Establishment of a zebrafish hematological disease model induced by 1,4-benzoquinone
Establishment of a zebrafish hematological disease model induced by 1,4-benzoquinone
复制标题
1,4-苯醌诱导斑马鱼血液病模型的建立
DOI：
10.1242/dmm.037903
复制
发表时间：
2019-01
影响因子：
4.3
通讯作者：
Zhang Yiyue
中科院分区：
文献类型：
--
作者：
Zhang Ao;Wu Mei;Tan Junliang;Yu Ning;Xu Mengchang;Yu Xutong;Liu Wei;Zhang Yiyue
摘要苯暴露与多种血液系统疾病有关，尤其是白血病。苯在骨髓中产生的反应性代谢物1，4-苯二酚(BQ)被认为是介导苯的血液毒性和致癌性的关键分子。然而，由于缺乏合适的脊椎动物整体模型，其致病作用在很大程度上仍不清楚。在这里，我们提出了一项体内研究，以揭示BQ暴露对斑马鱼血液毒性的影响。从胚胎期到成年期，BQ暴露抑制了红系和淋巴系的造血，但导致了髓系细胞和前体的异常聚集，这类似于苯引起的人类细胞减少和髓系发育不良。这种髓系扩张是由粒细胞而不是巨噬细胞、谱系引起的，强调了谱系特异性在BQ介导的造血毒性中的重要作用。对c-myb(也称为myb)缺陷突变体cmybhkz3的分析表明，bq以c-myb依赖的方式诱导中性粒细胞增多，表明c-myb是bq血液毒性的关键内在介质。我们的研究表明，BQ在斑马鱼从胚胎阶段到成年阶段都会引起特定血统的血液毒性。由于c-myb是BQ诱导中性粒细胞生成所必需的，c-myb可能成为逆转bq血液毒性的潜在药物靶点。摘要：急性暴露于1，4-苯二酚可导致斑马鱼从胚胎到成年期的谱系特异性血液毒性，类似于苯引起的人类细胞减少和髓系发育不良。
ABSTRACT Benzene exposure is associated with various hematological disorders, in particular leukemia. The reactive metabolite of benzene, 1,4-benzoquinone (BQ), generated in bone marrow, is suggested to be a key molecule in mediating benzene-induced hematotoxicity and carcinogenicity. However, its pathogenic role remains largely unknown due to a lack of suitable vertebrate whole-organism models. Here, we present an in vivo study to reveal the effect of BQ exposure on hematotoxicity in zebrafish. From embryonic stages to adulthood, BQ exposure suppressed erythroid and lymphoid hematopoiesis but led to abnormal accumulation of myeloid cells and precursors, which resembles benzene-induced cytopenia and myeloid dysplasia in humans. This myeloid expansion is caused by granulocyte, but not macrophage, lineage, emphasizing the significant role of lineage specificity in BQ-mediated hematopoietic toxicity. Analysis of the c-myb (also known as myb)-deficient mutant cmybhkz3 revealed that BQ induced neutrophilia in a c-myb-dependent manner, demonstrating that c-myb is a key intrinsic mediator of BQ hematotoxicity. Our study reveals that BQ causes lineage-specific hematotoxicity in zebrafish from embryonic stages to adulthood. Since c-myb is indispensable for BQ to induce neutrophilia, c-myb could serve as a potential drug target for reversing BQ hematotoxicity. Summary: Acute exposure to 1,4-benzoquinone leads to lineage-specific hematotoxicity in zebrafish from embryonic stages to adulthood, resembling benzene-induced cytopenia and myeloid dysplasia in humans.
登录
查看更多内容
影响因子：
20.3
作者：
Yiyue Zhang;H. Jin;Li Li-Li;F. Qin;Zilong Wen
通讯作者：
Yiyue Zhang;H. Jin;Li Li-Li;F. Qin;Zilong Wen
影响因子：
7.4
作者：
Circu, Magdalena L.;Aw, Tak Yee
通讯作者：
Aw, Tak Yee
影响因子：
--
作者：
Linda Wolff
通讯作者：
Linda Wolff
DOI：
10.1201/9781420061888_ch38
发表时间：
2007-08
期刊：
--
影响因子：
--
作者：
S. Wilbur;S. Keith;O. Faroon;D. Wohlers
通讯作者：
S. Wilbur;S. Keith;O. Faroon;D. Wohlers
c-Myb 与 Cebp1 并行协同作用来调节斑马鱼中性粒细胞的成熟
影响因子：
20.3
作者：
Jin, Hao;Huang, Zhibin;Zhang, Yiyue
通讯作者：
Zhang, Yiyue