Journal article
Proteomic consequences of the deletion of cytochrome P450 (CYP450) reductase in mice
Journal of Chromatography B, Vol.1179, Art. 122803
2021
Abstract
Microsomal cytochrome P450 (CYP450) reductase enzymes play a major role in drug and xenobiotic metabolism. Mice which are deficient in hepatic CYP450 reductase serve as excellent models in understanding CYP450 drug metabolism and alterations in the underlying biology and function of these enzymes. A reversed-phase nano-bore UPLC-MS-based proteomic analysis, using an untargeted data independent approach (DIA), has been utilized for liver tissue extracts to evaluate differences between the proteomes of C57Bl6 wild type (WT) and hepatic P450 reductase mice (HRN™). Statistically curated, differentially expressed protein groups highlighted a variety of molecular and biological functions, including binding and catalytic related activities. Thus, elevations were seen for a number of CYP450 enzymes (Cyp2a5; Cyp2b10; Cyp2b19; Cyp2d26; Cyp2a5, Cyp2e1) in the liver extracts of HRN animals. In addition, the major urinary protein 2 (Mup2) was found to be present only in the livers of the HRN group, whilst enoyl-CoA hydratase domain-containing protein 2 (Echdc2) was similarly unique to the the WT livers.
Pathway enrichment analysis of the WT liver data indicated perturbations of lipid and energy related pathways, which included bile acid biosynthesis, fatty acid omega oxidation and tricarboxylic acid (TCA) cycle as examples.
Details
- Title
- Proteomic consequences of the deletion of cytochrome P450 (CYP450) reductase in mice
- Authors/Creators
- L.A. Gethings (Author/Creator) - Waters (United States)N. Gray (Author/Creator) - Murdoch UniversityR.S. Plumb (Author/Creator) - Waters (United States)I.D. Wilson (Author/Creator) - Imperial College London
- Publication Details
- Journal of Chromatography B, Vol.1179, Art. 122803
- Publisher
- Elsevier B.V.
- Identifiers
- 991005541038707891
- Copyright
- © 2021 Elsevier B.V.
- Murdoch Affiliation
- Australian National Phenome Centre; Centre for Computational and Systems Medicine; Health Futures Institute
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.117 Pharmacology & Toxicology
- 1.117.179 Cytochrome P450
- Web Of Science research areas
- Biochemical Research Methods
- Chemistry, Analytical
- ESI research areas
- Chemistry