Suramin inhibits PDGF‐stimulated receptor phosphorylation, proteoglycan synthesis and glycosaminoglycan hyperelongation in human vascular smooth muscle cells. (24th April 2013)

• Record Type: Journal Article
• Authors: Little, Peter J.; Rostam, Muhamad Ashraf; Piva, Terrence J.; Getachew, Robel; Kamato, Danielle; Guidone, Daniel; Ballinger, Mandy L.; Zheng, Wenhua; Osman, Narin
• Is Part Of: Journal of pharmacy and pharmacology. Volume 65:Number 7(2013:Jul.)
• Page Start: 1055
• Page End: 1063
• Publication Date: 2013-04-24
• Subjects: Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/jphp.12064
• Languages: English
• ISSNs: 0022-3573

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="jphp12064-sec-0001" sec-type="section"> <title>Objectives</title> <p>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.</p> </sec> <sec id="jphp12064-sec-0002" sec-type="section"> <title>Methods</title> <p>Human vascular smooth muscle cells (VSMCs) were incubated in the presence and absence of PDGF and suramin with [<sup>3</sup>H]thymidine or <sup>35</sup>SO<sub>4</sub> as radiolabels. Mitogenic response was determined by [<sup>3</sup>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.</p> </sec> <sec id="jphp12064-sec-0003" sec-type="section"> <title>Key findings</title> <p>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.</p> </sec> <sec id="jphp12064-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>