The cytoplasmic thioredoxin system in Caenorhabditis elegans affords protection from methylmercury in an age-specific manner
- 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 reductaseMethylmercury (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.…
Verfasserangaben: | Joanna A. RuszkiewiczORCiD, Gabriel Teixeira de Macedo, Antonio Miranda-VizueteORCiD, Joao B. Teixeira da RochaORCiD, Aaron B. Bowman, Julia BornhorstORCiDGND, Tanja SchwerdtleORCiDGND, Michael AschnerORCiDGND |
---|---|
DOI: | https://doi.org/10.1016/j.neuro.2018.08.007 |
ISSN: | 0161-813X |
ISSN: | 1872-9711 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/30138651 |
Titel des übergeordneten Werks (Englisch): | Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system |
Verlag: | Elsevier |
Verlagsort: | Amsterdam |
Publikationstyp: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Jahr der Erstveröffentlichung: | 2018 |
Erscheinungsjahr: | 2018 |
Datum der Freischaltung: | 06.10.2021 |
Freies Schlagwort / Tag: | Age; C. elegans; Development; Methylmercury; Thioredoxin; Thioredoxin reductase |
Band: | 68 |
Seitenanzahl: | 14 |
Erste Seite: | 189 |
Letzte Seite: | 202 |
Fördernde Institution: | National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIEHS R01ES07331]; German Research Foundation (DFG)German Research Foundation (DFG) [BO 4103/2-1]; DFG Research Unit TraceAge [FOR 2558]; NIH Office of Research Infrastructure Programs [P40 OD010440]; NCI Cancer Grant [P30CA013330] |
Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
DDC-Klassifikation: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |