ArticleNeurotoxicology2017
p73 gene in dopaminergic neurons is highly susceptible to manganese neurotoxicity.
Article in Neurotoxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- A novel manganese metabolism- and immune-related prognostic risk model for acute myeloid leukemia.Translational cancer research · 2025Article
- Trace Elements in Medicinal Metallomics.Mini reviews in medicinal chemistry · 2025Review
- Development and verification of a manganese metabolism- and immune-related genes signature for prediction of prognosis and immune landscape in gastric cancer.Frontiers in immunology · 2024Article
- Scientific opinion on the tolerable upper intake level for manganese.EFSA journal. European Food Safety Authority · 2023Article
- Review
- Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update.International journal of molecular sciences · 2021Review
- Transcriptomic profile analysis of brain inferior colliculus following acute hydrogen sulfide exposure.Toxicology · 2020Article
- New Insights on the Role of Manganese in Alzheimer's Disease and Parkinson's Disease.International journal of environmental research and public health · 2019Review
- Exosomes as Mediators of Chemical-Induced Toxicity.Current environmental health reports · 2019Review
- Broad spectrum proteomics analysis of the inferior colliculus following acute hydrogen sulfide exposure.Toxicology and applied pharmacology · 2018Article
- The effect of manganese exposure in Atp13a2-deficient mice.Neurotoxicology · 2018Article
- Cobinamide is effective for treatment of hydrogen sulfide-induced neurological sequelae in a mouse model.Annals of the New York Academy of Sciences · 2017Article
- Characterizing a mouse model for evaluation of countermeasures against hydrogen sulfide-induced neurotoxicity and neurological sequelae.Annals of the New York Academy of Sciences · 2017Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Chronic exposure to elevated levels of manganese (Mn) has been linked to a Parkinsonian-like movement disorder, resulting from dysfunction of the extrapyramidal motor system within the basal ganglia. However, the exact cellular and molecular mechanisms of Mn-induced neurotoxicity remain elusive. In this study, we treated C57BL/6J mice with 30mg/kg Mn via oral gavage for 30 days. Interestingly, in nigral tissues of Mn-exposed mice, we found a significant downregulation of the truncated isoform of p73 protein at the N-terminus (ΔNp73). To further determine the functional role of Mn-induced p73 downregulation in Mn neurotoxicity, we examined the interrelationship between the effect of Mn on p73 gene expression and apoptotic cell death in an N27 dopaminergic neuronal model. Consistent with our animal study, 300μM Mn treatment significantly suppressed p73 mRNA expression in N27 dopaminergic cells. We further determined that protein levels of the ΔNp73 isoform was also reduced in Mn-treated N27 cells and primary striatal cultures. Furthermore, overexpression of ΔNp73 conferred modest cellular protection against Mn-induced neurotoxicity. Taken together, our results demonstrate that Mn exposure downregulates p73 gene expression resulting in enhanced susceptibility to apoptotic cell death. Thus, further characterization of the cellular mechanism underlying p73 gene downregulation will improve our understanding of the molecular underpinnings of Mn neurotoxicity.
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