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https://www.readbyqxmd.com/read/28331525/the-anti-ageing-molecule-sirt1-mediates-beneficial-effects-of-cardiac-rehabilitation
#1
Giusy Russomanno, Graziamaria Corbi, Valentina Manzo, Nicola Ferrara, Giuseppe Rengo, Annibale A Puca, Salvatore Latte, Albino Carrizzo, Maria Consiglia Calabrese, Ramaroson Andriantsitohaina, Walter Filippelli, Carmine Vecchione, Amelia Filippelli, Valeria Conti
BACKGROUND: An exercise-based Cardiac Rehabilitation Programme (CRP) is established as adjuvant therapy in heart failure (HF), nevertheless it is underutilized, especially in the elderly. While the functional and hemodynamic effects of CRP are well known, its underlying molecular mechanisms have not been fully clarified. The present study aims to evaluate the effects of a well-structured 4-week CRP in patients with stable HF from a molecular point of view. RESULTS: A prospective longitudinal observational study was conducted on patients consecutively admitted to cardiac rehabilitation...
2017: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/28329314/sirt1-polymorphisms-and-serum-induced-sirt1-protein-expression-in-aging-and-frailty-the-champ-study
#2
Shajjia Razi, Victoria C Cogger, Marina Kennerson, Vicky L Benson, Aisling C McMahon, Fiona M Blyth, David J Handelsman, Markus J Seibel, Vasant Hirani, Vasikaran Naganathan, Louise Waite, Rafael de Cabo, Robert G Cumming, David G Le Couteur
The nutrient sensing protein, SIRT1 influences aging and nutritional interventions such as caloric restriction in animals, however, the role of SIRT1 in human aging remains unclear. Here, the role of SIRT1 single-nucleotide polymorphisms (SNPs) and serum-induced SIRT1 protein expression (a novel assay that detects circulating factors that influence SIRT1 expression in vitro) were studied in the Concord Health and Ageing in Men Project (CHAMP), a prospective cohort of community dwelling men aged 70 years and older...
March 14, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28324774/methylation-changes-of-sirt1-klf4-dapk1-and-spg20-in-b-lymphocytes-derived-from-follicular-and-diffuse-large-b-cell-lymphoma
#3
Raffaele Frazzi, Eleonora Zanetti, Mariaelena Pistoni, Ione Tamagnini, Riccardo Valli, Luca Braglia, Francesco Merli
Diffuse large-B cell lymphomas (DLBCL) and follicular lymphomas (FL) are the most represented subtypes among mature B-cell neoplasms and originate from malignant B lymphocytes. Methylation represents one of the major epigenetic mechanisms of gene regulation. Silent information regulator 1 (SIRT1) is a class III lysine-deacetylase playing several functions and considered to be a context-dependent tumor promoter. We present the quantitative methylation, gene expression and tissue distribution of SIRT1 and some key mediators related to lymphoma pathogenesis in B lymphocytes purified from biopsies of follicular hyperplasias, FL and DLBCL...
March 9, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28323907/resveratrol-inhibits-androgen-production-of-human-adrenocortical-h295r-cells-by-lowering-cyp17-and-cyp21-expression-and-activities
#4
Nesa Marti, Nadia Bouchoucha, Kay-Sara Sauter, Christa E Flück
Resveratrol, a natural compound found in grapes, became very popular for its suggested protective effects against aging. It was reported to have similar positive effects on the human metabolism as caloric restriction. Recently, positive effects of resveratrol on steroid biosynthesis in cell systems and in humans suffering from polycystic ovary syndrome have also been reported, but the exact mechanism of this action remains unknown. Sirtuins seem targeted by resveratrol to mediate its action on energy homeostasis...
2017: PloS One
https://www.readbyqxmd.com/read/28301150/discovery-of-new-sirt2-inhibitors-by-utilizing-a-consensus-docking-scoring-strategy-and-structure-activity-relationship-analysis
#5
Shen-Zhen Huang, Chun-Li Song, Xiang Wang, Guo Zhang, Yan-Lin Wang, Xiao-Juan Jiang, Qi-Zheng Sun, Lu-Yi Huang, Rong Xiang, Yi-Guo Hu, Lin-Li Li, Sheng-Yong Yang
SIRT2, which is a NAD+ (nicotinamide adenine dinucleotide)-dependent deacetylase, has been demonstrated to play an important role in the occurrence and development of a variety of diseases such as cancer, ischemia-reperfusion, and neurodegenerative diseases. Small molecule inhibitors of SIRT2 are thought as potential interfering agents for relevant diseases. Discovery of SIRT2 inhibitor has attracted much attention recently. In this investigation, we first adopted a consensus docking/scoring strategy to screen for novel SIRT2 inhibitors...
March 16, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28300638/astaxanthin-attenuated-pressure-overload-induced-cardiac-dysfunction-and-myocardial-fibrosis-partially-by-activating-sirt1
#6
Jun Zhang, Quan-Zhen Wang, Shao-Hua Zhao, Xiang Ji, Jie Qiu, Jian Wang, Yi Zhou, Qian Cai, Jie Zhang, Hai-Qing Gao
BACKGROUND: Myocardial fibrosis contributes to cardiac dysfunction. Astaxanthin (AST), a member of the carotenoid family, is a well-known antioxidant, but its effect on and underlying mechanisms in myocardial fibrosis are poorly understood. METHODS: In vivo, myocardial fibrosis and cardiac dysfunction were induced using transverse aortic constriction (TAC). AST was administered to mice for 12weeks post-surgery. In vitro, transforming growth factor β1 (TGF-β1) was used to stimulate human cardiac fibroblasts (HCFs)...
March 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28298952/insights-for-oxidative-stress-and-mtor-signaling-in-myocardial-ischemia-reperfusion-injury-under-diabetes
#7
REVIEW
Dajun Zhao, Jian Yang, Lifang Yang
Diabetes mellitus (DM) displays a high morbidity. The diabetic heart is susceptible to myocardial ischemia/reperfusion (MI/R) injury. Impaired activation of prosurvival pathways, endoplasmic reticulum (ER) stress, increased basal oxidative state, and decreased antioxidant defense and autophagy may render diabetic hearts more vulnerable to MI/R injury. Oxidative stress and mTOR signaling crucially regulate cardiometabolism, affecting MI/R injury under diabetes. Producing reactive oxygen species (ROS) and reactive nitrogen species (RNS), uncoupling nitric oxide synthase (NOS), and disturbing the mitochondrial quality control may be three major mechanisms of oxidative stress...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28296029/cd38-promotes-angiotensin-ii-induced-cardiac-hypertrophy
#8
Xiao-Hui Guan, Xuan Hong, Ning Zhao, Xiao-Hong Liu, Yun-Fei Xiao, Ting-Tao Chen, Li-Bin Deng, Xiao-Lei Wang, Jian-Bin Wang, Guang-Ju Ji, Mingui Fu, Ke-Yu Deng, Hong-Bo Xin
Cardiac hypertrophy is an early hallmark during the clinical course of heart failure and regulated by various signalling pathways. Recently, we observed that mouse embryonic fibroblasts from CD38 knockout mice were significantly resistant to oxidative stress such as H2 O2 -induced injury and hypoxia/reoxygenation-induced injury. In addition, we also found that CD38 knockout mice protected heart from ischaemia reperfusion injury through activating SIRT1/FOXOs-mediated antioxidative stress pathway. However, the role of CD38 in cardiac hypertrophy is not explored...
March 12, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28295567/melatonin-reverses-h2-o2-induced-senescence-in-sh-sy5y-cells-by-enhancing-autophagy-via-sirtuin-1-deacetylation-of-the-rela-p65-subunit-of-nf-%C3%AE%C2%BAb
#9
Chutikorn Nopparat, Puritat Sinjanakhom, Piyarat Govitrapong
Autophagy, a degradation mechanism that plays a major role in maintaining cellular homeostasis and diminishes in aging, is considered an aging characteristic. Melatonin is an important hormone that plays a wide range of physiological functions, including the anti-aging effect, potentially via the regulation of the Sirtuin1 (SIRT1) pathway. The deacetylation ability of SIRT1 is important for controlling the function of several transcription factors, including nuclear factor kappa B (NF-ĸB). Apart from inflammation, NF-ĸB can regulate autophagy by inhibiting Beclin1, an initiator of autophagy...
March 14, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28295415/adipose-tissue-nad-biology-in-obesity-and-insulin-resistance-from-mechanism-to-therapy
#10
REVIEW
Shintaro Yamaguchi, Jun Yoshino
Nicotinamide adenine dinucleotide (NAD(+) ) biosynthetic pathway, mediated by nicotinamide phosphoribosyltransferase (NAMPT), a key NAD(+) biosynthetic enzyme, plays a pivotal role in controlling many biological processes, such as metabolism, circadian rhythm, inflammation, and aging. Over the past decade, NAMPT-mediated NAD(+) biosynthesis, together with its key downstream mediator, namely the NAD(+) -dependent protein deacetylase SIRT1, has been demonstrated to regulate glucose and lipid metabolism in a tissue-dependent manner...
March 15, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28288820/resveratrol-inhibits-bk-induced-cox-2-transcription-by-suppressing-acetylation-of-ap-1-and-nf-%C3%AE%C2%BAb-in-human-rheumatoid-arthritis-synovial-fibroblasts
#11
Chuen-Mao Yang, Yu-Wen Chen, Pei-Ling Chi, Chih-Chung Lin, Li-Der Hsiao
Bradykinin (BK) induces inflammation in rheumatoid arthritis (RA). Resveratrol is a potent activator of Sirt1 which could modulate inflammation through deacetylating histones of transcription factors. Here, we investigated the mechanisms underlying BK-induced COX-2 expression which is modulated by resveratrol/Sirt1 in human rheumatoid arthritis synovial fibroblasts (RASFs). We found that BK-induced COX-2 protein and mRNA expression associated with PGE2 synthesis, and promoter activity was mediated through B2R receptors, which were attenuated by selective B2R antagonist Hoe140 or transfection with B2R siRNA...
March 11, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28279889/polysaccharide-from-angelica-sinensis-ameliorates-high-fat-diet-and-stz-induced-hepatic-oxidative-stress-and-inflammation-in-diabetic-mice-by-activating-the-sirt1-ampk-pathway
#12
Kaiping Wang, Zhuohong Tang, Jinglin Wang, Peng Cao, Qiang Li, Weizhi Shui, Hongjing Wang, Ziming Zheng, Yu Zhang
Polysaccharide from Angelica sinensis (Oliv.) Diels (ASP) possesses many bioactivities, such as hematopoiesis, anti-inflammation, antioxidation and metabolism regulation. The aim of this study was to investigate the mechanisms underlying the protection of a combination of high-fat diet and streptozotocin-induced liver damage in diabetic Balb/c mice by ASP. Results showed that ASP had beneficial effects on ameliorating hyperglycemia, dyslipidemia and liver injury. Moreover, mechanistic study for the liver-protective role in vivo demonstrated that ASP enhanced the activities of superoxide dismutase and glutathione peroxidase and increased the glutathione content, which resulted in the reduction of hepatic reactive oxygen species (ROS) and malondialdehyde, and reduced the protein expression levels of liver IKKα/NF-κB/p-IκBα and the concentrations of serum tumor necrosis factor-α/interleukin-6...
February 10, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28275188/the-deacetylase-sirt1-regulates-the-replication-properties-of-human-papillomavirus-16-e1-and-e2
#13
Dipon Das, Nathan Smith, Xu Wang, Iain M Morgan
Human papillomaviruses (HPV) replicate their genomes in differentiating epithelium using the viral proteins E1 and E2 in association with host proteins. While the roles of E1 and E2 in this process are understood, the host factors involved and how they interact with and regulate E1-E2 are not. Our previous work identified the host replication and repair factor TopBP1 as an E2 partner protein essential for optimal E1-E2 replication and for the viral life cycle. The role of TopBP1 in host DNA replication is regulated by the class III deacetylase SIRT1; activation of the DNA damage response prevents SIRT1 deacetylation of TopBP1 resulting in a switch from DNA replication to repair functions for this protein and cell cycle arrest...
March 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28273448/mutations-that-allow-sir2-orthologs-to-function-in-a-nad-depleted-environment
#14
Caitlin R Ondracek, Vincent Frappier, Alison E Ringel, Cynthia Wolberger, Leonard Guarente
Sirtuin enzymes depend on NAD(+) to catalyze protein deacetylation. Therefore, the lowering of NAD(+) during aging leads to decreased sirtuin activity and may speed up aging processes in laboratory animals and humans. In this study, we used a genetic screen to identify two mutations in the catalytic domain of yeast Sir2 that allow the enzyme to function in an NAD(+)-depleted environment. These mutant enzymes give rise to a significant increase of yeast replicative lifespan and increase deacetylation by the Sir2 ortholog, SIRT1, in mammalian cells...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28273432/p53-and-mir-34a-feedback-promotes-lung-epithelial-injury-and-pulmonary-fibrosis
#15
Shwetha K Shetty, Nivedita Tiwari, Amarnath S Marudamuthu, Bijesh Puthusseri, Yashodhar P Bhandary, Jian Fu, Jeffrey Levin, Steven Idell, Sreerama Shetty
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. The pathogenesis of interstitial lung diseases, including its most common form, IPF, remains poorly understood. Alveolar epithelial cell (AEC) apoptosis, proliferation, and accumulation of myofibroblasts and extracellular matrix deposition results in progressive loss of lung function in IPF. We found induction of tumor suppressor protein, p53, and apoptosis with suppression of urokinase-type plasminogen activator (uPA) and the uPA receptor in AECs from the lungs of IPF patients, and in mice with bleomycin, cigarette smoke, silica, or sepsis-induced lung injury...
March 5, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28273169/reversible-modulation-of-sirt1-activity-in-a-mouse-strain
#16
Katherine V Clark-Knowles, Xiaohong He, Karen Jardine, Josée Coulombe, Danielle Dewar-Darch, Annabelle Z Caron, Douglas A Gray, Michael W McBurney
The SIRT1 protein deacetylase is reported to have a remarkably wide spectrum of biological functions affecting such varied processes as aging, cancer, metabolism, neurodegeneration and immunity. However, the SIRT1 literature is also full of contradictions. To help establish the role(s) of SIRT1 in these and other biological processes, we set out to create a mouse in which the SIRT1 activity could be toggled between on and off states by fusing the estrogen receptor ligand-binding domain (ER) to the C terminus of the SIRT1 protein...
2017: PloS One
https://www.readbyqxmd.com/read/28272704/a-minicircuitry-comprised-of-microrna-9-and-sirt1-contributes-to-leukemogenesis-in-t-8-21-acute-myeloid-leukemia
#17
L Zhou, L Fu, N Lv, X-S Chen, J Liu, Y Li, Q-Y Xu, S Huang, X-D Zhang, L-P Dou, L L Wang, Y-H Li, L Yu
OBJECTIVE: The AML1-ETO fusion protein (AE) resulting from the t(8;21) translocation is highly related to the pathogenesis and development of leukemia. microRNA-9 (miR-9) acts as a tumor suppressor gene in AE-positive acute myeloid leukemia (AML). Silent mating type information regulation 2 homolog-1 (SIRT1) is overexpressed in most cancer cells by increasing proliferation as a tumorigenic gene. The present study was performed to investigate the underlying interaction between miR-9 and SIRT1 in AE-positive AML...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28271186/suv39h1-mediated-sirt1-trans-repression-contributes-to-cardiac-ischemia-reperfusion-injury
#18
Guang Yang, Xinjian Zhang, Xinyu Weng, Peng Liang, Xin Dai, Sheng Zeng, Huihui Xu, Hailin Huan, Mingming Fang, Yuehua Li, Dachun Xu, Yong Xu
Ischemic reperfusion (I/R) contributes to deleterious cardiac remodeling and heart failure. The deacetylase SIRT1 has been shown to protect the heart from I/R injury. We examined the mechanism whereby I/R injury represses SIRT1 transcription in the myocardium. There was accumulation of trimethylated histone H3K9 on the proximal SIRT1 promoter in the myocardium in mice following I/R injury and in cultured cardiomyocytes exposed to hypoxia-reoxygenation (H/R). In accordance, the H3K9 trimethyltransferase SUV39H1 bound to the SIRT1 promoter and repressed SIRT1 transcription...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28270525/adipocyte-sirt1-controls-systemic-insulin-sensitivity-by-modulating-macrophages-in-adipose-tissue
#19
Xiaoyan Hui, Mingliang Zhang, Ping Gu, Kuai Li, Yuan Gao, Donghai Wu, Yu Wang, Aimin Xu
Adipose tissue inflammation, characterized by augmented infiltration and altered polarization of macrophages, contributes to insulin resistance and its associated metabolic diseases. The NAD(+)-dependent deacetylase SIRT1 serves as a guardian against metabolic disorders in multiple tissues. To dissect the roles of SIRT1 in adipose tissues, metabolic phenotypes of mice with selective ablation of SIRT1 in adipocytes and myeloid cells were monitored. Compared to myeloid-specific SIRT1 depletion, mice with adipocyte-selective deletion of SIRT1 are more susceptible to diet-induced insulin resistance...
March 7, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28263894/inhibition-of-autophagy-enhances-hydroquinone-induced-tk6-cell-death
#20
Longmei Xu, Jiaxian Liu, Yuting Chen, Lin Yun, Shaoyun Chen, Kairu Zhou, Bei Lai, Li Song, Hui Yang, Hairong Liang, Huanwen Tang
Hydroquinone (HQ), one of the metabolic products of benzene, is a carcinogen. It can induce apoptosis in lymphoma cells. However, whether HQ can induce autophagy and what roles autophagy plays in TK6 cells exposured to HQ remains unclear. In this study, we found that HQ could induce autophagy through techniques of qRT-PCR, Western blot, immunofluorescent assay of LC3 and transmission electron microscope. Furthermore, inhibiting autophagy using 3-methyladenine (3-MA) or chloroquine (CQ) significantly enhanced HQ-induced cell apoptosis, suggesting that autophagy may be a survival mechanism...
March 2, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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