Oxidative stress in methylmercury-induced cell toxicity

Alessandra Antunes dos Santos, Beatriz Ferrer, Filipe Marques Gonçalves, Aristides M. Tsatsakis, Elisavet A. Renieri, Anatoly V. Skalny, Marcelo Farina, João B.T. Rocha, Michael Aschner

Research output: Contribution to journalReview article

17 Scopus citations

Abstract

Methylmercury (MeHg) is a hazardous environmental pollutant, which elicits significant toxicity in humans. The accumulation of MeHg through the daily consumption of large predatory fish poses potential health risks, and the central nervous system (CNS) is the primary target of toxicity. Despite well-described neurobehavioral effects (i.e., motor impairment), the mechanisms of MeHg-induced toxicity are not completely understood. However, several lines of evidence point out the oxidative stress as an important molecular mechanism in MeHg-induced intoxication. Indeed, MeHg is a soft electrophile that preferentially interacts with nucleophilic groups (mainly thiols and selenols) from proteins and low-molecular-weight molecules. Such interaction contributes to the occurrence of oxidative stress, which can produce damage by several interacting mechanisms, impairing the function of various molecules (i.e., proteins, lipids, and nucleic acids), potentially resulting in modulation of different cellular signal transduction pathways. This review summarizes the general aspects regarding the interaction between MeHg with regulators of the antioxidant response system that are rich in thiol and selenol groups such as glutathione (GSH), and the selenoenzymes thioredoxin reductase (TrxR) and glutathione peroxidase (Gpx). A particular attention is directed towards the role of the PI3K/Akt signaling pathway and the nuclear transcription factor NF-E2-related factor 2 (Nrf2) in MeHg-induced redox imbalance.

Original languageEnglish (US)
Article number47
JournalToxics
Volume6
Issue number3
DOIs
StatePublished - Aug 9 2018

Keywords

  • Methylmercury
  • Molecular mechanisms
  • Oxidative stress

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Chemical Health and Safety

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    dos Santos, A. A., Ferrer, B., Gonçalves, F. M., Tsatsakis, A. M., Renieri, E. A., Skalny, A. V., Farina, M., Rocha, J. B. T., & Aschner, M. (2018). Oxidative stress in methylmercury-induced cell toxicity. Toxics, 6(3), [47]. https://doi.org/10.3390/toxics6030047