Search results for "Sirtuins"
showing 7 items of 17 documents
Muscle NAD+ depletion and Serpina3n as molecular determinants of murine cancer cachexia—the effects of blocking myostatin and activins
2020
Objective Cancer cachexia and muscle loss are associated with increased morbidity and mortality. In preclinical animal models, blocking activin receptor (ACVR) ligands has improved survival and prevented muscle wasting in cancer cachexia without an effect on tumour growth. However, the underlying mechanisms are poorly understood. This study aimed to identify cancer cachexia and soluble ACVR (sACVR) administration-evoked changes in muscle proteome. Methods Healthy and C26 tumour-bearing (TB) mice were treated with recombinant sACVR. The sACVR or PBS control were administered either prior to the tumour formation or by continued administration before and after tumour formation. Muscles were an…
Free [NADH]/[NAD+] regulates sirtuin expression
2011
Sirtuins are deacetylases involved in metabolic regulation and longevity. Our aim was to test the hypothesis that they are subjected to redox regulation by the [NADH]/[NAD(+)] ratio. We used NIH3T3 fibroblasts in culture, Drosophila fed with or without ethanol and exercising rats. In all three models an increase in [NADH]/[NAD(+)] came up with an increased expression of sirtuin mRNA and protein. PGC-1α (a substrate of sirtuins) protein level was significantly increased in fibroblasts incubated with lactate and pyruvate but this effect was lost in fibroblasts obtained from sirtuin-deficient mice. We conclude that the expression of sirtuins is subject to tight redox regulation by the [NADH]/[…
Different Patterns of Lung Sirtuin Expression in Smokers With and Without Chronic Obstructive Pulmonary Disease
2012
Background and Objective. Chronic obstructive pulmonary disease is characterized by persistent and modified inflammatory responses in lung. Human sirtuin, an antiaging and antiinflammatory protein, is a metabolic NAD(+)-dependent protein/histone deacetylase that regulates proinflammatory mediators by deacetylating histone and nonhistone proteins. The aim of our study was to compare the expression of sirtuin in large and small airways in nonsmokers, asymptomatic smokers, and smokers with chronic obstructive pulmonary disease. Material and Methods. A total of 12 nonsmokers, 14 asymptomatic smokers, and 12 smokers with moderate chronic obstructive pulmonary disease were enrolled into the study…
Yeast HAT1 and HAT2 deletions have different life-span and transcriptome phenotypes
2005
AbstractHAT-B is a yeast histone acetyltransferase composed of Hat1, Hat2 and Hif1 proteins. We demonstrate that a hat2 mutant or a hat1hat2 double mutant, but not a hat1 mutant, have an extended life-span. Transcriptome analysis shows that the single hat mutants are not very different from wild type. However, the comparison of the hat1 and hat2 transcriptomes shows that they are different. The hat1hat2 double mutant shows a transcriptional phenotype similar to that of the hat1 mutant but strongly enhanced. These results indicate that Hat2p could have additional functions in the cell to those of Hat1p.
Chromatin modifiers and recombination factors promote a telomere fold-back structure, that is lost during replicative senescence.
2020
Telomeres have the ability to adopt a lariat conformation and hence, engage in long and short distance intra-chromosome interactions. Budding yeast telomeres were proposed to fold back into subtelomeric regions, but a robust assay to quantitatively characterize this structure has been lacking. Therefore, it is not well understood how the interactions between telomeres and non-telomeric regions are established and regulated. We employ a telomere chromosome conformation capture (Telo-3C) approach to directly analyze telomere folding and its maintenance in S. cerevisiae. We identify the histone modifiers Sir2, Sin3 and Set2 as critical regulators for telomere folding, which suggests that a dis…
Novel Insights into the Cellular Localization and Regulation of the Autophagosomal Proteins LC3A, LC3B and LC3C
2020
Macroautophagy is a conserved degradative process for maintaining cellular homeostasis and plays a key role in aging and various human disorders. The microtubule-associated protein 1A/1B light chain 3B (MAP1LC3B or LC3B) is commonly analyzed as a key marker for autophagosomes and as a proxy for autophagic flux. Three paralogues of the LC3 gene exist in humans: LC3A, LC3B and LC3C. The molecular function, regulation and cellular localization of LC3A and LC3C have not been investigated frequently, even if a similar function to that described for LC3B appears likely. Here, we have selectively decapacitated LC3B by three separate strategies in primary human fibroblasts and analyzed the evoked e…
Mitochondrial function and sirtuin expression in hippocampus of young and old high- and low-capacity runner rats
2016
Introduction: Exercise and aerobic capacity are associated with improved learning in animals and humans. The hippocampus is a brain structure involved in learning and memory. High rates of neurogenesis have been shown to take place in the dental gyrus of hippocampus in response to physical exercise. It is not known whether mitochondrial dysfunction in the hippocampus is responsible for decline in cognitive function associated with low fitness level and aging, and whether intrinsic aerobic capacity is a risk factor for it. Methods: Mitochondrial function was investigated in the hippocampi of young and old highcapacity runner (HCR) and low-capacity runner (LCR) rats using high-performance res…