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

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 > Departement of Chemistry and Biochemistry

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 and 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:

22 Oct 2017 02:37

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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