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https://www.readbyqxmd.com/read/28222243/studies-on-the-binding-of-modest-modulators-of-the-human-enzyme-sirtuin-6-using-std-nmr
#1
Beatriz E Bolívar, John T Welch
Pyrazinamide (PZA), an essential constituent of short course tuberculosis chemotherapy, binds weakly but selectively to Sirtuin 6 (SIRT6). Despite structural similarities between nicotinamide (NAM), PZA, and pyrazinoic acid (POA), these inhibitors modulate SIRT6 via different mechanisms and binding sites, as suggested by Saturation Transfer Difference (STD) Nuclear Magnetic Resonance (NMR). Available experimental evidence, such as that derived from crystal structures and kinetic experiments, is of only limited utility in the elucidation of the mechanistic details of sirtuin inhibition by NAM or other inhibitors...
February 21, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28215636/sirtuin-6-prevents-matrix-degradation-through-inhibition-of-the-nf-%C3%AE%C2%BAb-pathway-in-intervertebral-disc-degeneration
#2
Liang Kang, Jia Hu, Yuxiong Weng, Jie Jia, Yukun Zhang
Intervertebral disc degeneration (IDD) is marked by imbalanced metabolism of the extracellular matrix (ECM) in the nucleus pulposus (NP) of intervertebral discs. This study aimed to determine whether sirtuin 6 (SIRT6), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, protects the NP from ECM degradation in IDD. Our study showed that expression of SIRT6 markedly decreased during IDD progression. Overexpression of wild-type SIRT6, but not a catalytically inactive mutant, prevented IL-1β-induced NP ECM degradation...
February 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28130175/up-regulation-of-sirt6-in-the-hippocampus-induced-rats-with-depression-like-behavior-via-the-block-akt-gsk3%C3%AE-signaling-pathway
#3
Qiang Mao, Xue Gong, Chanjuan Zhou, Zhe Tu, Libo Zhao, Ling Wang, Xinfa Wang, Lu Sun, Jinjun Xia, Bin Lian, Jianjun Chen, Jun Mu, Deyu Yang, Peng Xie
Major depression is the leading cause of disability worldwide, which is associated with diverse alterations in brain such as neuro-inflammation, synaptic dysfunction, and cognitive deficit. Accumulating evidences suggest sirtuins (SIRTs) are involved in brain developmental disorders, metabolic diseases and play a key role in cognition and synaptic plasticity, yet the role in mood regulation remains controversial. Hence, Western blotting and RT-qPCR were used to investigate whether SIRTs (SIRT1-7) expression levels were altered in the hippocampus of rats, which followed 5 weeks of chronic unpredictable mild stress (CUMS) treatment, the results showed depressive-like behaviors: like body weight, forced swim test and sucrose preference test and SIRT6 was a significant increase in the hippocampal of CUMS rats...
January 24, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28123310/cosmeceutical-product-consisting-of-biomimetic-peptides-antiaging-effects-in-vivo-and-in-vitro
#4
Zarema I Gazitaeva, Anna O Drobintseva, Yongji Chung, Victoria O Polyakova, Igor M Kvetnoy
BACKGROUND: Biomimetic peptides are synthetic compounds that are identical to amino acid sequence synthesized by an organism and can interact with growth factor receptors and provide antiaging clinical effects. PURPOSE: The purpose of this study was to investigate the effects of biomimetic peptides on the repair processes in the dermis using a model of cell cultures and in vivo. PATIENTS AND METHODS: Five female volunteers were subjected to the injection of biomimetic peptides 1 month prior to the abdominoplasty procedure...
2017: Clinical, Cosmetic and Investigational Dermatology
https://www.readbyqxmd.com/read/28108948/erratum-to-autophagy-induction-by-sirt6-is-involved-in-oxidative-stress-induced-neuronal-damage
#5
Jiaxiang Shao, Xiao Yang, Tengyuan Liu, Tingting Zhang, Qian Reuben Xie, Weiliang Xia
No abstract text is available yet for this article.
January 20, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28100421/osteoarthritis-year-in-review-2016-biology
#6
REVIEW
E N Blaney Davidson, A P M van Caam, P M van der Kraan
This review highlights a selection of literature in the area of osteoarthritis biology published between the 2015 and 2016 Osteoarthritis Research Society International (OARSI) World Congress. Highlights were selected from a pubmed search covering cartilage, bone, inflammation and pain. A personal selection was made based, amongst other things, on topics presented during the 2015 conference. This covers circadian rhythm, TGF-β signaling, autophagy, SIRT6, exercise, lubricin, TLR's, pain and NGF. Furthermore, in this review we have made an effort to connect these seemingly distant topics into one scheme of connections between them, revealing a theoretical big picture underneath...
December 17, 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28039864/sirtuin-6-attenuates-periapical-lesion-propagation-by-modulating-hypoxia-induced-ccl2-production-in-osteoblasts
#7
Y-L Lee, S-K Lin, K-L Hou, S-H Kok, E H-H Lai, H-W Wang, J Z-C Chang, H Yang, C-Y Hong
AIM: To investigate the attenuating effect of sirtuin 6 (SIRT6) on hypoxia-induced production of chemokine (C-C motif) ligand 2 (CCL2) by osteoblasts and the relevance of this action on the pathogenesis of periapical lesions. METHODOLOGY: SIRT6 was overexpressed in MC3T3-E1 murine osteoblasts by lentivirus-mediated gene transfer. The relationship between the anti-glycolytic/anti-oxidative activities of SIRT6 and its effect on hypoxia-induced CCL2 production were examined...
December 31, 2016: International Endodontic Journal
https://www.readbyqxmd.com/read/28032059/association-of-sirt6-gene-polymorphisms-with-human-longevity
#8
You Li, Jian Qin, Xiao Wei, Guiyun Liang, Liwei Shi, Meiyu Jiang, Tianlong Xia, Xue Liang, Min He, Zhiyong Zhang
BACKGROUND: We aimed to identify the role of SIRT6 gene polymorphism rs350846 in human longevity. METHODS: SIRT6 C/G genotypes were determined using Taqman SNP Genotyping Assays in 169 long-lived inhabitants (LG group aged 90-110 yr), 158 healthy internal controls (internal control group; aged 26-82 yr) and 176 healthy external controls (external control group; aged 20-82 yr) without a family history of exceptional longevity. Statistical analysis was conducted using SPSS 16...
November 2016: Iranian Journal of Public Health
https://www.readbyqxmd.com/read/27990725/structural-basis-of-sirtuin-6-activation-by-synthetic-small-molecules
#9
Weijie You, Dante Rotili, Tie-Mei Li, Christian Kambach, Marat Meleshin, Mike Schutkowski, Katrin F Chua, Antonello Mai, Clemens Steegborn
Sirtuins are protein deacylases regulating metabolism and stress responses, and are implicated in aging-related diseases. Small molecule activators for the human sirtuins Sirt1-7 are sought as chemical tools and potential therapeutics, such as for cancer. Activators are available for Sirt1 and exploit its unique N-terminus, whereas drug-like activators for Sirt2-7 are lacking. We synthesized and screened pyrrolo[1,2-a]quinoxaline derivatives, yielding the first synthetic Sirt6 activators. Biochemical assays show direct, substrate-independent compound binding to the Sirt6 catalytic core and potent activation of Sirt6-dependent deacetylation of peptide substrates and complete nucleosomes...
December 19, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27923994/sirt6-interacts-with-trf2-and-promotes-its-degradation-in-response-to-dna-damage
#10
Angela Rizzo, Sara Iachettini, Erica Salvati, Pasquale Zizza, Carmen Maresca, Carmen D'Angelo, Delphine Benarroch-Popivker, Angela Capolupo, Federica Del Gaudio, Sandro Cosconati, Salvatore Di Maro, Francesco Merlino, Ettore Novellino, Carla Azzurra Amoreo, Marcella Mottolese, Isabella Sperduti, Eric Gilson, Annamaria Biroccio
Telomere repeat binding factor 2 (TRF2) has been increasingly recognized to be involved in telomere maintenance and DNA damage response. Here, we show that TRF2 directly binds SIRT6 in a DNA independent manner and that this interaction is increased upon replication stress. Knockdown of SIRT6 up-regulates TRF2 protein levels and counteracts its down-regulation during DNA damage response, leading to cell survival. Moreover, we report that SIRT6 deactetylates in vivo the TRFH domain of TRF2, which in turn, is ubiquitylated in vivo activating the ubiquitin-dependent proteolysis...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27912097/lncpress1-is-a-p53-regulated-lncrna-that-safeguards-pluripotency-by-disrupting-sirt6-mediated-de-acetylation-of-histone-h3k56
#11
Abhinav K Jain, Yuanxin Xi, Ryan McCarthy, Kendra Allton, Kadir C Akdemir, Lalit R Patel, Bruce Aronow, Chunru Lin, Wei Li, Liuqing Yang, Michelle C Barton
Recent evidence suggests that lncRNAs play an integral regulatory role in numerous functions, including determination of cellular identity. We determined global expression (RNA-seq) and genome-wide profiles (ChIP-seq) of histone post-translational modifications and p53 binding in human embryonic stem cells (hESCs) undergoing differentiation to define a high-confidence set of 40 lncRNAs, which are p53 transcriptional targets. We focused on lncRNAs highly expressed in pluripotent hESCs and repressed by p53 during differentiation to identify lncPRESS1 as a p53-regulated transcript that maintains hESC pluripotency in concert with core pluripotency factors...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27904701/sirt6-suppresses-mitochondrial-defects-and-cell-death-via-the-nf-%C3%AE%C2%BAb-pathway-in-myocardial-hypoxia-reoxygenation-induced-injury
#12
Ming-Yue Cheng, You-Wei Cheng, Jun Yan, Xiao-Qin Hu, Hui Zhang, Zhi-Rong Wang, Qin Yin, Wei Cheng
The present study explored changes of the SIRT6/NF-κB pathway in myocardial hypoxia/reoxygenation induced injury and the effects on mitochondrial damage and myocardial damage by regulating SIRT6. SIRT6 expression decreased and NF-κB expression increased in H9c2 cells during hypoxic injury. Cell death and mitochondrial defects paralleled mPTP opening, and a decrease in ΔΨm occurred in hypoxic myocytes compared with normoxic control cells in annexin V and propidium iodide staining and TUNEL results. These effects were suppressed in cells overexpressing SIRT6, but reemerged in cells expressing the SIRT6 mutant...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27885875/epigenomic-therapies-the-potential-of-targeting-sirt6-for-the-treatment-of-pancreatic-cancer
#13
Ihsan Ekin Demir, Güralp O Ceyhan, Helmut Friess
No abstract text is available yet for this article.
January 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27882448/sirtuins-and-their-roles-in-brain-aging-and-neurodegenerative-disorders
#14
Henryk Jęśko, Przemysław Wencel, Robert P Strosznajder, Joanna B Strosznajder
Sirtuins (SIRT1-SIRT7) are unique histone deacetylases (HDACs) whose activity depends on NAD(+) levels and thus on the cellular metabolic status. SIRTs regulate energy metabolism and mitochondrial function. They orchestrate the stress response and damage repair. Through these functions sirtuins modulate the course of aging and affect neurodegenerative diseases. SIRTSs interact with multiple signaling proteins, transcription factors (TFs) and poly(ADP-ribose) polymerases (PARPs) another class of NAD(+)-dependent post-translational protein modifiers...
November 24, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27864740/expression-levels-of-warburg-effect-related-micrornas-correlate-with-each-other-and-that-of-histone-deacetylase-enzymes-in-adult-hematological-malignancies-with-emphasis-on-acute-myeloid-leukemia
#15
Zsuzsanna Gaál, Éva Oláh, László Rejtő, Bálint László Bálint, László Csernoch
Disruption of epigenetic regulation and characteristic metabolic alterations (known as the Warburg-effect) are well-known hallmarks of cancer. In our study we investigated the expression levels of microRNAs and histone deacetylase enzymes via RT-qPCR in bone marrow specimens of adult patients suffering from hematological malignancies (total cohort n = 40), especially acute myeloid leukemia (n = 27). The levels of the three examined Warburg-effect related microRNAs (miR-378*, miR-23b, miR-26a) positively correlated with each other and the oncogenic miR-155 and miR-125b, while negatively with the level of the tumorsuppressor miR-124...
November 18, 2016: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/27836583/sirt6-novel-mechanisms-and-links-to-aging-and-disease
#16
REVIEW
Luisa Tasselli, Wei Zheng, Katrin F Chua
SIRT6, a member of the Sirtuin family of NAD(+)-dependent enzymes, has established roles in chromatin signaling and genome maintenance. Through these functions, SIRT6 protects against aging-associated pathologies including metabolic disease and cancer, and can promote longevity in mice. Research from the past few years revealed that SIRT6 is a complex enzyme with multiple substrates and catalytic activities, and uncovered novel SIRT6 functions in the maintenance of organismal health span. Here, we review these new discoveries and models of SIRT6 biology in four areas: heterochromatin stabilization and silencing; stem cell biology; cancer initiation and progression; and regulation of metabolic homeostasis...
November 8, 2016: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/27829173/multiple-pathways-of-sirt6-at-the-crossroads-in-the-control-of-longevity-cancer-and-cardiovascular-diseases
#17
REVIEW
Milena Vitiello, Alberto Zullo, Luigi Servillo, Francesco Paolo Mancini, Adriana Borriello, Alfonso Giovane, Fulvio Della Ragione, Nunzia D'Onofrio, Maria Luisa Balestrieri
Sirtuin 6 (SIRT6) is a member of the sirtuin family NAD(+)-dependent deacetylases with multiple roles in controlling organism homeostasis, lifespan, and diseases. Due to its complex and opposite functional roles, this sirtuin is considered a two-edged sword in health and disease. Indeed, SIRT6 improves longevity, similarly to the founding yeast member, silent information regulator-2 (Sir2), and modulates genome stability, telomere integrity, transcription, and DNA repair. Its deficiency is associated with chronic inflammation, diabetes, cardiac hypertrophy, obesity, liver dysfunction, muscle/adipocyte disorders, and cancer...
November 6, 2016: Ageing Research Reviews
https://www.readbyqxmd.com/read/27824900/sirt6-depletion-suppresses-tumor-growth-by-promoting-cellular-senescence-induced-by-dna-damage-in-hcc
#18
Namgyu Lee, Hye Guk Ryu, Jung-Hee Kwon, Dae-Kyum Kim, Sae Rom Kim, Hee Jung Wang, Kyong-Tai Kim, Kwan Yong Choi
The role of Sirtuin 6 (SIRT6) as a tumor suppressor or oncogene in liver cancer remains controversial. Thus, we identified the specific role of SIRT6 in the progression of hepatocellular carcinoma (HCC). SIRT6 expression was significantly higher in HCC cell lines and HCC tissues from 138 patients than in an immortalized hepatocyte cell line, THLE-2 and non-tumor tissues, respectively. SIRT6 knockdown by shRNA suppressed the growth of HCC cells and inhibited HCC tumor growth in vivo. In addition, SIRT6 silencing significantly prevented the growth of HCC cell lines by inducing cellular senescence in the p16/Rb- and p53/p21-pathway independent manners...
2016: PloS One
https://www.readbyqxmd.com/read/27815076/sirt6-protects-against-lipopolysaccharide-lps-induced-apoptosis-in-human-dental-pulp-cells-by-deacetylation-of-ku70
#19
Wanhong Chen, Xun Chen, Yuhuan Sun
Progression of pulpitis is facilitated by the immune system's response to bacteria, enhancing the production of inflammatory regulators. Bacterial lipopolysaccharide (LPS) is the major structural component of the outer wall of all Gram-negative bacteria and a potent activator of the immune system. Apoptosis is believed to play an important role in the inflammatory process of pulpitis. SIRT6 is a member of class III of histone deacetylases (HDACs), also called sirtuins (SIRTs). The role of SIRT6 in apoptosis in pulpitis is unknown...
November 1, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27803663/environmental-enrichment-modified-epigenetic-mechanisms-in-samp8-mouse-hippocampus-by-reducing-oxidative-stress-and-inflammaging-and-achieving-neuroprotection
#20
Christian Griñan-Ferré, Dolors Puigoriol-Illamola, Verónica Palomera-Ávalos, David Pérez-Cáceres, Júlia Companys-Alemany, Antonio Camins, Daniel Ortuño-Sahagún, M Teresa Rodrigo, Mercè Pallàs
With the increase in life expectancy, aging and age-related cognitive impairments are becoming one of the most important issues for human health. At the same time, it has been shown that epigenetic mechanisms are emerging as universally important factors in life expectancy. The Senescence Accelerated Mouse P8 (SAMP8) strain exhibits age-related deterioration evidenced in learning and memory abilities and is a useful model of neurodegenerative disease. In SAMP8, Environmental Enrichment (EE) increased DNA-methylation levels (5-mC) and reduced hydroxymethylation levels (5-hmC), as well as increased histone H3 and H4 acetylation levels...
2016: Frontiers in Aging Neuroscience
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