Search results for "Methyltransferase"
showing 10 items of 260 documents
The COMT val158met Polymorphism Is Associated with Early Pubertal Development, Height and Cortical Bone Mass in Girls
2005
Estrogens are involved in accretion of bone mass during puberty. Catechol-O-Methyltransferase (COMT) is involved in the degradation of estrogens. In this cross-sectional study we investigated associations between the COMT val158met polymorphism, which results in a 60-75% difference in enzyme activity between the val (high activity = H) and the met (low activity = L) variant, and skeletal phenotypes in 246 healthy pre/early pubertal girls. Girls with COMT(LL) were 5.4 cm taller than COMT(HH) girls. Dual x-ray absorptiometry showed higher values of bone mineral content (BMC), and larger areas of total body, femur and spine in COMT(LL). Cortical BMC, measured by peripheral quantitative compute…
Association analysis between gene variants of the tyrosine hydroxylase and the serotonin transporter in borderline personality disorder.
2010
For patients with borderline personality disorder (BPD), we previously reported an independent effect of the catechol-o-methyl-transferase (COMT) low-activity (Met(158)) allele and an interaction with the low-expression allele of the deletion/insertion (short/long or S/L, resp.) polymorphism in the serotonin transporter-linked promoter region (5-HTTLPR). The purpose of the present study was to extend these findings to the tyrosine hydroxylase (TH) Val(81)Met single nucleotide polymorphism (SNP), the 5-HTTLPR S/L polymorphism incorporating the recently described functional A/G SNP within the long allele of the 5-HTTLPR (rs25531) as well as the variable number of tandem repeat (VNTR) polymorp…
O6-Alkylguanine DNA alkyltransferase activity in student embalmers
1997
O6-Alkylguanine-DNA alkyltransferase (AGT) activity was assessed in peripheral blood lymphocytes among 23 mortuary science students before and after 9 weeks in a laboratory course in techniques of embalming. Formaldehyde exposure was established by environmental monitoring. The average air concentration of formaldehyde during embalming was about 1.5 ppm. At the pre-exposure sampling, baseline DNA repair capacity tended to be reduced in subjects who reported a prior history of embalming (p = 0.08). From pre- to post-exposure, 17 subjects decreased in DNA repair capacity, while only 6 increased (p <0.05). Analysis of variance, including adjustment for age, sex, and smoking status, confirmed t…
Estradiol, acting through estrogen receptor alpha, restores dimethylarginine dimethylaminohydrolase activity and nitric oxide production in oxLDL-tre…
2011
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase. ADMA accumulation, mainly due to a decreased dimethylarginine dimethylaminohydrolase (DDAH) activity, has been related to the development of cardiovascular diseases. We investigate whether estradiol prevents the changes induced by oxidized low density lipoprotein (oxLDL) on the DDAH/ADMA/NO pathway in human umbilical artery endothelial cells (HUAEC). HUAEC were exposed to estradiol, native LDL (nLDL), oxLDL and their combinations for 24 h. In some experiments, cells were also exposed to the unspecific estrogen receptor (ER) antagonist ICI 182780, the specific ERα antagonist MPP or specific agonists …
Optimization of the treatment with immunosuppressants and biologics in inflammatory bowel disease
2014
Many placebo controlled trials and meta-analyses evaluated the efficacy of different drugs for the treatment of inflammatory bowel disease (IBD), including immunosuppressants and biologics. Their use is indicated in moderate to severe disease in non responders to corticosteroids and in steroid-dependent patients, as induction and maintainance treatment. Infliximab, as well as cyclosporine, is considered a second line therapy in the case of severe ulcerative colitis, or non-responders to intravenous corticosteroids. An adequate dosage and duration of therapy with thiopurines should be reached before evaluating their efficacy. Methotrexate is a valid option in patients with Crohn’s disease bu…
Catechol-O-Methyltransferase Gene Polymorphism Is Associated with Skeletal Muscle Properties in Older Women Alone and Together with Physical Activity
2008
BackgroundMuscle strength declines on average by one percent annually from midlife on. In postmenopausal women this decrement coincides with a rapid decline in estrogen production. The genetics underlying the effects of estrogen on skeletal muscle remains unclear. In the present study, we examined whether polymorphisms within COMT and ESR1 are associated with muscle properties and assessed their interaction and their combined effects with physical activity.Methodology/principal findingsA cross-sectional data analysis was conducted with 434 63-76-year-old women from the population-based Finnish Twin Study on Aging. Body anthropometry, muscle cross-sectional area (mCSA), isometric hand grip a…
Comprehensive analysis of interacting proteins and genome-wide location studies of the Sas3-dependent NuA3 histone acetyltransferase complex
2014
Highlights • We characterise Sas3p and Gcn5p active HAT complexes in WT and deleted TAP-strains. • We confirm that Pdp3p interacts with NuA3, histones and chromatin regulators. • Pdp3p MS-analysis reveals its phosphorylation, ubiquitination and methylation. • Sas3p can substitute Gcn5p in acetylation of histone H3K14 but not of H3K9. • Genome-wide profiling of Sas3p supports its involvement in transcriptional elongation.
Epigenetic siRNA and Chemical Screens Identify SETD8 Inhibition as a Therapeutic Strategy for p53 Activation in High-Risk Neuroblastoma
2017
Given the paucity of druggable mutations in high-risk neuroblastoma (NB), we undertook chromatin-focused small interfering RNA and chemical screens to uncover epigenetic regulators critical for the differentiation block in high-risk NB. High-content Opera imaging identified 53 genes whose loss of expression led to a decrease in NB cell proliferation and 16 also induced differentiation. From these, the secondary chemical screen identified SETD8, the H4K20me1 methyltransferase, as a druggable NB target. Functional studies revealed that SETD8 ablation rescued the pro-apoptotic and cell-cycle arrest functions of p53 by decreasing p53K382me1, leading to activation of the p53 canonical pathway. I…
Functional characterization of the human tRNA methyltransferases TRMT10A and TRMT10B
2020
Abstract The TRM10 family of methyltransferases is responsible for the N1-methylation of purines at position 9 of tRNAs in Archaea and Eukarya. The human genome encodes three TRM10-type enzymes, of which only the mitochondrial TRMT10C was previously characterized in detail, whereas the functional significance of the two presumably nuclear enzymes TRMT10A and TRMT10B remained unexplained. Here we show that TRMT10A is m1G9-specific and methylates a subset of nuclear-encoded tRNAs, whilst TRMT10B is the first m1A9-specific tRNA methyltransferase found in eukaryotes and is responsible for the modification of a single nuclear-encoded tRNA. Furthermore, we show that the lack of G9 methylation cau…
Eukaryotic rRNA Modification by Yeast 5-Methylcytosine-Methyltransferases and Human Proliferation-Associated Antigen p120.
2015
International audience; Modified nucleotide 5-methylcytosine (m(5)C) is frequently present in various eukaryotic RNAs, including tRNAs, rRNAs and in other non-coding RNAs, as well as in mRNAs. RNA: m(5)C-methyltranferases (MTases) Nop2 from S. cerevisiae and human proliferation-associated nucleolar antigen p120 are both members of a protein family called Nop2/NSUN/NOL1. Protein p120 is well-known as a tumor marker which is over-expressed in various cancer tissues. Using a combination of RNA bisulfite sequencing and HPLC-MS/MS analysis, we demonstrated here that p120 displays an RNA:m(5)C-MTase activity, which restores m(5)C formation at position 2870 in domain V of 25S rRNA in a nop2 Delta …