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histone deacetylase metabolic

H Jęśko, R P Strosznajder
Sirtuins (SIRT1 to -7) are unique histone deacetylases (HDACs) whose activity depends on NAD+, thus making them capable of sensing the cellular metabolic status. Sirtuins orchestrate the stress response and damage repair, and are able to modulate the course of ageing and neurodegenerative diseases. Despite their classification as HDACs, sirtuins deacetylate a vast number of targets in many cellular compartments, and some display additional enzymatic activities including mono(ADP-ribosyl)ation. SIRTs interact with multiple signalling proteins, transcription factors and enzymes including p53, FOXOs (forkhead box subgroup O), PPARs (peroxisome proliferator-activated receptors), NF-B, and DNA-PK (DNA-dependent protein kinase)...
2016: Folia Neuropathologica
Upendarrao Golla, Deepthi Joseph, Raghuvir Singh Tomar
Valproic acid (VA) is a pharmacologically important histone deacetylase inhibitor that recently garnered attention as an anticancer agent. Since the molecular mechanisms behind the multiple effects of VA are unclear, this study was aimed to unravel the comprehensive cellular processes affected by VA and its molecular targets in vivo using budding yeast as a model organism. Interestingly, genome-wide transcriptome analysis of cells treated with VA showed differential regulation of 30% of the genome. Functional enrichment analysis of VA transcriptome evidenced alteration of various cellular processes including cell cycle, cell wall biogenesis, DNA repair, ion homeostasis, metabolism, stress response, transport and ribosomal biogenesis, etc...
October 13, 2016: Scientific Reports
Hana Čipčić Paljetak, Linda Tomašković, Mario Matijašić, Mirjana Bukvić, Andrea Fajdetić, Donatella Verbanac, Mihaela Perića
5-LOX - 5-lipoxygenase; ACT - artemisinin-based combination therapies; ADME - absorption, distribution, metabolism and excretion; BAL - broncho alveolar lavage; CABP - community acquired bacterial pneumonia; cAMP - cyclic adenosine monophosphate; CAP - community-acquired pneumonia; CF - cystic fibrosis, BOS bronchiolitis obliterans syndrome; cGMP - cyclic guanosine monophosphate; COPD - chronic obstructive pulmonary disease; COX - cyclooxygenase; DPB - diffuse panbronchiolitis; HDACs - histone deacetylases; IBD - inflammatory bowel disease; IL-1p - interleukin 1p; IL-6 - interleukin 6; MIC - minimal inhibitory concentrations; MLSB - macrolide, lincosamide, streptogramin B; NSAIDs - non-steroidal anti-inflammatory drugs; OVA - ovalbumin; PDE4 - phosphodiesterase 4; PMA - phorbol 12-myristate 13-acetate; RA - rheumatoid arthritis; RTI - respiratory tract infections; SAHA - suberoylanilide hydroxamic acid; SAR - structure-activity-relationship; Th1 - type 1 helper T-cell; TNBS - trinitrobenzene sulfonic acid; TNF-α - tumour necrosis factor α; UN - United Nations, WHO - World Health Organisation...
September 27, 2016: Current Topics in Medicinal Chemistry
Arunava Bandyopadhaya, Amy Tsurumi, Damien Maura, Kate L Jeffrey, Laurence G Rahme
The mechanisms by which pathogens evade elimination without affecting host fitness are not well understood. For the pathogen Pseudomonas aeruginosa, this evasion appears to be triggered by excretion of the quorum-sensing molecule 2-aminoacetophenone, which dampens host immune responses and modulates host metabolism, thereby enabling the bacteria to persist at a high burden level. Here, we examined how 2-aminoacetophenone trains host tissues to become tolerant to a high bacterial burden, without compromising host fitness...
October 3, 2016: Nature Microbiology
Aneesa Ansari, Md Shahedur Rahman, Subbroto K Saha, Forhad K Saikot, Akash Deep, Ki-Hyun Kim
In mammals, seven members of the sirtuin protein family known as class III histone deacetylase have been identified for their characteristic features. These distinguished characteristics include the tissues where they are distributed or located, enzymatic activities, molecular functions, and involvement in diseases. Among the sirtuin members, SIRT3 has received much attention for its role in cancer genetics, aging, neurodegenerative disease, and stress resistance. SIRT3 controls energy demand during stress conditions such as fasting and exercise as well as metabolism through the deacetylation and acetylation of mitochondrial enzymes...
September 29, 2016: Aging Cell
Nan Hu, Jun Ren, Yingmei Zhang
Insulin resistance contributes to the high prevalence of type 2 diabetes mellitus, leading to cardiac anomalies. Emerging evidence depicts a pivotal role for mitochondrial injury in oxidative metabolism and insulin resistance. Mitochondrial aldehyde dehydrogenase (ALDH2) is one of metabolic enzymes detoxifying aldehydes although its role in insulin resistance remains elusive. This study was designed to evaluate the impact of ALDH2 overexpression on insulin resistance-induced myocardial damage and mechanisms involved with a focus on autophagy...
September 12, 2016: Oncotarget
Coralie Allain, Gaëlle Angenard, Bruno Clément, Cédric Coulouarn
Integrative genomics helped characterize molecular heterogeneity in HCC, leading to targeted drug candidates for specific HCC subtypes. However, no consensus was achieved for genes and pathways commonly altered in HCC. Here we performed a meta-analysis of 15 independent datasets (n=784 human HCC) and identified a comprehensive signature consisting of 935 genes commonly deregulated in HCC as compared to the surrounding non-tumor tissue. In the HCC signature, up-regulated genes were linked to early genomic alterations in hepatocarcinogenesis, particularly gains of 1q and 8q...
September 12, 2016: Cancer Research
Marina Maria Bellet, Selma Masri, Giuseppe Astarita, Paolo Sassone-Corsi, Maria Agnese Della Fazia, Giuseppe Servillo
Liver regeneration offers a distinctive opportunity to study cell proliferation in vivo. Mammalian Silent information regulator 1 (SIRT1), a NAD(+)-dependent histone deacetylase, is an important regulator of various cellular processes, including proliferation, metabolism and circadian rhythms. In the liver, SIRT1 coordinates the circadian oscillation of clock-controlled genes, including genes that encode enzymes involved in metabolic pathways. We performed partial hepatectomy in WT and liver-specific Sirt1 deficient mice and analysed the expression of cell cycle regulators in liver samples taken at different times during the regenerative process, by real time PCR, western blotting and immunohistochemistry...
September 15, 2016: Journal of Biological Chemistry
Feng Liu, Ming Zong, Xiaofei Wen, Xuezhu Li, Jun Wang, Yi Wang, Wei Jiang, Xiaojun Li, Zhongliang Guo, Hualin Qi
Podocyte dysfunction is important in the onset and development of diabetic nephropathy (DN). Histone deacetylases (HDACs) have been recently proved to play critical roles in the pathogenesis of DN. As one subtype of the class IIa HDACs, HDAC9 is capable to repress/de-repress their target genes in tumor, inflammation, atherosclerosis and metabolic diseases. In the present study, we investigate whether HDAC9 is involved in the pathophysiologic process of DN, especially the podocyte injury. Firstly, we explored the expression patterns and localization of HDAC9 and found that HDAC9 expression was significantly up-regulated in high glucose (HG)-treated mouse podocytes, as well as kidney tissues from diabetic db/db mice and patients with DN...
2016: Scientific Reports
Vidhi Gaur, Timothy Connor, Andrew Sanigorski, Sheree D Martin, Clinton R Bruce, Darren C Henstridge, Simon T Bond, Kevin A McEwen, Lyndal Kerr-Bayles, Trent D Ashton, Cassandra Fleming, Min Wu, Lisa S Pike Winer, Denise Chen, Gregg M Hudson, John W R Schwabe, Keith Baar, Mark A Febbraio, Paul Gregorevic, Frederick M Pfeffer, Ken R Walder, Mark Hargreaves, Sean L McGee
Drugs that recapitulate aspects of the exercise adaptive response have the potential to provide better treatment for diseases associated with physical inactivity. We previously observed reduced skeletal muscle class IIa HDAC (histone deacetylase) transcriptional repressive activity during exercise. Here, we find that exercise-like adaptations are induced by skeletal muscle expression of class IIa HDAC mutants that cannot form a corepressor complex. Adaptations include increased metabolic gene expression, mitochondrial capacity, and lipid oxidation...
September 13, 2016: Cell Reports
Laura E Downing, Bradley S Ferguson, Kelvin Rodriguez, Marie-Louise Ricketts
SCOPE: Histone deacetylases (HDACs) have emerged as epigenetic regulators of risk factors associated with the metabolic syndrome (MetS), and certain botanical extracts have proven to be potent HDAC inhibitors. Understanding the role of dietary procyanidins in HDAC inhibition is important in exploring the therapeutic potential of natural products. METHODS: C57BL/6 mice were gavaged with vehicle (water) or grape seed procyanidin extract (GSPE, 250 mg/kg) and terminated 14 hours later...
September 14, 2016: Molecular Nutrition & Food Research
Danielle Desjardins, Yueying Liu, Craig E Crosson, Zsolt Ablonczy
In diabetic individuals, macular edema is a major cause of vision loss. This condition is refractory to insulin therapy and has been attributed to metabolic memory. The retinal pigment epithelium (RPE) is central to maintaining fluid balance in the retina, and this function is compromised by the activation of advanced glycation end-product receptors (RAGE). Here we provide evidence that acute administration of the RAGE agonist, glycated-albumin (gAlb) or vascular endothelial growth factor (VEGF), increased histone deacetylase (HDAC) activity in RPE cells...
2016: PloS One
Jumei Xu, Xue Chen, Shuiqing Yu, Yong Su, Weiyun Zhu
Butyrate in the gut of animals has potential properties including regulating the innate immune, modulating the lipid metabolism, and protecting gut healthy. So far, only limited information on the impact of butyrate on the neonatal is available. This study aimed to investigate effects of oral administration of sodium butyrate (SB) on gut microbiota and the expression of inflammatory cytokine in neonatal piglets. Ten litters of crossbred newborn piglets were randomly allocated to the SB and control (CO) groups, each group consisted of five litters (replicates)...
2016: PloS One
Ana Latorre, Antonio Moscardó
Reversible acetylation of histones is a well-known mechanism of epigenetic regulation of gene expression. More recently, studies have demonstrated that acetylation/deacetylation in several proteins regulate multiple aspects of cellular activity, especially those associated with energetic metabolism. Platelets are key participants in haemostasis and cardiovascular diseases. Although metabolic changes such as diabetes or lipidemia are well recognized risk factors for cardiovascular diseases, there is very little information about the relationship between metabolism and platelet reactivity...
September 7, 2016: Current Medicinal Chemistry
Patrick Georgoff, Ihab Halaweish, Vahagn Nikolian, Gerald Higgins, Tess Bonham, Celia Tafatia, Henriette Remmer, Rajasree Menon, Baoling Liu, Yongqing Li, Hasan B Alam
BACKGROUND: High doses of the histone deacetylase inhibitor Valproic Acid (VPA, 150-400 mg/kg) improve outcomes in animal models of lethal insults. We are conducting an FDA approved phase 1, double blind, placebo-controlled trial to evaluate the safety and tolerability of ascending doses of VPA in human volunteers. We hypothesized that VPA would induce significant changes in the proteome of healthy humans when given at doses lower than those used in prior animal studies. METHODS: Peripheral blood mononuclear cells were obtained from three healthy subjects randomized to receive VPA (120 mg/kg over one hour) at baseline, 4, and 8 hours following infusion...
September 3, 2016: Journal of Trauma and Acute Care Surgery
Christophe Glorieux, Juan Marcelo Sandoval, Antoine Fattaccioli, Nicolas Dejeans, James C Garbe, Marc Dieu, Julien Verrax, Patricia Renard, Peng Huang, Pedro Buc Calderon
Regulation of ROS metabolism plays a major role in cellular adaptation to oxidative stress in cancer cells, but the molecular mechanism that regulates catalase, a key antioxidant enzyme responsible for conversion of hydrogen peroxide to water and oxygen, remains to be elucidated. Therefore, we investigated the transcriptional regulatory mechanism controlling catalase expression in three human mammary cell lines: the normal mammary epithelial 250MK primary cells, the breast adenocarcinoma MCF-7 cells and an experimental model of MCF-7 cells resistant against oxidative stress resulting from chronic exposure to H2O2 (Resox), in which catalase was overexpressed...
August 31, 2016: Free Radical Biology & Medicine
Yuan Tian, Myth T S Mok, Pengyuan Yang, Alfred S L Cheng
Non-alcoholic fatty liver disease (NAFLD), characterized by fat accumulation in liver, is closely associated with central obesity, over-nutrition and other features of metabolic syndrome, which elevate the risk of developing hepatocellular carcinoma (HCC). The Wnt/β-catenin signaling pathway plays a significant role in the physiology and pathology of liver. Up to half of HCC patients have activation of Wnt/β-catenin signaling. However, the mutation frequencies of CTNNB1 (encoding β-catenin protein) or other antagonists targeting Wnt/β-catenin signaling are low in HCC patients, suggesting that genetic mutations are not the major factor driving abnormal β-catenin activities in HCC...
2016: Cancers
Silvia Rodrigo, Lourdes Rodríguez, Paola Otero, María I Panadero, Antonia García, Coral Barbas, Núria Roglans, Sonia Ramos, Luis Goya, Juan C Laguna, Juan J Álvarez-Millán, Carlos Bocos
SCOPE: One of the features of metabolic syndrome caused by liquid fructose intake is an impairment of redox status. We have investigated whether maternal fructose ingestion modifies the redox status in pregnant rats and their fetuses. METHODS AND RESULTS: Fructose (10% wt/vol) in the drinking water of rats throughout gestation, leads to maternal hepatic oxidative stress. However, this change was also observed in glucose-fed rats and, in fact, both carbohydrates produced a decrease in antioxidant enzyme activity...
August 22, 2016: Molecular Nutrition & Food Research
Ana García-Aguilar, Carlos Guillén, Mark Nellist, Alberto Bartolomé, Manuel Benito
There is a growing evidence of the role of protein acetylation in different processes controlling metabolism. Sirtuins (histone deacetylases nicotinamide adenine dinucleotide-dependent) activate autophagy playing a protective role in cell homeostasis. This study analyzes tuberous sclerosis complex (TSC2) lysine acetylation, in the regulation of mTORC1 signaling activation, autophagy and cell proliferation. Nicotinamide 5mM (a concentration commonly used to inhibit SIRT1), increased TSC2 acetylation in its N-terminal domain, and concomitantly with an augment in its ubiquitination protein status, leading to mTORC1 activation and cell proliferation...
August 16, 2016: Biochimica et Biophysica Acta
Mitsuyasu Kawaguchi, Shohei Ikegawa, Naoya Ieda, Hidehiko Nakagawa
Sirtuins (SIRTs) are a family of NAD+-dependent histone deacetylases. In mammals, dysfunction of SIRTs is associated with age-related metabolic diseases and cancers, so SIRT modulators are considered attractive therapeutic targets. However, current screening methodologies are problematic, and no tools are available for imaging endogenous SIRT activity in living cells. In this work, we present a series of simple and highly sensitive novel SIRT activity probes. Fluorescence of these probes is activated by SIRT-mediated hydrolytic release of a 4-(4-dimethylaminophenylazo)benzoyl (Dabcyl)-based FRET quencher moiety from the -amino group of lysine in a histone H3K9-derived nonapeptide bearing a C-terminal fluorophore...
August 19, 2016: Chembiochem: a European Journal of Chemical Biology
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