Search results for "MT1"
showing 10 items of 37 documents
The effect of the HDACi JAHA on DNA methylation of breast cancer cells by down-regulating DNMT1 through ERK signaling
2014
Bypass of G1 arrest induced by DNMT1 posttranscriptional silencing triggers aneuploidy in human cells.
2010
Aneuploidy is a major source of genomic instability in cancer, resulting from chromosome segregation errors caused by defects in genes controlling correct mitotic spindle assembly, centrosome duplication and cell cycle checkpoints. Interestingly in aneuploid cells some of these genes, although not mutated, were underexpressed suggesting the involvement of epigenetic alterations. DNA methylation and histone modifications are the main epigenetic modifications occurring in cells. DNA methyl-transferase 1 (Dnmt1) is known to restore DNA methylation patterns during cell divisions. We investigated the effects of DNMT1 silencing by RNA-interference on the generation of aneuploidy in primary human …
DNA Methyltransferase1 post-transcriptional silencing induces aneuploidy and cell cycle arrest in human cells.
2009
The regulation of chromatin structure is a dynamic and complex process that is modulated by epigenetic mechanisms. Malfunctioning of these processes can cause gene expression alteration and could compromise important events such as chromosome condensation and segregation. Imbalance in cytosine methylation and deregulation of DNA-methyltransferases (DNMTs), and of DNMT1 in particular, is frequent in human cancers. To investigate DNMT1 implication in the generation of aneuploidy we evaluated the effects of its depletion by RNA-interference both in primary human cells (IMR90) and in near diploid human tumor (HCT116) cells. Posttranscriptional silencing of DNMT1 induced aneuploidy, cell prolife…
DNMT1 transient silencing induces aneuploidy, premature separated chromatids and centromeric chromatin alterations
2008
DNMT1 SILENCING ELICITS DIFFERENT CELL CYCLE RESPONSES IN PRIMARY VERSUS TUMOR CELLS AND IS ASSOCIATED WITH ANEUPLOIDY GENERATION
2011
DNMT1 depletion activates a pathway p14ARF/TP53 controlled that induces G1 arrest preventing DNA demethylation and aneuploidy
2011
Background: Aneuploidy is considered the result of chromosome segregation errors caused by defects in the mitotic spindle assembly, centrosome duplication, cell-cycle checkpoints and epigenetic changes. Usually, aneuploidy affects negatively proliferation of normal cells. However, it is frequently associated with cancer that is characterized by a uncontrolled proliferation. Thus, understanding the pathway(s) that block proliferation of aneuploid cells might open new avenue to exploit new cancer therapies. O bservations: We found that in primary human fi broblasts (IMR90) knocking down of DNMT1, a member of epigenetic machinery is perceived by the cell as a stress signal that induces p14ARF …
Synthesis of new melatoninergic hexahydroindenopyridines
2014
Hexahydroindenopyridine (HHIP) is an interesting heterocyclic framework that contains an indene core similar to ramelteon. This type of tricyclic piperidines aroused our interest as potential melatoninergic ligands. Melatonin receptor ligands have applications in insomnia and depression. We report herein an efficient two-step method to prepare new HHIP by the reaction of an enamine with 3-bromopropylamine hydrobromide. Some synthesized compounds showed moderate affinity for melatonin receptors in the nanomolar or low micromolar range. Furthermore, the methylenedioxy HHIPs 2d (N-phenylacetamide) and 2f (N,N-diethylacetamide), exhibited high selectivity at MT1 or MT2 receptors, respectively, …
Synthesis and Characterization of New Bivalent Agents as Melatonin- and Histamine H3-Ligands
2014
Melatonin is an endogenous molecule involved in many pathophysiological processes. In addition to the control of circadian rhythms, its antioxidant and neuroprotective properties have been widely described. Thus far, different bivalent compounds composed by a melatonin molecule linked to another neuroprotective agent were synthesized and tested for their ability to block neurodegenerative processes in vitro and in vivo. To identify a novel class of potential neuroprotective compounds, we prepared a series of bivalent ligands, in which a prototypic melatonergic ligand is connected to an imidazole-based H3 receptor antagonist through a flexible linker. Four imidazolyl-alkyloxy-anilinoethylami…
Efficient synthesis of hexahydroindenopyridines and their potential as melatoninergic ligands.
2014
Hexahydroindenopyridine (HHIP) is an interesting tricyclic piperidine nucleus that is structurally related to melatonin, a serotonin-derived neurohormone. Melatonin receptor ligands have applications in several cellular, neuroendocrine and neurophysiological disorders, including depression and/or insomnia. We report herein an efficient two-step method to prepare new HHIP via enamine C-alkylation-cyclization. The influence of substituents on the benzene ring and the nitrogen atom on melatoninergic receptors has been studied. Among the 25 synthesized HHIPs, some of them containing methylenedioxy (series 2) and 8-chloro-7-methoxy substituents (series 4) on the benzene ring revealed affinity fo…
Effects of 5-Azacitidine on Dnmt2/Trdmt1 expression levels and endoplasmic reticulum stress in cellular models of insulinoma
2021
Diabetes mellitus affects people all over the world of all ages or social groups making it a worldwide healthcare challenge. Moreover, untreated or badly treated diabetes carries a risk of serious complications including premature death (IDF Diabetes Atlas 9th edition, 2019). The main symptom of diabetes is insulin secretion and/or action disorder leading to hyperglycemia what results in impaired carbohydrate, fat, and protein metabolism (“Diagnosis and Classification of Diabetes Mellitus,” 2013). Dnmt2/ Trdmt1 in its structure and sequence is similar to DNA methyltransferases, however, it has been shown that mainly methylates aspartic acid transfer RNA, specifically at the cytosine-38 resi…