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Regulation of Human Platelet Activation and Prevention of Arterial Thrombosis in Mice by Auraptene through Inhibition of NF-κB Pathway
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 transcrip...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370278/ https://www.ncbi.nlm.nih.gov/pubmed/32646046 http://dx.doi.org/10.3390/ijms21134810 |
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author | Hsia, Chih-Wei Wu, Ming-Ping Shen, Ming-Yi Hsia, Chih-Hsuan Chung, Chi-Li Sheu, Joen-Rong |
author_facet | Hsia, Chih-Wei Wu, Ming-Ping Shen, Ming-Yi Hsia, Chih-Hsuan Chung, Chi-Li Sheu, Joen-Rong |
author_sort | Hsia, Chih-Wei |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7370278 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73702782020-08-07 Regulation of Human Platelet Activation and Prevention of Arterial Thrombosis in Mice by Auraptene through Inhibition of NF-κB Pathway Hsia, Chih-Wei Wu, Ming-Ping Shen, Ming-Yi Hsia, Chih-Hsuan Chung, Chi-Li Sheu, Joen-Rong Int J Mol Sci Article 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. MDPI 2020-07-07 /pmc/articles/PMC7370278/ /pubmed/32646046 http://dx.doi.org/10.3390/ijms21134810 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hsia, Chih-Wei Wu, Ming-Ping Shen, Ming-Yi Hsia, Chih-Hsuan Chung, Chi-Li Sheu, Joen-Rong Regulation of Human Platelet Activation and Prevention of Arterial Thrombosis in Mice by Auraptene through Inhibition of NF-κB Pathway |
title | Regulation of Human Platelet Activation and Prevention of Arterial Thrombosis in Mice by Auraptene through Inhibition of NF-κB Pathway |
title_full | Regulation of Human Platelet Activation and Prevention of Arterial Thrombosis in Mice by Auraptene through Inhibition of NF-κB Pathway |
title_fullStr | Regulation of Human Platelet Activation and Prevention of Arterial Thrombosis in Mice by Auraptene through Inhibition of NF-κB Pathway |
title_full_unstemmed | Regulation of Human Platelet Activation and Prevention of Arterial Thrombosis in Mice by Auraptene through Inhibition of NF-κB Pathway |
title_short | Regulation of Human Platelet Activation and Prevention of Arterial Thrombosis in Mice by Auraptene through Inhibition of NF-κB Pathway |
title_sort | regulation of human platelet activation and prevention of arterial thrombosis in mice by auraptene through inhibition of nf-κb pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370278/ https://www.ncbi.nlm.nih.gov/pubmed/32646046 http://dx.doi.org/10.3390/ijms21134810 |
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