGR and 10 appropriate for gestational age fullterm neonates were analyzed by two-dimensional electrophoresis and MS. Prominent changes of the alpha(2)-HS glycoprotein/fetuin-A were observed in IUGR cases. Specifically we showed that these changes occur primarily at the level of post-translational modifications of the protein. Using a combination of mass spectrometry and classical biochemical assays, single and heavy chain forms of fetuin-A were found to lack the normally present O-linked sialic acids in IUGR neonates. Fetuin A is a glycoprotein that has been associated with promotion of in vitro cell replication, fetal growth and osteogenesis, and protection from Gram-negative bacterial endotoxins. Prominent defects in glycosylation/sialylation of fetuin-A revealed by our study might be responsible for impaired function of fetuin-A, leading to deficient fetal growth, especially osteogenesis, and/or to the development of complications frequently seen later in the lives of IUGR neonates.