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• W2238574603 abstract "Caco-2 cells are widely used in studies of intestinal cell physiology and drug transport. Here, the global proteome of filter-grown Caco-2 cells was quantified using the total protein approach and compared with the human colon and jejunum proteomes. In total, 8096 proteins were identified. In-depth analysis of proteins defining enterocyte differentiation—including brush-border hydrolases, integrins, and adherens and tight junctions—gave near-complete coverage of the expected proteins. Three hundred twenty-seven absorption, distribution, metabolism and excretion proteins were identified, including 112 solute carriers and 20 ATP-binding cassette transporters. OATP2B1 levels were 16-fold higher in Caco-2 cells than in jejunum. To investigate the impact of this difference on in vitro-in vivo extrapolations, we studied the uptake kinetics of the OATP2B1 substrate pitavastatin in Caco-2 monolayers, and found that the contribution of OATP2B1 was 60%-70% at clinically relevant intestinal concentrations. Pitavastatin kinetics was combined with transporter concentrations to model the contribution of active transport and membrane permeation in the jejunum. The lower OATP2B1 expression in jejunum led to a considerably lower transporter contribution (<5%), suggesting that transmembrane diffusion dominates pitavastatin absorption in vivo. In conclusion, we present the first in-depth quantification of the filter-grown Caco-2 proteome. We also demonstrate the crucial importance of considering transporter expression levels for correct interpretation of drug transport routes across the human intestine." @default.
• W2238574603 created "2016-06-24" @default.
• W2238574603 creator A5007053305 @default.
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• W2238574603 creator A5029622436 @default.
• W2238574603 creator A5079220895 @default.
• W2238574603 date "2016-02-01" @default.
• W2238574603 modified "2023-10-16" @default.
• W2238574603 title "The Proteome of Filter-Grown Caco-2 Cells With a Focus on Proteins Involved in Drug Disposition" @default.
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• W2238574603 doi "https://doi.org/10.1016/j.xphs.2015.10.030" @default.
• W2238574603 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26869432" @default.
• W2238574603 hasPublicationYear "2016" @default.
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