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

Xu, Cang-Bao LU ; Zhang, Yaping LU ; Stenman, Emelie LU and Edvinsson, Lars LU (2002) In Atherosclerosis 164(2). p.237-243
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Atherosclerosis
volume
164
issue
2
pages
237 - 243
publisher
Elsevier
external identifiers
  • wos:000178068100004
  • pmid:12204793
  • scopus:0036802383
ISSN
1879-1484
DOI
10.1016/S0021-9150(02)00100-4
language
English
LU publication?
yes
id
fabc4113-011d-4ce1-aeda-31b9ffedbbb9 (old id 110410)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12204793&dopt=Abstract
date added to LUP
2007-07-02 09:45:59
date last changed
2017-02-12 03:30:07
@article{fabc4113-011d-4ce1-aeda-31b9ffedbbb9,
  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.},
  author       = {Xu, Cang-Bao and Zhang, Yaping and Stenman, Emelie and Edvinsson, Lars},
  issn         = {1879-1484},
  language     = {eng},
  number       = {2},
  pages        = {237--243},
  publisher    = {Elsevier},
  series       = {Atherosclerosis},
  title        = {D-erythro-N,N-dimethylsphingosine inhibits bFGF-induced proliferation of cerebral, aortic and coronary smooth muscle cells.},
  url          = {http://dx.doi.org/10.1016/S0021-9150(02)00100-4},
  volume       = {164},
  year         = {2002},
}