Document Detail

RhoE participates in the stimulation of the inflammatory response induced by ethanol in astrocytes.
MedLine Citation:
PMID:  17707794     Owner:  NLM     Status:  MEDLINE    
Astroglial cells are involved in the neuropathogenesis of several inflammatory diseases of the brain, where the activation of inflammatory mediators and cytokines plays an important role. We have previously demonstrated that ethanol up-regulates inflammatory mediators in both brain and astroglial cells. Since Rho GTPases are involved in inflammatory responses of astrocytes where loss of stress fibers takes place and RhoE/Rnd3 disorganizes the actin cytoskeleton, the aim of the present study was to investigate the implication of this protein in the stimulation of inflammatory signaling induced by ethanol. Our findings show that RhoE expression induces a decrease in both RhoA and Rac. In addition, RhoE not only induces actin cytoskeleton disorganization but it also stimulates both the IRAK/ERK/NF-kappaB pathway and the COX-2 expression associated with the inflammatory response in these cells. Our results also show that ethanol exposure induces RhoE signaling in astrocytes. Preincubation of astrocytes with GF109203X, an inhibitor of PKCs, reduces the RhoE levels and abolishes the ethanol-induced activation of IRAK, NF-kappaB and the COX-2 expression. Furthermore, RhoE overexpression restores ethanol responses in astrocytes treated with the PKCs inhibitor. Altogether, our findings suggest that this small GTPase is involved in the stimulation of the inflammatory signaling induced by ethanol in astrocytes. These findings provide new insights into the molecular mechanism involved in the inflammatory responses in astrocytes.
Rosa M Guasch; Ana M Blanco; Amparo Pérez-Aragó; Rebeca Miñambres; Raquel Talens-Visconti; Blanca Peris; Consuelo Guerri
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-07-25
Journal Detail:
Title:  Experimental cell research     Volume:  313     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-01     Completed Date:  2007-12-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3779-88     Citation Subset:  IM    
Department of Cellular Pathology, Centro de Investigación Príncipe Felipe, Valencia, Spain.
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MeSH Terms
Actins / metabolism
Astrocytes / drug effects*,  enzymology,  ultrastructure
Cytoskeletal Proteins / metabolism
Cytoskeleton / metabolism
Encephalitis / chemically induced*,  enzymology*,  pathology
Ethanol / toxicity*
Indoles / pharmacology
Maleimides / pharmacology
Protein Kinase C / antagonists & inhibitors
rac GTP-Binding Proteins / deficiency
rho GTP-Binding Proteins / genetics,  physiology*
rho-Associated Kinases / deficiency
rhoA GTP-Binding Protein / deficiency
Reg. No./Substance:
0/Actins; 0/Cytoskeletal Proteins; 0/Indoles; 0/Maleimides; 133052-90-1/bisindolylmaleimide I; 64-17-5/Ethanol; EC Kinases; EC Kinase C; EC GTP-Binding Proteins; EC GTP-Binding Proteins; EC GTP-Binding Protein

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