ArticleThe Journal of biological chemistry2013
Ferroportin and exocytoplasmic ferroxidase activity are required for brain microvascular endothelial cell iron efflux.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 89 citations in OpenAlex.
- How does iron cross the abluminal membrane of the blood-brain barrier.Experimental & molecular medicine · 2026Review
- Ferroptosis in neurological diseases: moving towards therapeutic intervention.Molecular psychiatry · 2026Review
- Amyloid Precursor Protein Abnormalities Destabilize Membrane Ferroportin: A Novel Mechanism Underlying Early Brain Pathologies and Memory Impairment in Alzheimer's Disease.International journal of molecular sciences · 2026Article
- Iron-dependent ferroptosis in cardiac microvascular endothelial cells: a key link between dysregulated iron homeostasis and microcirculatory injury during myocardial ischemia-reperfusion.Frontiers in cardiovascular medicine · 2026Review
- Ferroptosis and Alzheimer's disease: a new insight into neurodegeneration.Frontiers in immunology · 2026Review
- Ferroptosis and Iron Homeostasis: Molecular Mechanisms and Neurodegenerative Disease Implications.Antioxidants (Basel, Switzerland) · 2025Review
- Functional Characterization of the Hephaestin Variant D568H Provides Novel Mechanistic Insights on Iron-Dependent Asbestos-Induced Carcinogenesis.International journal of molecular sciences · 2025Article
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- The Ferroxidase-Permease System for Transport of Iron Across Membranes: From Yeast to Humans.International journal of molecular sciences · 2025Review
- Iron imbalance in neurodegeneration.Molecular psychiatry · 2024Review
- Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.Archives of toxicology · 2024Review
- Brain Iron Homeostasis and Mental Disorders.Antioxidants (Basel, Switzerland) · 2023Review
- Review
- Lactoferrin: from the structure to the functional orchestration of iron homeostasis.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Review
- The biology of mammalian multi-copper ferroxidases.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Review
- Apicobasal transferrin receptor localization and trafficking in brain capillary endothelial cells.Fluids and barriers of the CNS · 2023Article
- Iron homeostasis and post-hemorrhagic hydrocephalus: a review.Frontiers in neurology · 2023Review
- Iron Homeostasis in the CNS: An Overview of the Pathological Consequences of Iron Metabolism Disruption.International journal of molecular sciences · 2022Review
- Iron Dyshomeostasis and Ferroptosis: A New Alzheimer's Disease Hypothesis?Frontiers in aging neuroscience · 2022Review
- Hepcidin is upregulated and is a potential therapeutic target associated with immunity in glioma.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The mechanism(s) of iron flux across the brain microvasculature endothelial cells (BMVEC) of the blood-brain barrier remains unknown. Although both hephaestin (Hp) and the ferrous iron permease ferroportin (Fpn) have been identified in BMVEC, their roles in iron efflux have not been examined. Using a human BMVEC line (hBMVEC), we have demonstrated that these proteins are required for iron efflux from these cells. Expression of both Hp and Fpn protein was confirmed in hBMVEC by immunoblot and indirect immunofluorescence; we show that hBMVEC express soluble ceruloplasmin (Cp) transcript as well. Depletion of endogenous Hp and Cp via copper chelation leads to the reduction of hBMVEC Fpn protein levels as well as a complete inhibition of (59)Fe efflux. Both hBMVEC Fpn protein and (59)Fe efflux activity are restored upon incubation with 6.6 nm soluble plasma Cp. These results are independent of the source of cell iron, whether delivered as transferrin- or non-transferrin-bound (59)Fe. Our results demonstrate that iron efflux from hBMVEC Fpn requires the action of an exocytoplasmic ferroxidase, which can be either endogenous Hp or extracellular Cp.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.