Document Detail


HMG-CoA reductase inhibitor lovastatin causes reversible cytoskeleton perturbation by RhoA signalling suppression in peritoneal cell line Met5A.
MedLine Citation:
PMID:  20455727     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Increasing evidence indicates that statins increase peritoneal fibrinolysis through RhoA-linked pathway and may play a role in the prevention of postoperative adhesion. This study investigated whether lovastatin perturbs cytoskeletons and cell morphology by RhoA suppression in peritoneal Met5A cells. Subcellular distributions of RhoA protein and actin were assessed by immunocytochemical staining. Exposure to lovastatin caused actin filament reorganisation, decrease in the active (membrane-bound) form of RhoA and subsequently cellular shrinkage in Met5A cells. These lovastatin-induced changes were significantly overcome by the addition of geranylgeranyl pyrophosphate (downstream intermediate of HMG-CoA pathway). A RhoA protein inhibitor C3 transferase mimicked the effects of lovastatin on the Met5A cells. The effects of lovastatin on cytoskeleton alterations were correlated well with inhibition of the membrane localisation of RhoA. These results suggest that lovastatin induced reversible cytoskeleton reorganisation and cellular retraction through the reduction of RhoA geranylgeranylation, which in turn suppressed RhoA signalling-associated cellular events.
Authors:
N Suzuki; A Imai
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology     Volume:  30     ISSN:  1364-6893     ISO Abbreviation:  J Obstet Gynaecol     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-11     Completed Date:  2010-08-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8309140     Medline TA:  J Obstet Gynaecol     Country:  England    
Other Details:
Languages:  eng     Pagination:  404-7     Citation Subset:  IM    
Affiliation:
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Gifu, Japan.
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MeSH Terms
Descriptor/Qualifier:
Cell Line
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
Lovastatin / pharmacology*
Microfilaments / drug effects*
Peritoneal Diseases / metabolism*
Plasminogen Inactivators / metabolism
Signal Transduction / drug effects
Tissue Adhesions / metabolism
rhoA GTP-Binding Protein / metabolism*
Chemical
Reg. No./Substance:
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Plasminogen Inactivators; 75330-75-5/Lovastatin; EC 3.6.5.2/rhoA GTP-Binding Protein

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