Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA212633 | ENA |
REPOSITORIES: ENA
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Project description:Background and Aim: Liver cirrhosis is associated with decreased hepatic cytochrome P4503A (CYP3A) activity but the pathogenesis of this phenomenon is not well elucidated. In this study, we examined if certain microRNAs (miRNA) are associated with decreased hepatic CYP3A activity in cirrhosis. Hepatic CYP3A activity and miRNA microarray expression profiles were measured in cirrhotic (n=22) and normal (n=12) liver tissue. Hepatic CYP3A activity was measured via midazolam hydroxylation in human liver microsomes. Additionally, hepatic CYP3A4 protein concentration and the expression of CYP3A4 mRNA were measured. Analyses were conducted to identify miRNAs which were differentially expressed between two groups but also were significantly associated with lower hepatic CYP3A activity. Liver tissue was collected from individuals with established cirrhosis who were awaiting liver transplantation (n=22) at the time of their liver transplantation procedure in the operating room. Normal liver tissue (n=12) was obtained from patients undergoing liver resection for metastatic/benign liver lesions with no underlying chronic liver disease
2013-08-15 | E-GEOD-49012 | biostudies-arrayexpress
Project description:Background and Aim: Liver cirrhosis is associated with decreased hepatic cytochrome P4503A (CYP3A) activity but the pathogenesis of this phenomenon is not well elucidated. In this study, we examined if certain microRNAs (miRNA) are associated with decreased hepatic CYP3A activity in cirrhosis. Hepatic CYP3A activity and miRNA microarray expression profiles were measured in cirrhotic (n=22) and normal (n=12) liver tissue. Hepatic CYP3A activity was measured via midazolam hydroxylation in human liver microsomes. Additionally, hepatic CYP3A4 protein concentration and the expression of CYP3A4 mRNA were measured. Analyses were conducted to identify miRNAs which were differentially expressed between two groups but also were significantly associated with lower hepatic CYP3A activity.
2013-08-15 | GSE49012 | GEO
Project description:Microarray analysis to examine the relationship between hepatic phenotype and changes in gene expression in cytochrome P450 reductase (CPR) null mice.
2008-06-11 | E-GEOD-1468 | biostudies-arrayexpress
Project description:Microarray analysis to examine the relationship between hepatic phenotype and changes in gene expression in cytochrome P450 reductase (CPR) null mice. Keywords: ordered
2004-07-11 | GSE1468 | GEO
Project description:Analysis of liver with or without Cytochrome P450 (Cyp) 3a-cluster. Cyp3a family is one of the most important enzymes for drug metabolism. These results suggest the biological effects of Cyp3a-knockout on liver.
2018-11-15 | GSE103533 | GEO
Project description:Hepatocyte-like cells derived from human pluripotent stem cells (hPSC-HLCs) offer an alternative to primary hepatocytes commonly used for drug screenings and toxicological tests. However, these cells do not have hepatic functions comparable to those of hepatocytes in vivo due to insufficient hepatic differentiation. Here we showed that the hepatic functions of hPSC-HLCs were facilitated by applying physiological liver temperatures during hepatic differentiation. We identified the optimal temperature by treating HLCs derived from H9 human embryonic stem cells (hESC-HLCs) at 39 °C; the 42 °C treatment caused significantly greater cell death than the 39 °C treatment. We confirmed the improvement of hepatic functions, such as albumin secretion, cytochrome P450 3A activity, and collagen production, without severe cell damage. In combination with existing hepatic differentiation protocols, the method proposed here may further improve hepatic functions for hPSCs and lead to the realization of drug discovery efforts and drug toxicological tests.
2022-03-29 | GSE172227 | GEO
Project description:Analysis of small intestine with or without Cytochrome P450 (Cyp) 3a-cluster. Cyp3a family is one of the most important enzymes for drug metabolism. These results suggest the biological effects of Cyp3a-knockout on small intestine.
2018-11-15 | GSE103534 | GEO
Project description:NADPH-cytochrome P450 reductase (CPR) is important for the functions of many enzymes, such as microsomal cytochrome P450 (P450) monooxygenases and heme oxygenases. Two mouse models with deficient CPR expression in adults were recently generated in this laboratory: liver-Cpr-null (with liver-specific Cpr deletion) (Gu et al., J. Biol. Chem., 278, 25895–25901, 2003) and Cpr-low (with reduced CPR expression in all organs examined) (Wu et al. J. Pharmacol. Expt. Ther. 312, 35-43, 2005). The phenotypes included a reduced serum cholesterol level and an induction of hepatic P450 in both models, and hepatomegaly and fatty liver in the liver-Cpr-null mouse alone. Our aim was to identify hepatic gene-expression changes related to these phenotypes. Cpr-lox mice, which have normal CPR expression (Wu et al., Genesis, 36, 177-181, 2003.), were used as the control in microarray analysis. A detailed analysis of the gene-expression changes in lipid metabolism and transport pathways revealed potential mechanisms, such as an increased activation of constitutive androstane receptor (CAR) and a decreased activation of peroxisomal proliferators activated receptor alpha (PPAR-gamma) by precursors of cholesterol biosynthesis, that underlie common changes (e.g., induction of multiple P450s and inhibition of genes for fatty acids metabolism) in response to CPR-loss in the two mouse models. Moreover, we also uncovered model-specific gene-expression changes, such as the induction of a lipid translocase (CD36 antigen) and the suppression of carnitine O-palmitoyltransferase 1 (CPT1a) and acyl-CoA synthetase long-chain family member 1 (Acsl1), that are potentially responsible for the severe hepatic lipidosis observed in liver-Cpr-null, but not Cpr-low mice. Keywords = Cytochrome P450 Keywords = NADPH-cytochrome P450 reductase Keywords = transgenic mice Keywords = liver Keywords = nuclear receptor Keywords: other
2005-07-16 | GSE2362 | GEO
Project description: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. 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 wild type (C57Bl6) and hepatic P450 reductase mice (HRNTM). Statistically curated, differential expressed protein groups highlighted a variety of molecular and biological functions, including binding and catalytic related activities. Pathway enrichment analysis resulted in perturbation of lipid and energy related pathways, which included bile acid biosynthesis, fatty acid omega oxidation and tricarbonic acid (TCA) cycle as examples.
2022-05-26 | PXD024420 | Pride
Project description:Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on hepatic lipid metabolism and detailed serum lipid profiles, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and 1H nuclear magnetic resonance were used to measure quantitatively serum lipid profiles and whole genome microarray analysis was used to identify the responsible mechanisms in liver. There were no significant differences found in mean body weight, energy intake and hepatic lipid accumulation between the quercetin and control group. In serum of quercetin-fed mice, TG levels were decreased with 15%, poly unsaturated fatty acids (PUFA) were increased with 14% and saturated fatty acids were decreased. Palmitic acid, oleic acid, and linoleic acid were all decreased in quercetin-fed mice by 9-15%. Both palmitic acid and oleic acid can be oxidized by omega-oxidation. Indeed, gene expression profiling showed that quercetin increased hepatic lipid metabolism, especially omega-oxidation. At the gene level, this was reflected by the up regulation of cytochrome P450 (Cyp) 4a10, Cyp4a14, Cyp4a31 and Acyl-CoA thioesterase 3 (Acot3). Two relevant regulators, Cytochrome P450 oxidoreductase (Por, rate limiting for cytochrome P450s) and the transcription factor Constitutive androstane receptor (Car; official symbol Nr1i3) were also up regulated in the quercetin-fed mice. We conclude that quercetin intake increased hepatic lipid omega-oxidation and lowered corresponding circulating lipid levels, a process that may involve Por and Car, and results in a potential beneficial CVD preventive effect. Liver samples were obtained from 36 C57BL/6J male adult mice. All mice started with a three week adaptation phase, in which they were fed a mild-high-fat diet. 12 mice were sacrificed immediately after the adaptation phase (t=0). The other 24 mice received the mild-high-fat diet without (HF) or with supplementation of 0.33% (w/w) quercetin (HF-Q) for 12 weeks.
2013-02-05 | E-GEOD-39140 | biostudies-arrayexpress