Physiological pathway for low density lipoproteins across the blood-brain barrier: transcytosis through brain capillary endothelial cells in vitro

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Candela, Pietra | Gosselet, Fabien | Miller, Florence | Buée-Scherrer, Valérie | Torpier, Gérard | Cecchelli, Roméo | Tilloy-Fenart, Laurence

Edité par CCSD ; Taylor & Francis -

International audience. 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, we have demonstrated that low density lipoprotein 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, we have demonstrated that the LDL receptor is located in the caveolae membrane fraction. Then, low density lipoproteins internalized were detected by electron microscopy in multivesicular bodies. We identified in brain capillary ECs a novel endosomal compartment, mildly acidic, positive for marker Lamp-1 but devoid of any degradative capability. In terms of pH point of view, cellular location and caveolae derived formation, the multivesicular organelles described here can be related to the caveosome structure. Our results could allow us to 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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