ArticleBiometals : an international journal on the role of metal ions in biology, biochemistry, and medicine2012
Mechanistic analysis of iron accumulation by endothelial cells of the BBB.
Article in Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
- Temporal and cell-specific changes to cellular iron sequestration and lipid peroxidation in a murine model of neonatal hypoxic-ischemic brain injury.Neurobiology of disease · 2026Article
- How does iron cross the abluminal membrane of the blood-brain barrier.Experimental & molecular medicine · 2026Review
- Stress-Induced Dysregulation of Brain Iron Metabolism and Its Links to Neurological Disorders.Biology · 2025Review
- Astrocyte secretome remodeling under iron deficiency: potential implications for brain iron homeostasis.Biology open · 2025Article
- Genetic Markers of Postmortem Brain Iron.Journal of neurochemistry · 2025Article
- Pemetrexed sensitizes cisplatin therapy by inducing ferroptosis in NSCLC cells.Frontiers in pharmacology · 2025Article
- Iron imbalance in neurodegeneration.Molecular psychiatry · 2024Review
- Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.Archives of toxicology · 2024Review
- Inflammatory response in gastrointestinal cancers: Overview of six transmembrane epithelial antigens of the prostate in pathophysiology and clinical implications.World journal of clinical oncology · 2024Review
- Iron and Targeted Iron Therapy in Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Brain Iron Homeostasis and Mental Disorders.Antioxidants (Basel, Switzerland) · 2023Review
- Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Targeting ferroptosis as novel therapeutic approaches for epilepsy.Frontiers in pharmacology · 2023Review
- Quantitating Iron Transport across the Mouse Placenta In Vivo using Nonradioactive Iron Isotopes.Journal of visualized experiments : JoVE · 2022Article
- Aberrant Cerebral Iron Trafficking Co-morbid With Chronic Inflammation: Molecular Mechanisms and Pharmacologic Intervention.Frontiers in neurology · 2022Review
- Iron Dyshomeostasis and Ferroptosis: A New Alzheimer's Disease Hypothesis?Frontiers in aging neuroscience · 2022Review
- Quercetin attenuates neurotoxicity induced by iron oxide nanoparticles.Journal of nanobiotechnology · 2021Review
- The iron chelator, PBT434, modulates transcellular iron trafficking in brain microvascular endothelial cells.PloS one · 2021Article
- A holistic view of mammalian (vertebrate) cellular iron uptake.Metallomics : integrated biometal science · 2020Review
- The Intrinsic Biological Identities of Iron Oxide Nanoparticles and Their Coatings: Unexplored Territory for Combinatorial Therapies.Nanomaterials (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The mechanism(s) by which iron in blood is transported across the blood-brain barrier (BBB) remains controversial. Here we have examined the first step of this trans-cellular pathway, namely the mechanism(s) of iron uptake into human brain microvascular endothelial cells (hBMVEC). We show that hBMVEC actively reduce non-transferrin bound Fe(III) (NTBI) and transferrin-bound Fe(III) (TBI); this activity is associated with one or more ferrireductases. Efficient, exo-cytoplasmic ferri-reduction from TBI is dependent upon transferrin receptor (TfR), also. Blocking holo-Tf binding with an anti-TfR antibody significantly decreases the reduction of iron from transferrin by hBMVEC, suggesting that holo-Tf needs to bind to TfR in order for efficient reduction to occur. Ferri-reduction from TBI significantly decreases when hBMVEC are pre-treated with Pt(II), an inhibitor of cell surface reductase activity. Uptake of (59)Fe from (59)Fe-Tf by endothelial cells is inhibited by 50 % when ferrozine is added to solution; in contrast, no inhibition occurs when cells are alkalinized with NH(4)Cl. This indicates that the iron reduced from holo-transferrin at the plasma membrane accounts for at least 50 % of the iron uptake observed. hBMVEC-dependent reduction and uptake of NTBI utilizes a Pt(II)-insensitive reductase. Reductase-independent uptake of Fe(II) by hBMVEC is inhibited up to 50 % by Zn(II) and/or Mn(II) by a saturable process suggesting that redundant Fe(II) transporters exist in the hBMVEC plasma membrane. These results are the first to demonstrate multiple mechanism(s) of TBI and NTBI reduction and uptake by endothelial cells (EC) of the BBB.
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Registered trials
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