scholarly journals Reduced Duodenal Cytochrome P450 3A Protein Expression and Catalytic Activity in Patients With Cirrhosis

2009 ◽  
Vol 85 (4) ◽  
pp. 387-393 ◽  
Author(s):  
DJ McConn II ◽  
YS Lin ◽  
TL Mathisen ◽  
DK Blough ◽  
Y Xu ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Catalytic Activity ◽  
Protein Expression ◽  
Cytochrome P450 3A

Evidence for cytochrome P450 3A expression and catalytic activity in rat blood lymphocytes

Life Sciences ◽  
2006 ◽  
Vol 79 (18) ◽  
pp. 1729-1735 ◽  
Author(s):  
Aparajita Dey ◽  
Sanjay Yadav ◽  
Alok Dhawan ◽  
Prahlad K. Seth ◽  
Devendra Parmar
Keyword(s):  
Cytochrome P450 ◽  
Catalytic Activity ◽  
Cytochrome P450 3A ◽  
Rat Blood ◽  
Blood Lymphocytes

scholarly journals Functional impact of cytochrome P450 3A (CYP3A) missense variants in cattle

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mery Giantin ◽  
Minna Rahnasto-Rilla ◽  
Roberta Tolosi ◽  
Lorena Lucatello ◽  
Marianna Pauletto ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Catalytic Activity ◽  
Ex Vivo ◽  
Liver Microsomes ◽  
Individual Variability ◽  
Cytochrome P450 3A ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Functional Impact ◽  
Genotype Variation

AbstractCytochrome P450 3A is the most important CYP subfamily in humans, and CYP3A4/CYP3A5 genetic variants contribute to inter-individual variability in drug metabolism. However, no information is available for bovine CYP3A (bCYP3A). Here we described bCYP3A missense single nucleotide variants (SNVs) and evaluated their functional effects. CYP3A28, CYP3A38 and CYP3A48 missense SNVs were identified in 300 bulls of Piedmontese breed through targeted sequencing. Wild-type and mutant bCYP3A cDNAs were cloned and expressed in V79 cells. CYP3A-dependent oxidative metabolism of testosterone (TST) and nifedipine (NIF) was assessed by LC-MS/MS. Finally, SNVs functional impact on TST hydroxylation was measured ex vivo in liver microsomes from individually genotyped animals. Thirteen missense SNVs were identified and validated. Five variants showed differences in CYP3A catalytic activity: three CYP3A28 SNVs reduced TST 6β-hydroxylation; one CYP3A38 variant increased TST 16β-hydroxylation, while a CYP3A48 SNV showed enhanced NIF oxidation. Individuals homozygous for rs384467435 SNV showed a reduced TST 6β-hydroxylation. Molecular modelling showed that most of SNVs were distal to CYP3A active site, suggesting indirect effects on the catalytic activity. Collectively, these findings demonstrate the importance of pharmacogenetics studies in veterinary species and suggest bCYP3A genotype variation might affect the fate of xenobiotics in food-producing species such as cattle.

scholarly journals Proteomic profiling of murine biliary-derived hepatic organoids and their capacity for drug disposition, bioactivation and detoxification

2021 ◽  
Author(s):  
Lawrence Howell ◽  
Rosalind E. Jenkins ◽  
Stephen Lynch ◽  
Carrie Duckworth ◽  
B. Kevin Park ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Rna Polymerase Ii ◽  
Liver Tissue ◽  
Drug Disposition ◽  
Multiple Drug ◽  
Proteomic Profiling ◽  
Cytochrome P450 3A ◽  
Drug Induced

AbstractHepatic organoids are a recent innovation in in vitro modeling. Initial studies suggest that organoids better recapitulate the liver phenotype in vitro compared to pre-existing proliferative cell models. However, their potential for drug metabolism and detoxification remains poorly characterized, and their global proteome has yet to be compared to their tissue of origin. This analysis is urgently needed to determine what gain-of-function this new model may represent for modeling the physiological and toxicological response of the liver to xenobiotics. Global proteomic profiling of undifferentiated and differentiated hepatic murine organoids and donor-matched livers was, therefore, performed to assess both their similarity to liver tissue, and the expression of drug-metabolizing enzymes and transporters. This analysis quantified 4405 proteins across all sample types. Data are available via ProteomeXchange (PXD017986). Differentiation of organoids significantly increased the expression of multiple cytochrome P450, phase II enzymes, liver biomarkers and hepatic transporters. While the final phenotype of differentiated organoids is distinct from liver tissue, the organoids contain multiple drug metabolizing and transporter proteins necessary for liver function and drug metabolism, such as cytochrome P450 3A, glutathione-S-transferase alpha and multidrug resistance protein 1A. Indeed, the differentiated organoids were shown to exhibit increased sensitivity to midazolam (10–1000 µM) and irinotecan (1–100 µM), when compared to the undifferentiated organoids. The predicted reduced activity of HNF4A and a resulting dysregulation of RNA polymerase II may explain the partial differentiation of the organoids. Although further experimentation, optimization and characterization is needed relative to pre-existing models to fully contextualize their use as an in vitro model of drug-induced liver injury, hepatic organoids represent an attractive novel model of the response of the liver to xenobiotics. The current study also highlights the utility of global proteomic analyses for rapid and accurate evaluation of organoid-based test systems.

Cytochrome P450 3A activity in mothers and their neonates as determined by plasma 4β-hydroxycholesterol

2011 ◽  
Vol 67 (7) ◽  
pp. 715-722 ◽  
Author(s):  
Hanna Nylén ◽  
Sofia Sergel ◽  
Lisa Forsberg ◽  
Synnöve Lindemalm ◽  
Leif Bertilsson ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 3A

Metabolism of Drugs by Cytochrome P450 3A Isoforms

1995 ◽  
Vol 29 (Supplement 1) ◽  
pp. 33-44 ◽  
Author(s):  
Lisa L. von Moltke ◽  
David J. Greenblatt ◽  
Jürgen Schmider ◽  
Jerold S. Harmatz ◽  
Richard I. Shader
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 3A
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