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肠道上皮中的筏及相关富含糖鞘脂的微结构域:与营养吸收相关的细菌靶点

Rafts and related glycosphingolipid-enriched microdomains in the intestinal epithelium: bacterial targets linked to nutrient absorption.

作者信息

Taïeb Nadira, Yahi Nouara, Fantini Jacques

机构信息

Laboratoire de Biochimie et Physicochimie des Membranes Biologiques, Institut Méditerranéen de Recherche en Nutrition, INRA-UMR 1111, Faculté des Sciences de Saint-Jérôme, 13397 Marseille Cedex 20, France.

出版信息

Adv Drug Deliv Rev. 2004 Apr 19;56(6):779-94. doi: 10.1016/j.addr.2003.09.007.

Abstract

Plasma membrane microdomains such as lipid rafts or caveolae play a major role in host-pathogen interactions. Although this field of research has been extensively studied, two important points have been poorly addressed: (i) the molecular basis of raft-pathogen interactions, and (ii) the effect of such interactions on nutrient absorption. The aim of this review was to propose a biochemical analysis of bacterial adhesion to lipid raft components exposed on the mucosal surface of the intestinal epithelium. A special attention has been given to CH-pi interactions that allow the sugar rings of glycosphingolipids (GSL) to stack against aromatic side chains of bacterial adhesins and toxins. These interactions are controlled by cholesterol molecules intercalated between membrane GSL and/or by the presence of an alpha-OH group in the acyl chain of the ceramide backbone of GSL. In the second part of the review, we analysed the experimental data suggesting the involvement of lipid rafts in the intestinal absorption of nutrients, the mechanisms by which bacteria could impair intestinal functions, and possible therapeutic strategies based on the biochemistry of raft-pathogen interactions.

摘要

质膜微区,如脂筏或小窝,在宿主-病原体相互作用中起主要作用。尽管该研究领域已得到广泛研究,但有两个重要问题尚未得到充分解决:(i)脂筏-病原体相互作用的分子基础,以及(ii)这种相互作用对营养吸收的影响。本综述的目的是对细菌粘附于肠上皮粘膜表面暴露的脂筏成分进行生化分析。特别关注了CH-π相互作用,这种相互作用使糖鞘脂(GSL)的糖环与细菌粘附素和毒素的芳香侧链堆叠在一起。这些相互作用受插入膜GSL之间的胆固醇分子控制,和/或受GSL神经酰胺主链酰基链中α-OH基团的存在控制。在综述的第二部分,我们分析了实验数据,这些数据表明脂筏参与了肠道营养吸收、细菌可能损害肠道功能的机制,以及基于脂筏-病原体相互作用生物化学的可能治疗策略。

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