Characterization of Iron Uptake from Transferrin by Murine Endothelial Cells
العنوان: | Characterization of Iron Uptake from Transferrin by Murine Endothelial Cells |
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المؤلفون: | Rupert Hallmann, Donna L. Savigni, Evan H. Morgan, Erica Baker |
المصدر: | Endothelium. 7:135-147 |
بيانات النشر: | Informa UK Limited, 2000. |
سنة النشر: | 2000 |
مصطلحات موضوعية: | Lipopolysaccharides, Necrosis, Lipopolysaccharide, Physiology, Iron, Transferrin receptor, Iron Chelating Agents, Ferric Compounds, Arsenicals, Cell Line, Mice, chemistry.chemical_compound, Receptors, Transferrin, medicine, Animals, Endothelium, Enzyme Inhibitors, Receptor, chemistry.chemical_classification, Tumor Necrosis Factor-alpha, Chemistry, Transferrin, Brain, Cell Biology, General Medicine, Molecular biology, Endocytosis, Anti-Bacterial Agents, Endothelial stem cell, Biochemistry, Blood-Brain Barrier, Ethylmaleimide, Cell culture, Lymph Nodes, Macrolides, Efflux, medicine.symptom |
الوصف: | Iron is required by the brain for normal function, however, the mechanisms by which it crosses the blood-brain barrier (BBB) are poorly understood. The uptake and efflux of transferrin (Tf) and Fe by murine brain-derived (bEND3) and lymph node-derived (m1END1) endothelial cell lines was compared. The effects of iron chelators, metabolic inhibitors and the cellular activators, lipopolysaccharide (LPS) and tumour necrosis factor-alpha (TNF-alpha), on Tf and Fe uptake were investigated. Cells were incubated with 59Fe-125I-Tf; Fe uptake was shown to increase linearly over time for both cell lines, while Tf uptake reached a plateau within 2 h. Both Tf and Fe uptake were saturable. bEND3 cells were shown to have half as many Tf receptors as m1END1 cells, but the mean cycling times of a Tf molecule were the same. Tf and Fe efflux from the cells were measured over time, revealing that after 2 h only 25% of the Tf but 80% of the Fe remained associated with the cells. Of 7 iron chelators, only deferriprone (L1) markedly decreased Tf uptake. However, Fe uptake was reduced by more than 50% by L1, pyridoxal isonicotinoyl hydrazone (PIH) and desferrithiocin (DFT). The cellular activators TNF-alpha or LPS had little effect on Tf turnover, but they accelerated Fe uptake in both endothelial cell types. Phenylarsenoxide (PhAsO) and N-ethyl maleimide (NEM), inhibitors of Tf endocytosis, reduced both Tf and Fe uptake in both cell lines, while bafilomycin A1, an inhibitor of endosomal acidification, reduced Fe uptake but did not affect Tf uptake. The results suggest that Tf and Fe uptake by both bEND3 and m1END1 is via receptor-mediated endocytosis with release of Fe from Tf within the cell and recycling of apo-Tf. On the basis of Tf- and Fe-metabolism both cell lines are similar and therefore well suited for use in in vitro models for Fe transport across the BBB. |
تدمد: | 1029-2373 1062-3329 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0afc80c2bc7dc77fb13fccd34635673a https://doi.org/10.3109/10623320009072208 |
رقم الأكسشن: | edsair.doi.dedup.....0afc80c2bc7dc77fb13fccd34635673a |
قاعدة البيانات: | OpenAIRE |
تدمد: | 10292373 10623329 |
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