Regulation of human platelet activation and prevention of arterial thrombosis in mice by auraptene through inhibition of nf-κb pathway

Chih Wei Hsia, Ming Ping Wu, Ming Yi Shen, Chih Hsuan Hsia, Chi Li Chung, Joen Rong Sheu

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Platelets are major players in the occurrence of cardiovascular diseases. Auraptene is the most abundant coumarin derivative from plants, and it has been demonstrated to possess a potent capacity to inhibit platelet activation. Although platelets are anucleated cells, they also express the transcription factor, nuclear factor-κB (NF-κB), that may exert non-genomic functions in platelet activation. In the current study, we further investigated the inhibitory roles of auraptene in NF-κB-mediated signal events in platelets. MG-132 (an inhibitor of proteasome) and BAY11-7082 (an inhibitor of IκB kinase; IKK), obviously inhibited platelet aggregation; however, BAY11-7082 exhibited more potent activity than MG-132 in this reaction. The existence of NF-κB (p65) in platelets was observed by confocal microscopy, and auraptene attenuated NF-κB activation such as IκBα and p65 phosphorylation and reversed IκBα degradation in collagen-activated platelets. To investigate cellular signaling events between PLCγ2-PKC and NF-κB, we found that BAY11-7082 abolished PLCγ2-PKC activation; nevertheless, neither U73122 nor Ro31-8220 had effect on NF-κB activation. Furthermore, both auraptene and BAY11-7082 significantly diminished HO• formation in activated platelets. For in vivo study, auraptene prolonged the occlusion time of platelet plug in mice. In conclusion, we propose a novel inhibitory pathway of NF-κB-mediated PLCγ2-PKC activation by auraptene in human platelets, and further supported that auraptene possesses potent activity for thromboembolic diseases.

Original languageEnglish
Article number4810
Pages (from-to)1-14
Number of pages14
JournalInternational journal of molecular sciences
Volume21
Issue number13
DOIs
Publication statusPublished - Jul 2020

Keywords

  • Arterial thrombosis
  • Auraptene
  • Human platelet
  • Hydroxyl radical
  • NF-κB
  • PLCγ2-PKC activation

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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