Environmental Toxicology and Pharmacology ( IF 4.2 ) Pub Date : 2022-06-25 , DOI: 10.1016/j.etap.2022.103921 Jonathan C Bastick 1 , Mayukh Banerjee 1 , J Christopher States 1
Environmentally relevant (100 nM) inorganic arsenic (iAs) exposure displaces zinc from zinc fingers of upstream splice regulator ZRANB2 disrupting the splicing of its target TRA2B. Excess zinc displaced iAs from ZRANB2 zinc fingers in cell free system. Thus, the hypothesis that zinc supplementation could prevent iAs-mediated disruption of ZRANB2 splice function in human keratinocytes was tested. The data show that zinc supplementation prevented iAs-induced dysregulation of TRA2B splicing by ZRANB2 as well as the induction of ZRANB2 protein expression. These results provide additional support for the hypothesis that zinc supplementation could prevent iAs-mediated disease in iAs-exposed populations.
中文翻译:
补充锌可防止砷引起的 ZRANB2 剪接功能失调
环境相关的 (100 nM) 无机砷 (iAs) 暴露会取代上游剪接调节因子 ZRANB2 锌指中的锌,从而破坏其目标 TRA2B 的剪接。在无细胞系统中,过量的锌取代了 ZRANB2 锌指中的 iAs。因此,我们测试了补充锌可以防止人角质形成细胞中 iAs 介导的 ZRANB2 剪接功能破坏的假设。数据显示,补充锌可以防止 iAs 诱导的 ZRANB2 TRA2B 剪接失调以及 ZRANB2 蛋白表达的诱导。这些结果为补充锌可以预防 iAs 暴露人群中 iAs 介导的疾病这一假设提供了额外的支持。