Chrysin restores PDGF-induced inhibition on protein tyrosine phosphatase and reduces PDGF signaling in cultured VSMCs

Huey Ming Lo, Min Wen Wu, Shiow Lin Pan, Chieh Yu Peng, Pi Hui Wu, Wen Bin Wu

研究成果: 雜誌貢獻文章同行評審

18 引文 斯高帕斯(Scopus)

摘要

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 H2O2 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.
原文英語
頁(從 - 到)667-678
頁數12
期刊Journal of Nutritional Biochemistry
23
發行號6
DOIs
出版狀態已發佈 - 六月 2012
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 臨床生物化學
  • 分子生物學
  • 內分泌學、糖尿病和代謝
  • 營養與營養學

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