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https://www.readbyqxmd.com/read/28803211/melatonin-protects-chondrocytes-from-impairment-induced-by-glucocorticoids-via-nad-dependent-sirt1
#1
Wei Yang, Xiaomin Kang, Na Qin, Feng Li, Xinxin Jin, Zhengmin Ma, Zhuang Qian, Shufang Wu
Intra-articular injection of glucocorticoids is used to relieve pain and inflammation in osteoarthritis patients, which is occasionally accompanied with the serious side effects of glucocorticoids in collagen-producing tissue. Melatonin is the major hormone released from the pineal gland and its beneficial effects on cartilage has been suggested. In the present study, we investigated the protective role of melatonin on matrix degeneration in chondrocytes induced by dexamethasone (Dex). The chondrocytes isolated from mice knee joint were treated with Dex, melatonin, EX527 and siRNA targeted for SIRT6, respectively...
August 9, 2017: Steroids
https://www.readbyqxmd.com/read/28767699/molecular-evolutionary-patterns-of-nad-sirtuin-aging-signaling-pathway-across-taxa
#2
Uma Gaur, Jianbo Tu, Diyan Li, Yue Gao, Ting Lian, Boyuan Sun, Deying Yang, Xiaolan Fan, Mingyao Yang
A deeper understanding of the conserved molecular mechanisms in different taxa have been made possible only because of the evolutionary conservation of crucial signaling pathways. In the present study, we explored the molecular evolutionary pattern of selection signatures in 51 species for 10 genes which are important components of NAD+/Sirtuin pathway and have already been directly linked to lifespan extension in worms and mice. Selection pressure analysis using PAML program revealed that MRPS5 and PPARGC1A were under significant constraints because of their functional significance...
2017: PloS One
https://www.readbyqxmd.com/read/28765271/sirt6-regulates-metabolic-homeostasis-in-skeletal-muscle-through-activation-of-ampk
#3
Xiaona Cui, Lu Yao, Xiaoying Yang, Yong Gao, Fude Fang, Jun Zhang, Qinghua Wang, Yongsheng Chang
Due to the mass and functions in metabolism, skeletal muscle is one of major organs regulating whole-body metabolic homeostasis. SIRT6, a histone deacetylase, has been shown to regulate metabolism in liver and brain, however, its specific role in skeletal muscle is undetermined. In the present study we explored physiological function of SIRT6 in muscle. We generated a muscle-specific SIRT6 knockout mouse model. The mice with SIRT6 deficiency in muscle displayed impaired glucose homeostasis and insulin sensitivity, attenuated whole-body energy expenditure and weakened exercise performance...
August 1, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28756638/structure-based-discovery-of-new-selective-small-molecule-sirtuin-5-inhibitors
#4
Sha Liu, Sen Ji, Zhu-Jun Yu, Hua-Li Wang, Xu Cheng, Wei-Jian Li, Li Jing, Yamei Yu, Qiang Chen, Ling-Ling Yang, Guo-Bo Li, Yong Wu
Human sirtuin 5 (SIRT5) is a protein deacylase regulating metabolic pathways and stress responses, and is implicated in metabolism-related diseases. Small molecule inhibitors for SIRT5 are sought as chemical tools and potential therapeutics. Herein we proposed a customized virtual screening approach targeting catalytically important and unique residues Tyr102 and Arg105 of SIRT5. Of the 20 tested virtual screening hits, 6 compounds displayed marked inhibitory activities against SIRT5. For the hit compound 19, a series of new synthesized (E)-2-cyano-N-phenyl-3-(5-phenylfuran-2-yl)acrylamide derivatives/analogues were carried out structure-activity relationship analyses, resulting in new more potent inhibitors, among which 37 displayed the most potent inhibition to SIRT5 with an IC50 value of 5...
July 30, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28753566/overexpression-of-sirt6-attenuates-the-tumorigenicity-of-hepatocellular-carcinoma-cells
#5
Yadong Wang, Teng Pan, Haiyu Wang, Li Li, Jiangmin Li, Ding Zhang, Haiyan Yang
OBJECTIVE: This study aimed to explore the effects of overexpression of sirtuin 6 (SIRT6) on the tumorigenicity of hepatocellular carcinoma (HCC) cells. METHODS: Stable SIRT6-overexpressed HCC cell lines were established by transfecting SIRT6 plasmid. Soft agar assay and tumor xenograft assay in nude mice were applied. Flow cytometry was employed to detect cell cycle distribution. Western blotting analysis was used to detect the expression of proteins. RESULTS: Overexpression of SIRT6 attenuated HepG2 and HCCLM3 cells proliferation, colony formation in vitro and tumor formation in nude mice, and resulted in the G1 phase cell cycle arrest...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28747973/effect-of-ionizing-radiation-at-low-dose-on-transgenerational-carcinogenesis-by-epigenetic-regulation
#6
Lan Li, Jong-Hyun Kim, Hee-Tae Park, Jae-Hoon Lee, Min-Koo Park, Ji-Won Lee, Jeong-Chan Lee, Min-Jae Lee
The objective of this study was to determine the effect of ionizing radiation (IR) exposure of parents on carcinogenesis of the next generation focusing on the epigenetic perspective to clarify the relationship between radiation dose and carcinogenesis in F1 generation SD rats. F1 generations from pregnant rats (F0) who were exposed to gamma rays were divided into three groups according to the dose of radiation: 10 rad, 30 rad, and untreated. They were intraperitoneally injected with 50 mg/kg of diethylnitrosamine (DEN)...
June 2017: Laboratory Animal Research
https://www.readbyqxmd.com/read/28723567/cold-inducible-sirt6-regulates-thermogenesis-of-brown-and-beige-fat
#7
Lu Yao, Xiaona Cui, Qi Chen, Xiaoying Yang, Fude Fang, Jun Zhang, Guoqing Liu, Wanzhu Jin, Yongsheng Chang
Promoting development and function of brown and beige fat may reduce obesity. Here, we show that fat SIRT6 expression is markedly induced by cold exposure and a β-adrenergic agonist. Deletion of SIRT6 in adipose tissue impairs the thermogenic function of brown adipocytes, causing a morphological "whitening" of brown fat, reduced oxygen (O2) consumption, obesity, decreased core body temperature, and cold sensitivity. Fat SIRT6-deleted mice exhibit increased blood glucose levels, severe insulin resistance, and hepatic steatosis...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28698968/inhibition-of-poly-adp-ribose-polymerase-1-enhances-gene-expression-of-selected-sirtuins-and-app-cleaving-enzymes-in-amyloid-beta-cytotoxicity
#8
Przemysław L Wencel, Walter J Lukiw, Joanna B Strosznajder, Robert Piotr Strosznajder
Poly(ADP-ribose) polymerases (PARPs) and sirtuins (SIRTs) are involved in the regulation of cell metabolism, transcription, and DNA repair. Alterations of these enzymes may play a crucial role in Alzheimer's disease (AD). Our previous results indicated that amyloid beta (Aβ) peptides and inflammation led to activation of PARP1 and cell death. This study focused on a role of PARP1 in the regulation of gene expression for SIRTs and beta-amyloid precursor protein (βAPP) cleaving enzymes under Aβ42 oligomers (AβO) toxicity in pheochromocytoma cells (PC12) in culture...
July 12, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28685526/glycyrrhetinic-acid-suppressed-hmgb1-release-by-up-regulation-of-sirt6-in-nasal-inflammation
#9
D Chen, L M Bellussi, S Cocca, J Wang, G C Passali, X Hao, L Chen, D Passali
To extend our understanding of previous studies on the pathogenesis and mechanism of high mobility group box 1 (HMGB1) in chronic rhinosinusitis with nasal polyps (CRSwNP), here we show that Sirtuin 6 (Sirt6), one of the Sirtuin family members which are widely studied in aging, DNA repair, metabolism, inflammation and cancer, was expressed in normal nasal mucosa using immunohistochemical staining and Western blot assay. Sirt6 expression levels were decreased in CRSwNP tissue. Sirt6 expression levels were modulated by small interfering RNA transfection in human nasal epithelial cells (HNE)...
April 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28677777/suppression-of-sirt6-by-mir-33a-facilitates-tumor-growth-of-glioma-through-apoptosis-and-oxidative-stress-resistance
#10
Mingze Chang, Lin Qiao, Bin Li, Juanhong Wang, Gejuan Zhang, Wenzhen Shi, Zhiqin Liu, Naibing Gu, Zhengli Di, Xinlai Wang, Ye Tian
microRNA-33a (miR-33a) belongs to the miR-33 family that is implicated in the progression of various types of cancers. Aberrant expression of miR-33a has been detected in several human cancers, and has been shown to regulate the migration and invasion as well as proliferation and apoptosis of tumor cells. However, the clinical significance and precise mechanisms underlying the dysfunction of miR-33a in glioma have not been well investigated in previous studies. In this study, overexpression of miR-33a was observed in clinical glioma specimens and cell lines...
July 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28661724/sirt1-and-sirt6-signaling-pathways-in-cardiovascular-disease-protection
#11
Nunzia D'Onofrio, Luigi Servillo, Maria Luisa Balestrieri
SIGNIFICANCE: Oxidative stress represents the common hallmark of pathological conditions associated with cardiovascular disease (CVD), including atherosclerosis, heart failure, hypertension, aging, diabetes, and other vascular system-related diseases. The sirtuin (SIRT) family, comprising seven proteins (SIRT1-SIRT7) sharing a highly conserved nicotinamide adenine dinucleotide (NAD(+))-binding catalytic domain, attracted a great attention for the past few years as stress adaptor and epigenetic enzymes involved in the cellular events controlling aging-related disorder, cancer, and CVD...
June 29, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28659816/cardioprotective-effects-of-sirt6-in-a-mouse-model-of-transverse-aortic-constriction-induced-heart-failure
#12
Yongming Li, Xianda Meng, Wenguang Wang, Fu Liu, Zhiru Hao, Yang Yang, Jinbo Zhao, Wensi Yin, Lijuan Xu, Ruiping Zhao, Jiang Hu
SIRT6, a member of the NAD (+)-dependent class III deacetylase sirtuin family, plays important roles in the maintenance of cardiovascular homeostasis. Telomere shortening is a risk factor for age-associated diseases, including heart disease. In the present study, we investigated the role of SIRT6 and telomerase in a mouse model of transverse aortic constriction (TAC)-induced heart failure. SIRT6, telomerase reverse transcriptase (TERT), and telomere repeat binding factor (TRF)-1 were significantly downregulated in TAC mice compared with their expression in sham-operated mice...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28656307/sirt6-inhibits-growth-of-gastric-cancer-by-inhibiting-jak2-stat3-pathway
#13
Jianmei Zhou, Ang Wu, Xiaoting Yu, Jianwei Zhu, Hui Dai
SIRT6, a member of NAD positivity-dependent class III deacetylase sirtuin family, played versatile roles in human cancers. However, the expression and biological function of SIRT6 in gastric cancer (GC) remain to be investigated. In this study, we found that SIRT6 expression level was decreased in gastric cancer tissues and cell lines. Decreased SIRT6 expression was associated with unfavorable clinical parameters including tumor differentiation, tumor size and TNM stage. Importantly, decreased level of SIRT6 was associated with decreased rate of overall survival (OS) and disease‑free survival (DFS)...
June 27, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28644902/sirt6-alters-adult-hippocampal-neurogenesis
#14
Eitan Okun, Daniel Marton, Daniel Cohen, Kathleen Griffioen, Yariv Kanfi, Tomer Illouz, Ravit Madar, Haim Y Cohen
Sirtuins are pleiotropic NAD+ dependent histone deacetylases involved in metabolism, DNA damage repair, inflammation and stress resistance. SIRT6, a member of the sirtuin family, regulates the process of normal aging and increases the lifespan of male mice over-expressing Sirt6 by 15%. Neurogenesis, the formation of new neurons within the hippocampus of adult mammals, involves several complex stages including stem cell proliferation, differentiation, migration and network integration. During aging, the number of newly generated neurons continuously declines, and this is correlated with a decline in neuronal plasticity and cognitive behavior...
2017: PloS One
https://www.readbyqxmd.com/read/28642687/is-sirt6-activity-neuroprotective-and-how-does-it-differ-from-sirt1-in-this-regard
#15
Bor L Tang
No abstract text is available yet for this article.
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28635654/the-identification-of-a-sirt6-activator-from-brown-algae-fucus-distichus
#16
Minna K Rahnasto-Rilla, Padraig McLoughlin, Tomasz Kulikowicz, Maire Doyle, Vilhelm A Bohr, Maija Lahtela-Kakkonen, Luigi Ferrucci, Maria Hayes, Ruin Moaddel
Brown seaweeds contain many bioactive compounds, including polyphenols, polysaccharides, fucosterol, and fucoxantin. These compounds have several biological activities, including anti-inflammatory, hepatoprotective, anti-tumor, anti-hypertensive, and anti-diabetic activity, although in most cases their mechanisms of action are not understood. In this study, extracts generated from five brown algae (Fucus dichitus, Fucus vesiculosus (Linnaeus), Cytoseira tamariscofolia, Cytoseira nodacaulis, Alaria esculenta) were tested for their ability to activate SIRT6 resulting in H3K9 deacetylation...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28607107/myeloid-sirtuin-6-deficiency-causes-insulin-resistance-in-high-fat-diet-fed-mice-by-eliciting-macrophage-polarization-toward-an-m1-phenotype
#17
Youngyi Lee, Sun-O Ka, Hye-Na Cha, Yu-Na Chae, Mi-Kyung Kim, So-Young Park, Eun Ju Bae, Byung-Hyun Park
Obesity-related insulin resistance is closely associated with macrophage accumulation and subsequent cytokine release in local tissues. Sirtuin (Sirt) 6 is known to exert an anti-inflammatory function but its role in macrophages in the context of obesity has not been investigated. Here, we generated myeloid-specific Sirt6 knockout mice (mS6KO) and investigated the metabolic characteristics after high-fat diet (HFD) feeding for 16 weeks. Compared with their wild type littermates, HFD-fed mS6KO mice exhibited greater increases in body weight, fasting blood glucose- and insulin-levels, hepatic steatosis, glucose intolerance, and insulin resistance...
June 12, 2017: Diabetes
https://www.readbyqxmd.com/read/28558631/ursolic-acid-mediates-hepatic-protection-through-enhancing-of-anti-aging-biomarkers
#18
Shadi Gharibi, Nuredin Bakhtiari, Elham-Moslemee Jalalvand
BACKGROUND: Age-associated loss of liver function has been recognized for decades. But, the mechanism driving liver regeneration and its decline with age remains elusive. OBJECTIVE: Hence, to support of our previous studies about anti-aging effects of Ursolic Acid (UA), a compound which extensively present in apple peels. The aim of this study is to address whether UA might alter sensors of the cell metabolic state such as SIRT1, SIRT6, PGC-1β and Klotho proteins...
May 30, 2017: Current Aging Science
https://www.readbyqxmd.com/read/28536482/nad-loss-a-new-player-in-ahr-biology-prevention-of-thymus-atrophy-and-hepatosteatosis-by-nad-repletion
#19
Silvia Diani-Moore, Jenny Shoots, Rubi Singh, Joshua B Zuk, Arleen B Rifkind
Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) is a carcinogenic and highly toxic industrial byproduct that persists in the environment and produces a pleiotropic toxicity syndrome across vertebrate species that includes wasting, hepatosteatosis, and thymus atrophy. Dioxin toxicities require binding and activation of the aryl hydrocarbon receptor (AhR), a ligand activated transcription factor. However, after nearly 50 years of study, it remains unknown how AhR activation by dioxin produces toxic effects...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536120/hepatocyte-specific-sirtuin-6-deletion-predisposes-to-nonalcoholic-steatohepatitis-by-up-regulation-of-bach1-an-nrf2-repressor
#20
Sun-O Ka, In Hyuk Bang, Eun Ju Bae, Byung-Hyun Park
Sirtuin (Sirt)6 has been implicated in negative regulation of inflammation and lipid metabolism, although its function in the progression from simple steatosis to nonalcoholic steatohepatitis (NASH) remains to be defined. To explore the role of hepatocyte Sirt6 in NASH development, we generated hepatocyte-specific Sirt6 knockout (KO) mice that were fed a high-fat and high-fructose (HFHF) diet for 16 wk. HFHF-fed KO mice had increased hepatic steatosis and inflammation and aggravated glucose intolerance and insulin resistance compared with wild-type mice...
May 23, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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