Reduction of NF-κB signals in platelets and prolongation of platelet plug formation against high shear flow in whole blood on human subject by Columbianadin

Chih Wei Hsia, Chih Hao Yang, Joen Rong Sheu, Chih Hsuan Hsia, Cheng Lin Tsai, Wei Chieh Huang, Ting Yu Chen, Periyakali Saravana Bhavan, Yi Chang

研究成果: 雜誌貢獻文章同行評審

摘要

Myocardial infarction and cerebral ischemic stroke during the process of arterial thrombosis are prominently causes of death worldwide. Platelets are anucleated cells and play a critical factor in these diseases. Columbianadin (CBN), a coumarin derivative from plants, inhibits effective platelet activation. In this study, platelet function analysis revealed that the closure time of the platelet plug in human whole blood significantly prolonged by CBN, whereas CBN did not pointedly prolong the bleeding time in mice. BAY11-7082 (an inhibitor of IκB kinase) and MG-132 (an inhibitor of proteasome) inhibited collagen-stimulated platelet aggregation and ATP-release in human platelets, BAY11-7082 exhibited a higher potency than MG-132. Moreover, CBN markedly reduced NF-κB activation (e.g., IκBα and p65 phosphorylation) and reversed IκBα degradation in activated platelets. We investigated intercellular signaling events between mitogen-activated protein kinases and NF-κB, and found that BAY11-7082 abolished JNK1/2 and ERK1/2 phosphorylation. Interestingly, SP600125 (an inhibitor of JNK) but not PD98059 (an inhibitor of ERK) had no effect in NF-κB activation in activated platelets. Moreover, CBN but not BAY11-7082 significantly reduced hydroxyl radical (HO•) formation in platelets. Therefore, we propose that CBN inhibits NF-κB activation in human platelets and could present a potent clinical treatment for thromboembolic diseases.
原文英語
文章編號7323
頁(從 - 到)1-15
頁數15
期刊Applied Sciences (Switzerland)
10
發行號20
DOIs
出版狀態已發佈 - 十月 2 2020

ASJC Scopus subject areas

  • 材料科學(全部)
  • 儀器
  • 工程 (全部)
  • 製程化學與技術
  • 電腦科學應用
  • 流體流動和轉移過程

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