16 research outputs found
Growing partnerships: Leveraging the power of collaboration through the medical education partnership initiative
Transport Characteristics of Ebastine and Its Metabolites across Human Intestinal Epithelial Caco-2 Cell Monolayers.
Apparent Low Frequency of Sequence Variability within the Proximal Promoter Region of the Cytochrome P450 (CYP) 3A5 Gene in Established Cell Lines from Japanese Individuals.
Biotransformation in vitro of the 22R and 22S epimers of budesonide by human liver, bronchus, colonic mucosa and skin
Effects of yogurt and bifidobacteria supplementation on the colonic microbiota in lactose-intolerant subjects
Characterisation of CYP3A gene subfamily expression in human gastrointestinal tissues.
The human CYP3A subfamily is of interest due to its multiplicity, activity toward known carcinogens, and extrahepatic expression. In situ hybridisation analysis of formalin fixed, routinely processed biopsy specimens was used to localise CYP3A mRNA in human gastrointestinal tissues from several individuals. CYP3A mRNA is abundant in human liver and in mucosal epithelial cells of all segments of the human small intestine. RNA blot analyses showed that the mRNA species observed in most livers and in human small intestine represent CYP3A3/3A4 transcripts. This was confirmed at the protein level by immunoblot comparison of small intestine microsomes to in vitro expressed CYP3A4 and CYP3A5 proteins. In liver and small intestine, CYP3A mRNA is not uniformly distributed, with grain density highest in cells within the respective non-proliferative compartments. CYP3A mRNA was also observed in human oesophagus and colon. RNA blot analysis of multiple colons showed heterogeneity in the CYP3A mRNAs present. Two CYP3A mRNAs (CYP3A3/3A4 and CYP3A5) were detected in colon samples from several individuals. In addition to those localisation studies, the capacity of expressed CYP3A4 and CYP3A5 to activate the dietary heterocyclic amine MeIQ in the presence of alpha-naphthoflavone was shown. These results show that there is considerable heterogeneity in the expression of the CYP3A subfamily in human gastrointestinal tissues