Search results for "NMT"

The Histone Deacetylase Inhibitor JAHA Down-Regulates pERK and Global DNA Methylation in MDA-MB231 Breast Cancer Cells

2015

The histone deacetylase inhibitor N-1-(ferrocenyl)-N-8-hydroxyoctanediamide (JAHA) down-regulates extracellular-signal-regulated kinase (ERK) and its activated form in triple-negative MDA-MB231 breast cancer cells after 18 h and up to 30 h of treatment, and to a lesser extent AKT and phospho-AKT after 30 h and up to 48 h of treatment. Also, DNA methyltransferase 1 (DNMT1), 3b and, to a lesser extent, 3a, downstream ERK targets, were down-regulated already at 18 h with an increase up to 48 h of exposure. Methylation-sensitive restriction arbitrarily-primed (MeSAP) polymerase chain reaction (PCR) analysis confirmed the ability of JAHA to induce genome-wide DNA hypomethylation at 48 h of expos…

“DNA Methyl transferase 1 post-trascriptional silencing indues aneuploidy and cell cycle arrest in human cells”,

2009

Reactivation of SNURF-SNRPN gene by DNA Methyltransferase inhibitors in a Prader-Willi lymphoblastoid cell line.

2014

Epigenetic Mechanisms as Key Regulators in Disease

2016

Epigenetics is a rapidly growing field of research which studies the changes in the gene expression that do not involve changes in the nucleotide sequence. The cellular metabolism is directly connected to epigenetic regulation through the inflow of different metabolites such as S-adenosylmethionine, acetyl-CoA, and α-ketoglutarate among others, which serve as substrates or cofactors for chromatin-modifying enzymes. These metabolites define how our lifestyle (i.e., nutrition, physical activity, and other healthy behaviors) acts on gene expression by epigenetic mechanisms. Therefore, proper coordination between components of the epigenetic machineries is essential for the correct control of t…

Bypass of cell cycle arrest induced by transient DNMT1 post-transcriptional silencing triggers aneuploidy in human cells

2012

Abstract Background Aneuploidy has been acknowledged as a major source of genomic instability in cancer, and it is often considered the result of chromosome segregation errors including those caused by defects in genes controlling the mitotic spindle assembly, centrosome duplication and cell-cycle checkpoints. Aneuploidy and chromosomal instability has been also correlated with epigenetic alteration, however the molecular basis of this correlation is poorly understood. Results To address the functional connection existing between epigenetic changes and aneuploidy, we used RNA-interference to silence the DNMT1 gene, encoding for a highly conserved member of the DNA methyl-transferases. DNMT1…

Redox regulation of genome stability by effects on gene expression, epigenetic pathways and DNA damage/repair

2015

Reactive oxygen and nitrogen species (e.g. H2O2, nitric oxide) confer redox regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. In addition, classical regulation of gene expression or activity, including gene transcription to RNA followed by translation to the protein level, by transcription factors (e.g. NF-κB, HIF-1α) and mRNA binding proteins (e.g. GAPDH, HuR) is subject to redox regulation. This review will give an update of recent discoveries in this field, and specifically highlight the impact of reactive oxygen and nitrogen species on DNA repair systems that contribute to genomic stability. Emphasis will be placed …

Caracterización molecular de las leucemias mieloides agudas de novo

2013

La secuenciación es la técnica de elección para identificar mutaciones. Sin embargo, tiene un coste elevado, es laboriosa y su sensibilidad es limitada. Recientemente, el nuevo método de análisis de alta resolución con curvas de fusión (High Resolution Melt, HRM) permite detectar de forma rápida y específica mutaciones, polimorfismos y cambios epigenéticos. La leucemia mieloide aguda (LMA) son enfermedades heterogéneas con distintos comportamientos clínicos. El 40-50% de los pacientes no presentan alteraciones cromosómicas específicas y los mecanismos moleculares que subyacen en su patogenia son en su mayor parte desconocidos. Avances en la caracterización molecular han permitido la identif…

Fatty Liver and Fibrosis in Glycine N-Methyltransferase Knockout Mice Is Prevented by Nicotinamide

2010

Deletion of glycine N-methyltransferase (GNMT), the main gene involved in liver S-adenosylmethionine (SAM) catabolism, leads to the hepatic accumulation of this molecule and the development of fatty liver and fibrosis in mice. To demonstrate that the excess of hepatic SAM is the main agent contributing to liver disease in GNMT knockout (KO) mice, we treated 1.5-month-old GNMT-KO mice for 6 weeks with nicotinamide (NAM), a substrate of the enzyme NAM N-methyltransferase. NAM administration markedly reduced hepatic SAM content, prevented DNA hypermethylation, and normalized the expression of critical genes involved in fatty acid metabolism, oxidative stress, inflammation, cell proliferation, …

Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma

2000

Abstract Background/Aims: It has been known for at least 50 years that alterations in methionine metabolism occur in human liver cirrhosis. However, the molecular basis of this alteration is not completely understood. In order to gain more insight into the mechanisms behind this condition, mRNA levels of methionine adenosyltransferase ( MAT1A ), glycine methyltransferase ( GNMT ), methionine synthase ( MS ), betaine homocysteine methyltransferase ( BHMT ) and cystathionine β-synthase ( CBS ) were examined in 26 cirrhotic livers, five hepatocellular carcinoma (HCC) tissues and ten control livers. Methods: The expression of the above-mentioned genes was determined by quantitative RT-PCR analy…

RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis.

2012

The function of cytosine-C5 methylation, a widespread modification of tRNAs, has remained obscure, particularly in mammals. We have now developed a mouse strain defective in cytosine-C5 tRNA methylation, by disrupting both the Dnmt2 and the NSun2 tRNA methyltransferases. Although the lack of either enzyme alone has no detectable effects on mouse viability, double mutants showed a synthetic lethal interaction, with an underdeveloped phenotype and impaired cellular differentiation. tRNA methylation analysis of the double-knockout mice demonstrated complementary target-site specificities for Dnmt2 and NSun2 and a complete loss of cytosine-C5 tRNA methylation. Steady-state levels of unmethylate…