Transportomics: screening for substrates of ABC transporters in body fluids using vesicular transport assays
| Autor: | Krumpochova, P, Sapthu, S., Brouwers, J.F.H.M., de Haas, M., de Vos, R., Borst, P., van de Wetering, K., Biology of Reproductive Cells, Membrane Enzymology, Sub Membrane Enzymology begr. 01-06-12, Dep Biochemie en Celbiologie |
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| Přispěvatelé: | Biology of Reproductive Cells, Membrane Enzymology, Sub Membrane Enzymology begr. 01-06-12, Dep Biochemie en Celbiologie, BioAnalytical Chemistry, AIMMS, Cancer Center Amsterdam, Medical Biochemistry |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
mice
Biological Transport Active Phytoestrogens ATP-binding cassette transporter Sf9 Biology Spodoptera Biochemistry Xenobiotics multidrug-resistance protein Genetics Animals Humans tandem mass-spectrometry gene Molecular Biology Mice Knockout disease Multidrug resistance-associated protein 2 Vesicle glucuronides Metabolism biology.organism_classification Multidrug Resistance-Associated Protein 2 Recombinant Proteins Transmembrane protein Body Fluids Vesicular transport protein rats Kinetics International (English) mrp2 Metabolome BIOS Applied Metabolic Systems ATP-Binding Cassette Transporters Multidrug Resistance-Associated Proteins mutation metabolism Biotechnology |
| Zdroj: | FASEB Journal, 26, 738. FASEB Krumpochova, P, Sapthu, S, Brouwers, J F, de Haas, M, de Vos, R, Borst, P & van de Wetering, K 2012, ' Transportomics: screening for substrates of ABC transporters in body fluids using vesicular transport assays ', FASEB Journal, no. 26, pp. 738-747 . https://doi.org/10.1096/fj.11-195743 FASEB Journal, 26(2), 738-747 FASEB Journal, 738-747. FASEB ISSUE=26;STARTPAGE=738;ENDPAGE=747;ISSN=0892-6638;TITLE=FASEB Journal FASEB journal, 26(2), 738-747. FASEB FASEB Journal 26 (2012) 2 |
| ISSN: | 0892-6638 |
| DOI: | 10.1096/fj.11-195743 |
| Popis: | The ATP-binding cassette (ABC) genes encode the largest family of transmembrane proteins. ABC transporters translocate a wide variety of substrates across membranes, but their physiological function is often incompletely understood. We describe a new method to study the substrate spectrum of ABC transporters: We incubate extracts of mouse urine with membrane vesicles prepared from Spodoptera frugiperda Sf9 insect cells overproducing an ABC transporter and determine the compounds transported into the vesicles by LC/MS-based metabolomics. We illustrate the power of this simple “transportomics” approach using ABCC2, a protein present at sites of uptake and elimination. We identified many new substrates of ABCC2 in urine. These included glucuronides of plant-derived xenobiotics, a class of compounds to which humans are exposed on a daily basis. Moreover, we show that the excretion of these compounds in vivo depends on ABCC2: compared to wild-type mice, the urinary excretion of several glucuronides was increased up to 20-fold in Abcc2-/- mice. Transportomics has broad applicability, as it is not restricted to urine and can be applied to other ATP-dependent transport proteins as well.—Krumpochova, P., Sapthu, S., Brouwers, J. F., de Haas, M., de Vos, R., Borst, P., van de Wetering, K. Transportomics: screening for substrates of ABC transporters in body fluids using vesicular transport assays |
| Databáze: | OpenAIRE |
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