Protection from Clostridium difficile toxin B-catalysed Rac1/Cdc42 glucosylation by tauroursodeoxycholic acid-induced Rac1/Cdc42 phosphorylation

被引：21

作者：

Brandes, Vanessa ^{[1
]}

Schelle, Ilona ^{[1
]}

Brinkmann, Sophie ^{[1
]}

Schulz, Florian ^{[1
]}

Schwarz, Janett ^{[1
]}

Gerhard, Ralf ^{[1
]}

Genth, Harald ^{[1
]}

机构：

[1] Hannover Med Sch, Inst Toxikol, D-30625 Hannover, Germany

来源：

BIOLOGICAL CHEMISTRY | 2012年 / 393卷 / 1-2期

关键词：

actin cytoskeleton; Akt kinase; bile acid; cytopathic effect; SORDELLII LETHAL TOXIN; RHO-PROTEINS; AKT ACTIVATION; BINDING; INHIBITORS; KINASE; CONSEQUENCES; MECHANISM; CLEAVAGE; RAC1;

D O I：

10.1515/BC-2011-198

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：

Toxin A (TcdA) and toxin B (TcdB) are the major virulence factors of Clostridium difficile-associated diarrhoea (CDAD). TcdA and TedB mono-glucosylate small GTPases of the Rho family, thereby causing actin re-organisation in colonocytes, resulting in the loss of colonic barrier function. The hydrophilic bile acid tauroursodeoxycholic acid (TUDCA) is an approved drug for the treatment of cholestasis and biliary cirrhosis. In this study, TUDCA-induced activation of Akt1 is presented to increase cellular levels of pS71-Rac1/Cdc42 in human hepatocarcinoma (HepG2) cells, showing for the first time that bile acid signalling affects the activity of Rho proteins. Rac1/Cdc42 phosphorylation, in turn, protects Rac1/Cdc42 from TcdB-catalysed glucosylation and reduces the TcdB-induced cytopathic effects in HepG2 cells. The results of this study indicate that TUDCA may prove useful as a therapeutic agent for the treatment of CDAD.

引用

页码：77 / 84

页数：8

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