Quantification of Proteins Involved in Intestinal Epithelial Handling of Xenobiotics

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • Narciso Couto
  • Matthew D Harwood
  • Gordon Carlson
  • Geoffrey Warhurst

Abstract

The intestinal epithelium represents a natural barrier against harmful xenobiotics, whilst facilitating the uptake
of nutrients and other substances. Understanding the interaction of chemicals with constituents of the
intestinal epithelium and their fate in the body requires quantitative measurement of relevant proteins in in
vitro systems and intestinal epithelium. Recent studies have highlighted the mismatch between mRNA and
protein abundance for several drug-metabolising enzymes and transporters in the highly dynamic environment
of the intestinal epithelium; mRNA abundances cannot therefore be used as a proxy for protein abundances in
the gut, necessitating direct measurements. The objective was to determine the expression of a wide range
proteins pertinent to metabolism and disposition of chemicals and nutrients in the intestinal epithelium. Ileum
and jejunum biopsy specimens were obtained from 16 patients undergoing gastrointestinal elective surgery.
Mucosal fractions were prepared and analysed using targeted and global proteomic approaches. A total of 29
enzymes, 32 transporters, 6 tight junction proteins, 2 adhesion proteins, alkaline phosphatase, thioredoxin, 5
markers and 1 regulatory protein were quantified; 60 for the first time. The global proteomic method
identified a further 5222 proteins, which are retained as an open database for interested parties to explore. This
study significantly expand our knowledge of a wide array of proteins important for xenobiotic handling in the
intestinal epithelium. Quantitative systems biology models will benefit from the novel systems data generated
in the present study and the translation path offered for in vitro to in vivo translation.

Bibliographical metadata

Original languageEnglish
JournalClinical Pharmacology & Therapeutics
DOIs
Publication statusPublished - 28 Oct 2020

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