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Self-assembled α-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Aeschimann Walter, Staats Stefanie, Kammer Stephan, Olieric Natacha, Jeckelmann Jean-Marc, Fotiadis Dimitrios, Netscher Thomas, Rimbach Gerald, Cascella Michele, Stocker Achim,
Project The role of CRALBP in the chemistry of vision
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Original article (peer-reviewed)

Journal Scientific Reports
Volume (Issue) 7(1)
Page(s) 4970 - 4970
Title of proceedings Scientific Reports
DOI 10.1038/s41598-017-05148-9

Open Access

URL http://doi.org/10.1038/s41598-017-05148-9
Type of Open Access Publisher (Gold Open Access)

Abstract

Vitamin E is one of the most important natural antioxidants, protecting polyunsaturated fatty acids in the membranes of cells. Among different chemical isoforms assimilated from dietary regimes, RRR-α-tocopherol is the only one retained in higher animals. This is possible thanks to α-Tocopherol Transfer Protein (α-TTP), which extracts α-tocopherol from endosomal compartments in liver cells, facilitating its distribution into the body. Here we show that, upon binding to its substrate, α-TTP acquires tendency to aggregation into thermodynamically stable high molecular weight oligomers. Determination of the structure of such aggregates by X-ray crystallography revealed a spheroidal particle formed by 24 protein monomers. Oligomerization is triggered by refolding of the N-terminus. Experiments with cultured cell monolayers demonstrate that the same oligomers are efficiently transported through an endothelial barrier (HUVEC) and not through an epithelial one (Caco-2). Discovery of a human endogenous transport protein with intrinsic capability of crossing endothelial tissues opens to new ways of drug delivery into the brain or other tissues protected by endothelial barriers.
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