Lovastatin blocks basic fibroblast growth factor-induced mitogen-activated protein kinase signaling in coronary smooth muscle cells via phosphatase inhibition.
Eur J Cell Biol
; 80(3): 207-12, 2001 Mar.
Article
em En
| MEDLINE
| ID: mdl-11322384
ABSTRACT
We have recently reported that the activation of mitogen-activated protein kinase (MAPK) through specific protein kinase C (PKC) isoforms is required for basic fibroblast growth factor (bFGF)-induced proliferation of coronary smooth muscle cells (cSMC). In this study, we investigated the effects of the 3hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitor lovastatin on bFGF-induced signal transduction in cSMC. The present study shows that lovastatin inhibits bFGF-stimulated DNA synthesis in cSMC, and that this inhibition is reversed by mevalonate (50 micromol/l) and by geranylgeranyl-pyrophosphate (1-5 micromol/l). Although lovastatin prevented Ras farnesylation the amount of bFGF-stimulated MAPK phosphorylation decreased only partially after lovastatin treatment. In addition, lovastatin pretreatment resulted in a sustained phosphorylation of MAPK. We observed a dose-dependent lovastatin-dependent increase in PKC activity, which could be prevented by mevalonate. This increase was comparable to the one induced by calyculin A (2 nmol/l), an inhibitor of protein phosphatase PP-1 and PP-2A. Lovastatin inhibited the expression of the PP-1 protein, which is involved in bFGF-induced DNA synthesis in cSMC. Thus, our data suggest that, lovastatin possibly affects the dephosphorylation processes of PKC and MAPK by inhibition of PP-1/PP-2A protein phosphatases which are involved in the bFGF-induced mitogenesis in cSMC.
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Base de dados:
MEDLINE
Assunto principal:
Lovastatina
/
Fator 2 de Crescimento de Fibroblastos
/
Monoéster Fosfórico Hidrolases
/
Inibidores de Hidroximetilglutaril-CoA Redutases
/
Sistema de Sinalização das MAP Quinases
/
Músculo Liso
/
Miocárdio
Limite:
Animals
Idioma:
En
Revista:
Eur J Cell Biol
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Alemanha