Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1997-12-8
pubmed:abstractText
The Rho GTPases are involved in actin cytoskeleton organization and signal transduction. They need polyisoprenylation for membrane association and activation. Lovastatin, a hydroxymethylglutaryl coenzyme A inhibitor, prevents isoprene synthesis and thereby lipid modification of the Rho protein carboxy terminus. Because lovastatin causes rounding up of cultured cells, we investigated whether the compound acts on the actin cytoskeleton through Rho proteins. Lovastatin treatment decreased F-actin content in a time- and concentration-dependent manner. G-actin content remained unchanged. In lovastatin-treated NIH 3T3 cells, the amount of Rho protein which was ADP-ribosylated by Clostridium botulinum exoenzyme C3 decreased in membranes and increased in the cytosol fraction. Cycloheximide prevented lovastatin-induced rounding up of cells. However, after microinjection or direct application of exoenzyme C3, cells treated with cycloheximide and lovastatin rounded up again. On the contrary, lovastatin-treated, round Swiss 3T3 cells reverted to a flat morphology when microinjected with dominant active RhoA (Val14RhoA). Escherichia coli cytotoxic necrotizing factor (CNF1) which activates Rho proteins caused flattening of round, lovastatin-treated NIH 3T3 cells. These results suggest that lovastatin affects the actin cytoskeleton through inactivation of Rho proteins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
901-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Role of Rho protein in lovastatin-induced breakdown of actin cytoskeleton.
pubmed:affiliation
Institut für Pharmakologie und Toxikologie, Universität Freiburg, D-79104 Freiburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't