Antunes Dos Santos Alessandra, Ferrer Beatriz, Marques Gonçalves Filipe, Tsatsakis Aristides M, Renieri Elisavet A, Skalny Anatoly V, Farina Marcelo, Rocha João B T, Aschner Michael
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Laboratory of Toxicology, Medical School, University of Crete, 71003 Heraklion, Greece.
Toxics. 2018 Aug 9;6(3):47. doi: 10.3390/toxics6030047.
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.
甲基汞（MeHg）是一种有害的环境污染物，会对人类产生显著毒性。通过日常食用大型掠食性鱼类而累积的甲基汞会带来潜在的健康风险，而中枢神经系统（CNS）是毒性的主要作用靶点。尽管甲基汞诱导的神经行为效应（即运动障碍）已有详细描述，但其毒性作用机制尚未完全明确。然而，多条证据表明氧化应激是甲基汞中毒的重要分子机制。事实上，甲基汞是一种软亲电试剂，它优先与蛋白质和低分子量分子中的亲核基团（主要是硫醇和硒醇）相互作用。这种相互作用会导致氧化应激的发生，氧化应激可通过多种相互作用机制造成损伤，损害各种分子（即蛋白质、脂质和核酸）的功能，可能导致不同细胞信号转导途径的调节异常。本综述总结了甲基汞与富含硫醇和硒醇基团的抗氧化反应系统调节因子（如谷胱甘肽（GSH）、硒酶硫氧还蛋白还原酶（TrxR）和谷胱甘肽过氧化物酶（Gpx））之间相互作用的一般情况。特别关注磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/Akt）信号通路和核转录因子E2相关因子2（Nrf2）在甲基汞诱导的氧化还原失衡中的作用。
