ArticleJournal of neurochemistry2010
Ferroportin is a manganese-responsive protein that decreases manganese cytotoxicity and accumulation.
Article in Journal of neurochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 152 citations in OpenAlex.
- Overlaps in mammalian iron and manganese homeostasis: recent advances.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Excess Dietary Manganese Impairs Iron Nutrition via Modulating Duodenal Transporters in Weaned Pigs.Veterinary sciences · 2025Article
- Removal of Toxic Metabolites-Chelation: Manganese Disorders.Journal of inherited metabolic disease · 2025Review
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- Gut to brain: essential micronutrient and trace element manganese transport, function and toxicity.Frontiers in physiology · 2025Review
- Studies of Slc30a10 Deficiency in Mice Reveal That Intestinal Iron Transporters Dmt1 and Ferroportin Transport Manganese.Cellular and molecular gastroenterology and hepatology · 2025Article
- Metal-Based Nanomedicines for Inducing Programmed Cell Death to Enhance the Efficacy of Cancer Immunotherapy.International journal of nanomedicine · 2025Review
- Manganese transporter SLC30A10 and iron transporters SLC40A1 and SLC11A2 impact dietary manganese absorption.bioRxiv : the preprint server for biology · 2024Article
- Hepatic HIF2 is a key determinant of manganese excess and polycythemia in SLC30A10 deficiency.JCI insight · 2024Article
- Divalent metal content in diet affects severity of manganese toxicity in Drosophila.Biology open · 2024Article
- Consequences of Disturbing Manganese Homeostasis.International journal of molecular sciences · 2023Review
- Hypoxia-inducible factor 2 is a key determinant of manganese excess and polycythemia in SLC30A10 deficiency.bioRxiv : the preprint server for biology · 2023Article
- Direct Cell Radiolabeling forChemical reviews · 2022Review
- Chronic Alcohol Abuse Alters Hepatic Trace Element Concentrations-Metallomic Study of Hepatic Elemental Composition by Means of ICP-OES.Nutrients · 2022Article
- Manganese-induced reactive oxygen species activate IκB kinase to upregulate YY1 and impair glutamate transporter EAAT2 function in human astrocytes in vitro.Neurotoxicology · 2021Article
- Manganese methionine hydroxy analog chelated affects growth performance, trace element deposition and expression of related transporters of broilers.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2021Article
- Downregulation of FPN1 acts as a prognostic biomarker associated with immune infiltration in lung cancer.Aging · 2021Article
- Iron and manganese transport in mammalian systems.Biochimica et biophysica acta. Molecular cell research · 2021Review
- Manganese Accumulation in the Brain via Various Transporters and Its Neurotoxicity Mechanisms.Molecules (Basel, Switzerland) · 2020Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Although manganese (Mn) is an essential trace element for human development and growth, chronic exposure to excessive Mn levels can result in psychiatric and motor disturbances, referred to as manganism. However, there are no known mechanism(s) for efflux of excess Mn from mammalian cells. Here, we test the hypothesis that the cytoplasmic iron (Fe) exporter ferroportin (Fpn) may also function as a Mn exporter to attenuate Mn toxicity. Using an inducible human embryonic kidney (HEK293T) cell model, we examined the influence of Fpn expression on Mn-induced cytotoxicity and intracellular Mn concentrations. We found that induction of an Fpn-green fluorescent protein fusion protein in HEK293T cells was cytoprotective against several measures of Mn toxicity, including Mn-induced cell membrane leakage and Mn-induced reductions in glutamate uptake. Fpn-green fluorescent protein mediated cytoprotection correlated with decreased Mn accumulation following Mn exposure. Thus, Fpn expression reduces Mn toxicity concomitant with reduced Mn accumulation. To determine if mammalian cells may utilize Fpn in response to increased intracellular Mn concentrations and toxicity, we assessed endogenous Fpn levels in Mn-exposed HEK293T cells and in mouse brain in vivo. We find that 6 h of Mn exposure in HEK293T cells is associated with a significant increase in Fpn levels. Furthermore, mice exposed to Mn showed an increase in Fpn levels in both the cerebellum and cortex. Collectively, these results indicate that (i) Mn exposure promotes Fpn protein expression, (ii) Fpn expression reduces net Mn accumulation, and (iii) reduces cytotoxicity associated with exposure to this metal.
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