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https://www.readbyqxmd.com/read/28533489/sirtuin-6-inhibits-epithelial-to-mesenchymal-transition-during-idiopathic-pulmonary-fibrosis-via-inactivating-tgf-%C3%AE-1-smad3-signaling
#1
Kunming Tian, Panpan Chen, Zhiping Liu, Shutian Si, Qian Zhang, Yong Mou, Lianyong Han, Qin Wang, Xue Zhou
Sirt6 which is implicated in the control of aging, cancer, and metabolism, has been shown to have anti-fibrosis function in heart and liver. However, whether Sirt6 inhibits idiopathic pulmonary fibrosis remains elusive. Epithelial to mesenchymal transition has been found to be involved in the pathogenesis of idiopathic pulmonary fibrosis. In the present study, forced expression of Sirt6 significantly abrogated TGF-β1-induced epithelial to mesenchymal transition-like phenotype and cell behaviors in A549 cells...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28506746/the-nad-dependent-deacetylase-bifidobacterium-longum-sir2-in-response-to-oxidative-stress-by-deacetylating-foxo3a-and-sigh-%C3%AF-h-in-bifidobacterium-longum-and-hek293t-cells-respectively
#2
Qing Guo, Shiyu Li, Yajie Xie, Qian Zhang, Mengge Liu, Zhenrui Xu, Hanxiao Sun, Yan Yang
Silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation. The mammalian sirtuin family SIRT1, SIRT2, SIRT3 and SIRT6 can regulate oxidative stress. The probiotics (Bifidobacterium longum(B.longum) and Lactobacillus acidophilus(L. acidophilus)) have Sir2 gene family and have antioxidant activity in human body. it remains unknown whether probiotics Sir2 has a direct role in regulating oxidative stress. To this end, we knockout BL-sir2(sir2 B. longum) and LA-sir2(sir2 L...
May 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28478957/sirt6-regulated-nucleosomal-occupancy-affects-hexokinase-2-expression
#3
Piyushi Gupta, Touseef Sheikh, Ellora Sen
To understand the molecular association between inflammation and dysregulated metabolism in glioblastoma, the effect of IL-1β on Hexokinase 2 (HK2) expression was investigated. IL-1β induced HK2 expression was accompanied by heightened SIRT6 and MZF1 levels. IL-1β mediated overall decrease in chromatin compactness on HK2 promoter involved diminished nucleosomal occupancy around the most labile region bearing MZF1 sites. Importantly, SIRT6 and MZF1 served as negative regulators of HK2. Ectopic SIRT6 induced formation and recruitment of MZF1-SIRT6 complex to MZF1 site was concomitant with increased nucleosomal occupancy...
May 4, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28448551/characterization-of-physiological-defects-in-adult-sirt6-mice
#4
Victoria Peshti, Alexey Obolensky, Liat Nahum, Yariv Kanfi, Moran Rathaus, Maytal Avraham, Simon Tinman, Fredrick W Alt, Eyal Banin, Haim Y Cohen
The NAD+-dependent SIRT6 deacetylase was shown to be a major regulator of lifespan and healthspan. Mice deficient for SIRT6 develop a premature aging phenotype and metabolic defects, and die before four weeks of age. Thus, the effect of SIRT6 deficiency in adult mice is unknown. Here we show that SIRT6-/- mice in mixed 129/SvJ/BALB/c background reach adulthood, allowing examination of SIRT6-related metabolic and developmental phenotypes in adult mice. In this mixed background, at 200 days of age, more than 80% of the female knock-out mice were alive whereas only 10% of male knock-out mice survived...
2017: PloS One
https://www.readbyqxmd.com/read/28443459/astragaloside-iv-sensitizes-non-small-cell-lung-cancer-cells-to-gefitinib-potentially-via-regulation-of-sirt6
#5
Peng-Chen Dai, De-Ling Liu, Lei Zhang, Jia Ye, Qing Wang, Hong-Wen Zhang, Xiu-Hua Lin, Guo-Xiang Lai
Astragaloside IV, the active component of Astragalus membranaceus, exhibits diverse biological roles including the anti-tumor activity. In this study, we evaluated the chemosensitive role of astragaloside IV in non-small cell lung cancer cells. Cell Counting Kit-8 analysis was performed to determine cell viability. Real-time polymerase chain reaction and western blot were used to measure the messenger RNA and protein expression. Results showed that astragaloside IV treatment could suppress the proliferation of non-small cell lung cancer cells...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28406396/sirt6-regulates-ras-related-protein-r-ras2-by-lysine-defatty-acylation
#6
Xiaoyu Zhang, Nicole A Spiegelman, Ornella D Nelson, Hui Jing, Hening Lin
The Ras family of GTPases are important in cell signaling and frequently mutated in human tumors. Understanding their regulation is thus important for studying biology and human diseases. Here, we report that a novel posttranslational mechanism, reversible lysine fatty acylation, regulates R-Ras2, a member of the Ras family. SIRT6, a sirtuin with established tumor suppressor function, regulates the lysine fatty acylation of R-Ras2. In mouse embryonic fibroblasts (MEFs), Sirt6 knockout (KO) increased R-Ras2 lysine fatty acylation...
April 13, 2017: ELife
https://www.readbyqxmd.com/read/28399814/sirt6-polymorphism-rs117385980-is-associated-with-longevity-and-healthy-aging-in-finnish-men
#7
Katariina Hirvonen, Hannele Laivuori, Jari Lahti, Timo Strandberg, Johan G Eriksson, Peter Hackman
BACKGROUND: Sirtuin-6 (SIRT6) is involved in various crucial cellular pathways, being a key regulator of telomere structure, DNA repair, metabolism, transcriptional control and the NF-kappa B pathway. Sirt6 knock-out mice have been reported to develop typical features of aging and senescence at the age of 2-3 weeks and die within 4 weeks. The aim of this study was to investigate whether sequence variations of SIRT6 are associated with aging and longevity in Finnish men. METHODS: The sample of this study consisted of 43 longer-living and healthy males and 92 male control subjects who have died of natural causes at an average age of 66,6 (±4,1) years and who belonged to the Helsinki Birth Cohort Study (HBCS)...
April 11, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28393212/sirt6-is-upregulated-and-associated-with-cancer-aggressiveness-in-papillary-thyroid-cancer-via-braf-erk-mcl%C3%A2-1-pathway
#8
Ning Qu, Jia-Qian Hu, Liang Liu, Ting-Ting Zhang, Guo-Hua Sun, Rong-Liang Shi, Qing-Hai Ji
Sirtuin 6 (SIRT6) is a member of the SIRT family NAD+‑dependent deacetylases reported to function in controlling organism homeostasis, lifespan, and diseases. This study investigated the role of SIRT6 in papillary thyroid cancer (PTC). Data of 391 PTC patients was extracted from The Cancer Genome Atlas database to investigate the expression of SIRTs (SIRT1‑7) and their relationship with clinicopathological parameters. Additional 45 pairs of PTC tumor tissues and corresponding non‑tumor tissues were studied using microarray analysis for SIRT6 expression...
May 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28386046/pharmacological-sirt6-inhibition-improves-glucose-tolerance-in-a-type-2-diabetes-mouse-model
#9
Giovanna Sociali, Mirko Magnone, Silvia Ravera, Patrizia Damonte, Tiziana Vigliarolo, Maria Von Holtey, Valerio G Vellone, Enrico Millo, Irene Caffa, Michele Cea, Marco Daniele Parenti, Alberto Del Rio, Maximilien Murone, Raul Mostoslavsky, Alessia Grozio, Alessio Nencioni, Santina Bruzzone
Sirtuin 6 (SIRT6) is a sirtuin family member involved in a wide range of physiologic and disease processes, including cancer and glucose homeostasis. Based on the roles played by SIRT6 in different organs, including its ability to repress the expression of glucose transporters and glycolytic enzymes, inhibiting SIRT6 has been proposed as an approach for treating type 2 diabetes mellitus (T2DM). However, so far, the lack of small molecule Sirt6 inhibitors has hampered the conduct of in vivo studies to assess the viability of this strategy...
April 6, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28385723/fabp4-cre-mediated-sirt6-deletion-impairs-adipose-tissue-function-and-metabolic-homeostasis-in-mice
#10
Xiwen Xiong, Cuicui Zhang, Yang Zhang, Rui Fan, Xinlai Qian, Xiaocheng Charlie Dong
SIRT6 is a member of sirtuin family of deacetylases involved in diverse processes including genome stability, metabolic homeostasis, and anti-inflammation. However, its function in the adipose tissue is not well understood. To examine the metabolic function of SIRT6 in the adipose tissue, we generated two mouse models that are deficient in Sirt6 using the Cre-lox approach. Two commonly used Cre lines that are driven by either the mouse Fabp4 or Adipoq gene promoter were chosen for this study. The Sirt6 knockout mice generated by the Fabp4-Cre line (Sirt6f/f:Fabp4-Cre) had a significant increase in both body weight and fat mass, and exhibited glucose intolerance and insulin resistance as compared with the control wildtype mice...
April 6, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28355567/sirt6-is-essential-for-adipocyte-differentiation-by-regulating-mitotic-clonal-expansion
#11
Qiang Chen, Wenhui Hao, Cuiying Xiao, Ruihong Wang, Xiaoling Xu, Huiyan Lu, Weiping Chen, Chu-Xia Deng
Preadipocytes initiate differentiation into adipocytes through a cascade of events. Mitotic clonal expansion, as one of the earliest events, is essential for adipogenesis. However, the underlying mechanisms that regulate mitotic clonal expansion remain elusive. SIRT6 is a member of the evolutionarily conserved sirtuin family of nicotinamide adenine dinucleotide (NAD)+-dependent protein deacetylases. Here, we show that SIRT6 deficiency in preadipocytes blocks their adipogenesis. Analysis of gene expression during adipogenesis reveals that KIF5C, which belongs to the kinesin family, is negatively regulated by SIRT6...
March 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28355558/neuroprotective-functions-for-the-histone-deacetylase-sirt6
#12
Shai Kaluski, Miguel Portillo, Antoine Besnard, Daniel Stein, Monica Einav, Lei Zhong, Uwe Ueberham, Thomas Arendt, Raul Mostoslavsky, Amar Sahay, Debra Toiber
The histone deacetylase SIRT6 promotes DNA repair, but its activity declines with age with a concomitant accumulation of DNA damage. Furthermore, SIRT6 knockout mice exhibit an accelerated aging phenotype and die prematurely. Here, we report that brain-specific SIRT6-deficient mice survive but present behavioral defects with major learning impairments by 4 months of age. Moreover, the brains of these mice show increased signs of DNA damage, cell death, and hyperphosphorylated Tau-a critical mark in several neurodegenerative diseases...
March 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28355287/the-sirt6-gene-does-it-play-a-role-in-tooth-development
#13
Xueyang Liao, Bo Feng, Demao Zhang, Peng Liu, Xuedong Zhou, Ruimin Li, Ling Ye
Dental Mesenchymal Cells (DMCs) are known to play a role in tooth development as well as in the repair and regeneration of dental tissue. A large number of signaling molecules regulate the proliferation and differentiation of DMC, though the underlying mechanisms are still not fully understood. Sirtuin-6 (SIRT6), a key regulator of aging, can exert an impact on embryonic stem cell (ESC) differentiation. The experimental deletion of Sirt6 in mouse bone marrow cells has been found to have an inhibiting impact on the bone mineral density and the osteogenic differentiation of these cells...
2017: PloS One
https://www.readbyqxmd.com/read/28351995/sirt6-deficiency-results-in-progression-of-glomerular-injury-in-the-kidney
#14
Wen Huang, Hua Liu, Shuang Zhu, Michael Woodson, Rong Liu, Ronald G Tilton, Jordan D Miller, Wenbo Zhang
Aging is associated with an increased incidence and prevalence of renal glomerular diseases. Sirtuin (Sirt) 6, a nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase, has been shown to protect against multiple age-associated phenotypes; however it is unknown whether Sirt6 has a direct pathophysiologic role in the kidney. In the present study, we demonstrate that Sirt6 is expressed in the kidney and aging Sirt6-deficient mice exhibit renal hypertrophy with glomerular enlargement. Sirt6 deletion induces podocyte injury, including decreases in slit diaphragm proteins, foot process effacement, and cellular loss, resulting in proteinuria...
March 28, 2017: Aging
https://www.readbyqxmd.com/read/28329681/sirt6-promotes-dna-end-joining-in-ipscs-derived-from-old-mice
#15
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
#16
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
#17
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
#18
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 nonhomologous end joining and homologous recombination double-strand breaks 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
#19
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
#20
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
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