Search results for "CYP"
showing 10 items of 480 documents
Differential modulation of CYP2E1 activity by cAMP-dependent protein kinase upon Ser129 replacement.
1998
Many toxic compounds are activated by cytochrome P450 (CYP) 2E1 to reactive metabolites, which represents a potential hazard for cellular homeostasis. Therefore knowledge about CYP2E1 regulation could be of great biological importance. It has been shown that CYP2E1 is controlled transcriptionally and post-translationally by phosphorylation. In the present study we investigated the role of serine-129 (Ser129) in the protein kinase A (PKA) recognition sequence motif Arg-Arg-Phe-Ser129. To gain further insights into the possible relevance of Ser129 for CYP2E1 function, Ser129 was replaced by alanine (Ala) or glycine (Gly) by site-directed mutations of the cDNA coding for CYP2E1. The mutant cDN…
The anti-inflammatory drugs diclofenac, naproxen and ibuprofen are found in the bile of wild fish caught downstream of a wastewater treatment plant.
2012
Pharmaceutical residues are ubiquitous in rivers, lakes, and at coastal waters affected by discharges from municipal wastewater treatment plants. In this study, the presence of 17 different pharmaceuticals and six different phase I metabolites was determined in the bile of two wild fish species, bream (Abramis brama) and roach (Rutilus rutilus). The fish were caught from a lake that receives treated municipal wastewater via a small river. Prior to analyses, the bile content was enzymatically hydrolyzed to convert the glucuronide metabolites into the original pharmaceuticals or phase I metabolites. The solid phase extracts of hydrolyzates were analyzed by liquid chromatography-tandem mass sp…
Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior
2010
Contains fulltext : 89305.pdf (Publisher’s version ) (Closed access) Smoking is a common risk factor for many diseases. We conducted genome-wide association meta-analyses for the number of cigarettes smoked per day (CPD) in smokers (n = 31,266) and smoking initiation (n = 46,481) using samples from the ENGAGE Consortium. In a second stage, we tested selected SNPs with in silico replication in the Tobacco and Genetics (TAG) and Glaxo Smith Kline (Ox-GSK) consortia cohorts (n = 45,691 smokers) and assessed some of those in a third sample of European ancestry (n = 9,040). Variants in three genomic regions associated with CPD (P < 5 x 10(-8)), including previously identified SNPs at 15q25 repre…
Liver subcellular fractions from rats treated by organosulfur compounds from Allium modulate mutagen activation
2000
The effects of in vivo administration of naturally occurring organosulfur compounds (OSCs) from Allium species were studied on the activation of several mutagens. Male SPF Wistar rats were given p.o. one of either diallyl sulfide (DAS), diallyl disulfide (DADS), dipropyl sulfide (DPS) or dipropyl disulfide (DPDS) during 4 consecutive days and the ability of hepatic S9 and microsomes from treated rats to activate benzo[a]pyrene (BaP), cyclophosphamide (CP), dimethylnitrosamine (DMN), N-nitrosopiperidine (N-PiP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was determined in the Ames test. Administration of DAS, DPS and DPDS resulted in a significant increase of the activation of…
Effects of gender, diet, exogenous melatonin and subchronic PCB exposure on plasma immunoglobulin G in mink
2002
Abstract Effects of different fish-based diets (freshwater smelt, Baltic herring, marine herring/cod offal or their mixtures), gender, β-glucan supplement, exogenous melatonin, and PCB exposure (Aroclor 1242®, 1 mg per animal per day in feed) on plasma immunoglobulin G (IgG) in the mink (Mustela vison) were studied. The aims of the study were to find out whether plasma IgG of the mink is affected by the subchronic PCB exposure, and whether biological, nutritional and hormonal effects are large enough to mask the possible IgG response. The concentration of IgG was determined using enzyme-linked immunosorbent assay (ELISA). Sexual dimorphism was detected, the males having higher levels of pla…
Infection ecology of Philometra ovata (Nematoda: Philometridae) in a wild European minnow (Phoxinus phoxinus) population in Finland
2015
SUMMARYSeasonal life cycle of body cavity dwelling (BCD) Philometra ovata (Nematoda: Philometridae) has been reported in southern and central European countries, but its swim bladder dwelling (SBD) stage and northern populations have remained unstudied. In this study, we investigated the seasonal life cycle and infection ecology of P. ovata in both swim bladder and body cavity in the European minnow (Phoxinus phoxinus) in Finland. The larval P. ovata infected the swim bladder of minnows mainly in August. Female SBD P. ovata emigrated to body cavity mostly in September, grew to their full size by the end of the next June, and evacuated from minnows in July. In addition, female SBD P. ovata r…
Cocaine hepatotoxicity: two different toxicity mechanisms for phenobarbital-induced and non-induced rat hepatocytes.
1993
Abstract Hepatocytes isolated from both phenobarbital-induced and control rats were short-term cultured and exposed to cocaine (8–2000 μM) for varying times. Intracellular lactate dehydrogenase activity, free calcium levels ([Ca 2+ ] i ), reduced glutathione (GSH) and lipid peroxidation were investigated to evaluate the toxic effect of cocaine on hepatocytes. Cytochrome P450 induction by phenobarbital potentiated the in vitro cytotoxicity of cocaine by a factor of 13 (IC 50 = 84 μ M induced cells vs 1100 μM in non-induced cells). This difference in the susceptibility of the two types of hepatocytes to cocaine correlated well with the activity of cytochrome P450 2 B 1 2 . Rapid depletion of …
Pregnane X receptor and yin yang 1 contribute to the differential tissue expression and induction of CYP3A5 and CYP3A4.
2012
The hepato-intestinal induction of the detoxifying enzymes CYP3A4 and CYP3A5 by the xenosensing pregnane X receptor (PXR) constitutes a key adaptive response to oral drugs and dietary xenobiotics. In contrast to CYP3A4, CYP3A5 is additionally expressed in several, mostly steroidogenic organs, which creates potential for induction-driven disturbances of the steroid homeostasis. Using cell lines and mice transgenic for a CYP3A5 promoter we demonstrate that the CYP3A5 expression in these organs is non-inducible and independent from PXR. Instead, it is enabled by the loss of a suppressing yin yang 1 (YY1)-binding site from the CYP3A5 promoter which occurred in haplorrhine primates. This YY1 sit…
Factors affecting the intensity of epidermal papillomatosis in populations of roach, Rutilus rutilus (L.), estimated as scale coverage
2006
Studies of epidermal papillomatosis in fish populations have only rarely focused on the intensity of the disease, i.e. the number and size of papillomas. Furthermore, the methods used to evaluate the intensity of papillomatosis have not been standardized. We tested the reliability of a method based on counting of scales covered by papilloma tumours in roach, Rutilus rutilus (L). In addition, we studied the frequency distributions of the number of scales covered by papillomas within populations, evaluated the correlation between the prevalence and mean intensity of the disease among populations and examined the intensity of papillomatosis in roach with respect to sex and size of fish. Reliab…
Epizootic cutaneous papillomatosis in roach Rutilus rutilus: sex and size dependence, seasonal occurrence and between-population differences.
2003
Epidemiology of epidermal papillomatosis in roach Rutilus rutilus was studied in 11 roach populations in Finland in 1999 and 2000 during the spawning period. In addition, the seasonal pattern of the disease was described in 1 population. Papilloma tumours were observed on the skin and fins of roach in 8 populations out of 11. Prevalence of papillomatosis varied from 0 to 62%, being higher in populations subject to industrial or sewage effluents. Males and large fish had higher prevalence of papilloma tumours. The disease outbreak peaked during the spawning period and signs of recovered skin on fish were observed later during the year. The gender dependence in the disease prevalence found in…