D-erythro-N,N-dimethylsphingosine inhibits bFGF-induced proliferation of cerebral, aortic and coronary smooth muscle cells

Cang-Bao Xu, Yaping Zhang, Emelie Stenman, Lars Edvinsson

21 Citationer (Scopus)

Abstract

The role of sphingosine kinase (SphK) on basic fibroblast growth factor (bFGF)-induced proliferation of cerebral, aortic and coronary smooth muscle cells (SMC) was addressed using D-erythro-N,N-dimethylsphingosine (DMS), an inhibitor of SphK which blocks conversion of sphingosine to sphingosine-1-phosphate (S1P). DMS concentration-dependently reduced the bFGF-induced proliferation of rat cerebral and aortic, and human coronary SMC. This suggests that SphK is one of the key enzymes in the mitogenic response to bFGF in vascular SMC as supported by the finding that S1P stimulated proliferation of SMC. Fumonisin B1, a dihydroceramidesynthase inhibitor which blocks the conversion of dihydrosphingosine to seramide, did not affect SMC proliferation induced by bFGF. Staurosporine, an inhibitor of protein kinase C (PKC), inhibited proliferation of SMC induced by bFGF, and both bFGF- and S1P-induced proliferation of SMC was sensitive to pertussis toxin (PTX), an inhibitor of Gi-protein activity. The present study thus demonstrates that SphK, PKC and Gi-protein activities are required for bFGF-mitogenic signaling in SMC. The bFGF mitogenic effect in vascular SMC might at least in part act via the SphK pathway and a Gi-protein.

OriginalsprogEngelsk
TidsskriftAtherosclerosis
Vol/bind164
Udgave nummer2
Sider (fra-til)237-43
Antal sider7
ISSN0021-9150
StatusUdgivet - okt. 2002
Udgivet eksterntJa

Fingeraftryk

Dyk ned i forskningsemnerne om 'D-erythro-N,N-dimethylsphingosine inhibits bFGF-induced proliferation of cerebral, aortic and coronary smooth muscle cells'. Sammen danner de et unikt fingeraftryk.

Citationsformater