Lovastatin blocks basic fibroblast growth factor-induced mitogen-activated protein kinase signaling in coronary smooth muscle cells via phosphatase inhibition

European Journal of Cell Biology
A Skaletz-RorowskiG Breithardt

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 ...Continue Reading

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Citations

Oct 21, 2006·International Immunopharmacology·Antonio G Tristano, Kathy Fuller
Aug 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Martha M MonickGary W Hunninghake
Feb 15, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Ying WangYun Zhang
Sep 6, 2006·The Biochemical Journal·Maria Isabel Cerezo-GuisadoMaria Jesús Lorenzo
Nov 7, 2002·International Journal of Cardiology·Filomena de NigrisClaudio Napoli

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