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

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-Tocoph...

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Autores principales:	Walter Aeschimann, Stefanie Staats, Stephan Kammer, Natacha Olieric, Jean-Marc Jeckelmann, Dimitrios Fotiadis, Thomas Netscher, Gerald Rimbach, Michele Cascella, Achim Stocker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/512e4f179f3b4a209cf8087efad82f43
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spelling	oai:doaj.org-article:512e4f179f3b4a209cf8087efad82f432021-12-02T16:06:11ZSelf-assembled α-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier10.1038/s41598-017-05148-92045-2322https://doaj.org/article/512e4f179f3b4a209cf8087efad82f432017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05148-9https://doaj.org/toc/2045-2322Abstract 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.Walter AeschimannStefanie StaatsStephan KammerNatacha OliericJean-Marc JeckelmannDimitrios FotiadisThomas NetscherGerald RimbachMichele CascellaAchim StockerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Walter Aeschimann Stefanie Staats Stephan Kammer Natacha Olieric Jean-Marc Jeckelmann Dimitrios Fotiadis Thomas Netscher Gerald Rimbach Michele Cascella Achim Stocker Self-assembled α-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier
description	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.
format	article
author	Walter Aeschimann Stefanie Staats Stephan Kammer Natacha Olieric Jean-Marc Jeckelmann Dimitrios Fotiadis Thomas Netscher Gerald Rimbach Michele Cascella Achim Stocker
author_facet	Walter Aeschimann Stefanie Staats Stephan Kammer Natacha Olieric Jean-Marc Jeckelmann Dimitrios Fotiadis Thomas Netscher Gerald Rimbach Michele Cascella Achim Stocker
author_sort	Walter Aeschimann
title	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_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_sort	self-assembled α-tocopherol transfer protein nanoparticles promote vitamin e delivery across an endothelial barrier
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/512e4f179f3b4a209cf8087efad82f43
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Self-assembled α-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier

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