文献类型：期刊文献

英文题名：Inhibition of red blood cell development by arsenic-induced disruption of GATA-1

作者：Zhou, Xixi[1];Medina, Sebastian[1,2];Bolt, Alicia M.[1];Zhang, Haikun[1];Wan, Guanghua[1];Xu, Huan[3];Lauer, Fredine T.[1];Wang, Shu Chun[4];Burchiel, Scott W.[1];Liu, Ke Jian[1]

机构：[1]Univ New Mexico, Coll Pharm, Dept Pharmaceut Sci, 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;[4]Chinese Acad Med Sci & Peking Union Med Coll, Inst Hematol & Blood Dis Hosp, Tianjin 300020, Peoples R China

年份：2020

卷号：10

期号：1

外文期刊名：SCIENTIFIC REPORTS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000587638900010)】；

基金：This work was supported by National Institutes of Environmental Health Sciences R01 ES029369 (KJL), R01 ES019968 (SWB), and University of New Mexico Clinical and Translational Science Center Grant Number UL1TR001449 (SWB).

语种：英文

摘要：Anemia is a hematological disorder that adversely affects the health of millions of people worldwide. Although many variables influence the development and exacerbation of anemia, one major contributing factor is the impairment of erythropoiesis. Normal erythropoiesis is highly regulated by the zinc finger transcription factor GATA-1. Disruption of the zinc finger motifs in GATA-1, such as produced by germline mutations, compromises the function of this critical transcription factor and causes dyserythropoietic anemia. Herein, we utilize a combination of in vitro and in vivo studies to provide evidence that arsenic, a widespread environmental toxicant, inhibits erythropoiesis likely through replacing zinc within the zinc fingers of the critical transcription factor GATA-1. We found that arsenic interacts with the N- and C-terminal zinc finger motifs of GATA-1, causing zinc loss and inhibition of DNA and protein binding activities, leading to dyserythropoiesis and an imbalance of hematopoietic differentiation. For the first time, we show that exposures to a prevalent environmental contaminant compromises the function of a key regulatory factor in erythropoiesis, producing effects functionally similar to inherited GATA-1 mutations. These findings highlight a novel molecular mechanism by which arsenic exposure may cause anemia and provide critical insights into potential prevention and intervention for arsenic-related anemias.