Search results for "Sirtuin"
showing 10 items of 67 documents
Resveratrol as a Gene Regulator in the Vasculature
2014
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) possesses multiple protective properties in the vasculature, including anti-oxidative and anti-inflammatory effects and improvement of endothelial function. A substantial part of these effects is attributable to gene expression changes induced by the compound. Resveratrol can activate the NAD-dependent deacetylase sirtuin 1 (SIRT1), leading to deacetylation of SIRT1 target molecules such as NF-kB and forkhead box O (FOXO) transcription factors. The inhibition of NF-kB by resveratrol reduces the expression of inflammation mediators. FOXO factors are implicated in the upregulation of antioxidant enzymes and the endothelial-type nitric oxide synth…
Use of Saccharomyces cerevisiae and Caenorhabditis elegans as model organisms to study the effect of cocoa polyphenols in the resistance to oxidative…
2011
Developing functional foods to improve the quality of life for elderly people has great economic and social impact. Searching for and validating ingredients with in vivo antioxidant effects is one of the key steps in developing this kind of food. Here we describe the combined use of simple biological models and transcriptomics to define the functional intracellular molecular targets of a polyphenol-enriched cocoa powder. Cocoa powder supplemented culture medium led to increased resistance to oxidative stress, in both the budding yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans, and, in the latter, lifespan was also increased. These effects are fully dependent on the po…
The histone deacetylase sirtuin 2 is a new player in the regulation of platelet function
2015
SummaryBackground Histone deacetylases (HDACs) play a key role in signaling in many cell types. However, little is known about the participation of HDACs, particularly sirtuins (SIRTs), in platelet reactivity. Objective To investigate the role of HDACs in platelets, we examined the effects of SIRT inhibition on platelet function and protein acetylation in human platelets. Methods We used washed platelets obtained from healthy subjects. Cambinol (SIRT1 and SIRT2 inhibitor), AGK2 (specific SIRT2 inhibitor) and EX527 (specific SIRT1 inhibitor) were used as SIRT inhibitors. Platelets were stimulated with collagen, thrombin, or U46619, and platelet responses were determined according to optical …
Carbocysteine counteracts the effects of cigarette smoke on cell growth and on the SIRT1/FoxO3 axis in bronchial epithelial cells
2016
Abstract Background Cigarette smoke may accelerate cellular senescence by increasing oxidative stress. Altered proliferation and altered expression of anti-aging factors, including SIRT1 and FoxO3, characterise cellular senescence. The effects of carbocysteine on the SIRT1/FoxO3 axis and on downstream molecular mechanisms in human bronchial epithelial cells exposed to cigarette smoke are largely unknown. Aims Aim of this study was to explore whether carbocysteine modulated SIRT1/FoxO3 axis, and downstream molecular mechanisms associated to cellular senescence, in a bronchial epithelial cell line (16-HBE) exposed to cigarette smoke. Methods 16HBE cells were stimulated with/without cigarette …
Abstract PR10: Inhibition of deacetylase SIRT1 offers a novel treatment option in metastatic Ewing sarcoma
2014
Abstract Metastasis is the major cause of disease-related death in Ewing sarcoma. Patients, who present with clinically overt disseminated disease at diagnosis and those who relapse early with distant metastases have a poor outcome despite multi-modal high-dose chemotherapy. Therefore, new treatment options are highly warranted. Ewing sarcoma pathogenesis is driven by the chimeric ETS oncogene EWS-FLI1. We here describe regulation of sirtuin SIRT1 by EWS-FLI1 and its role in metastasis. SIRT1 belongs to a family of NAD+-dependent group III deacetylases that target histone and non-histone proteins in response to metabolic stress resulting in widespread gene expression changes through epigene…
Resveratrol-mediated apoptosis of hodgkin lymphoma cells involves SIRT1 inhibition and FOXO3a hyperacetylation
2012
Resveratrol (RSV), a plant-derived stilbene, induces cell death in Hodgkin lymphoma (HL)-derived L-428 cells in a dose-dependent manner (IC50 = 27 μM, trypan blue exclusion assay). At a lower range (25 μM), RSV treatment for 48 hr causes arrest in the S-phase of the cell cycle, while at a higher concentration range (50 μM), apoptosis can be detected, with activation of caspase-3. The histone/protein deacetylase SIRT1 has been described as a putative target of RSV action in other model systems, even though its role in cancer cells is still controversial. Here we show that RSV, at both concentration ranges, leads to a marked increase in p53, while a decrease of SIRT1 expression level, as well…
Cell volume homeostatically controls the rDNA repeat copy number and rRNA synthesis rate in yeast
2021
[Abstract] The adjustment of transcription and translation rates to the changing needs of cells is of utmost importance for their fitness and survival. We have previously shown that the global transcription rate for RNA polymerase II in budding yeast Saccharomyces cerevisiae is regulated in relation to cell volume. Total mRNA concentration is constant with cell volume since global RNApol II-dependent nascent transcription rate (nTR) also keeps constant but mRNA stability increases with cell size. In this paper, we focus on the case of rRNA and RNA polymerase I. Contrarily to that found for RNA pol II, we detected that RNA polymerase I nTR increases proportionally to genome copies and cell s…
Cardiovascular effects and molecular targets of resveratrol
2012
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol phytoalexin present in a variety of plant species and has been implicated to explain the health benefits of red wine. A wide range of health beneficial effects have been demonstrated for resveratrol in animal studies. In this review, we summarize the cardiovascular effects of resveratrol with emphasis on the molecular targets of the compound. In this regard, resveratrol stimulates endothelial production of nitric oxide, reduces oxidative stress, inhibits vascular inflammation and prevents platelet aggregation. In animal models of cardiovascular disease, resveratrol protects the heart from ischemia-reperfusion injury, reduces blo…
Fibroblast growth factor-21 enhances mitochondrial functions and increases the activity of PGC-1α in human dopaminergic neurons via Sirtuin-1
2014
Abstract Mitochondrial dysfunctions accompany several neurodegenerative disorders and contribute to disease pathogenesis among others in Parkinson’s disease (PD). Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a major regulator of mitochondrial functions and biogenesis, and was suggested as a therapeutic target in PD. PGC-1α is regulated by both transcriptional and posttranslational events involving also the action of growth factors. Fibroblast growth factor-21 (FGF21) is a regulator of glucose and fatty acid metabolism in the body but little is known about its action in the brain. We show here that FGF21 increased the levels and activity of PGC-1α and elevated mito…
Characterization of the NAD-Dependent Human Histone Deacetylases Gene Sirtuin 1 and Its Implications on Aging and the Development of Malignant Diseas…
2006
Abstract A dysregulation of the tightly controlled equilibrium of acetylation and deacetylation plays a causative role in the generation as well as in the suppression of cancer. Histone acetylation modifiers are therefore gaining increasing attention as potential targets in the treatment of cancer. Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, which belongs to the silent information regulator 2 (Sir2) family of sirtuin histone deacetylases (HDACs). The yeast Sir2 protein and its mammalian derivatives play a central role in epigenetic gene silencing, DNA repair and recombination, cell-cycle, microtubule organization, and in the regulation of aging. We…