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Physiological Pathway for Low-Density Lipoproteins across the Blood-Brain Barrier: Transcytosis through Brain Capillary Endothelial Cells In Vitro
Open accessAbstract
Although an immense knowledge has accumulated concerning regulation of cholesterol homeostasis in the body, this does not include the brain, where details are just emerging. Using an in vitro blood-brain barrier model, the authors have demonstrated that low-density lipoprotein (LDL) underwent transcytosis through the endothelial cells (ECs) by a receptor-mediated process, bypassing the lysosomal compartment. Moreover, caveolae might be involved in these blood-borne molecule transports from the blood to the brain. Although several ligands are known to be internalized through cell surface caveolae, the subsequent intracellular pathways have remained elusive. By cell fractionation experiment and Western blot, the authors have demonstrated that the LDL receptor is located in the caveolae membrane fraction. Then, LDLs internalized were detected by electron microscopy in multivesicular bodies. The authors identified in brain capillary ECs a novel endosomal compartment, mildly acidic, positive for marker Lamp-1 but devoid of any degradative capability. From the point of view of pH, cellular location, and caveolae-derived formation, the multivesicular organelles described here can be related to the caveosome structure. These results could provide clues to physiological functions of caveolae-caveosome transcellular pathway in brain capillary ECs and may help in the rational design of more effective therapeutic drugs to the brain.
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Metadata
- Authors
- Candela, P., Gosselet, F., Miller, F., Buee-Scherrer, V., Torpier, G., Cecchelli, R., & Fenart, L.
- Affiliations
- Laboratoire Jean Perrin (FR)
- Inserm (FR)
- Venue
- Endothelium
- Publisher
- Informa UK Limited
- Published
- 2008-01
- Volume
- 15
- Issue
- 5-6
- Pages
- 254-264
- ISSN
- 1026-793X (ISSN-L)
- 1062-3329
- 1029-2373
- OpenAlex
- W2147613942
- Cited by
- 117
- References
- 52
- Citations by year
- 2025: 6 · 2024: 6 · 2023: 5 · 2022: 5 · 2021: 6 · 2020: 11 · 2019: 4 · 2018: 7 · 2017: 6 · 2016: 5 · 2015: 10 · 2014: 12 · 2013: 8 · 2012: 8
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- Endothelium (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- low-density lipoprotein, blood-brain barrier, transcytosis, brain microvascular endothelial cells, caveolae, LDL receptor, multivesicular bodies, LAMP1, cholesterol homeostasis, receptor-mediated transport, endosomes
- MeSH terms
- Animals, Astrocytes, Blood-Brain Barrier, Brain, Capillaries, Cattle, Cell Membrane, Cells, Cultured, Cerebral Arteries, Cholesterol, Endocytosis, Endothelium, Vascular, Lipoproteins, LDL, Receptors, LDL, Endosomes, Coculture Techniques, Protein Transport, Caveolae, Transport Vesicles, Endothelial Cells, Microscopy, Electron, Transmission, Rats, Lysosomal Membrane Proteins, Lysosomal-Associated Membrane Protein 1
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