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乳蛋白组的时空调控揭示了乳汁功能的发育变化。

Temporal changes in milk proteomes reveal developing milk functions.

机构信息

Mead Johnson Nutrition Pediatric Nutrition Institute, 2400 West Lloyd Expressway, Evansville, Indiana 47721, USA.

出版信息

J Proteome Res. 2012 Jul 6;11(7):3897-907. doi: 10.1021/pr3004002. Epub 2012 Jun 21.

DOI:10.1021/pr3004002
PMID:22676802
Abstract

Human milk proteins provide essential nutrition for growth and development, and support a number of vital developmental processes in the neonate. A complete understanding of the possible functions of human milk proteins has been limited by incomplete knowledge of the human milk proteome. In this report, we have analyzed the proteomes of whey from human transitional and mature milk using ion-exchange and SDS-PAGE based protein fractionation methods. With a larger-than-normal sample loading approach, we are able to largely extend human milk proteome to 976 proteins. Among them, 152 proteins are found to render significant regulatory changes between transitional milk and mature milk. We further found that immunoglobulins sIgA and IgM are more abundant in transitional milk, whereas IgG is more abundant in mature milk, suggesting a transformation in defense mechanism from newborns to young infants. Additionally, we report a more comprehensive view of a complement system and associated regulatory apparatus in human milk, demonstrating the presence and function of a system similar to that found in the circulation but prevailed by alternative pathway in complement activation. Proteins involved in various aspects of carbohydrate metabolism are also described, revealing either a transition in milk functionality to accommodate carbohydrate-rich secretions as lactation progresses, or a potentially novel way of looking at the metabolic state of the mammary tissue. Lately, a number of extracellular matrix (ECM) proteins are found to be in higher abundance in transitional milk and may be relevant to the development of infants' gastrointestinal tract in early life. In contrast, the ECM protein fibronectin and several of the actin cytoskeleton proteins that it regulates are more abundant in mature milk, which may indicate the important functional role for milk in regulating reactive oxygen species.

摘要

人乳蛋白质为生长和发育提供必需营养,并支持新生儿的许多重要发育过程。由于对人乳蛋白质组的不完全了解,对人乳蛋白质可能功能的全面理解受到限制。在本报告中,我们使用基于离子交换和 SDS-PAGE 的蛋白质分级分离方法分析了乳清中的乳蛋白质组。通过采用大于正常样品加载的方法,我们能够将人乳蛋白质组在很大程度上扩展到 976 种蛋白质。其中,152 种蛋白质在过渡乳和成熟乳之间呈现出显著的调节变化。我们进一步发现,免疫球蛋白 sIgA 和 IgM 在过渡乳中更为丰富,而 IgG 在成熟乳中更为丰富,这表明新生儿到幼儿的防御机制发生了转变。此外,我们报告了人乳中补体系统及其相关调节装置的更全面观点,证明了存在类似于循环中发现的系统,但补体激活的替代途径占主导地位。还描述了参与碳水化合物代谢各个方面的蛋白质,揭示了随着泌乳的进行,乳汁功能向适应富含碳水化合物的分泌物的转变,或者是一种观察乳腺组织代谢状态的潜在新方法。最近,发现许多细胞外基质(ECM)蛋白质在过渡乳中更为丰富,可能与人在生命早期胃肠道的发育有关。相比之下,ECM 蛋白纤维连接蛋白和它调节的几种肌动蛋白细胞骨架蛋白在成熟乳中更为丰富,这可能表明乳汁在调节活性氧方面的重要功能作用。

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