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 language | English (US) |
|---|---|
| Article number | 47 |
| Journal | Toxics |
| Volume | 6 |
| Issue number | 3 |
| DOIs | |
| State | Published - Aug 9 2018 |
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Keywords
- Methylmercury
- Molecular mechanisms
- Oxidative stress
ASJC Scopus subject areas
- Toxicology
- Health, Toxicology and Mutagenesis
- Chemical Health and Safety
Cite this
Oxidative stress in methylmercury-induced cell toxicity. / dos Santos, Alessandra Antunes; Ferrer, Beatriz; Gonçalves, Filipe Marques; Tsatsakis, Aristides M.; Renieri, Elisavet A.; Skalny, Anatoly V.; Farina, Marcelo; Rocha, João B.T.; Aschner, Michael.
In: Toxics, Vol. 6, No. 3, 47, 09.08.2018.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Oxidative stress in methylmercury-induced cell toxicity
AU - dos Santos, Alessandra Antunes
AU - Ferrer, Beatriz
AU - Gonçalves, Filipe Marques
AU - Tsatsakis, Aristides M.
AU - Renieri, Elisavet A.
AU - Skalny, Anatoly V.
AU - Farina, Marcelo
AU - Rocha, João B.T.
AU - Aschner, Michael
PY - 2018/8/9
Y1 - 2018/8/9
N2 - 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.
AB - 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.
KW - Methylmercury
KW - Molecular mechanisms
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=85054308800&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054308800&partnerID=8YFLogxK
U2 - 10.3390/toxics6030047
DO - 10.3390/toxics6030047
M3 - Review article
AN - SCOPUS:85054308800
VL - 6
JO - Toxics
JF - Toxics
SN - 2305-6304
IS - 3
M1 - 47
ER -