Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin, Atrium-B Meriter Hospital, 202 South Park Street Madison, WI 53715, USA.
Alcohol. 2010 Nov-Dec;44(7-8):691-7. doi: 10.1016/j.alcohol.2009.10.010. Epub 2010 Jan 6.
Currently, no single marker is sensitive and specific enough to be considered a reliable biomarker for prenatal alcohol exposure. To identify a proteomic signature profile for maternal alcohol consumption, we carried out high-throughput proteomics on maternal endothelial caveolae exposed to moderate binge-like alcohol conditions. In these specialized lipid-ordered microdomains that contain a rich assembly of proteins, we demonstrate that moderate binge-like alcohol resulted in a distinctive maternal caveolar proteomic signature with important proteins being dramatically decreased/knocked out in the alcoholic profile. These proteins span from histones and basic structural proteins like α tubulin to proteins involved in trafficking, deubiquitination, cell signaling, and cell-cell adhesion. The profile also suggests an important role for the mother and the uteroplacental compartment in the pathogenesis of fetal alcohol spectrum disorders (FASD). These data demonstrate that the caveolar proteomic signature created by alcohol shows a promising direction for early detection of FASD.
目前,还没有一种单一的标志物足够敏感和特异,可以被认为是产前酒精暴露的可靠生物标志物。为了确定母体酒精摄入的蛋白质组特征谱,我们对暴露于适度 binge-like 酒精条件下的母体血管内皮小窝进行了高通量蛋白质组学研究。在这些富含蛋白质的富含脂质的有序微域中,我们证明适度 binge-like 酒精会导致母体小窝蛋白质组特征谱的独特变化,酒精谱中的重要蛋白质显著减少/敲除。这些蛋白质涵盖了从组蛋白和α微管蛋白等基本结构蛋白到参与运输、去泛素化、细胞信号转导和细胞-细胞黏附的蛋白。该特征谱还表明母亲和胎盘腔在胎儿酒精谱系障碍(FASD)发病机制中起着重要作用。这些数据表明,酒精引起的小窝蛋白质组特征谱为早期检测 FASD 提供了一个有前途的方向。