ArticleThe Journal of biological chemistry2012
Potential biological functions of cytochrome P450 reductase-dependent enzymes in small intestine: novel link to expression of major histocompatibility complex class II genes.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Comparative Transcriptomic Analysis Reveals the Functionally Segmented Intestine in Tunicate Ascidian.International journal of molecular sciences · 2023Article
- Impacts of Dietary Protein and Prebiotic Inclusion on Liver and Spleen Gene Expression in Hy-Line Brown Caged Layers.Animals : an open access journal from MDPI · 2020Article
- Hepatic and intestinal biotransformation gene expression and drug disposition in a dextran sulfate sodium-induced colitis mouse model.Acta pharmaceutica Sinica. B · 2020Article
- Regulation of Fgf15 expression in the intestine by glucocorticoid receptor.Molecular medicine reports · 2019Article
- An update on the role of intestinal cytochrome P450 enzymes in drug disposition.Acta pharmaceutica Sinica. B · 2016Review
- Intestinal epithelium-specific knockout of the cytochrome P450 reductase gene exacerbates dextran sulfate sodium-induced colitis.The Journal of pharmacology and experimental therapeutics · 2015Article
- Mice deficient in intestinal epithelium cytochrome P450 reductase are prone to acute toxin-induced mucosal damage.Scientific reports · 2014Article
- Regulation of intestinal cytochrome P450 expression by hepatic cytochrome P450: possible involvement of fibroblast growth factor 15 and impact on systemic drug exposure.Molecular pharmacology · 2014Article
- Dietary regulation of mouse intestinal P450 expression and drug metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Disruption of P450-mediated vitamin E hydroxylase activities alters vitamin E status in tocopherol supplemented mice and reveals extra-hepatic vitamin E metabolism.Journal of lipid research · 2012Article
- Role of intestinal cytochrome p450 enzymes in diclofenac-induced toxicity in the small intestine.The Journal of pharmacology and experimental therapeutics · 2012Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
NADPH-cytochrome P450 reductase (POR) is essential for the functioning of microsomal cytochrome P450 (P450) monooxygenases and heme oxygenases. The biological roles of the POR-dependent enzymes in the intestine have not been defined, despite the wealth of knowledge on the biochemical properties of the various oxygenases. In this study, cDNA microarray analysis revealed significant changes in gene expression in enterocytes isolated from the small intestine of intestinal epithelium-specific Por knock-out (named IE-Cpr-null) mice compared with that observed in wild-type (WT) littermates. Gene ontology analyses revealed significant changes in terms related to P450s, transporters, cholesterol biosynthesis, and, unexpectedly, antigen presentation/processing. The genomic changes were confirmed at either mRNA or protein level for selected genes, including those of the major histocompatibility complex class II (MHC II). Cholesterol biosynthetic activity was greatly reduced in the enterocytes of the IE-Cpr-null mice, as evidenced by the accumulation of the lanosterol metabolite, 24-dihydrolanosterol. However, no differences in either circulating or enterocyte cholesterol levels were observed between IE-Cpr-null and WT mice. Interestingly, the levels of the cholesterol precursor farnesyl pyrophosphate and its derivative geranylgeranyl pyrophosphate were also increased in the enterocytes of the IE-Cpr-null mice. Furthermore, the expression of STAT1 (signal transducer and activator of transcription 1), a downstream target of geranylgeranyl pyrophosphate signaling, was enhanced. STAT1 is an activator of CIITA, the class II transactivator for MHC II expression; CIITA expression was concomitantly increased in IE-Cpr-null mice. Overall, these findings provide a novel and mechanistic link between POR-dependent enzymes and the expression of MHC II genes in the small intestine.
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