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Sirt6

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https://www.readbyqxmd.com/read/28329681/sirt6-promotes-dna-end-joining-in-ipscs-derived-from-old-mice
#1
Wen Chen, Nana Liu, Hongxia Zhang, Haiping Zhang, Jing Qiao, Wenwen Jia, Songcheng Zhu, Zhiyong Mao, Jiuhong Kang
Induced pluripotent stem cells (iPSCs) have great potential for treating age-related diseases, but the genome integrity of iPSCs is critically important. Here, we demonstrate that non-homologous end joining (NHEJ), rather than homologous recombination (HR), is less efficient in iPSCs from old mice than young mice. We further find that Sirt6 is downregulated in iPSCs from old mice. Sirt6 directly binds to Ku80 and facilitates the Ku80/DNA-PKcs interaction, thus promoting DNA-PKcs phosphorylation at residue S2056, leading to efficient NHEJ...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28296196/sirt6-reduces-macrophage-foam-cell-formation-by-inducing-autophagy-and-cholesterol-efflux-under-ox-ldl-condition
#2
Jiangping He, Guangya Zhang, Qi Pang, Cong Yu, Jie Xiong, Jing Zhu, Fengling Chen
SIRT6 is a pivotal regulator of lipid metabolism. It is also closely connected to cardiovascular diseases, which are the main cause of death in diabetic patients. We observed a decrease in the expression of SIRT6 and key autophagy effectors (ATG5, LC3B, and LAMP1) in ox-LDL-induced foam cells, a special form of lipid-laden macrophages. In these cells, SIRT6 WT but not SIRT6 H133Y overexpression markedly reduced foam cell formation, as shown by Oil Red O staining, while inducing autophagy flux, as determined by both mRFP-GFP-LC3 labeling and transmission electron microscopy...
March 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28250020/fat-specific-sirt6-ablation-sensitizes-mice-to-high-fat-diet-induced-obesity-and-insulin-resistance-by-inhibiting-lipolysis
#3
Jiangying Kuang, Yuwei Zhang, Qinhui Liu, Jing Shen, Shiyun Pu, Shihai Cheng, Lei Chen, Hong Li, Tong Wu, Rui Li, Yanping Li, Min Zou, Zhiyong Zhang, Wei Jiang, Guoheng Xu, Aijuan Qu, Wen Xie, Jinhan He
Sirt6 is an NAD(+)-dependent deacetylase that is involved in the control of energy metabolism. However, the tissue-specific function of Sirt6 in the adipose tissue remains unknown. Here we showed that fat-specific Sirt6 knockout (FKO) sensitized mice to high-fat diet (HFD)-induced obesity, which was attributed to adipocyte hypertrophy rather than adipocyte hyperplasia. The adipocyte hypertrophy in FKO mice likely resulted from compromised lipolytic activity as an outcome of decreased expression of adipose triglyceride lipase (ATGL), a key lipolytic enzyme...
March 1, 2017: Diabetes
https://www.readbyqxmd.com/read/28249904/nr1d1-recruitment-to-sites-of-dna-damage-inhibits-repair-and-is-associated-with-chemosensitivity-of-breast-cancer
#4
Na-Lee Ka, Tae-Young Na, Hyelin Na, Min-Ho Lee, Han-Su Park, Sewon Hwang, Il-Yong Kim, Je Kyung Seong, Mi-Ock Lee
DNA repair capacity is critical for survival of cancer cells upon therapeutic DNA damage and thus is an important determinant of susceptibility to chemotherapy in cancer patients. In this study, we identified a novel function of nuclear receptor NR1D1 in DNA repair, which enhanced chemosensitivity in breast cancer cells. NR1D1 inhibited both non-homologous end joining and homologous recombination double strand breaks (DSB) repair, and delayed the clearance of γH2AX DNA repair foci that formed after treatment of doxorubicin...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28238784/deacetylation-of-ku70-by-sirt6-attenuates-bax-mediated-apoptosis-in-hepatocellular-carcinoma
#5
Na-Na Tao, Ji-Hua Ren, Hua Tang, Long-Kuan Ran, Hong-Zhong Zhou, Bo Liu, Ai-Long Huang, Juan Chen
SIRT6 is a class III histone deacetylase that has been implicated in HCC development. We previously reported that SIRT6 potentiated apoptosis evasion in hepatocellular carcinoma by inhibiting both Bax expression and mitochondrial translocalization. However, the mechanism underlying SIRT6-mediated inhibition of Bax mitochondrial localization remains elusive. In this study, we found that although SIRT6 had no effect on the expression level of Ku70, SIRT6 could interact with Ku70 and deacetylate it. The increased acetylation of Ku70 in SIRT6-depleted cells disrupt its interaction with Bax, which finally resulted in Bax mitochondrial translocalization...
April 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28228253/sirt6-suppresses-cancer-stem-like-capacity-in-tumors-with-pi3k-activation-independently-of-its-deacetylase-activity
#6
Rafael M Ioris, Mirco Galié, Giorgio Ramadori, Jason G Anderson, Anne Charollais, Georgia Konstantinidou, Xavier Brenachot, Ebru Aras, Algera Goga, Nicholas Ceglia, Carlos Sebastián, Denis Martinvalet, Raul Mostoslavsky, Pierre Baldi, Roberto Coppari
Cancer stem cells (CSCs) have high tumorigenic capacity. Here, we show that stem-like traits of specific human cancer cells are reduced by overexpression of the histone deacetylase sirtuin 6 (SIRT6). SIRT6-sensitive cancer cells bear mutations that activate phosphatidylinositol-3-kinase (PI3K) signaling, and overexpression of SIRT6 reduces growth, progression, and grade of breast cancer in a mouse model with PI3K activation. Tumor metabolomic and transcriptomic analyses reveal that SIRT6 overexpression dampens PI3K signaling and stem-like characteristics and causes metabolic rearrangements in this cancer model...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28222243/studies-on-the-binding-of-modest-modulators-of-the-human-enzyme-sirtuin-6-using-std-nmr
#7
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
#8
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...
March 15, 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
#9
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...
April 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28123310/cosmeceutical-product-consisting-of-biomimetic-peptides-antiaging-effects-in-vivo-and-in-vitro
#10
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
#11
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
#12
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-chemokine-c-c-motif-ligand-2-production-in-osteoblasts
#13
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: Sirtuin 6 was overexpressed in MC3T3-E1 murine osteoblasts by lentivirus-mediated gene transfer. The relationship between the antiglycolytic/antioxidative 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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...
March 2017: Neurochemical Research
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