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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, Fuli1,2; Li, Qing1,2; Wang, Dongliang1,2; Xie, Shuangfeng3; Song, Fenglin4; Gallant, Reid C.5,6,7; Tian, Zezhong1,2; Wan, Jianbo8; Ling, Wenhua1,2; Yang, Yan1,2,9
2018-07
Source PublicationTHROMBOSIS AND HAEMOSTASIS
ISSN0340-6245
Volume118Issue:7Pages:1215-1229
Abstract

Apoptotic-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
Fulltext Access
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Cited Times [WOS]:7   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, China
2.Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, China
3.Department of Hematology, 2nd Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, China
4.School of Food Science, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China
5.Toronto Platelet Immunobiology Group, Toronto, Ontario, Canada
6.Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada
7.Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
8.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
9.School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong Province, China
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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