ArticlePloS one2014
Glial cell ceruloplasmin and hepcidin differentially regulate iron efflux from brain microvascular endothelial cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 106 citations in OpenAlex.
- Parkinson's disease LRRK2 mutations dysregulate iron homeostasis and promote oxidative stress and ferroptosis in human neurons and astrocytes.Molecular neurodegeneration · 2026Article
- How does iron cross the abluminal membrane of the blood-brain barrier.Experimental & molecular medicine · 2026Review
- L-DOPA influences transferrin-dependent iron release at the blood-brain barrier.Fluids and barriers of the CNS · 2026Article
- Extracellular vesicles released from blood-brain barrier endothelial cells mediate brain iron accumulation during LPS-induced brain inflammation.The Journal of biological chemistry · 2026Article
- The Ferroxidase-Permease System for Transport of Iron Across Membranes: From Yeast to Humans.International journal of molecular sciences · 2025Review
- Normalization of Fetal Cerebral and Hepatic Iron by Parental Iron Therapy to Pregnant Rats with Systemic Iron Deficiency without Anemia.Nutrients · 2024Article
- Review
- Insights into Iron Metabolism Parameters in Ischemic Stroke: A Single-Center Prospective Cohort Study.International journal of molecular sciences · 2024Article
- Hepcidin depending on astrocytic NEO1 ameliorates blood-brain barrier dysfunction after subarachnoid hemorrhage.Cell death & disease · 2024Article
- Review
- The Iron Metabolism with a Specific Focus on the Functioning of the Nervous System.Biomedicines · 2024Review
- Brain Iron Homeostasis and Mental Disorders.Antioxidants (Basel, Switzerland) · 2023Review
- Amyloid-β exposed astrocytes induce iron transport from endothelial cells at the blood-brain barrier by altering the ratio of apo- and holo-transferrin.Journal of neurochemistry · 2023Article
- Induction of Hepcidin Expression in the Renal Cortex of Sickle Cell Disease Mice.International journal of molecular sciences · 2023Article
- Apo- and holo-transferrin differentially interact with hephaestin and ferroportin in a novel mechanism of cellular iron release regulation.Journal of biomedical science · 2023Article
- 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
- Perturbed iron biology in the prefrontal cortex of people with schizophrenia.Molecular psychiatry · 2023Article
- Apo- and holo- transferrin differentially interact with ferroportin and hephaestin to regulate iron release at the blood-brain barrier.Research square · 2023Article
- Apo- and holo- transferrin differentially interact with ferroportin and hephaestin to regulate iron release at the blood-brain barrier.bioRxiv : the preprint server for biology · 2023Article
- Ceruloplasmin-Deficient Mice Show Dysregulation of Lipid Metabolism in Liver and Adipose Tissue Reduced by a Protein Replacement.International journal of molecular sciences · 2023Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
We have used an in vitro model system to probe the iron transport pathway across the brain microvascular endothelial cells (BMVEC) of the blood-brain barrier (BBB). This model consists of human BMVEC (hBMVEC) and C6 glioma cells (as an astrocytic cell line) grown in a transwell, a cell culture system commonly used to quantify metabolite flux across a cell-derived barrier. We found that iron efflux from hBMVEC through the ferrous iron permease ferroportin (Fpn) was stimulated by secretion of the soluble form of the multi-copper ferroxidase, ceruloplasmin (sCp) from the co-cultured C6 cells. Reciprocally, expression of sCp mRNA in the C6 cells was increased by neighboring hBMVEC. In addition, data indicate that C6 cell-secreted hepcidin stimulates internalization of hBMVEC Fpn but only when the end-feet projections characteristic of this glia-derived cell line are proximal to the endothelial cells. This hepcidin-dependent loss of Fpn correlated with knock-down of iron efflux from the hBMVEC; this result was consistent with the mechanism by which hepcidin regulates iron efflux in mammalian cells. In summary, the data support a model of iron trafficking across the BBB in which the capillary endothelium induce the underlying astrocytes to produce the ferroxidase activity needed to support Fpn-mediated iron efflux. Reciprocally, astrocyte proximity modulates the effective concentration of hepcidin at the endothelial cell membrane and thus the surface expression of hBMVEC Fpn. These results are independent of the source of hBMVEC iron (transferrin or non-transferrin bound) indicating that the model developed here is broadly applicable to brain iron homeostasis.
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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.