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Cyanidin-3-o-β-Glucoside Induces Megakaryocyte Apoptosis via PI3K/Akt- and MAPKs-Mediated Inhibition of NF-κB Signalling
Ya F.1; Li Q.1; Wang D.1; Xie S.1; Song F.3; Gallant R.C.2; Tian Z.1; Wan J.6; Ling W.1; Yang Y.1
2018-07-01
Source PublicationThrombosis and Haemostasis
ISSN03406245
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-β-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 cytochrome c 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-κB) p65 activation by down-regulating inhibitor of NF-κB kinase (IKK)α and IKKβ expression, followed by the inhibition of inhibitor of NF-κB (IκB)α 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-κB 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-κB signalling, which may play important roles in regulating thrombopoiesis.
Keywordanthocyanins apoptosis Cy-3-g megakaryocyte thrombopoiesis
DOI10.1055/s-0038-1656551
URLView the original
Language英語
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Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Sun Yat-Sen University
2.Toronto Platelet Immunobiology Group
3.Guangdong College of Pharmacy
4.Li Ka Shing Knowledge Institute
5.University of Toronto
6.Universidade de Macau
Recommended Citation
GB/T 7714
Ya F.,Li Q.,Wang D.,et al. Cyanidin-3-o-β-Glucoside Induces Megakaryocyte Apoptosis via PI3K/Akt- and MAPKs-Mediated Inhibition of NF-κB Signalling[J]. Thrombosis and Haemostasis,2018,118(7):1215-1229.
APA Ya F..,Li Q..,Wang D..,Xie S..,Song F..,...&Yang Y..(2018).Cyanidin-3-o-β-Glucoside Induces Megakaryocyte Apoptosis via PI3K/Akt- and MAPKs-Mediated Inhibition of NF-κB Signalling.Thrombosis and Haemostasis,118(7),1215-1229.
MLA Ya F.,et al."Cyanidin-3-o-β-Glucoside Induces Megakaryocyte Apoptosis via PI3K/Akt- and MAPKs-Mediated Inhibition of NF-κB Signalling".Thrombosis and Haemostasis 118.7(2018):1215-1229.
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