UM
Suramin inhibits PDGF-stimulated receptor phosphorylation, proteoglycan synthesis and glycosaminoglycan hyperelongation in human vascular smooth muscle cells
Little P.J.1; Rostam M.A.1; Piva T.J.2; Getachew R.1; Kamato D.1; Guidone D.1; Ballinger M.L.4; Zheng W.3; Osman N.1
2013-07-01
Source PublicationJournal of Pharmacy and Pharmacology
ISSN00223573 20427158
Volume65Issue:7Pages:1055-1063
AbstractObjectives: Suramin is a polysulfonated naphthylurea with antiparasitic and potential antineoplastic activity. Suramin's pharmacological actions, which have not yet been fully elucidated, include antagonism of the action of platelet-derived growth factor (PDGF) at its receptor. We investigated the effects of suramin on PDGF-stimulated proteoglycan synthesis. Methods: Human vascular smooth muscle cells (VSMCs) were incubated in the presence and absence of PDGF and suramin with [H]thymidine or SO as radiolabels. Mitogenic response was determined by [H]thymidine incorporation. PDGFβ receptor phosphorylation was assessed by western blotting. Proteoglycan size and glycosaminoglycan chain synthesis and size were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The Alphascreen phosphotyrosine assay kit was used to investigate PDGFβ receptor tyrosine kinase inhibition by suramin. Key findings: Suramin decreased PDGF-stimulated proliferation, proteoglycan synthesis and GAG chain hyperelongation. Suramin also directly inhibited PDGFβ receptor kinase activity as well as PDGFβ receptor phosphorylation in intact VSMCs. Conclusions: These data show that inhibition of PDGFβ receptor phosphorylation in intact cells is necessary to define a fully active PDGF antagonist. They also confirm that PDGFβ receptor kinase activity is necessary for PDGF-mediated atherogenic changes in proteoglycan synthesis and support efforts to develop PDGFβ receptor antagonists as potential anti-atherosclerotic agents. © 2013 Royal Pharmaceutical Society.
Keywordatherosclerosis biglycan imatinib PDGFβ receptor kinase activity PDGFβ receptor phosphorylation
DOI10.1111/jphp.12064
URLView the original
Language英語
Fulltext Access
Citation statistics
Cited Times [WOS]:13   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.School of Medical Sciences
2.Monash University
3.Sun Yat-Sen University
4.RMIT University
Recommended Citation
GB/T 7714
Little P.J.,Rostam M.A.,Piva T.J.,et al. Suramin inhibits PDGF-stimulated receptor phosphorylation, proteoglycan synthesis and glycosaminoglycan hyperelongation in human vascular smooth muscle cells[J]. Journal of Pharmacy and Pharmacology,2013,65(7):1055-1063.
APA Little P.J..,Rostam M.A..,Piva T.J..,Getachew R..,Kamato D..,...&Osman N..(2013).Suramin inhibits PDGF-stimulated receptor phosphorylation, proteoglycan synthesis and glycosaminoglycan hyperelongation in human vascular smooth muscle cells.Journal of Pharmacy and Pharmacology,65(7),1055-1063.
MLA Little P.J.,et al."Suramin inhibits PDGF-stimulated receptor phosphorylation, proteoglycan synthesis and glycosaminoglycan hyperelongation in human vascular smooth muscle cells".Journal of Pharmacy and Pharmacology 65.7(2013):1055-1063.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Little P.J.]'s Articles
[Rostam M.A.]'s Articles
[Piva T.J.]'s Articles
Baidu academic
Similar articles in Baidu academic
[Little P.J.]'s Articles
[Rostam M.A.]'s Articles
[Piva T.J.]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Little P.J.]'s Articles
[Rostam M.A.]'s Articles
[Piva T.J.]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.