Iron Uptake in Blood‐Brain Barrier Endothelial Cells Cultured in Iron‐Depleted and Iron‐Enriched Media

Abstract

Iron is essential in the cellular metabolism of all mammalian tissues, including the brain. Intracerebral iron concentrations vary with age and in several (neurological) diseases. Although it is evident that endothelial cells lining the capillaries in the brain are of importance, factors governing the regulation of intracerebral iron concentration are unknown. To investigate the role of blood‐brain barrier endothelial cells in cerebral iron regulation, primary cultures of porcine blood‐brain barrier endothelial cells were grown in either iron‐enriched or iron‐depleted medium. Iron‐enriched cells showed a reduction in surface‐bound and total transferrin receptor numbers compared with iron‐depleted cells. Transferrin receptor kinetics showed that the transferrin receptor internalization rate in iron‐enriched cultures was higher, whereas the transferrin receptor externalization rate in iron‐enriched cultures was lower than the rate in iron‐depleted cultures. Moreover, blood‐brain barrier endothelial cells cultured in iron‐enriched medium were able to accumulate more iron intracellularly, which underlines our kinetic data on transferrin receptors. Our results agree with histopathological studies on brain tissue of patients with hemochromatosis, suggesting that at high peripheral iron concentrations, the rate of iron transport across the blood‐brain barrier endothelial cells is to some extent proportional to the peripheral iron concentration.

Essential Oil from Lemon Peels Inhibit Key Enzymes Linked to Neurodegenerative Conditions and Pro-oxidant Induced Lipid Peroxidation

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Transcytosis: Crossing Cellular Barriers

“…While several in vivo studies have reported that injected 125 I-Tf does not accumulate to the same extent as 59 Fe administered similarly (104), others report equivalent accumulations (152,635). Tf receptors are definitely present on brain endothelium (248), and Tf is internalized by brain endothelium in vivo via clathrin-coated vesicles (476), leading some to speculate that plasma Tf may be carrying Fe across and then recycling back unloaded (52, 384,429,430,545,591,635). Such a scenario would require a milieu on the basal side of sufficiently low pH to effect iron's release.…”

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