Protection from Clostridium difficile toxin B-catalysed Rac1/Cdc42 glucosylation by tauroursodeoxycholic acid-induced Rac1/Cdc42 phosphorylation
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Vanessa Brandes
Abstract
Toxin A (TcdA) and toxin B (TcdB) are the major virulence factors of Clostridium difficile-associated diarrhoea (CDAD). TcdA and TcdB 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.
©2012 by Walter de Gruyter Berlin Boston
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Articles in the same Issue
- Publisher’s Note
- Publisher’s Note
- Reviews
- Transporters in cholelithiasis
- Oxidative stress in Fanconi anaemia: from cells and molecules towards prospects in clinical management
- Genes and Nucleic Acids
- Dye selection for live cell imaging of intact siRNA
- Protein Structure and Function
- Reactive cysteine in the active-site motif of Bacteroides thetaiotaomicron dipeptidyl peptidase III is a regulatory residue for enzyme activity
- Proteome analysis of protein partners to nucleosomes containing canonical H2A or the variant histones H2A.Z or H2A.X
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- Molecular Medicine
- 99mTc(CO)3-Ibritumomab tiuxetan; a novel radioimmunoimaging (RII) agent of B cell non-Hodgkin’s lymphoma (NHL)
- Protection from Clostridium difficile toxin B-catalysed Rac1/Cdc42 glucosylation by tauroursodeoxycholic acid-induced Rac1/Cdc42 phosphorylation
- Oleic acid is a key cytotoxic component of HAMLET-like complexes
- Cell Biology and Signaling
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- A novel role for reciprocal CD30-CD30L signaling in the cross-talk between natural killer and dendritic cells
- Mast cells express tyrosine hydroxylase and store dopamine in a serglycin-dependent manner
