Zinc supplementation prevents arsenic-induced dysregulation of ZRANB2 splice function

Jonathan C Bastick; Mayukh Banerjee; J Christopher States

doi:10.1016/j.etap.2022.103921

Zinc supplementation prevents arsenic-induced dysregulation of ZRANB2 splice function

Environ Toxicol Pharmacol. 2022 Aug:94:103921. doi: 10.1016/j.etap.2022.103921. Epub 2022 Jun 25.

Authors

Jonathan C Bastick¹, Mayukh Banerjee¹, J Christopher States²

Affiliations

¹ Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA.
² Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA. Electronic address: jcstates@louisville.edu.

Abstract

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.

Keywords: Alternative splicing; Arsenic; TRA2B; ZRANB2; Zinc supplementation.

MeSH terms

Arsenic* / metabolism
Arsenic* / toxicity
Dietary Supplements
Humans
RNA-Binding Proteins / metabolism
Zinc / metabolism
Zinc / pharmacology

Substances

RNA-Binding Proteins
ZRANB2 protein, human
Zinc
Arsenic

Abstract

MeSH terms

Substances

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