ArticleNeurotoxicology2013
Iron depletion increases manganese uptake and potentiates apoptosis through ER stress.
Article in Neurotoxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 74 citations in OpenAlex.
- Emergent latent neurotoxic effects of manganese following nominal chronic exposures in human stem cell and Caenorhabditis elegans models.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Iron deficiency aggravates hepatic inflammation in suckling piglets via endoplasmic reticulum stress-driven NF-κB pathway activation.Journal of animal science and biotechnology · 2026Article
- Systematic analysis of naturally occurring missense mutations in human manganese transporters: prediction and structural insights.bioRxiv : the preprint server for biology · 2025Article
- Dietary manganese intake is positively associated with metabolic dysfunction-associated steatotic liver disease: a multicohort study.European journal of nutrition · 2025Article
- Role of manganese in brain health and disease: Focus on oxidative stress.Free radical biology & medicine · 2025Review
- Hepatic Dysfunction and Neuropsychiatric Sequelae Through Manganese Toxicity.Journal of Brown hospital medicine · 2025Article
- Chronic Manganese Neuro-Toxicity in a Patient With Cirrhosis and the Role of Iron-Deficiency Anaemia.Cureus · 2024Article
- Signal Transduction Associated with Mn-induced Neurological Dysfunction.Biological trace element research · 2024Review
- Transcriptome and metabolome analyses reveal new insights into chlorophyll, photosynthesis, metal ion and phenylpropanoids related pathways during sugarcane ratoon chlorosis.BMC plant biology · 2022Article
- Multi-Elemental Analysis of Human Optic Chiasm-A New Perspective to Reveal the Pathomechanism of Nerve Fibers' Degeneration.International journal of environmental research and public health · 2022Article
- Manganese-Induced Neurotoxicity through Impairment of Cross-Talk Pathways in Human Neuroblastoma Cell LineToxics · 2021Article
- Alteration of iron (Fe), copper (Cu), zinc (Zn), and manganese (Mn) tissue levels and speciation in rats with desferioxamine-induced iron deficiency.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2021Article
- Metal-induced neurotoxicity in a RAGE-expressing C. elegans model.Neurotoxicology · 2020Article
- Siderophores induce mitophagy-dependent apoptosis in platelets.Annals of translational medicine · 2020Article
- Heavy Metals Exposure and Alzheimer's Disease and Related Dementias.Journal of Alzheimer's disease : JAD · 2020Review
- Prenatal manganese and cord blood mitochondrial DNA copy number: Effect modification by maternal anemic status.Environment international · 2019Article
- Manganese-induced cellular disturbance in the baker's yeast, Saccharomyces cerevisiae with putative implications in neuronal dysfunction.Scientific reports · 2019Article
- Ferroportin disease mutations influence manganese accumulation and cytotoxicity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Metal bashing: iron deficiency and manganese overexposure impact on peripheral nerves.Journal of toxicology and environmental health. Part A · 2019Article
- Manganese transport and toxicity in polarized WIF-B hepatocytes.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Iron deficiency is a risk factor for manganese (Mn) accumulation. Excess Mn promotes neurotoxicity but the mechanisms involved and whether iron depletion might affect these pathways is unknown. To study Mn intoxication in vivo, iron deficient and control rats were intranasally instilled with 60mg MnCl2/kg over 3 weeks. TUNEL staining of olfactory tissue revealed that Mn exposure induced apoptosis and that iron deficiency potentiated this effect. In vitro studies using the dopaminergic SH-SY5Y cell line confirmed that Mn-induced apoptosis was enhanced by iron depletion using the iron chelator desferrioxamine. Mn has been reported to induce apoptosis through endoplasmic reticulum stress. In SH-SY5Y cells, Mn exposure induced the ER stress genes glucose regulated protein 94 (GRP94) and C/EBP homologous protein (CHOP). Increased phosphorylation of the eukaryotic translation initiation factor 2α (phospho-eIF2α) was also observed. These effects were accompanied by the activation of ER resident enzyme caspase-12, and the downstream apoptotic effector caspase-3 was also activated. All of the Mn-induced responses were enhanced by DFO treatment. Inhibitors of ER stress and caspases significantly blocked Mn-induced apoptosis and its potentiation by DFO, indicating that ER stress and subsequent caspase activation underlie cell death. Taken together, these data reveal that Mn induces neuronal cell death through ER stress and the UPR response pathway and that this apoptotic effect is potentiated by iron deficiency most likely through upregulation of DMT1.
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