Abstract
Methylmercury (MeHg) is an environmental pollutant linked to many neurological defects, especially in developing individuals. The thioredoxin (TRX) system is a key redox regulator affected by MeHg toxicity, however the mechanisms and consequences of MeHg-induced dysfunction are not completely understood. This study evaluated the role of the TRX system in C. elegans susceptibility to MeHg during development. Worms lacking or overexpressing proteins from the TRX family were exposed to MeHg for 1 h at different developmental stage: L1, L4 and adult. Worms without cytoplasmic thioredoxin system exhibited age-specific susceptibility to MeHg when compared to wild-type (wt). This susceptibility corresponded partially to decreased total glutathione (GSH) levels and enhanced degeneration of dopaminergic neurons. In contrast, the overexpression of the cytoplasmic system TRX-1/TRXR-1 did not provide substantial protection against MeHg. Moreover, transgenic worms exhibited decreased protein expression for cytoplasmic thioredoxin reductase (TRXR-1). Both mitochondrial thioredoxin system TRX-2/TRXR-2, as well as other thioredoxin-like proteins: TRX-3, TRX-4, TRX-5 did not show significant role in C. elegans resistance to MeHg. Based on the current findings, the cytoplasmic thioredoxin system TRX-1/TRXR-1 emerges as an important age-sensitive protectant against MeHg toxicity in C. elegans.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 189-202 |
| Number of pages | 14 |
| Journal | NeuroToxicology |
| Volume | 68 |
| DOIs | |
| State | Published - Sep 1 2018 |
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Keywords
- Age
- C. elegans
- Development
- Methylmercury
- Thioredoxin
- Thioredoxin reductase
ASJC Scopus subject areas
- Neuroscience(all)
- Toxicology
Cite this
The cytoplasmic thioredoxin system in Caenorhabditis elegans affords protection from methylmercury in an age-specific manner. / Ruszkiewicz, Joanna A.; Teixeira de Macedo, Gabriel; Miranda-Vizuete, Antonio; Teixeira da Rocha, João B.; Bowman, Aaron B.; Bornhorst, Julia; Schwerdtle, Tanja; Aschner, Michael.
In: NeuroToxicology, Vol. 68, 01.09.2018, p. 189-202.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The cytoplasmic thioredoxin system in Caenorhabditis elegans affords protection from methylmercury in an age-specific manner
AU - Ruszkiewicz, Joanna A.
AU - Teixeira de Macedo, Gabriel
AU - Miranda-Vizuete, Antonio
AU - Teixeira da Rocha, João B.
AU - Bowman, Aaron B.
AU - Bornhorst, Julia
AU - Schwerdtle, Tanja
AU - Aschner, Michael
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Methylmercury (MeHg) is an environmental pollutant linked to many neurological defects, especially in developing individuals. The thioredoxin (TRX) system is a key redox regulator affected by MeHg toxicity, however the mechanisms and consequences of MeHg-induced dysfunction are not completely understood. This study evaluated the role of the TRX system in C. elegans susceptibility to MeHg during development. Worms lacking or overexpressing proteins from the TRX family were exposed to MeHg for 1 h at different developmental stage: L1, L4 and adult. Worms without cytoplasmic thioredoxin system exhibited age-specific susceptibility to MeHg when compared to wild-type (wt). This susceptibility corresponded partially to decreased total glutathione (GSH) levels and enhanced degeneration of dopaminergic neurons. In contrast, the overexpression of the cytoplasmic system TRX-1/TRXR-1 did not provide substantial protection against MeHg. Moreover, transgenic worms exhibited decreased protein expression for cytoplasmic thioredoxin reductase (TRXR-1). Both mitochondrial thioredoxin system TRX-2/TRXR-2, as well as other thioredoxin-like proteins: TRX-3, TRX-4, TRX-5 did not show significant role in C. elegans resistance to MeHg. Based on the current findings, the cytoplasmic thioredoxin system TRX-1/TRXR-1 emerges as an important age-sensitive protectant against MeHg toxicity in C. elegans.
AB - Methylmercury (MeHg) is an environmental pollutant linked to many neurological defects, especially in developing individuals. The thioredoxin (TRX) system is a key redox regulator affected by MeHg toxicity, however the mechanisms and consequences of MeHg-induced dysfunction are not completely understood. This study evaluated the role of the TRX system in C. elegans susceptibility to MeHg during development. Worms lacking or overexpressing proteins from the TRX family were exposed to MeHg for 1 h at different developmental stage: L1, L4 and adult. Worms without cytoplasmic thioredoxin system exhibited age-specific susceptibility to MeHg when compared to wild-type (wt). This susceptibility corresponded partially to decreased total glutathione (GSH) levels and enhanced degeneration of dopaminergic neurons. In contrast, the overexpression of the cytoplasmic system TRX-1/TRXR-1 did not provide substantial protection against MeHg. Moreover, transgenic worms exhibited decreased protein expression for cytoplasmic thioredoxin reductase (TRXR-1). Both mitochondrial thioredoxin system TRX-2/TRXR-2, as well as other thioredoxin-like proteins: TRX-3, TRX-4, TRX-5 did not show significant role in C. elegans resistance to MeHg. Based on the current findings, the cytoplasmic thioredoxin system TRX-1/TRXR-1 emerges as an important age-sensitive protectant against MeHg toxicity in C. elegans.
KW - Age
KW - C. elegans
KW - Development
KW - Methylmercury
KW - Thioredoxin
KW - Thioredoxin reductase
UR - http://www.scopus.com/inward/record.url?scp=85052314481&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052314481&partnerID=8YFLogxK
U2 - 10.1016/j.neuro.2018.08.007
DO - 10.1016/j.neuro.2018.08.007
M3 - Article
C2 - 30138651
AN - SCOPUS:85052314481
VL - 68
SP - 189
EP - 202
JO - NeuroToxicology
JF - NeuroToxicology
SN - 0161-813X
ER -