Suramin inhibits PDGF-stimulated receptor phosphorylation, proteoglycan synthesis and glycosaminoglycan hyperelongation in human vascular smooth muscle cells
Objectives 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...
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Wiley
2013
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| Online Access: | http://irep.iium.edu.my/55280/ http://irep.iium.edu.my/55280/ http://irep.iium.edu.my/55280/ http://irep.iium.edu.my/55280/1/7.%20Little-2013-Suramin%20inhibits%20PDGF-stimulated%20r.pdf |
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iium-552802017-03-23T02:02:59Z http://irep.iium.edu.my/55280/ Suramin inhibits PDGF-stimulated receptor phosphorylation, proteoglycan synthesis and glycosaminoglycan hyperelongation in human vascular smooth muscle cells Little, Peter J. Rostam, Muhamad Ashraf Piva, Terence J. Getachew, Robel Kamato, Danielle Guidone, Daniel Ballinger, Mandy L. Zheng, Wenhua Osman, Narin QP Physiology RM Therapeutics. Pharmacology Objectives 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 [3H]thymidine or 35SO4 as radiolabels. Mitogenic response was determined by [3H]thymidine incorporation. PDGFb 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 PDGFb receptor tyrosine kinase inhibition by suramin. Key findings Suramin decreased PDGF-stimulated proliferation, proteoglycan synthesis and GAG chain hyperelongation. Suramin also directly inhibited PDGFb receptor kinase activity as well as PDGFb receptor phosphorylation in intact VSMCs. Conclusions These data show that inhibition of PDGFb receptor phosphorylation in intact cells is necessary to define a fully active PDGF antagonist. They also confirm that PDGFb receptor kinase activity is necessary for PDGF-mediated atherogenic changes in proteoglycan synthesis and support efforts to develop PDGFb receptor antagonists as potential anti-atherosclerotic agents. Wiley 2013-07 Article PeerReviewed application/pdf en http://irep.iium.edu.my/55280/1/7.%20Little-2013-Suramin%20inhibits%20PDGF-stimulated%20r.pdf Little, Peter J. and Rostam, Muhamad Ashraf and Piva, Terence J. and Getachew, Robel and Kamato, Danielle and Guidone, Daniel and Ballinger, Mandy L. and Zheng, Wenhua and Osman, Narin (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). pp. 1055-1063. E-ISSN 2042-7158 http://onlinelibrary.wiley.com/doi/10.1111/jphp.12064/abstract 10.1111/jphp.12064 |
| repository_type |
Digital Repository |
| institution_category |
Local University |
| institution |
International Islamic University Malaysia |
| building |
IIUM Repository |
| collection |
Online Access |
| language |
English |
| topic |
QP Physiology RM Therapeutics. Pharmacology |
| spellingShingle |
QP Physiology RM Therapeutics. Pharmacology Little, Peter J. Rostam, Muhamad Ashraf Piva, Terence J. Getachew, Robel Kamato, Danielle Guidone, Daniel Ballinger, Mandy L. Zheng, Wenhua Osman, Narin Suramin inhibits PDGF-stimulated receptor phosphorylation, proteoglycan synthesis and glycosaminoglycan hyperelongation in human vascular smooth muscle cells |
| description |
Objectives 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 [3H]thymidine or 35SO4 as radiolabels.
Mitogenic response was determined by [3H]thymidine incorporation.
PDGFb 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 PDGFb receptor tyrosine kinase inhibition
by suramin.
Key findings Suramin decreased PDGF-stimulated proliferation, proteoglycan
synthesis and GAG chain hyperelongation. Suramin also directly inhibited PDGFb
receptor kinase activity as well as PDGFb receptor phosphorylation in intact
VSMCs.
Conclusions These data show that inhibition of PDGFb receptor phosphorylation
in intact cells is necessary to define a fully active PDGF antagonist. They also
confirm that PDGFb receptor kinase activity is necessary for PDGF-mediated
atherogenic changes in proteoglycan synthesis and support efforts to develop
PDGFb receptor antagonists as potential anti-atherosclerotic agents. |
| format |
Article |
| author |
Little, Peter J. Rostam, Muhamad Ashraf Piva, Terence J. Getachew, Robel Kamato, Danielle Guidone, Daniel Ballinger, Mandy L. Zheng, Wenhua Osman, Narin |
| author_facet |
Little, Peter J. Rostam, Muhamad Ashraf Piva, Terence J. Getachew, Robel Kamato, Danielle Guidone, Daniel Ballinger, Mandy L. Zheng, Wenhua Osman, Narin |
| author_sort |
Little, Peter J. |
| title |
Suramin inhibits PDGF-stimulated receptor phosphorylation, proteoglycan synthesis and
glycosaminoglycan hyperelongation in human vascular smooth muscle cells |
| title_short |
Suramin inhibits PDGF-stimulated receptor phosphorylation, proteoglycan synthesis and
glycosaminoglycan hyperelongation in human vascular smooth muscle cells |
| title_full |
Suramin inhibits PDGF-stimulated receptor phosphorylation, proteoglycan synthesis and
glycosaminoglycan hyperelongation in human vascular smooth muscle cells |
| title_fullStr |
Suramin inhibits PDGF-stimulated receptor phosphorylation, proteoglycan synthesis and
glycosaminoglycan hyperelongation in human vascular smooth muscle cells |
| title_full_unstemmed |
Suramin inhibits PDGF-stimulated receptor phosphorylation, proteoglycan synthesis and
glycosaminoglycan hyperelongation in human vascular smooth muscle cells |
| title_sort |
suramin inhibits pdgf-stimulated receptor phosphorylation, proteoglycan synthesis and
glycosaminoglycan hyperelongation in human vascular smooth muscle cells |
| publisher |
Wiley |
| publishDate |
2013 |
| url |
http://irep.iium.edu.my/55280/ http://irep.iium.edu.my/55280/ http://irep.iium.edu.my/55280/ http://irep.iium.edu.my/55280/1/7.%20Little-2013-Suramin%20inhibits%20PDGF-stimulated%20r.pdf |
| first_indexed |
2023-09-18T21:18:09Z |
| last_indexed |
2023-09-18T21:18:09Z |
| _version_ |
1777411701114667008 |