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Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-Induced Platelet Reactivity Independent of Reactive Oxygen Species(†)

BACKGROUND: Piperlongumine (PL) is a compound isolated from the piper longum plant. It possesses anti-cancer activities through blocking the transcription factor STAT3 and by inducing reactive oxygen species (ROS) in cancer, but not normal cells. It also inhibits platelet aggregation induced by coll...

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Autores principales: Yuan, Hengjie, Houck, Katie L., Tian, Ye, Bharadwaj, Uddalak, Hull, Ken, Zhou, Zhou, Zhou, Mingzhao, Wu, Xiaoping, Tweardy, David J., Romo, Daniel, Fu, Xiaoyun, Zhang, Yanjun, Zhang, Jianning, Dong, Jing-fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4672935/
https://www.ncbi.nlm.nih.gov/pubmed/26645674
http://dx.doi.org/10.1371/journal.pone.0143964
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author Yuan, Hengjie
Houck, Katie L.
Tian, Ye
Bharadwaj, Uddalak
Hull, Ken
Zhou, Zhou
Zhou, Mingzhao
Wu, Xiaoping
Tweardy, David J.
Romo, Daniel
Fu, Xiaoyun
Zhang, Yanjun
Zhang, Jianning
Dong, Jing-fei
author_facet Yuan, Hengjie
Houck, Katie L.
Tian, Ye
Bharadwaj, Uddalak
Hull, Ken
Zhou, Zhou
Zhou, Mingzhao
Wu, Xiaoping
Tweardy, David J.
Romo, Daniel
Fu, Xiaoyun
Zhang, Yanjun
Zhang, Jianning
Dong, Jing-fei
author_sort Yuan, Hengjie
collection PubMed
description BACKGROUND: Piperlongumine (PL) is a compound isolated from the piper longum plant. It possesses anti-cancer activities through blocking the transcription factor STAT3 and by inducing reactive oxygen species (ROS) in cancer, but not normal cells. It also inhibits platelet aggregation induced by collagen, but the underlying mechanism is not known. OBJECTIVE: We conducted in vitro experiments to test the hypothesis that PL regulates a non-transcriptional activity of STAT3 to specifically reduce the reactivity of human platelets to collagen. RESULTS: PL dose-dependently blocked collagen-induced platelet aggregation, calcium influx, CD62p expression and thrombus formation on collagen with a maximal inhibition at 100 μM. It reduced platelet microvesiculation induced by collagen. PL blocked the activation of JAK2 and STAT3 in collagen-stimulated platelets. This inhibitory effect was significantly reduced in platelets pretreated with a STAT3 inhibitor. Although PL induced ROS production in platelets; quenching ROS using excessive reducing agents: 20 μM GSH and 0.5 mM L-Cysteine, did not block the inhibitory effects. The NADPH oxidase inhibitor Apocynin also had no effect. CONCLUSIONS: PL inhibited collagen-induced platelet reactivity by targeting the JAK2-STAT3 pathway. We also provide experimental evidence that PL and collagen induce different oxidants that have differential effects on platelets. Studying these differential effects may uncover new mechanisms of regulating platelet functions by oxidants in redox signals.
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spelling pubmed-46729352015-12-16 Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-Induced Platelet Reactivity Independent of Reactive Oxygen Species(†) Yuan, Hengjie Houck, Katie L. Tian, Ye Bharadwaj, Uddalak Hull, Ken Zhou, Zhou Zhou, Mingzhao Wu, Xiaoping Tweardy, David J. Romo, Daniel Fu, Xiaoyun Zhang, Yanjun Zhang, Jianning Dong, Jing-fei PLoS One Research Article BACKGROUND: Piperlongumine (PL) is a compound isolated from the piper longum plant. It possesses anti-cancer activities through blocking the transcription factor STAT3 and by inducing reactive oxygen species (ROS) in cancer, but not normal cells. It also inhibits platelet aggregation induced by collagen, but the underlying mechanism is not known. OBJECTIVE: We conducted in vitro experiments to test the hypothesis that PL regulates a non-transcriptional activity of STAT3 to specifically reduce the reactivity of human platelets to collagen. RESULTS: PL dose-dependently blocked collagen-induced platelet aggregation, calcium influx, CD62p expression and thrombus formation on collagen with a maximal inhibition at 100 μM. It reduced platelet microvesiculation induced by collagen. PL blocked the activation of JAK2 and STAT3 in collagen-stimulated platelets. This inhibitory effect was significantly reduced in platelets pretreated with a STAT3 inhibitor. Although PL induced ROS production in platelets; quenching ROS using excessive reducing agents: 20 μM GSH and 0.5 mM L-Cysteine, did not block the inhibitory effects. The NADPH oxidase inhibitor Apocynin also had no effect. CONCLUSIONS: PL inhibited collagen-induced platelet reactivity by targeting the JAK2-STAT3 pathway. We also provide experimental evidence that PL and collagen induce different oxidants that have differential effects on platelets. Studying these differential effects may uncover new mechanisms of regulating platelet functions by oxidants in redox signals. Public Library of Science 2015-12-08 /pmc/articles/PMC4672935/ /pubmed/26645674 http://dx.doi.org/10.1371/journal.pone.0143964 Text en © 2015 Yuan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Yuan, Hengjie
Houck, Katie L.
Tian, Ye
Bharadwaj, Uddalak
Hull, Ken
Zhou, Zhou
Zhou, Mingzhao
Wu, Xiaoping
Tweardy, David J.
Romo, Daniel
Fu, Xiaoyun
Zhang, Yanjun
Zhang, Jianning
Dong, Jing-fei
Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-Induced Platelet Reactivity Independent of Reactive Oxygen Species(†)
title Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-Induced Platelet Reactivity Independent of Reactive Oxygen Species(†)
title_full Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-Induced Platelet Reactivity Independent of Reactive Oxygen Species(†)
title_fullStr Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-Induced Platelet Reactivity Independent of Reactive Oxygen Species(†)
title_full_unstemmed Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-Induced Platelet Reactivity Independent of Reactive Oxygen Species(†)
title_short Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-Induced Platelet Reactivity Independent of Reactive Oxygen Species(†)
title_sort piperlongumine blocks jak2-stat3 to inhibit collagen-induced platelet reactivity independent of reactive oxygen species(†)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4672935/
https://www.ncbi.nlm.nih.gov/pubmed/26645674
http://dx.doi.org/10.1371/journal.pone.0143964
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