Document Detail


Protection from C. difficile Toxin B-catalysed Rac/Cdc42 glucosylation by tauroursodeoxycholic acid-induced Rac/Cdc42 phosphorylation.
MedLine Citation:
PMID:  22059737     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Abstract Toxin A (TcdA) and Toxin B (TcdB) are the major virulence factors of Clostridium difficile-associated diarrhea (CDAD). TcdA and TcdB mono-glucoslyate 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, TUDCAinduced activation of Akt 1 is presented to increase cellular levels of pS71-Rac1/Cdc42 in human hepatocarcinoma (Hep-G2) 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 Hep-G2 cells. The results of this study indicate that TUDCA may prove useful as a therapeutic agent for the treatment of CDAD.
Authors:
Vanessa Brandes; Ilona Schelle; Sophie Brinkmann; Florian Schulz; Janett Schwarz; Ralf Gerhard; Harald Genth
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-7
Journal Detail:
Title:  Biological chemistry     Volume:  -     ISSN:  1437-4315     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9700112     Medline TA:  Biol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Institut für Toxikologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
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