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Cyanidin-3-o-beta-Glucoside Induces Megakaryocyte Apoptosis via PI3K/Akt- and MAPKs-Mediated Inhibition of NF-kappa B Signalling
Ya, Fuli; Li, Qing; Wang, Dongliang; Xie, Shuangfeng; Song, Fenglin; Gallant, Reid C.; Tian, Zezhong; Wan, Jianbo; Ling, Wenhua; Yang, Yan
2018-07
Source PublicationTHROMBOSIS AND HAEMOSTASIS
ISSN0340-6245
Volume118Issue:7Pages:1215-1229
AbstractApoptotic-like phase is an essential step in thrombopoiesis from megakaryocytes. Anthocyanins are natural flavonoid pigments that possess a wide range of biological activities, including protection against cardiovascular diseases and induction of tumour cell apoptosis. We investigated the effects and underlying mechanisms of cyanidin-3-o-beta-glucoside (Cy-3-g,the major bioactive compound in anthocyanins) on the apoptosis of human primary megakaryocytes and Meg-01 cell line in vitro. We found that Cy-3-g dose-dependently increased the dissipation of the mitochondrial membrane potential, caspase-9 and caspase-3 activity in megakaryocytes from patients with newly diagnosed acute myeloid leukaemia but not in those from healthy volunteers. In Meg-01 cells, Cy-3-g regulated the distribution of Bak, Bax and Bcl-xL proteins in the mitochondria and cytosol, subsequently increasing cytochromec release and stimulating caspase-9 and caspase-3 activation and phosphatidylserine exposure. However, Cy-3-g did not exert significant effects on factor-associated suicide (Fas), Fas ligand, caspase-8 or Bid expression. Cy-3-g inhibited nuclear factor kappa B (NF-kappa B) p65 activation by down-regulating inhibitor of NF-kappa B kinase (IKK)alpha and IKK beta expression, followed by the inhibition of inhibitor of NF-kappa B (I kappa B)alpha not equal phosphorylation and degradation and subsequent inhibition of the translocation of the p65 sub-unit into the nucleus, and finally stimulating caspase-3 activation and phosphatidylserine exposure. The inhibitory effect of Cy-3-g on NF-kappa B activation was mediated by the activation of extracellular signal-regulated kinases (Erk1/2) and p38 mitogen-activated protein kinase (MAPK) and the inhibition of phosphoinositide 3-kinase (PI3K)/Akt signalling. U0126 (Erk1/2 inhibitor), SB203580 (p38 MAPK inhibitor) and 740 Y-P (PI3K agonist) significantly reversed Cy-3-g-reduced phosphorylation of p65. Taken together, our data indicate that Cy-3-g induces megakaryocyte apoptosis via the inhibition of NF-kappa B signalling, which may play important roles in regulating thrombopoiesis.
Keywordmegakaryocyte thrombopoiesis anthocyanins Cy-3-g apoptosis
DOI10.1055/s-0038-1656551
URLView the original
Indexed BySCI
Language英语
WOS Research AreaHematology ; Cardiovascular System & Cardiology
WOS SubjectHematology ; Peripheral Vascular Disease
WOS IDWOS:000436984900011
PublisherGEORG THIEME VERLAG KG
The Source to ArticleWOS
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Cited Times [WOS]:4   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Recommended Citation
GB/T 7714
Ya, Fuli,Li, Qing,Wang, Dongliang,et al. Cyanidin-3-o-beta-Glucoside Induces Megakaryocyte Apoptosis via PI3K/Akt- and MAPKs-Mediated Inhibition of NF-kappa B Signalling[J]. THROMBOSIS AND HAEMOSTASIS,2018,118(7):1215-1229.
APA Ya, Fuli.,Li, Qing.,Wang, Dongliang.,Xie, Shuangfeng.,Song, Fenglin.,...&Yang, Yan.(2018).Cyanidin-3-o-beta-Glucoside Induces Megakaryocyte Apoptosis via PI3K/Akt- and MAPKs-Mediated Inhibition of NF-kappa B Signalling.THROMBOSIS AND HAEMOSTASIS,118(7),1215-1229.
MLA Ya, Fuli,et al."Cyanidin-3-o-beta-Glucoside Induces Megakaryocyte Apoptosis via PI3K/Akt- and MAPKs-Mediated Inhibition of NF-kappa B Signalling".THROMBOSIS AND HAEMOSTASIS 118.7(2018):1215-1229.
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