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https://www.readbyqxmd.com/read/28039864/sirtuin-6-attenuates-periapical-lesion-propagation-by-modulating-hypoxia-induced-ccl2-production-in-osteoblasts
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/27794562/sirt6-delays-cellular-senescence-by-promoting-p27kip1-ubiquitin-proteasome-degradation
#15
Ganye Zhao, Hui Wang, Chenzhong Xu, Pan Wang, Jun Chen, Pengfeng Wang, Zhaomeng Sun, Yuanyuan Su, Zhao Wang, Limin Han, Tanjun Tong
Sirtuin6(SIRT6) has been implicated as a key factor in aging and aging-related diseases. However, the role of SIRT6 in cellular senescence has not been fully understood. Here, we show that SIRT6 repressed the expression of p27(Kip1) (p27) in cellular senescence. The expression of SIRT6 was reduced during cellular senescence, whereas enforced SIRT6 expression promoted cell proliferation and antagonized cellular senescence. In addition, we demonstrated that SIRT6 promoted p27 degradation by proteasome and SIRT6 decreased the acetylation level and protein half-life of p27...
September 16, 2016: Aging
https://www.readbyqxmd.com/read/27791113/spatial-dynamics-of-sirt1-and-the-subnuclear-distribution-of-nadh-species
#16
Lorena Aguilar-Arnal, Suman Ranjit, Chiara Stringari, Ricardo Orozco-Solis, Enrico Gratton, Paolo Sassone-Corsi
Sirtuin 1 (SIRT1) is an NAD(+)-dependent deacetylase that functions as metabolic sensor of cellular energy and modulates biochemical pathways in the adaptation to changes in the environment. SIRT1 substrates include histones and proteins related to enhancement of mitochondrial function as well as antioxidant protection. Fluctuations in intracellular NAD(+) levels regulate SIRT1 activity, but how SIRT1 enzymatic activity impacts on NAD(+) levels and its intracellular distribution remains unclear. Here, we show that SIRT1 determines the nuclear organization of protein-bound NADH...
October 24, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27777384/upregulation-of-sirt6-predicts-poor-prognosis-and-promotes-metastasis-of-non-small-cell-lung-cancer-via-the-erk1-2-mmp9-pathway
#17
Lihong Bai, Gengpeng Lin, Longhua Sun, Yangli Liu, Xinyan Huang, Chuangjie Cao, Yubiao Guo, Canmao Xie
Sirtuin6 (SIRT6), a member of the sirtuins protein family, plays multiple complex roles in cancer. Here, we report that elevated SIRT6 expression was correlated with clinicopathological parameters such as T and N classification in non-small cell lung cancer (NSCLC) patient tumors. SIRT6 overexpression in NSCLC cell lines increased extracellular signal-regulated kinase (p-ERK)1/2 phosphorylation, activated matrix metalloproteinase 9 (MMP9) and promoted tumor cell migration and invasion. Upon treatment with a specific mitogen-activated protein kinase (MEK) 1/2 inhibitor, these effects were abolished...
June 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27767101/oxidative-stress-dependent-microrna-34a-activation-via-pi3k%C3%AE-reduces-the-expression-of-sirtuin-1-and-sirtuin-6-in-epithelial-cells
#18
J R Baker, C Vuppusetty, T Colley, Andriana I Papaioannou, P Fenwick, Louise Donnelly, K Ito, P J Barnes
Sirtuin-1 (SIRT1) and SIRT6, NAD(+)-dependent Class III protein deacetylases, are putative anti-aging enzymes, down-regulated in patients with chronic obstructive pulmonary disease (COPD), which is characterized by the accelerated ageing of the lung and associated with increased oxidative stress. Here, we show that oxidative stress (hydrogen peroxide) selectively elevates microRNA-34a (miR-34a) but not the related miR-34b/c, with concomitant reduction of SIRT1/-6 in bronchial epithelial cells (BEAS2B), which was also observed in peripheral lung samples from patients with COPD...
October 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27766571/strong-correlation-between-the-expression-levels-of-hdac4-and-sirt6-in-hematological-malignancies-of-the-adults
#19
Zsuzsanna Gaál, Éva Oláh, László Rejtő, Ferenc Erdődi, László Csernoch
Histone deacetylase enzymes, confirmed to have important role in the pathogenesis of leukemia, are promising targets of epigenetic treatment. However, in acute myeloid leukemia, our knowledge on their expression levels is limited, and controversial data have been published about their potential oncogenic or tumorsuppressor properties in solid tumors. In our study, the expression levels of HDAC4 and SIRT6 were evaluated via Western blot analysis in 45 bone marrow samples (2 uninfiltrated and 43 concerned by different kinds of hematological malignancies), including 32 specimens obtained from patients with newly diagnosed AML...
October 20, 2016: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/27763519/segmental-aging-underlies-the-development-of-a-parkinson-phenotype-in-the-as-agu-rat
#20
Sohair M Khojah, Anthony P Payne, Dagmara McGuinness, Paul G Shiels
There is a paucity of information on the molecular biology of aging processes in the brain. We have used biomarkers of aging (SA β-Gal, p16(Ink4a), Sirt5, Sirt6, and Sirt7) to demonstrate the presence of an accelerated aging phenotype across different brain regions in the AS/AGU rat, a spontaneous Parkinsonian mutant of PKCγ derived from a parental AS strain. P16(INK4a) expression was significantly higher in AS/AGU animals compared to age-matched AS controls (p < 0.001) and displayed segmental expression across various brain regions...
October 17, 2016: Cells
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