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https://www.readbyqxmd.com/read/28928419/the-histone-deacetylase-sirt6-blocks-myostatin-expression-and-development-of-muscle-atrophy
#1
Sadhana A Samant, Abhinav Kanwal, Vinodkumar B Pillai, Riyue Bao, Mahesh P Gupta
Muscle wasting, also known as cachexia, is associated with many chronic diseases, which worsens prognosis of primary illness leading to enhanced mortality. Molecular basis of this metabolic syndrome is not yet completely understood. SIRT6 is a chromatin-bound member of the sirtuin family, implicated in regulating many cellular processes, ranging from metabolism, DNA repair to aging. SIRT6 knockout (SIRT6-KO) mice display loss of muscle, fat and bone density, typical characteristics of cachexia. Here we report that SIRT6 depletion in cardiac as well as skeletal muscle cells promotes myostatin (Mstn) expression...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28921546/neuroblastoma-cells-undergo-transcriptomic-alterations-upon-dissemination-into-the-bone-marrow-and-subsequent-tumor-progression
#2
Fikret Rifatbegovic, Christian Frech, M Reza Abbasi, Sabine Taschner-Mandl, Tamara Weiss, Wolfgang M Schmidt, Iris Schmidt, Ruth Ladenstein, Inge M Ambros, Peter F Ambros
Neuroblastoma is the most common extracranial solid tumor in childhood. The vast majority of metastatic (M) stage patients present with disseminated tumor cells (DTCs) in the bone marrow (BM) at diagnosis and relapse. Although these cells represent a major obstacle in the treatment of neuroblastoma patients, insights into their expression profile remained elusive. The present RNA-Seq study of stage 4/M primary tumors, enriched BM-derived diagnostic and relapse DTCs, as well as the corresponding BM-derived mononuclear cells (MNCs) from 53 patients revealed 322 differentially expressed genes in DTCs as compared to the tumors (q < 0...
September 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28904859/sirtuin-6-contributes-to-migration-and-invasion-of-osteosarcoma-cells-via-the-erk1-2-mmp9-pathway
#3
Hang Lin, Yi Hao, Zhengxu Zhao, Yongjun Tong
Dysregulation of sirtuin 6 (SIRT6) is actively involved in tumor progression. High levels of SIRT6 have been associated with hepatocellular carcinoma and non-small cell lung cancer, and SIRT6 facilitates growth and metastasis of cancer cells. However, the clinical significance and biological function of SIRT6 are not known for osteosarcoma (OS). Here, we report that SIRT6 was notably overexpressed in OS tissues compared with non-cancerous specimens. The high level of SIRT6 was prominently correlated with malignant clinical parameters and poor prognosis of OS patients...
September 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28891317/the-role-of-sirtuins-in-antioxidant-and-redox-signaling
#4
Chandra K Singh, Gagan Chhabra, Mary Ndiaye, Liz Mariely Garcia-Peterson, Nicholas John Mack, Nihal Ahmad
SIGNIFICANCE: Antioxidant and redox signaling (ARS) events are regulated by critical molecules that modulate antioxidants, reactive oxygen or nitrogen species (ROS/RNS) and/or oxidative stress within the cell. Imbalances in these molecules can disturb cellular functions to become pathogenic. Sirtuins serve as important regulators of ARS in cells. Recent Advances: Sirtuins (SIRTs 1-7) are a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases with the ability to deacetylate histone and non-histone targets...
September 11, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28887543/the-oxidative-state-of-cysteine-thiol-144-regulates-the-sirt6-glucose-homeostat
#5
David Long, Hanzhi Wu, Allen W Tsang, Leslie B Poole, Barbara K Yoza, Xianfeng Wang, Vidula Vachharajani, Cristina M Furdui, Charles E McCall
Control of glucose homeostasis plays a critical role in health and lifespan and its dysregulation contributes to inflammation, cancer and aging. NAD + dependent Sirtuin 6 (SIRT6) is a glucose homeostasis regulator in animals and humans and its regulation at the molecular level is unknown. Here, we report that a cysteine thiol redox sensor contributes to the role of SIRT6 in controlling glucose homeostasis. Sulfenylation of SIRT6 occurs in THP1 cells and primary human promonocytes during inflammation and in splenocytes from mice with sepsis...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877980/nad-metabolism-fuels-human-and-mouse-intestinal-inflammation
#6
Romana R Gerner, Victoria Klepsch, Sophie Macheiner, Kathrin Arnhard, Timon E Adolph, Christoph Grander, Verena Wieser, Alexandra Pfister, Patrizia Moser, Natascha Hermann-Kleiter, Gottfried Baier, Herbert Oberacher, Herbert Tilg, Alexander R Moschen
OBJECTIVE: Nicotinamide phosphoribosyltransferase (NAMPT, also referred to as pre-B cell colony-enhancing factor or visfatin) is critically required for the maintenance of cellular nicotinamide adenine dinucleotide (NAD) supply catalysing the rate-limiting step of the NAD salvage pathway. NAMPT is strongly upregulated in inflammation including IBD and counteracts an increased cellular NAD turnover mediated by NAD-depleting enzymes. These constitute an important mechanistic link between inflammatory, metabolic and transcriptional pathways and NAD metabolism...
September 6, 2017: Gut
https://www.readbyqxmd.com/read/28871079/sirt6-deficiency-exacerbates-podocyte-injury-and-proteinuria-through-targeting-notch-signaling
#7
Min Liu, Kaili Liang, Junhui Zhen, Meng Zhou, Xiaojie Wang, Ziying Wang, Xinbing Wei, Yan Zhang, Yu Sun, Zhuanli Zhou, Hua Su, Chun Zhang, Ningjun Li, Chengjiang Gao, Jun Peng, Fan Yi
Podocyte injury is a major determinant of proteinuric kidney disease and the identification of potential therapeutic targets for preventing podocyte injury has clinical importance. Here, we show that histone deacetylase Sirt6 protects against podocyte injury through epigenetic regulation of Notch signaling. Sirt6 is downregulated in renal biopsies from patients with podocytopathies and its expression correlates with glomerular filtration rate. Podocyte-specific deletion of Sirt6 exacerbates podocyte injury and proteinuria in two independent mouse models, diabetic nephropathy, and adriamycin-induced nephropathy...
September 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28870631/the-sirtuin-family-members-sirt1-sirt3-and-sirt6-their-role-in-vascular-biology-and-atherogenesis
#8
REVIEW
Bożena Sosnowska, Mohsen Mazidi, Peter Penson, Anna Gluba-Brzózka, Jacek Rysz, Maciej Banach
The sirtuins, silent mating-type information regulation 2 (SIRTs), are a family of nicotinamide adenine dinucleotide (NAD(+))-dependent histone deacetylases with important roles in regulating energy metabolism and senescence. Activation of SIRTs appears to have beneficial effects on lipid metabolism and antioxidants, prompting investigation of the roles of these proteins in atherogenesis. Although clinical data are currently limited, the availability and safety of SIRT activators such as metformin and resveratrol provide an excellent opportunity to conduct research to better understand the role of SIRTs in human atherosclerosis...
August 26, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28860594/sirt6-promotes-osteogenic-differentiation-of-mesenchymal-stem-cells-through-bmp-signaling
#9
Ping Zhang, Yunsong Liu, Yuejun Wang, Min Zhang, Longwei Lv, Xiao Zhang, Yongsheng Zhou
SIRT6 has been identified as an H3K9 deacetylase and a critical regulator of genome stability, telomere integrity, and metabolic homeostasis. Sirt6-deficient mice displayed dramatic phenotypes including profound lymphopenia, loss of subcutaneous fat, lordokyphosis and low bone marrow density. Here, we report that SIRT6 regulates osteogenic differentiation independent of its deacetylase activity in vitro. Further mechanistic studies showed that SIRT6 involves the cell fate determination by modulating bone morphogenetic protein (BMP) signaling...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28856570/sirt6-knockout-cells-resist-apoptosis-initiation-but-not-progression-a-computational-method-to-evaluate-the-progression-of-apoptosis
#10
Sergii Domanskyi, Justin W Nicholatos, Joshua E Schilling, Vladimir Privman, Sergiy Libert
Apoptosis is essential for numerous processes, such as development, resistance to infections, and suppression of tumorigenesis. Here, we investigate the influence of the nutrient sensing and longevity-assuring enzyme SIRT6 on the dynamics of apoptosis triggered by serum starvation. Specifically, we characterize the progression of apoptosis in wild type and SIRT6 deficient mouse embryonic fibroblasts using time-lapse flow cytometry and computational modelling based on rate-equations and cell distribution analysis...
August 30, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28803211/melatonin-protects-chondrocytes-from-impairment-induced-by-glucocorticoids-via-nad-dependent-sirt1
#11
Wei Yang, Xiaomin Kang, Na Qin, Feng Li, Xinxin Jin, Zhengmin Ma, Zhuang Qian, Shufang Wu
Intra-articular injection of glucocorticoids is used to relieve pain and inflammation in osteoarthritis patients, which is occasionally accompanied with the serious side effects of glucocorticoids in collagen-producing tissue. Melatonin is the major hormone released from the pineal gland and its beneficial effects on cartilage has been suggested. In the present study, we investigated the protective role of melatonin on matrix degeneration in chondrocytes induced by dexamethasone (Dex). The chondrocytes isolated from mice knee joint were treated with Dex, melatonin, EX527 and siRNA targeted for SIRT6, respectively...
October 2017: Steroids
https://www.readbyqxmd.com/read/28767699/molecular-evolutionary-patterns-of-nad-sirtuin-aging-signaling-pathway-across-taxa
#12
Uma Gaur, Jianbo Tu, Diyan Li, Yue Gao, Ting Lian, Boyuan Sun, Deying Yang, Xiaolan Fan, Mingyao Yang
A deeper understanding of the conserved molecular mechanisms in different taxa have been made possible only because of the evolutionary conservation of crucial signaling pathways. In the present study, we explored the molecular evolutionary pattern of selection signatures in 51 species for 10 genes which are important components of NAD+/Sirtuin pathway and have already been directly linked to lifespan extension in worms and mice. Selection pressure analysis using PAML program revealed that MRPS5 and PPARGC1A were under significant constraints because of their functional significance...
2017: PloS One
https://www.readbyqxmd.com/read/28765271/sirt6-regulates-metabolic-homeostasis-in-skeletal-muscle-through-activation-of-ampk
#13
Xiaona Cui, Lu Yao, Xiaoying Yang, Yong Gao, Fude Fang, Jun Zhang, Qinghua Wang, Yongsheng Chang
Due to the mass and functions in metabolism, skeletal muscle is one of major organs regulating whole-body metabolic homeostasis. SIRT6, a histone deacetylase, has been shown to regulate metabolism in liver and brain, however, its specific role in skeletal muscle is undetermined. In the present study we explored physiological function of SIRT6 in muscle. We generated a muscle-specific SIRT6 knockout mouse model. The mice with SIRT6 deficiency in muscle displayed impaired glucose homeostasis and insulin sensitivity, attenuated whole-body energy expenditure and weakened exercise performance...
August 1, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28756638/structure-based-discovery-of-new-selective-small-molecule-sirtuin-5-inhibitors
#14
Sha Liu, Sen Ji, Zhu-Jun Yu, Hua-Li Wang, Xu Cheng, Wei-Jian Li, Li Jing, Yamei Yu, Qiang Chen, Ling-Ling Yang, Guo-Bo Li, Yong Wu
Human sirtuin 5 (SIRT5) is a protein deacylase regulating metabolic pathways and stress responses and is implicated in metabolism-related diseases. Small-molecule inhibitors for SIRT5 are sought as chemical tools and potential therapeutics. Herein, we proposed a customized virtual screening approach targeting catalytically important and unique residues Tyr102 and Arg105 of SIRT5. Of the 20 tested virtual screening hits, six compounds displayed marked inhibitory activities against SIRT5. For the hit compound 19, a series of newly synthesized (E)-2-cyano-N-phenyl-3-(5-phenylfuran-2-yl)acrylamide derivatives/analogues were carried out structure-activity relationship analyses, resulting in new more potent inhibitors, among which 37 displayed the most potent inhibition to SIRT5 with an IC50 value of 5...
July 30, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28753566/overexpression-of-sirt6-attenuates-the-tumorigenicity-of-hepatocellular-carcinoma-cells
#15
Yadong Wang, Teng Pan, Haiyu Wang, Li Li, Jiangmin Li, Ding Zhang, Haiyan Yang
OBJECTIVE: This study aimed to explore the effects of overexpression of sirtuin 6 (SIRT6) on the tumorigenicity of hepatocellular carcinoma (HCC) cells. METHODS: Stable SIRT6-overexpressed HCC cell lines were established by transfecting SIRT6 plasmid. Soft agar assay and tumor xenograft assay in nude mice were applied. Flow cytometry was employed to detect cell cycle distribution. Western blotting analysis was used to detect the expression of proteins. RESULTS: Overexpression of SIRT6 attenuated HepG2 and HCCLM3 cells proliferation, colony formation in vitro and tumor formation in nude mice, and resulted in the G1 phase cell cycle arrest...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28747973/effect-of-ionizing-radiation-at-low-dose-on-transgenerational-carcinogenesis-by-epigenetic-regulation
#16
Lan Li, Jong-Hyun Kim, Hee-Tae Park, Jae-Hoon Lee, Min-Koo Park, Ji-Won Lee, Jeong-Chan Lee, Min-Jae Lee
The objective of this study was to determine the effect of ionizing radiation (IR) exposure of parents on carcinogenesis of the next generation focusing on the epigenetic perspective to clarify the relationship between radiation dose and carcinogenesis in F1 generation SD rats. F1 generations from pregnant rats (F0) who were exposed to gamma rays were divided into three groups according to the dose of radiation: 10 rad, 30 rad, and untreated. They were intraperitoneally injected with 50 mg/kg of diethylnitrosamine (DEN)...
June 2017: Laboratory Animal Research
https://www.readbyqxmd.com/read/28723567/cold-inducible-sirt6-regulates-thermogenesis-of-brown-and-beige-fat
#17
Lu Yao, Xiaona Cui, Qi Chen, Xiaoying Yang, Fude Fang, Jun Zhang, Guoqing Liu, Wanzhu Jin, Yongsheng Chang
Promoting development and function of brown and beige fat may reduce obesity. Here, we show that fat SIRT6 expression is markedly induced by cold exposure and a β-adrenergic agonist. Deletion of SIRT6 in adipose tissue impairs the thermogenic function of brown adipocytes, causing a morphological "whitening" of brown fat, reduced oxygen (O2) consumption, obesity, decreased core body temperature, and cold sensitivity. Fat SIRT6-deleted mice exhibit increased blood glucose levels, severe insulin resistance, and hepatic steatosis...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28698968/inhibition-of-poly-adp-ribose-polymerase-1-enhances-gene-expression-of-selected-sirtuins-and-app-cleaving-enzymes-in-amyloid-beta-cytotoxicity
#18
Przemysław L Wencel, Walter J Lukiw, Joanna B Strosznajder, Robert Piotr Strosznajder
Poly(ADP-ribose) polymerases (PARPs) and sirtuins (SIRTs) are involved in the regulation of cell metabolism, transcription, and DNA repair. Alterations of these enzymes may play a crucial role in Alzheimer's disease (AD). Our previous results indicated that amyloid beta (Aβ) peptides and inflammation led to activation of PARP1 and cell death. This study focused on a role of PARP1 in the regulation of gene expression for SIRTs and beta-amyloid precursor protein (βAPP) cleaving enzymes under Aβ42 oligomers (AβO) toxicity in pheochromocytoma cells (PC12) in culture...
July 12, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28685526/glycyrrhetinic-acid-suppressed-hmgb1-release-by-up-regulation-of-sirt6-in-nasal-inflammation
#19
D Chen, L M Bellussi, S Cocca, J Wang, G C Passali, X Hao, L Chen, D Passali
To extend our understanding of previous studies on the pathogenesis and mechanism of high mobility group box 1 (HMGB1) in chronic rhinosinusitis with nasal polyps (CRSwNP), here we show that Sirtuin 6 (Sirt6), one of the Sirtuin family members which are widely studied in aging, DNA repair, metabolism, inflammation and cancer, was expressed in normal nasal mucosa using immunohistochemical staining and Western blot assay. Sirt6 expression levels were decreased in CRSwNP tissue. Sirt6 expression levels were modulated by small interfering RNA transfection in human nasal epithelial cells (HNE)...
April 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28677777/suppression-of-sirt6-by-mir-33a-facilitates-tumor-growth-of-glioma-through-apoptosis-and-oxidative-stress-resistance
#20
Mingze Chang, Lin Qiao, Bin Li, Juanhong Wang, Gejuan Zhang, Wenzhen Shi, Zhiqin Liu, Naibing Gu, Zhengli Di, Xinlai Wang, Ye Tian
microRNA-33a (miR-33a) belongs to the miR-33 family that is implicated in the progression of various types of cancers. Aberrant expression of miR-33a has been detected in several human cancers, and has been shown to regulate the migration and invasion as well as proliferation and apoptosis of tumor cells. However, the clinical significance and precise mechanisms underlying the dysfunction of miR-33a in glioma have not been well investigated in previous studies. In this study, overexpression of miR-33a was observed in clinical glioma specimens and cell lines...
July 3, 2017: Oncology Reports
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