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学科主题: 药学
题名:
Antimalarial drug artemisinin depletes erythrocytes by activating apoptotic pathways in zebrafish
作者: Yang, Ran1; Yan, Shouyu1; Zhu, Xiaojun1; Li, Chuan-Yun1; Liu, Zhenming2; Xiong, Jing-Wei1
刊名: EXPERIMENTAL HEMATOLOGY
发表日期: 2015-04-01
DOI: 10.1016/j.exphem.2014.11.012
卷: 43, 期:4, 页:331-341
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Hematology ; Medicine, Research & Experimental
研究领域[WOS]: Hematology ; Research & Experimental Medicine
关键词[WOS]: CONGENITAL SIDEROBLASTIC ANEMIA ; CAUSES POLYCYTHEMIA-VERA ; STEM-CELL DEVELOPMENT ; JAK2 MUTATION ; MYELOPROLIFERATIVE DISORDERS ; HEMATOPOIESIS ; EMBRYO ; THERAPY ; GENE ; PATHOGENESIS
英文摘要:

Despite its extraordinary efficacy, administration of the major antimalarial drug artemisinin leads to anemia, and the underlying cellular and molecular mechanisms are not well understood. Here, we report the effects of artemisinin on erythroid development and apoptosis in zebrafish and human cells. By performing a small-molecule screen with zebrafish embryos, we found that artemisinin treatment depleted red blood cells and slightly decreased definitive hematopoietic stem cells, but had no effect on primitive hematopoietic progenitors. RNA-Seq revealed that artemisinin suppressed a cluster of genes in the heme biosynthesis and globin synthesis pathways. Furthermore, artemisinin induced apoptosis in erythrocytes in zebrafish embryos, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and preferentially acted on differentiated erythrocytes by elevating caspase 8 and caspase 9 activity in differentiated human K562 cells. Consistently, artemisinin suppressed the ectopic expression of erythroid genes in jak2aV581F-injected embryos, a zebrafish model for human polycythemia vera in which the bone marrow makes too many red blood cells. Taken together, our data suggested that artemisinin, in addition to killing parasites, has a direct action on differentiated erythrocytes other than definitive hematopoietic stem cells and causes erythroid apoptosis by interfering with the heme biosynthesis pathway in zebrafish and human cells. Copyright (C) 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc.

语种: 英语
所属项目编号: 2010CB529503 ; 2012CB944501 ; 31430059 ; 31271549 ; 31221002 ; 81270164
项目资助者: National Basic Research Program of China ; National Natural Science Foundation of China
WOS记录号: WOS:000352826100009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52981
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Peking Univ, Inst Mol Med, Beijing Key Lab Cardiometab Mol Med, Beijing 100871, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100871, Peoples R China

Recommended Citation:
Yang, Ran,Yan, Shouyu,Zhu, Xiaojun,et al. Antimalarial drug artemisinin depletes erythrocytes by activating apoptotic pathways in zebrafish[J]. EXPERIMENTAL HEMATOLOGY,2015,43(4):331-341.
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