Genistein inhibits PDGF-stimulated proteoglycan synthesis in vascular smooth muscle without blocking PDGFβ receptor phosphorylation

Little, Peter J., Getachew, Robel, Rezaei, Hossein Babaahmadi, Sanchez-Guerrero, Estella, Khachigian, Levon M., Wang, Haitao, Liao, Sufen, Zheng, Wenhua, Ballinger, Mandy L. and Osman, Narin (2012) Genistein inhibits PDGF-stimulated proteoglycan synthesis in vascular smooth muscle without blocking PDGFβ receptor phosphorylation. Archives of Biochemistry and Biophysics, 525 1: 25-31. doi:10.1016/j.abb.2012.05.025


Author Little, Peter J.
Getachew, Robel
Rezaei, Hossein Babaahmadi
Sanchez-Guerrero, Estella
Khachigian, Levon M.
Wang, Haitao
Liao, Sufen
Zheng, Wenhua
Ballinger, Mandy L.
Osman, Narin
Title Genistein inhibits PDGF-stimulated proteoglycan synthesis in vascular smooth muscle without blocking PDGFβ receptor phosphorylation
Journal name Archives of Biochemistry and Biophysics   Check publisher's open access policy
ISSN 0003-9861
1096-0384
Publication date 2012-09-01
Year available 2012
Sub-type Article (original research)
DOI 10.1016/j.abb.2012.05.025
Open Access Status
Volume 525
Issue 1
Start page 25
End page 31
Total pages 7
Place of publication Maryland Heights, MO United States
Publisher Academic Press
Language eng
Abstract The signaling pathways that regulate the synthesis and structure of proteoglycans secreted by vascular smooth muscle cells are potential therapeutic targets for preventing lipid deposition in the early stage of atherosclerosis. PDGF stimulates both core protein expression and elongation of glycosaminoglycan (GAG) chains on proteoglycans. In this study we investigated the effects of the tyrosine kinase inhibitor genistein on PDGF mediated receptor phosphorylation and proteoglycan synthesis in human vascular smooth muscle cells. We demonstrate that genistein does not block phosphorylation of the activation site of the PDGF receptor at Tyr857 and two other downstream sites Tyr 751 and Tyr1021. Genistein blocked PDGF-mediated proteoglycan core protein synthesis however it had no effect on GAG chain elongation. These results differ markedly to two other tyrosine kinase inhibitors, imatinib and Ki11502, that block PDGF receptor phosphorylation and PDGF mediated GAG elongation. We conclude that the action of genistein on core protein synthesis does not involve the PDGF receptor and that PDGF mediates GAG elongation via the PDGF receptor.
Keyword Genistein
Glycosaminoglycans
PDGF receptor phosphorylation
Proteoglycans
Vascular smooth muscle
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
 
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