Aeschimann, Walter; Staats, Stefanie; Kammer, Stephan Martin; Olieric, Natacha; Jeckelmann, Jean-Marc; Fotiadis, Dimitrios José; Netscher, Thomas; Rimbach, Gerald; Cascella, Michele; Stocker, Achim (2017). Self-assembled α-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier. Scientific Reports, 7(1) Nature Publishing Group 10.1038/s41598-017-05148-9
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Aeschimann, Walter, Kammer, Stephan Martin, Jeckelmann, Jean-Marc, Fotiadis, Dimitrios José, Cascella, Michele, Stocker, Achim |
Subjects: |
500 Science > 570 Life sciences; biology 500 Science > 540 Chemistry 600 Technology > 610 Medicine & health |
ISSN: |
2045-2322 |
Publisher: |
Nature Publishing Group |
Funders: |
Organisations 31003 not found.; Organisations 31003 not found.; Organisations 179568 not found. |
Language: |
English |
Submitter: |
Achim Stocker |
Date Deposited: |
16 Oct 2017 08:41 |
Last Modified: |
05 Dec 2022 15:07 |
Publisher DOI: |
10.1038/s41598-017-05148-9 |
BORIS DOI: |
10.7892/boris.104903 |
URI: |
https://boris.unibe.ch/id/eprint/104903 |
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