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Mass spectrometry‐based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin

ABC transporters (ATP‐binding cassette transporter) traffic drugs and their metabolites across membranes, making ABC transporter expression levels a key factor regulating local drug concentrations in different tissues and individuals. Yet, quantification of ABC transporters remains challenging becau...

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Autores principales: Al‐Majdoub, Zubida M., Achour, Brahim, Couto, Narciso, Howard, Martyn, Elmorsi, Yasmine, Scotcher, Daniel, Alrubia, Sarah, El‐Khateeb, Eman, Vasilogianni, Areti‐Maria, Alohali, Noura, Neuhoff, Sibylle, Schmitt, Lutz, Rostami‐Hodjegan, Amin, Barber, Jill
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756589/
https://www.ncbi.nlm.nih.gov/pubmed/33128234
http://dx.doi.org/10.1002/1873-3468.13982
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author Al‐Majdoub, Zubida M.
Achour, Brahim
Couto, Narciso
Howard, Martyn
Elmorsi, Yasmine
Scotcher, Daniel
Alrubia, Sarah
El‐Khateeb, Eman
Vasilogianni, Areti‐Maria
Alohali, Noura
Neuhoff, Sibylle
Schmitt, Lutz
Rostami‐Hodjegan, Amin
Barber, Jill
author_facet Al‐Majdoub, Zubida M.
Achour, Brahim
Couto, Narciso
Howard, Martyn
Elmorsi, Yasmine
Scotcher, Daniel
Alrubia, Sarah
El‐Khateeb, Eman
Vasilogianni, Areti‐Maria
Alohali, Noura
Neuhoff, Sibylle
Schmitt, Lutz
Rostami‐Hodjegan, Amin
Barber, Jill
author_sort Al‐Majdoub, Zubida M.
collection PubMed
description ABC transporters (ATP‐binding cassette transporter) traffic drugs and their metabolites across membranes, making ABC transporter expression levels a key factor regulating local drug concentrations in different tissues and individuals. Yet, quantification of ABC transporters remains challenging because they are large and low‐abundance transmembrane proteins. Here, we analysed 200 samples of crude and membrane‐enriched fractions from human liver, kidney, intestine, brain microvessels and skin, by label‐free quantitative mass spectrometry. We identified 32 (out of 48) ABC transporters: ABCD3 was the most abundant in liver, whereas ABCA8, ABCB2/TAP1 and ABCE1 were detected in all tissues. Interestingly, this atlas unveiled that ABCB2/TAP1 may have TAP2‐independent functions in the brain and that biliary atresia (BA) and control livers have quite different ABC transporter profiles. We propose that meaningful biological information can be derived from a direct comparison of these data sets.
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spelling pubmed-77565892020-12-28 Mass spectrometry‐based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin Al‐Majdoub, Zubida M. Achour, Brahim Couto, Narciso Howard, Martyn Elmorsi, Yasmine Scotcher, Daniel Alrubia, Sarah El‐Khateeb, Eman Vasilogianni, Areti‐Maria Alohali, Noura Neuhoff, Sibylle Schmitt, Lutz Rostami‐Hodjegan, Amin Barber, Jill FEBS Lett Research Article ABC transporters (ATP‐binding cassette transporter) traffic drugs and their metabolites across membranes, making ABC transporter expression levels a key factor regulating local drug concentrations in different tissues and individuals. Yet, quantification of ABC transporters remains challenging because they are large and low‐abundance transmembrane proteins. Here, we analysed 200 samples of crude and membrane‐enriched fractions from human liver, kidney, intestine, brain microvessels and skin, by label‐free quantitative mass spectrometry. We identified 32 (out of 48) ABC transporters: ABCD3 was the most abundant in liver, whereas ABCA8, ABCB2/TAP1 and ABCE1 were detected in all tissues. Interestingly, this atlas unveiled that ABCB2/TAP1 may have TAP2‐independent functions in the brain and that biliary atresia (BA) and control livers have quite different ABC transporter profiles. We propose that meaningful biological information can be derived from a direct comparison of these data sets. John Wiley and Sons Inc. 2020-12-03 2020-12 /pmc/articles/PMC7756589/ /pubmed/33128234 http://dx.doi.org/10.1002/1873-3468.13982 Text en © 2020 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Al‐Majdoub, Zubida M.
Achour, Brahim
Couto, Narciso
Howard, Martyn
Elmorsi, Yasmine
Scotcher, Daniel
Alrubia, Sarah
El‐Khateeb, Eman
Vasilogianni, Areti‐Maria
Alohali, Noura
Neuhoff, Sibylle
Schmitt, Lutz
Rostami‐Hodjegan, Amin
Barber, Jill
Mass spectrometry‐based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin
title Mass spectrometry‐based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin
title_full Mass spectrometry‐based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin
title_fullStr Mass spectrometry‐based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin
title_full_unstemmed Mass spectrometry‐based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin
title_short Mass spectrometry‐based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin
title_sort mass spectrometry‐based abundance atlas of abc transporters in human liver, gut, kidney, brain and skin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756589/
https://www.ncbi.nlm.nih.gov/pubmed/33128234
http://dx.doi.org/10.1002/1873-3468.13982
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