IR@PKUHSC  > 北京大学药学院
学科主题药学
Antimalarial drug artemisinin depletes erythrocytes by activating apoptotic pathways in zebrafish
Yang, Ran1; Yan, Shouyu1; Zhu, Xiaojun1; Li, Chuan-Yun1; Liu, Zhenming2; Xiong, Jing-Wei1
刊名EXPERIMENTAL HEMATOLOGY
2015-04-01
DOI10.1016/j.exphem.2014.11.012
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
WOS记录号WOS:000352826100009
引用统计
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52981
专题北京大学药学院
北京大学药学院_药物化学系
北京大学口腔医学院_急诊科
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
推荐引用方式
GB/T 7714
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.
APA Yang, Ran,Yan, Shouyu,Zhu, Xiaojun,Li, Chuan-Yun,Liu, Zhenming,&Xiong, Jing-Wei.(2015).Antimalarial drug artemisinin depletes erythrocytes by activating apoptotic pathways in zebrafish.EXPERIMENTAL HEMATOLOGY,43(4),331-341.
MLA Yang, Ran,et al."Antimalarial drug artemisinin depletes erythrocytes by activating apoptotic pathways in zebrafish".EXPERIMENTAL HEMATOLOGY 43.4(2015):331-341.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Yang, Ran]的文章
[Yan, Shouyu]的文章
[Zhu, Xiaojun]的文章
百度学术
百度学术中相似的文章
[Yang, Ran]的文章
[Yan, Shouyu]的文章
[Zhu, Xiaojun]的文章
必应学术
必应学术中相似的文章
[Yang, Ran]的文章
[Yan, Shouyu]的文章
[Zhu, Xiaojun]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。