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HERO ID
4325287
Reference Type
Journal Article
Title
Chrysin restores PDGF-induced inhibition on protein tyrosine phosphatase and reduces PDGF signaling in cultured VSMCs
Author(s)
Lo, HM; Wu, MW; Pan, SL; Peng, CY; Wu, PH; Wu, WB
Year
2012
Is Peer Reviewed?
1
Journal
Journal of Nutritional Biochemistry
ISSN:
0955-2863
EISSN:
1873-4847
Volume
23
Issue
6
Page Numbers
667-678
Language
English
PMID
21803557
DOI
10.1016/j.jnutbio.2011.03.011
Web of Science Id
WOS:000304786000020
Abstract
Previous studies have shown that an increased intake of dietary flavonoids is associated with a decreased risk of cardiovascular diseases (CVDs). PDGF is a major mitogen for vascular smooth muscle cell (VSMC) and participates in the pathogenesis of many CVDs. The study investigated whether the flavone chrysin affected PDGF functions in VSMCs and neointma formation in rat artery. We found that chrysin concentration-dependently inhibited PDGF-induced proliferation and chemotaxis and reduced PDGF signaling in VSMCs. Chrysin attenuated H(2)O(2) signaling and PDGF-induced reactive oxygen species production and NADPH oxidase activation but did not interfere with PDGF binding to VSMCs. The further analyses revealed that chrysin relieved PDGF-induced inhibition on activity of protein tyrosine phosphatase (PTP) and reduced PDGF-induced oxidation of PTP cysteinyl active site. Moreover, it inhibited PDGF receptor autophosphorylation induced by low-dose vanadate (an inhibitor for PTP). The effect of chrysin, but not of the flavonoid (-)-epigallocatechin-3-gallate and antioxidant N-acetylcysteine, on PDGF signaling and PTP activity was reversed by depletion of intracellular glutathione (GSH), suggesting an involvement of chrysin on GSH/glutaredoxin system for PTP reactivation. Finally, to demonstrate the effectiveness of chrysin in vivo, we showed that oral administration of chrysin before and after angioplasty could reduce neointima formation in balloon-injured carotid artery in rats. In conclusion, we provide here evidence that chrysin can regulate intracellular PTP activity during PDGF signaling, inhibits PDGF-induced VSMC proliferation and chemotaxis, and reduces arterial intima hyperplasia in vivo.
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