HMG-CoA reductase inhibitor lovastatin causes reversible cytoskeleton perturbation by RhoA signalling suppression in peritoneal cell line Met5A.
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.
Suzuki
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N
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Gifu, Japan.
Imai
A
A
D008841:Actin Cytoskeleton / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology*; D010532:Peritoneal Diseases / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000267:Tissue Adhesions / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015849:Plasminogen Inactivators; D008148:Lovastatin; D020742:rhoA GTP-Binding Protein