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

Aeschimann, Walter, Staats, Stefanie, Kammer, Stephan, Olieric, Natacha, Jeckelmann, Jean-Marc, Fotiadis, Dimitrios, Netscher, Thomas, Rimbach, Gerald, Cascella, Michele and Stocker, Achim (2017) Self-assembled α-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier. Scientific Reports, 7 (1). DOI 10.1038/s41598-017-05148-9.

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Supplementary data:

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.

Document Type: Article
Research affiliation: Kiel University > Kiel Marine Science
OceanRep > The Future Ocean - Cluster of Excellence
Kiel University
Refereed: Yes
Open Access Journal?: Yes
DOI etc.: 10.1038/s41598-017-05148-9
ISSN: 2045-2322
Projects: Future Ocean
Date Deposited: 19 Dec 2017 15:31
Last Modified: 12 Apr 2019 14:45
URI: http://oceanrep.geomar.de/id/eprint/40946

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