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

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 Tran...

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Autores principales: Aeschimann, Walter, Staats, Stefanie, Kammer, Stephan, Olieric, Natacha, Jeckelmann, Jean-Marc, Fotiadis, Dimitrios, Netscher, Thomas, Rimbach, Gerald, Cascella, Michele, Stocker, Achim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504013/
https://www.ncbi.nlm.nih.gov/pubmed/28694484
http://dx.doi.org/10.1038/s41598-017-05148-9
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author Aeschimann, Walter
Staats, Stefanie
Kammer, Stephan
Olieric, Natacha
Jeckelmann, Jean-Marc
Fotiadis, Dimitrios
Netscher, Thomas
Rimbach, Gerald
Cascella, Michele
Stocker, Achim
author_facet Aeschimann, Walter
Staats, Stefanie
Kammer, Stephan
Olieric, Natacha
Jeckelmann, Jean-Marc
Fotiadis, Dimitrios
Netscher, Thomas
Rimbach, Gerald
Cascella, Michele
Stocker, Achim
author_sort Aeschimann, Walter
collection PubMed
description 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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spelling pubmed-55040132017-07-12 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 Stocker, Achim Sci Rep Article 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. Nature Publishing Group UK 2017-07-10 /pmc/articles/PMC5504013/ /pubmed/28694484 http://dx.doi.org/10.1038/s41598-017-05148-9 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Aeschimann, Walter
Staats, Stefanie
Kammer, Stephan
Olieric, Natacha
Jeckelmann, Jean-Marc
Fotiadis, Dimitrios
Netscher, Thomas
Rimbach, Gerald
Cascella, Michele
Stocker, Achim
Self-assembled α-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier
title Self-assembled α-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier
title_full Self-assembled α-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier
title_fullStr Self-assembled α-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier
title_full_unstemmed Self-assembled α-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier
title_short Self-assembled α-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier
title_sort self-assembled α-tocopherol transfer protein nanoparticles promote vitamin e delivery across an endothelial barrier
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504013/
https://www.ncbi.nlm.nih.gov/pubmed/28694484
http://dx.doi.org/10.1038/s41598-017-05148-9
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