Search results for "Demethylation"
showing 10 items of 24 documents
Methylation and Demethylation in Cobaltabis(dicarbollide) Derivatives
2003
B(8)−R and B(8‘)−R (R = alkyl) disubstituted derivatives of the cobaltabis(dicarbollide) anion [3,3‘-Co(C2B9H11)2]- are reported. The synthesis was achieved by application of a modified Kumada reac...
Stable Oxidative Cytosine Modifications Accumulate in Cardiac Mesenchymal Cells From Type2 Diabetes Patients
2018
Rationale: Human cardiac mesenchymal cells (CMSCs) are a therapeutically relevant primary cell population. Diabetes mellitus compromises CMSC function as consequence of metabolic alterations and incorporation of stable epigenetic changes. Objective: To investigate the role of α-ketoglutarate (αKG) in the epimetabolic control of DNA demethylation in CMSCs. Methods and Results: Quantitative global analysis, methylated and hydroxymethylated DNA sequencing, and gene-specific GC methylation detection revealed an accumulation of 5-methylcytosine, 5-hydroxymethylcytosine, and 5-formylcytosine in the genomic DNA of human CMSCs isolated from diabetic donors. Whole heart genomic DNA analysis reveale…
Ethoxyquin as an inducer and inhibitor of phenobarbital-type cytochrome P-450 in rat liver microsomes.
1977
Abstract The effect of ethoxyquin in vivo and in vitro on drug metabolism in rat liver microsomes was studied. In feeding experiments, a threshold dose of induction was found at 0.05% ethoxyquin for 14 days. At 0.5% ethoxyquin, relative liver weight, cytochrome P-450 content, cytochrome b5 content, ethylmorphine demethylation, and ethoxycoumarin deethylation were increased by a factor of 1.5 to 2. Aryl hydrocarbon hydroxylase activity was, however, not induced but even decreased by 0.5% ethoxyquin in food. Induction of epoxide hydratase was marked, amounting to 400% of control after 0.5% ethoxyquin. The induced enzyme was similar to the phenobarbital-inducible cytochrome P-450 in its CO spe…
Metabolic pathways of 4-bromo-2,5-dimethoxyphenethylamine (2C-B): analysis of phase I metabolism with hepatocytes of six species including human
2004
Abstract 4-Bromo-2,5-dimethoxyphenethylamine (2C-B) is a psychoactive designer drug of abuse that is sold under the street names “Venus”, “Bromo”, “Erox”, “XTC” or “Nexus”. Concern has been raised because only little is known about its toxicity and metabolism in humans. In the present study we incubated 2C-B with human, monkey, dog, rabbit, rat and mouse hepatocytes to identify the metabolites formed and to determine possible toxic effects as evidenced by an ATP assay. Our data allow construction of the main metabolic pathways of 2C-B. Oxidative deamination results in the 2-(4-bromo-2,5-dimethoxyphenyl)-ethanol (BDMPE) and 4-bromo-2,5-dimethoxyphenylacetic acid (BDMPAA) metabolites. Additio…
Quantitative analysis of the EEG effects produced by imipramine, desipramine, promazine, and monodesmethyl promazine in the isolated perfused rat bra…
1974
The effects of imipramine, desipramine, promazine and monodesmethyl promazine on the EEG of the isolated perfused rat brain were studied. The brain preparation was perfused for 30 min with simulated blood, containing of the drugs in a concentration of 10−5 M. Control experiments were performed without a drug added to the simplified blood. The EEG was recorded at various times on a magnetic tape and was evaluated visually and quantitatively (amplitude and interval histography). The EEG effects of imipramine and promazine as well as the effects of these drugs with their monodesmethyl metabolites were compared. The drugs produced clear EEG changes compared with the control EEG. An increase of …
Epigenetic Control of the foxp3 Locus in Regulatory T Cells
2007
Compelling evidence suggests that the transcription factor Foxp3 acts as a master switch governing the development and function of CD4+ regulatory T cells (Tregs). However, whether transcriptional control of Foxp3 expression itself contributes to the development of a stable Treg lineage has thus far not been investigated. We here identified an evolutionarily conserved region within the foxp3 locus upstream of exon-1 possessing transcriptional activity. Bisulphite sequencing and chromatin immunoprecipitation revealed complete demethylation of CpG motifs as well as histone modifications within the conserved region in ex vivo isolated Foxp3+CD25+CD4+ Tregs, but not in naïve CD25−CD4+ T cells. …
Interrelationship between demethylation of p-nitroanisole and conjugation of p-nitrophenol in rat liver
1973
The metabolism of p-nitroanisole (pNA) and p-nitrophenol (pNP) was studied in isolated rat livers perfused with a hemoglobin-free medium. The activity and viability of the surviving organ was tested by recording pH, “arterial” and “venous” oxygen tension as well as the disappearance of added pNP. pNA is converted to its primary metabolite pNP which, in turn, is excreted into the perfusion medium as conjugates. The coordination of pNA oxidation and the conjugation reactions of pNP were investigated. When 50 μM pNA is added as substrate 0.4±0.1 nmoles×ml−1×(g liver)−1 are excreted as pNP-glucuronide and 3.5±0.2 nmoles×ml−1×(g liver)−1 as the sulphate within 90 min. When pNP itself (50 μM) is …
Reductive Drug Metabolism in Isolated Perfused Rat Liver under Restricted Oxygen Supply
1978
1. Hepatic azo and nitro reductase activities were studied in the perfused rat liver under normal and restricted oxygen supply. 2. Formation of sulphanilamide or p-aminobenzoic acid from neoprontosil or p-nitrobenzoic acid under aerobic conditions of liver perfusion was negligible, even at a reduced oxygen saturation of a pO2 of 300 mm Hg in the haemoglobinfree perfusion system. At a pO2 of 200 mm Hg reductase activities were almost maximal. 3. Conjugation of sulphanilamide (0-08 mM) was similar under aerobic and anaerobic conditions. Hepatic elimination of p-aminobenzoic acid (0-08 mM) showed an oxygen-dependent increase for 15 min after addition of substrate. 4. p-Nitroanisole demethylati…
Influence of disulfiram on oxidative drug demethylation.
1970
In clinical antiepileptie therapy it has been observed that the simultaneous administration of diphenylhydantoin and various other drugs causes toxic reactions to diphenylhydantoin. I t was found that disulfiram (Olesen, 1966) as well as ehloramphenieol (Christensen and Skovsted, 1969) cause toxic effects in patients treated with diphenylhydantoin. They are attributed to an increased concentration of diphenylhydantoin in the plasma. Analogous observations show that chloramphenieol enhances the clinical effects of tolbutamide and dicoumarol (Christensen and Skovsted, 1969). Since diphenylhydantoin is metabolized chiefly by p-hydroxylation to 5-(p-hydroxyphenyl)-5-phenyl-hydantoin (Butler, 19…
Untersuchungen zurFriesschen Verschiebung von Estern derortho- undpara-Methoxybenzoes�ure
1979
TheFries rearrangement of different methoxy benzoates has been investigated. Frompara-methoxy benzoates the corresponding hydroxy-4′-methoxy benzophenones could be obtained in good yields by treatment withLewis acids (especially TiCl4) in nitromethane at 20°C (4-hydroxy derivatives) or without solvent at 120°C (2-hydroxy derivatives). Under the same conditions only demethylation occurs withortho-methoxy benzoates leading to the corresponding salicylates. Small amounts of hydroxy-2′-methoxy benzophenones were obtained by treatment with polyphosphoric acid.