ArticleNeurotoxicity research2017
Manganese-Mediated Decrease in Levels of c-RET and Tyrosine Hydroxylase Expression In Vitro.
Article in Neurotoxicity research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Emerging Inverse Association Between Low Exposure to Vanadium and Kidney Function Impairment: a Cross-Sectional Analysis of Japanese Residents.Biological trace element research · 2026Article
- The Role of Epigenetics in Manganese Neurotoxicity: An Update with a Focus on Non-Coding RNAs and Histone Modifications.Neurochemical research · 2025Review
- Tamoxifen attenuates manganese-induced dysregulation of neuronal REST via the genomic ER-Frontiers in molecular neuroscience · 2025Article
- Dopaminergic REST is implicated in the tamoxifen-induced neuroprotection against manganese toxicity in female mice.Frontiers in pharmacology · 2025Article
- Manganese in autism spectrum disorder and attention deficit hyperactivity disorder: The state of the art.Current research in toxicology · 2024Review
- Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update.International journal of molecular sciences · 2021Review
- The impact of manganese on neurotransmitter systems.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2020Review
- Early postnatal manganese exposure causes arousal dysregulation and lasting hypofunctioning of the prefrontal cortex catecholaminergic systems.Journal of neurochemistry · 2020Article
- Multidisciplinary approach to assess the toxicities of arsenic and barium in drinking water.Environmental health and preventive medicine · 2020Review
- The transcription factor REST up-regulates tyrosine hydroxylase and antiapoptotic genes and protects dopaminergic neurons against manganese toxicity.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Previous studies showed that overexposure to manganese causes parkinsonism, a disorder of dopaminergic neurons. Previous studies also showed that activity of c-RET kinase controls dopamine production through regulation of tyrosine hydroxylase (TH) expression, suggesting the involvement of c-RET in the development of parkinsonism. To our knowledge, however, there is no report showing a correlation between manganese-mediated parkinsonism and c-RET. In this study, we examined the effect of manganese on the expression and/or activation levels of c-RET and TH in human TH-expressing cells (TGW cells). We first found that treatment with 30 and 100 μM manganese resulted in reduction of c-RET transcript level and degradation of c-RET protein through promotion of ubiquitination. We then examined the biological significance of manganese-mediated decrease of c-RET protein expression. Decreased TH expression with decreased c-RET kinase activity was observed in c-RET protein-depleted TGW cells by treatment with manganese (30 μM) as well as by c-RET siRNA transfection. Since TH protein has been shown to be involved in the dopamine-producing pathway in previous studies, our results indicate the possibility that manganese-mediated reduction of TH expression and phosphorylation via decreased expression of c-RET protein in neural cells is involved in parkinsonism induced by manganese.
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Registered trials
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