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https://www.readbyqxmd.com/read/29322219/sirt6-mediated-transcriptional-suppression-of-txnip-is-critical-for-pancreatic-beta-cell-function-and-survival-in-mice
#1
Kunhua Qin, Ning Zhang, Zhao Zhang, Michael Nipper, Zhenxin Zhu, Jake Leighton, Kexin Xu, Nicolas Musi, Pei Wang
AIMS/HYPOTHESIS: Better understanding of how genetic and epigenetic components control beta cell differentiation and function is key to the discovery of novel therapeutic approaches to prevent beta cell dysfunction and failure in the progression of type 2 diabetes. Our goal was to elucidate the role of histone deacetylase sirtuin 6 (SIRT6) in beta cell development and homeostasis. METHODS: Sirt6 endocrine progenitor cell conditional knockout and beta cell-specific knockout mice were generated using the Cre-loxP system...
January 10, 2018: Diabetologia
https://www.readbyqxmd.com/read/29319170/sirt6-deacetylase-transcriptionally-regulates-glucose-metabolism-in-heart
#2
Danish Khan, Mohsen Sarikhani, Subhajit Dasgupta, Babukrishna Maniyadath, Anwit Shriniwas Pandit, Sneha Mishra, Faiz Ahamed, Abhinav Dubey, Nowrin Fathma, Hanudatta S Atreya, Ullas Kolthur-Seetharam, Nagalingam R Sundaresan
Sirtuins are a family of enzymes, which govern a number of cellular processes essential for maintaining physiological balance. SIRT6, a nuclear localized sirtuin, is implicated in the development of metabolic disorders. The role of SIRT6 in regulation of cardiac metabolism is unexplored. Although glucose is not the primary energy source of heart, defects in glucose oxidation have been linked to heart failure. SIRT6+/- mice hearts exhibit increased inhibitory phosphorylation of PDH subunit E1α. SIRT6 deficiency enhances FoxO1 nuclear localization that results in increased expression of PDK4...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29317652/sirt6-dependent-cysteine-monoubiquitination-in-the-pre-set-domain-of-suv39h1-regulates-the-nf-%C3%AE%C2%BAb-pathway
#3
Irene Santos-Barriopedro, Laia Bosch-Presegué, Anna Marazuela-Duque, Carolina de la Torre, Carlota Colomer, Berta N Vazquez, Thomas Fuhrmann, Bárbara Martínez-Pastor, Wenfu Lu, Thomas Braun, Eva Bober, Thomas Jenuwein, Lourdes Serrano, Manel Esteller, Zhenbang Chen, Silvia Barceló-Batllori, Raúl Mostoslavsky, Lluis Espinosa, Alejandro Vaquero
Sirtuins are NAD+-dependent deacetylases that facilitate cellular stress response. They include SirT6, which protects genome stability and regulates metabolic homeostasis through gene silencing, and whose loss induces an accelerated aging phenotype directly linked to hyperactivation of the NF-κB pathway. Here we show that SirT6 binds to the H3K9me3-specific histone methyltransferase Suv39h1 and induces monoubiquitination of conserved cysteines in the PRE-SET domain of Suv39h1. Following activation of NF-κB signaling Suv39h1 is released from the IκBα locus, subsequently repressing the NF-κB pathway...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29290628/the-role-of-sirt6-in-tumors
#4
EDITORIAL
Vanessa Desantis, Aurelia Lamanuzzi, Angelo Vacca
No abstract text is available yet for this article.
January 2018: Haematologica
https://www.readbyqxmd.com/read/29286133/hydroxytyrosol-inhibits-the-inflammatory-response-of-osteoarthritis-chondrocytes-via-sirt6-mediated-autophagy
#5
Li-Qiang Zhi, Shu-Xin Yao, Hong-Liang Liu, Meng Li, Ning Duan, Jian-Bing Ma
Osteoarthritis (OA) is a common degenerative joint disease. Inflammation may exaggerate the catabolism and degeneration in the pathogenesis of OA. Hydroxytyrosol (HT) has been used in the management of inflammatory diseases. In addition, reports have revealed that autophagy was a therapeutic target of diseases caused by inflammation. Sirtuin 6 (SIRT6) has also been demonstrated to prevent OA development by reducing both the inflammatory response and chondrocyte senescence. However, the roles of SIRT6 and autophagy in cartilage and its underlying anti‑inflammatory mechanism are unknown...
December 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29246685/silica-nanoparticle-releases-sirt6-induced-epigenetic-silencing-of-follistatin
#6
Lingda Zhang, Bing Han, Jie Xiang, Kangli Liu, Haojie Dong, Xiangwei Gao
Follistatin (FST) plays a protective role during silica nanoparticle (SiO2 NP) exposure. SiO2 NP treatment induces FST transcription with an unknown mechanism. We herein reported that SIRT6, one of the sirtuin family members, induced epigenetic silencing of FST. The expression of FST was elevated after SIRT6 knockdown while reduced after SIRT6 overexpression. Chromatin immunoprecipitation revealed a direct interaction between SIRT6 with FST promoter. Knockdown of SIRT6 increased both Ac-H3K9 level and Ac-H3K56 level at FST promoter region...
December 12, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29234488/sirt6-histone-deacetylase-functions-as-a-potential-oncogene-in-human-melanoma
#7
Liz Mariely Garcia-Peterson, Mary Ann Ndiaye, Chandra K Singh, Gagan Chhabra, Wei Huang, Nihal Ahmad
Melanoma is an aggressive skin cancer that can rapidly metastasize to become fatal, if not diagnosed early. Despite recent therapeutic advances, management of melanoma remains difficult. Therefore, novel molecular targets and strategies are required to manage this neoplasm. This study was undertaken to determine the role of the sirtuin SIRT6 in melanoma. Employing a panel of human melanoma cells and normal human melanocytes, we found significant SIRT6 mRNA and protein upregulation in melanoma cells. Further, using a tissue microarray coupled with quantitative Vectra analysis, we demonstrated significant SIRT6 overexpression in human melanoma tissues...
September 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29234485/regulation-of-sirtuin-mediated-protein-deacetylation-by-cardioprotective-phytochemicals
#8
REVIEW
Niria Treviño-Saldaña, Gerardo García-Rivas
Modulation of posttranslational modifications (PTMs), such as protein acetylation, is considered a novel therapeutic strategy to combat the development and progression of cardiovascular diseases. Protein hyperacetylation is associated with the development of numerous cardiovascular diseases, including atherosclerosis, hypertension, cardiac hypertrophy, and heart failure. In addition, decreased expression and activity of the deacetylases Sirt1, Sirt3, and Sirt6 have been linked to the development and progression of cardiac dysfunction...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29233643/trichostatin-a-inhibits-deacetylation-of-histone-h3-and-p53-by-sirt6
#9
Marci Wood, Stacia Rymarchyk, Song Zheng, Yana Cen
SIRT6 is an epigenetic modification enzyme that regulates gene transcription through its deacetylase activity. In addition to histone protein, SIRT6 also modify other proteins and enzymes, some of which are central players in metabolic reprogramming and aging process. Therefore, SIRT6 has emerged as a therapeutic target for the treatment of metabolic disorder and age-related diseases. Here, we report that SIRT6 deacetylates lysine 382 of p53 in short synthetic peptide sequence and in full length p53. Further studies showed that the deacetylation of H3K9Ac and p53K382Ac are insensitive to nicotinamide inhibition, but are sensitive to trichostatin A (TSA) inhibition...
December 9, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29227545/overexpression-of-sirt6-is-a-novel-biomarker-of-malignant-human-colon-carcinoma
#10
Chang-Hui Geng, Chun-Ling Zhang, Jing-Yan Zhang, Ping Gao, Miao He, Yan-Lin Li
Sirt family has been reported playing a significant role in the cancer develop, special its deacetylase activity plays a key function, but whether SIRT6 plays a role in mediating tumor EMT and metastasis in colon cancer has not been explored. Here, the mass spectrometry and co-immunoprecipitation assays were utilized to detect that SIRT6 was physically associated with transcription factor snail. Most important, HCT116 cells transfected with SIRT6 shRNA reversed EMT, while increased the expression of TET1, and the HCT116 cells transfected with SIRT6 displayed the contrary tendency...
December 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29217762/sirt6-is-a-target-of-regulation-by-ube3a-that-contributes-to-liver-tumorigenesis-in-an-anxa2-dependent-manner
#11
Saishruti Kohli, Abhishek Bhardwaj, Richa Kumari, Sanjeev Das
UBE3A is an E3 ubiquitin ligase well known for its role in the proteasomal degradation of p53 in human papillomavirus (HPV)-associated cancers. Here we report that UBE3A ubiquitylates and triggers degradation of the tumor suppressive sirtuin SIRT6 in hepatocellular carcinoma. UBE3A ubiquitylated the highly conserved Lys160 residue on SIRT6. FOXO1-mediated transcriptional repression of UBE3A was sufficient to stabilize SIRT6 and epigenetically repress ANXA2, a key mediator of UBE3A oncogenic function. Thus, UBE3A-mediated SIRT6 degradation promoted the proliferative capacity, migration potential and invasiveness of cells...
December 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/29215322/aberrant-sirt6-expression-contributes-to-melanoma-growth-role-of-the-autophagy-paradox-and-igf-akt-signaling
#12
Liwen Wang, Weinan Guo, Jinyuan Ma, Wei Dai, Lin Liu, Sen Guo, Jiaxi Chen, Huina Wang, Yuqi Yang, Xiuli Yi, Gang Wang, Tianwen Gao, Guannan Zhu, Chunying Li
Melanoma is among the most life-threatening cancer. The pathogenesis of melanoma has not been fully elucidated. Recently, dysregulated macroautophagy/autophagy has been found to play a critical but inconsistent role in modulating melanoma growth at different stages, with the regulatory mechanism unclear. The histone deacetylase SIRT6 (sirtuin 6) is a known autophagy regulator, and its involvement in cancer development has been reported. Therefore, we sought to determine the role of SIRT6 in melanoma growth and detect its possible link with autophagy in the current study...
December 7, 2017: Autophagy
https://www.readbyqxmd.com/read/29208611/perturbations-of-nad-salvage-systems-impact-mitochondrial-function-and-energy-homeostasis-in-mouse-myoblasts-and-intact-skeletal-muscle
#13
Marianne Agerholm, Morten Dall, Benjamin A H Jensen, Clara Prats, Søren Madsen, Astrid L Basse, Anne-Sofie Graae, Steve Risis, Julie Goldenbaum, Bjørn Quistorff, Steen Larsen, Sara G Vienberg, Jonas T Treebak
Nicotinamide adenine dinucleotide (NAD+) can be synthesized by nicotinamide phosphoribosyltransferase (NAMPT). We aimed to determine the role of NAMPT for maintaining NAD+ levels, mitochondrial function, and metabolic homeostasis in skeletal muscle cells. We generated stable Nampt knockdown (shNampt KD) C2C12 cells using a shRNA lentiviral approach. Moreover, we applied gene electrotransfer to express cre recombinase in tibialis anterior muscle of floxed Nampt mice. In shNampt KD C2C12 myoblasts, Nampt and NAD+ levels were reduced by 70% and 50%, respectively, and maximal respiratory capacity was reduced by 25%...
December 5, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29204192/rassf1a-and-sirt6-in-non-small-cell-lung-cancer-relationship-with-clinical-outcome
#14
Tao Chen, Zhaojun Sun, Fengling Liu, Qiang Wang
This study investigated the expression of RASSF1A and SIRT6 in non-small cell lung cancer (NSCLC) and its relationship with clinical prognosis. The expression in 122 cases of NSCLC tissues (NSCLC group) and 122 cases of normal lung tissues (NOR group) during the same period were detected by immunohistochemical Super Pic Ture™ Polymer two-step method, and the relationship between its expression and the clinicopathological features and prognosis of patients was analyzed. The positive expression rates of RASSF1A and SIRT6 in NSCLC group were lower than those in the normal group (55...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29197589/sirt6-expression-and-oxidative-dna-damage-in-individuals-with-prediabetes-and-type-2-diabetes-mellitus
#15
Z Caliskan, T Mutlu, M Guven, M Tuncdemir, M Niyazioğlu, Y Hacioglu, Y Dincer
Sirtuins (SIRTs) is a family of NAD+ dependent histone deacetylases. SIRT6 takes play in glucose homeostasis, genomic stability and DNA repair. Although increased oxidative DNA damage and decreased DNA repair activity were determined in diabetes mellitus, the possible relation between level of oxidative DNA damage and SIRT6 expression has not been investigated so far. We determined SIRT6 expression and urinary 8-hydroxy deoxyguanosine (8-OHdG) levels, marker of oxidative DNA damage, in cases with prediabetes (PreDM) and type 2 diabetes mellitus (T2DM)...
November 29, 2017: Gene
https://www.readbyqxmd.com/read/29177909/stem-cells-and-progenitors-in-human-peripheral-blood-get-activated-by-extremely-active-resveratrol-xar%C3%A2
#16
Vinaykumar Tripathi, Sagar Chhabria, Vaibhav Jadhav, Deepa Bhartiya, Ashish Tripathi
Resveratrol generated enormous interest as it improved functions of multiple organs and could delay aging in animal models. However, basic mechanism of action was not understood and due to poor bioavailability, it has failed to enter the market. A highly active nano-formulation of resveratrol (XAR™) with enhanced bioavailability is now available. Present study was undertaken to evaluate its effects on stem cells biology in the human peripheral blood. Twelve healthy participants were enrolled of which five received XAR™, five were age-matched placebo controls and two were 76 and 85 years old...
November 24, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/29177584/sirtuin-6-a-possible-therapeutic-target-for-type-2-diabetes
#17
REVIEW
Eun Ju Bae
Sirtuin 6 (SIRT6), one of the seven members of mammalian sirtuin family, localizes in the nucleus and primarily regulates chromatin signaling and genomic integrity. Recent studies established the critical role of SIRT6 in the pathophysiology of metabolic disease, as well as its roles in longevity and cancer. These roles that were determined by genetic studies include promoting pancreatic insulin secretion, inhibiting hepatic gluconeogenesis and triglyceride synthesis, and suppressing adiposity, suggesting that SIRT6 activators are promising molecules for treating obesity and diabetes...
November 25, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29162538/metformin-promotes-the-proliferation-and-differentiation-of-murine-preosteoblast-by-regulating-the-expression-of-sirt6-and-oct4
#18
Wei Mu, Zhuoran Wang, Chuanyu Ma, Yunyun Jiang, Nannan Zhang, Kaiqiang Hu, Liyuan Li, Zhao Wang
Osteopenia, osteoporosis and bone salt metabolism disorder are common diseases in the aged and diabetics. From case reports of patients with T2DM, we have observed that metformin can decrease risk of bone fracture and promote bone formation. However, the underlying mechanism of metformin's effect on bone metabolism remains unknown. In our research, we show that metformin can promote proliferation of murine preosteoblast by regulating AMPK-mTORC2 and AKT-mTORC1 signaling axis. Furthermore, we have observed that metformin can promote SIRT6 expression before and during differentiation of murine preosteoblast...
November 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29143563/mammalian-target-of-rapamycin-complex-2-mtorc2-controls-glycolytic-gene-expression-by-regulating-histone-h3-lysine-56-acetylation
#19
Raghavendra Vadla, Devyani Haldar
Metabolic reprogramming is a hallmark of cancer cells, but the mechanisms are not well understood. The mammalian target of rapamycin complex 2 (mTORC2) controls cell growth and proliferation and plays a critical role in metabolic reprogramming in glioma. mTORC2 regulates cellular processes such as cell survival, metabolism, and proliferation by phosphorylation of AGC kinases. Components of mTORC2 are shown to localize to the nucleus, but whether mTORC2 modulates epigenetic modifications to regulate gene expression is not known...
November 16, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29132743/nuclear-sirtuins-and-inflammatory-signaling-pathways
#20
REVIEW
Keila Lopes Mendes, Deborah de Farias Lelis, Sérgio Henrique Sousa Santos
The regulation of chronic inflammation has received considerable research attention in recent years because of its contribution to the pathogenesis of chronic diseases such as arthritis, diabetes, metabolic syndrome and obesity. Thus, strategies that inhibit the inflammatory state may be beneficial in improving the pathophysiology of several inflammation-related disorders. Sirtuins are a family of histone deacetylases that contain seven enzymatic activities in mammals (SIRT1-SIRT7) and function to suppress gene transcription by epigenetic mechanisms...
November 7, 2017: Cytokine & Growth Factor Reviews
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