Ochratoxin A displaces claudins from detergent resistant membrane microdomains

被引：38

作者：

Lambert, Daniel ^{[1
]}

Padfield, Philip J. ^{[1
]}

McLaughlin, John ^{[1
]}

Cannell, Stephanie ^{[1
]}

O'Neill, Catherine A. ^{[1
]}

机构：

[1] Univ Manchester, Sch Med, Sect Gastrointestinal Sect, Manchester, Lancs, England

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2007年 / 358卷 / 02期

基金：

英国生物技术与生命科学研究理事会;

关键词：

tight junction; claudin; detergent resistant membrane microdomain; ochratoxin A; Caco-2;

D O I：

10.1016/j.bbrc.2007.04.180

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Ochratoxin A (OchA) is a food-borne mycotoxin with multiple effects in vivo. Previously, we have demonstrated that the toxin can significantly impair the barrier function of the gut epithelial cell line, Caco-2. Barrier disruption involved loss of claudins 3 and 4, but not claudin 1 from the tight junction complex. In this study, we demonstrate for the first time, that OchA is able to remove claudins 3 and 4 from the detergent insoluble membrane microdomains associated with the tight junctions. However, cholesterol distribution within the microdomain was unaffected by the toxin. In addition, the thiol antioxidant, N-acetyl cysteine, preserved the microdomain localisation of claudins and also the barrier function of Caco-2 cells. This work suggests that OchA-mediated barrier toxicity is due to removal of claudins from detergent insoluble membrane microdomains. Moreover, loss of microdomain association may be due to oxidative events. (C) 2007 Elsevier Inc. All rights reserved.

引用

页码：632 / 636

页数：5

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