SIRT1,HDAC

Protein acetylation, which is dynamically maintained by histone acetyltransferases (HATs) and deacetylases (HDACs), might play essential roles in hippocampal exercise physiology. However, whether HATs/HDACs are imbalanced during the recovery phase following acute exercise has not been determined. Groups of exercised mice with different recovery periods after acute exercise (0 h, 0.5 h, 1 h, 4 h, 7 h, and 24 h) were constructed, and a group of sham-exercised mice was used as the control...

Aspirin, also named acetylsalicylate, can directly acetylate the side-chain of lysine in protein, which leads to the possibility of unexplained drug effects. Here, the study used isotopic-labeling aspirin-d3 with mass spectrometry analysis to discover that aspirin directly acetylates 10 HDACs proteins, including SIRT1, the most studied NAD+ -dependent deacetylase. SIRT1 is also acetylated by aspirin in vitro. It is also identified that aspirin directly acetylates lysine 408 of SIRT1, which abolishes SIRT1 deacetylation activity by impairing the substrates binding affinity...

Silent mating type information regulation 2 homolog 1 (SIRT1) is a class III histone deacetylase (HDAC) that is NAD + dependent and essential for metabolism, senescence, and cell survival. SIRT1 is overexpressed in several cancers, including breast cancer. SIRT1 is a well-known target gene of the estrogen receptor alpha (ER alpha) and is closely related to ER alpha deacetylation. Transcription factor Estrogen-related receptors (ERRs) share sequence homology with ERs in the DNA-binding domain, therefore, the possibility of sharing target genes between them is high...

INTRODUCTION: Epigenetic enzymes can interact with a wide range of genes that actively participate in the progression or repression of a diseased condition, as they are involved in maintaining cellular homeostasis. Sirtuins are a family of Class III epigenetic modifying enzymes that regulate cellular processes by removing acetyl groups from proteins. They rely on NAD+ as a coenzyme in contrast to classical histone deacetylases (HDACs) (Class I, II, and IV) that depend on Zn+ for their activation, linking their function to cellular energy levels...

Breast cancer (BC) is a heterogeneous condition and comprises molecularly distinct subtypes. An imbalance in the levels of epigenetic histone deacetylases (HDACs), modulating estrogen accumulation, especially 17β-estradiol (E2), promotes breast tumorigenesis. In the present study, analyses of The Cancer Genome Atlas (TCGA) pan-cancer normalized RNA-Seq datasets revealed the dysregulation of 16 epigenetic enzymes (among a total of 18 members) in luminal BC subtypes, in comparison to their non-cancerous counterparts...

PURPOSE: Chemokine-driven leukocyte infiltration and sustained inflammation contribute to alcohol-associated liver disease (ALD). Elevated hepatic CCL2 expression, seen in ALD, is associated with disease severity. However, mechanisms of CCL2 regulation are not completely elucidated. Post-translational modifications (PTMs) of proteins, particularly acetylation, modulate gene expression. This study examined the acetylation changes of promoter-associated histone-H3 and key transcription factor-NFκB in regulating hepatic CCL2 expression and subsequent inflammation and injury...

Histone acetylation that controlled by two mutually antagonistic enzyme families, histone acetyl transferases (HATs) and histone deacetylases (HDACs), as one of major epigenetic mechanisms controls transcription and its abnormal regulation was implicated in various aspects of cancer. However, the comprehensive understanding of HDACs and HATs in cancer is still lacking. Systematically analysis through 33 cancer types based on next-generation sequence data reveals heterogeneous expression pattern of HDACs and HATs across different cancer types...

Sirtuins (SIRT) are a class of histone deacetylases that regulate important metabolic pathways and play a role in several disease processes. Of the seven mammalian homologs currently identified, sirtuin 1 (SIRT1) is the best understood and most studied. It has been associated with several neurodegenerative diseases and cancers. As such, it has been further investigated as a therapeutic target in the treatment of disorders such as Parkinson's disease (PD), Huntington's disease (HD), and Alzheimer's disease (AD)...

Background Ultraviolet radiation causes DNA damage in keratinocytes, aggravating cutaneous lupus erythematosus (CLE). High mobility group box 1 (HMGB1) participates in nucleotide excision and may transfer from the nucleus to the cytoplasm in immune active cells and the translocation of HMGB1 may result in DNA repair defects. HMGB1 was observed to transfer from the nucleus to the cytoplasm in the keratinocytes of CLE patients. As a class III histone deacetylases (HDACs), sirtuin-1 (SIRT1) can induce HMGB1 deacetylation...

Epigenetic mechanisms finely regulate gene expression and represent potential therapeutic targets. Cambinol is a synthetic heterocyclic compound that inhibits class III histone deacetylases known as sirtuins (SIRTs). The acetylating action that results could be crucial in modulating cellular functions via epigenetic regulations. The main aim of this research was to investigate the effects of cambinol, and its underlying mechanisms, on cell differentiation by combining wet experiments with bioinformatics analyses and molecular docking simulations...

Atherosclerosis (AS) is a chronic metabolic disorder and primary cause of cardiovascular diseases, resulting in substantial morbidity and mortality worldwide. Initiated by endothelial cell stimulation, AS is characterized by arterial inflammation, lipid deposition, foam cell formation, and plaque development. Nutrients such as carotenoids, polyphenols, and vitamins can prevent the atherosclerotic process by modulating inflammation and metabolic disorders through the regulation of gene acetylation states mediated with histone deacetylases (HDACs)...

Members of the HDAC family are predictive biomarkers and regulate the tumorigenesis in several cancers. However, the role of these genes in the biology of intracranial ependymomas (EPNs) remains unexplored. Here, an analysis of eighteen HDACs genes in an EPN transcriptomic dataset, revealed significantly higher levels of HDAC4 in supratentorial ZFTA fusion (ST-ZFTA) compared with ST-YAP1 fusion and posterior fossa EPNs, while HDAC7 and SIRT2 were downregulated in ST-ZFTA. HDAC4 was also overexpressed in ST-ZFTA as measured by single-cell RNA-Seq, quantitative real time-polymerase chain reaction, and immunohistochemistry...

It is important to understand whether endothelial cells are epigenetically affected by titanium-enriched media when angiogenesis is required during bone development and it is expected to be recapitulated during osseointegration of biomaterials. To better address this issue, titanium-enriched medium was obtained from incubation of titanium discs for up to 24 h as recommended by ISO 10993-5:2016, and further used to expose human umbilical vein endothelial cells (HUVECs) for up to 72 h, when the samples were properly harvested to allow molecular analysis and epigenetics...

The sirtuin family, a group of NAD+-dependent class 3 histone deacetylases (HDACs), was extensively studied initially as a group of longevity genes that are activated in caloric restriction and act in concert with nicotinamide adenine dinucleotides to extend the lifespan. Subsequent studies have found that sirtuins are involved in various physiological processes, including cell proliferation, apoptosis, cell cycle progression, and insulin signaling, and they have been extensively studied as cancer genes. In recent years, it has been found that caloric restriction increases ovarian reserves, suggesting that sirtuins may play a regulatory role in reproductive capacity, and interest in the sirtuin family has continued to increase...

Bioactive compounds (BCs) are known to exhibit antioxidant, anti-inflammatory, and anti-cancer properties by regulating the cellular redox balance and histone acetylation state. BCs can control chronic oxidative states caused by dietary stress, i.e., alcohol, high-fat, or high-glycemic diet, and adjust the redox balance to recover physiological conditions. Unique functions of BCs to scavenge reactive oxygen species (ROS) can resolve the redox imbalance due to the excessive generation of ROS. The ability of BCs to regulate the histone acetylation state contributes to the activation of transcription factors involved in immunity and metabolism against dietary stress...

Ethanol tolerance is the first type of behavioral plasticity and neural plasticity that is induced by ethanol intake, and yet its molecular and circuit bases remain largely unexplored. Here, we characterize three distinct forms of ethanol tolerance in male Drosophila: rapid, chronic, and repeated. Rapid tolerance is composed of two short-lived memory-like states, one that is labile and one that is consolidated. Chronic tolerance, induced by continuous exposure, lasts for two days, induces ethanol preference, and hinders the development of rapid tolerance through the activity of histone deacetylases (HDACs)...

Sirtuins and autophagy are well-characterized agents that can promote longevity and protect individual organisms from age-associated diseases like neurodegenerative disorders. In recent years, more and more data has been obtained that discerned potential overlaps and crosstalk between Sirtuin proteins and autophagic activity. This review aims to summarize the advances within the field for each individual Sirtuin in mammalian systems. In brief, most Sirtuins have been implicated in promoting autophagy, with Sirtuin 1 and Sirtuin 6 showing the highest immediate involvement, while Sirtuin 4 and Sirtuin 5 only demonstrate occasional influence...

Huntington's Disease (HD) is a fatal neurodegenerative disorder caused by the expansion of a polyglutamine-coding CAG repeat in the Huntingtin gene. One of the main causes of neurodegeneration in HD is transcriptional dysregulation that, in part, is caused by the inhibition of histone acetyltransferase (HAT) enzymes. HD pathology can be alleviated by increasing the activity of specific HATs or by inhibiting histone deacetylase (HDAC) enzymes. To determine which histone's post-translational modifications (PTMs) might play crucial roles in HD pathology, we investigated the phenotype-modifying effects of PTM mimetic mutations of variant histone H3...

Toxoplasma gondii is an opportunistic pathogenic protozoan that can infect almost all kinds of warm-blooded animals, including humans. T. gondii can evade the host's immune response, a process known as immune evasion. Our main objective was to evaluate the role played by Sirtuin1 (SIRT1) [one of the sirtuins (SIRTs) that are a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases (HDACs)] in the T. gondii infection of RAW264.7 macrophages. In this study, we evaluated and observed alterations in the activity, expression, and localization of SIRT1 and assessed its involvement in the CD154/IFN-γ (CD40 ligand/interferon gamma) killing pathway and in autophagy during T...

Alzheimer's disease (AD), the most common cause of dementia, causes irreversible memory loss and cognitive deficits. Current AD drugs do not significantly improve cognitive function or cure the disease. Novel bioproducts are promising options for treating a variety of diseases, including neurodegenerative disorders. Targeting the epigenetic apparatus with bioactive compounds (epidrugs) may aid AD prevention treatment. The aims of this study were to determine the composition of a porcine brain-derived extract Nosustrophine, and whether treating young and older trigenic AD mice produced targeted epigenetic and neuroprotective effects against neurodegeneration...