Arsenic-protein interactions as a mechanism of arsenic toxicity

Toxicol Appl Pharmacol. 2021 Nov 15:431:115738. doi: 10.1016/j.taap.2021.115738. Epub 2021 Oct 4.

Abstract

Millions of people worldwide are exposed to arsenic, a metalloid listed as one of the top chemical pollutants of concern to human health. Epidemiological and experimental studies link arsenic exposure to the development of cancer and other diseases. Several mechanisms have been proposed to explain the effects induced by arsenic. Notably, arsenic and its metabolites interact with proteins by direct binding to individual cysteine residues, cysteine clusters, zinc finger motifs, and RING finger domains. Consequently, arsenic interactions with proteins disrupt the functions of proteins and may lead to the development and progression of diseases. In this review, we focus on current evidence in the literature that implicates the interaction of arsenic with proteins as a mechanism of arsenic toxicity. Data show that arsenic-protein interactions affect multiple cellular processes and alter epigenetic regulation, cause endocrine disruption, inhibit DNA damage repair mechanisms, and deregulate gene expression, among other adverse effects.

Keywords: Arsenic; Cysteine; Interaction; Protein; Zinc finger.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arsenic Poisoning / etiology*
  • Arsenic Poisoning / genetics
  • Arsenic Poisoning / metabolism
  • Arsenicals / adverse effects*
  • Arsenicals / metabolism
  • Cysteine
  • DNA Repair / drug effects
  • Endocrine Disruptors / adverse effects*
  • Endocrine Disruptors / metabolism
  • Environmental Pollutants / adverse effects*
  • Environmental Pollutants / metabolism
  • Epigenesis, Genetic / drug effects
  • Humans
  • Protein Binding
  • Proteins / genetics
  • Proteins / metabolism*
  • RING Finger Domains
  • Risk Assessment
  • Zinc Fingers

Substances

  • Arsenicals
  • Endocrine Disruptors
  • Environmental Pollutants
  • Proteins
  • Cysteine