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Subcellular fractionation of human liver reveals limits in global proteomic quantification from isolated fractions
Max Planck Inst Biochem, Dept Prote & Signal Transduct, Biochem Prote Grp, D-82152 Martinsried, Germany..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. AstraZeneca, Innovat Med & Early Dev Biotech Unit, Cardiovasc & Metab Dis, Pepparedsleden 1, S-43183 Molndal, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, Science for Life Laboratory, SciLifeLab.
2016 (English)In: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 509, 82-88 p.Article in journal (Refereed) Published
Abstract [en]

The liver plays an important role in metabolism and elimination of xenobiotics, including drugs. Determination of concentrations of proteins involved in uptake, distribution, metabolism, and excretion of xenobiotics is required to understand and predict elimination mechanisms in this tissue. In this work, we have fractionated homogenates of snap -frozen human liver by differential centrifugation and performed quantitative mass spectrometry -based proteomic analysis of each fraction. Concentrations of proteins were calculated by the "total protein approach". A total of 4586 proteins were identified by at least five peptides and were quantified in all fractions. We found that the xenobiotics transporters of the canalicular and basolateral membranes were differentially enriched in the subcellular fractions and that phase I and II metabolizing enzymes, the cytochrome P450s and the UDP glucuronyl transferases, have complex subcellular distributions. These findings show that there is no simple way to scale the data from measurements in arbitrarily selected membrane fractions using a single scaling factor for all the proteins of interest. This study also provides the first absolute quantitative subcellular catalog of human liver proteins obtained from frozen tissue specimens. Our data provide quantitative insights into the sub cellular distribution of proteins and can be used as a guide for development of fractionation procedures.

Place, publisher, year, edition, pages
2016. Vol. 509, 82-88 p.
Keyword [en]
Human liver, Subcellular fractionation, Absolute quantitative proteomics, Total protein approach, Drug metabolism, Drug transport
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-303255DOI: 10.1016/j.ab.2016.06.006ISI: 000380866800013PubMedID: 27311553OAI: oai:DiVA.org:uu-303255DiVA: diva2:971502
Funder
Swedish Research Council, 2822
Available from: 2016-09-16 Created: 2016-09-15 Last updated: 2016-09-16Bibliographically approved

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Wegler, ChristineArtursson, Per
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