文献类型：期刊文献

英文题名：Arsenite and monomethylarsonous acid disrupt erythropoiesis through combined effects on differentiation and survival pathways in early erythroid progenitors

作者：Medina, Sebastian[1,2];Bolt, Alicia M.[1];Zhou, Xixi[1];Wan, Guanghua[1];Xu, Huan[3];Lauer, Fredine T.[1];Liu, Ke Jian[1];Burchiel, Scott W.[1]

机构：[1]Univ New Mexico, Dept Pharmaceut Sci, Coll Pharm, Albuquerque, NM 87131 USA;[2]New Mexico Highlands Univ, Dept Biol, Las Vegas, NM 87701 USA;[3]East China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China

年份：2021

卷号：350

起止页码：111

外文期刊名：TOXICOLOGY LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000691222600012)】；

基金：This work was supported by the National Institutes of Environmental Health SciencesRO1 ES029369, R01 ES029369-03S1 (K.J.L) ; RO1 ES019968 (S.W.B.) ; the UNM Clinical and Translational Science Center Grant Number UL1TR001449 (S.W. B.) ; the National Institute of Environmental Health Sciences and UNM METALS Superfund Research Program Grant Number P42 ES025589 (S.W.B. and K.J.L.) ; and the National Institute of General Medical Sciences Grant Number P20GM130422 (A.M.B.) .

语种：英文

外文关键词：Arsenic; Erythropoiesis; STAT5; GATA-1; Arsenite (As+3); Monomethylarsonous acid (MMA(+3))

摘要：Strong epidemiological evidence demonstrates an association between chronic arsenic exposure and anemia. We recently found that As+3 impairs erythropoiesis by disrupting the function of GATA-1; however the downstream pathways impacted by the loss of GATA-1 function have not been evaluated. Additionally, our previous findings indicate that the predominant arsenical in the bone marrow of mice exposed to As+3 in their drinking water for 30 days was MMA+3, but the impacts of this arsenical on erythorpoisis also remain largely unknown. The goal of this study was to address these critical knowledge gaps by evaluating the comparative effects of arsenite (As+3) and the As+3 metabolite, monomethyarsonous acid (MMA+3) on two critical regulatory pathways that control the differentiation and survival of early erythroid progenitor cells. We found that 500 nM As+3 and 100 and 500 nM MMA+3 suppress erythropoiesis by impairing the differentiation of early stage erythroid progenitors. The suppression of early erythroid progenitor cell development was attributed to combined effects on differentiation and survival pathways mediated by disruption of GATA-1 and STAT5. Our results show that As+3 primarily disrupted GATA-1 function; whereas, MMA+3 suppressed both GATA-1 and STAT5 activity. Collectively, these findings provide novel mechanistic insights into arsenic-induced dyserythropoiesis and suggest that MMA+3 may be more toxic than As+3 to early developing erythroid cells. (c) 2021 Elsevier B.V. All rights reserved.