Search results for "Cytochrome"
showing 10 items of 607 documents
Drug-metabolizing enzymes in the skin of man, rat, and pig.
2007
The mammalian skin has long been considered to be poor in drug metabolism. However, many reports clearly show that most drug metabolizing enzymes also occur in the mammalian skin albeit at relatively low specific activities. This review summarizes the current state of knowledge on drug metabolizing enzymes in the skin of human, rat, and pig, the latter, because it is often taken as a model for human skin on grounds of anatomical similarities. However only little is known about drug metabolizing enzymes in pig skin. Interestingly, some cytochromes P450 (CYP) have been observed in the rat skin which are not expressed in the rat liver, such as CYP 2B12 and CYP2D4. As far as investigated most d…
Fast Regulation of Cytochrome P450 Activities by Phosphorylation and Consequences for Drug Metabolism and Toxicity
2002
In contrast to the well-known regulation of cytochrome P450 (CYP) activity by enzyme induction, which represents a process with slow onset and slow offset, more recent studies revealed phosphorylation as a fast (within observation instantaneous) and isoenzyme-selective regulation. The phosphorylated enzyme (investigated isozyme: CYP2B1) was fully inactive. The phosphorylation is mediated by PKA and hence under control of hormones and drugs that alter cellular cAMP levels. The consequences for the metabolic control of toxic species derived from drugs and environmental carcinogens are discussed. This information will help to improve therapy with drugs metabolized by CYPs which are phosphoryla…
Cell Lines: A Tool for In Vitro Drug Metabolism Studies
2008
Primary cultured hepatocytes are a valuable in vitro model for drug metabolism studies. However, their widespread use is greatly hindered by the scarcity of suitable human liver samples. Moreover, the well-known in vitro phenotypic instability of hepatocytes, the irregular availability of fresh human liver for cell harvesting purposes, and the high batch-to-batch functional variability of hepatocyte preparations obtained from different human liver donors, seriously complicate their use in routine testing. To overcome these limitations, different cell line models have been proposed for drug metabolism screening. Human liver-derived cell lines would be ideal models for this purpose given thei…
Woc (without children) gene control of ecdysone biosynthesis in Drosophila melanogaster.
2001
Abstract The first step in ecdysteroidogenesis, i.e. the 7,8-dehydrogenation of dietary cholesterol (C) to 7-dehydrocholesterol (7dC), is blocked in Drosophila melanogaster homozygous woc (without children) third instar larval ring glands (source of ecdysone). Unlike ring glands from wild-type D. melanogaster larvae, glands from woc mutants cannot convert radiolabelled C or 25-hydroxycholesterol (25C) to 7dC or 7-dehydro-25-hydroxycholesterol (7d25C) in vitro, nor to ecdysone (E). Yet, when these same glands are incubated with synthetic tracer 7d25C, the rate of metabolism of this polar Δ5,7-sterol into E is identical to that observed with glands from comparably staged wild-type larvae. The…
Xenobiotic metabolizing enzyme activities and viability are well preserved in EDTA-isolated rat liver parenchymal cells after cryopreservation
1995
Rat liver parenchymal cells (PC) were isolated by EDTA perfusion and were purified by a subsequent Percoll centrifugation. The isolated PC had a viability of 95%, as judged by trypan blue exclusion. Freshly isolated PC were cryopreserved with an optimized protocol in a computer-controlled freezer. After thawing, the PC still retained a viability of 89%. The activities of representative xenobiotic metabolizing enzymes were compared between freshly isolated and cryopreserved PC after thawing. The cytochrome P450 content and the cytochrome P450 2C11 isoenzyme activity, determined by hydroxylation of testosterone in intact cells, were not affected by the cryopreservation. The following phase II…
Evidence of a complex phylogeographic structure in the common dormouse, Muscardinus avellanarius (Rodentia: Gliridae)
2012
Contact: amouton@ulg.ac.be; International audience; This is the first mitochondrial phylogeography of the common dormouse, Muscardinus avellanarius (Linnaeus, 1758), a hibernating rodent strictly protected in Europe (Habitat Directive, annex IV; Bern Convention, annex III). The 84 individuals of M. avellanarius, sampled throughout the distributional range of the species, have been sequenced at the mitochondrial DNA gene (cytochrome b, 704 base pairs). The results revealed two highly divergent lineages, with an ancient separation around 7.7 Mya and a genetic divergence of 7.7%. Lineage 1 occurs in Western Europe (France, Belgium, and Switzerland) and Italy, and lineage 2 occurs in CentralNor…
p53 triggers apoptosis in oncogene-expressing fibroblasts by the induction of Noxa and mitochondrial Bax translocation.
2003
The mechanism of p53-dependent apoptosis is still only partly defined. Using early-passage embryonic fibroblasts (MEF) from wild-type (wt), p53(-/-) and bax(-/-) mice, we observe a p53-dependent translocation of Bax to the mitochondria and a release of mitochondrial Cytochrome c during stress-induced apoptosis. These events proceed independent of zVAD-inhibitable caspase activation, are not prevented by dominant negative FADD (DN-FADD), but are negatively regulated by Mdm-2. Bcl-x(L) expression prevents the release of mitochondrial Cytochrome c and apoptosis, but not Bax translocation. At a single-cell level, enforced expression of p53 is sufficient to induce Bax translocation and Cytochrom…
Apoptosis induced in hepatoblastoma HepG2 cells by the proteasome inhibitor MG132 is associated with hydrogen peroxide production, expression of Bcl-…
2002
This report is focused on the apoptotic effect induced by MG132, an inhibitor of 26S proteasome, in human hepatoma HepG2 cells. The results were compared with those obtained with non-transformed human Chang liver cells. MG132 reduced the viability of HepG2 cells in a time- and dose-dependent manner. The effect was in tight connection with the induction of apoptosis, as indicated by fluorescence microscopy and cytometric analysis, and was accompanied by a remarkable increase in the production of H2O2 and a reduction in mitochondrial transmembrane potential (Deltapsim). In addition cell death was prevented by antioxidants such as GSH, N-acetylcysteine or catalase. Western blot analysis showed…
Comparison of the chemopreventive efficacies of garlic powders with different alliin contents against aflatoxin B1 carcinogenicity in rats
2004
Garlic (Allium sativum) is well known for its beneficial effects on health and particularly for its chemopreventive potential against cancer. The present study was designed to compare the chemopreventive efficacies of several garlic powders with various levels of alliin, a precursor of active sulfur compounds. For this purpose we used the medium-term hepatocarcinogenesis protocol (resistant hepatocyte model), which allows the detection of preneoplasic foci expressing the placental form of glutathione S-transferase (GST-P) as an end-point. Rats were fed diets containing three garlic powders (5% of the diet) with various alliin contents for 3 weeks. Garlic powders were obtained from bulbs gro…
Isomer-nonspecific action of dichlorodiphenyltrichloroethane on aryl hydrocarbon receptor and G-protein-coupled receptor 30 intracellular signaling i…
2014
Abstract Extended residual persistence of the pesticide dichlorodiphenyltrichloroethane (DDT) raises concerns about its long-term neurotoxic effects. Little is known, however, about DDT toxicity during the early stages of neural development. This study demonstrated that DDT-induced apoptosis of mouse embryonic neuronal cells is a caspase-9-, caspase-3-, and GSK-3β-dependent process, which involves p,p’ -DDT-specific impairment of classical ERs. It also provided evidence for DDT-isomer-nonspecific alterations of AhR- and GPR30-mediated intracellular signaling, including changes in the levels of the receptor and receptor-regulated mRNAs, and also changes in the protein levels of the receptors…