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https://www.readbyqxmd.com/read/29138502/crystal-structures-of-the-mitochondrial-deacylase-sirtuin-4-reveal-isoform-specific-acyl-recognition-and-regulation-features
#1
Martin Pannek, Zeljko Simic, Matthew Fuszard, Marat Meleshin, Dante Rotili, Antonello Mai, Mike Schutkowski, Clemens Steegborn
Sirtuins are evolutionary conserved NAD(+)-dependent protein lysine deacylases. The seven human isoforms, Sirt1-7, regulate metabolism and stress responses and are considered therapeutic targets for aging-related diseases. Sirt4 locates to mitochondria and regulates fatty acid metabolism and apoptosis. In contrast to the mitochondrial deacetylase Sirt3 and desuccinylase Sirt5, no prominent deacylase activity and structural information are available for Sirt4. Here we describe acyl substrates and crystal structures for Sirt4...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29136592/human-sirtuin-3-sirt3-deacetylates-histone-h3-lysine-56-to-promote-nonhomologous-end-joining-repair
#2
Amrita Sengupta, Devyani Haldar
Human sirtuin 3 (SIRT3) is a conserved NAD(+) dependent deacetylase, which functions in important cellular processes including transcription, metabolism, oxidative stress response. It is a robust mitochondrial deacetylase; however, few studies have indicated its nuclear functions. Here we report interaction of SIRT3 with core histones and identified acetylated histone H3 lysine 56 (H3K56ac) as its novel substrate, in addition to known substrates acetylated H4K16 and H3K9. Further, we showed in response to DNA damage SIRT3 localizes to the repair foci colocalizing with γH2AX and nonhomologous end joining (NHEJ) marker p53-binding protein 1 (53BP1)...
November 8, 2017: DNA Repair
https://www.readbyqxmd.com/read/29130578/sirt3-deregulation-is-linked-to-mitochondrial-dysfunction-in-alzheimer-s-disease
#3
Junghee Lee, Yunha Kim, Tian Liu, Yu Jin Hwang, Seung Jae Hyeon, Hyeonjoo Im, Kyungeun Lee, Victor E Alvarez, Ann C McKee, Soo-Jong Um, Manwook Hur, Inhee Mook-Jung, Neil W Kowall, Hoon Ryu
Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Despite decades of study, effective treatments for AD are lacking. Mitochondrial dysfunction has been closely linked to the pathogenesis of AD, but the relationship between mitochondrial pathology and neuronal damage is poorly understood. Sirtuins (SIRT, silent mating type information regulation 2 homolog in yeast) are NAD-dependent histone deacetylases involved in aging and longevity. The objective of this study was to investigate the relationship between SIRT3 and mitochondrial function and neuronal activity in AD...
November 11, 2017: Aging Cell
https://www.readbyqxmd.com/read/29129747/mitochondrial-sirt3-and-neurodegenerative-brain-disorders
#4
REVIEW
Anamika, Archita Khanna, Papia Acharjee, Arup Acharjee, Surendra Kumar Trigun
Sirtuins are highly conserved NAD(+) dependent class III histone deacetylases and catalyze deacetylation and ADP ribosylation of a number of non-histone proteins. Since, they require NAD(+) for their activity, the cellular level of Sirtuins represents redox status of the cells and thereby serves as bona fide metabolic stress sensors. Out of seven homologues of Sirtuins identified in mammals, SIRT3, 4 & 5 have been found to be localized and active in mitochondria. During recent past, clusters of protein substrates for SIRT3 have been identified in mitochondria and thereby advocating SIRT3 as the main mitochondrial Sirtuin which could be involved in protecting stress induced mitochondrial integrity and energy metabolism...
November 9, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/29118033/trimethylamine-n-oxide-induces-vascular-inflammation-by-activating-the-nlrp3-inflammasome-through-the-sirt3-sod2-mtros-signaling-pathway
#5
(no author information available yet)
No abstract text is available yet for this article.
November 8, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29108235/regulation-of-sirt3-signal-related-metabolic-reprogramming-in-gastric-cancer-by-helicobacter-pylori-oncoprotein-caga
#6
Do Yeon Lee, Dawoon E Jung, Sung Sook Yu, Yeo Song Lee, Beom Ku Choi, Yong Chan Lee
Injection of the Helicobacter pylori cytotoxin-associated gene A (CagA) is closely associated with the development of chronic gastritis and gastric cancer. Individuals infected with H. pylori possessing the CagA protein produce more reactive oxygen species (ROS) and show an increased risk of developing gastric cancer. Sirtuins (SIRTs) are nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylases and mitochondrial SIRT3 is known to be a tumor suppressor via its ability to suppress ROS and hypoxia inducible factor 1α (HIF-1α)...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29103158/sirt3-deacetylates-and-promotes-degradation-of-p53-in-pten-defective-non-small-cell-lung-cancer
#7
Yanlu Xiong, Lei Wang, Shan Wang, Mingxing Wang, Jinbo Zhao, Zhipei Zhang, Xiaofei Li, Lintao Jia, Yong Han
PURPOSE: In non-small cell lung cancer (NSCLC), success of targeted therapy has promoted researches explicitly orientated based on genetic background. Although PTEN deficiency is common in NSCLC, carcinogenesis about such genetic type has not been fully explored. Here, we have found that classical tumor suppressor P53 could be modulated by deacetylase sirtuin-3 (SIRT3) depending on the PTEN condition in NSCLC, which may be a novel breakpoint for handling PTEN deficiency NSCLC. METHODS: First, we examined SIRT3 and P53 expression files in PTEN-deficient NSCLC clinical samples and investigated their correlation...
November 4, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29081897/mitochondrial-respiration-in-intact-peripheral-blood-mononuclear-cells-and-sirtuin-3-activity-in-patients-with-movement-disorders
#8
Slawomir Michalak, Jolanta Florczak-Wyspiańska, Joanna Rybacka-Mossakowska, Wojciech Ambrosius, Krystyna Osztynowicz, Aleksandra Baszczuk, Wojciech Kozubski, Ewa Wysocka
OBJECTIVE: Mitochondrial dysfunction is considered a unifying pathophysiological explanation for movement disorders. Sirtuin 3 (SIRT3) exhibits deacetylase activity and antioxidant properties. The aim of the study was to analyze the mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) and the SIRT3 activity in patients with movement disorders. METHODS: Mitochondrial respiration was analyzed in intact PBMCs using the ROUTINE, LEAK, electron transfer system (ETS), and residual oxygen consumption (ROX) protocol by means of high-resolution respirometry...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29081026/2-3-7-8-tetrachlorodibenzo-p-dioxin-influences-bovine-herpesvirus-1-replication-through-upregulation-of-sirt3-and-cytoskeletal-reorganization
#9
Filomena Fiorito, Valentina Iovane, Annarosaria Marullo, Anna Costagliola, Giovanna Elvira Granato, Luisa De Martino
Infection of kidney cells (MDBK) with Bovine Herpesvirus 1 (BoHV-1) is affected by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which accelerates BoHV-1-induced apoptosis and increases virus replication. Herein, to elucidate the mechanism through TCDD modifies BoHV-1 infection, we analyzed the modulation of a members of Sirtuin proteins family in MDBK cells. We found that mitochondrial SIRT3 was upregulated during infection. This change was accompanied by cytoskeletal rearrangements and cell extensions. All these trends were drastically modified by TCDD...
December 2017: Veterinary Research Communications
https://www.readbyqxmd.com/read/29076061/decreased-neuron-number-and-synaptic-plasticity-in-sirt3-knockout-mice-with-poor-remote-memory
#10
Hyopil Kim, Somi Kim, Ja Eun Choi, DaeHee Han, Soo Min Koh, Hyun-Seok Kim, Bong-Kiun Kaang
The sirtuin family of proteins consists of nicotinamide adenine dinucleotide-dependent deacetylases that are involved in the response to calorie restriction and various physiological phenomena, such as aging and cognition. One of these proteins, sirtuin 3 (SIRT3), is localized in the mitochondria and protects the cell against oxidative or metabolic stress. Sirtuin protein deficiencies have been shown to accelerate neurodegeneration in neurotoxic conditions. The mechanisms underlying the involvement of SIRT3 in cognition remain unclear...
October 26, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29072685/sirt3-protects-hepatocytes-from-oxidative-injury-by-enhancing-ros-scavenging-and-mitochondrial-integrity
#11
Jingxin Liu, Dan Li, Tian Zhang, Qiang Tong, Richard Dequan Ye, Ligen Lin
Evidences of oxidative stress and mitochondrial dysfunction have been recognized in most of clinical and experimental liver diseases. SIRT3, a member of NAD(+)-dependent deacetylases, is mainly localized in mitochondria. So far, the role of SIRT3 in protecting hepatocytes against oxidative stress remains elusive. Herein, we found SIRT3 protein expression is decreased in tert-butyl hydroperoxide (t-BHP)-treated AML12 cells in vitro and primary hepatocytes from CCl4-injured mice in vivo. To further verify the role of SIRT3 in protecting hepatocytes from t-BHP-induced injury, SIRT3 overexpressed AML12 cell line and primary hepatocytes were generated...
October 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29070699/inhibition-of-pyruvate-dehydrogenase-kinase-improves-pulmonary-arterial-hypertension-in-genetically-susceptible-patients
#12
Evangelos D Michelakis, Vikram Gurtu, Linda Webster, Gareth Barnes, Geoffrey Watson, Luke Howard, John Cupitt, Ian Paterson, Richard B Thompson, Kelvin Chow, Declan P O'Regan, Lan Zhao, John Wharton, David G Kiely, Adam Kinnaird, Aristeidis E Boukouris, Chris White, Jayan Nagendran, Darren H Freed, Stephen J Wort, J Simon R Gibbs, Martin R Wilkins
Pulmonary arterial hypertension (PAH) is a progressive vascular disease with a high mortality rate. It is characterized by an occlusive vascular remodeling due to a pro-proliferative and antiapoptotic environment in the wall of resistance pulmonary arteries (PAs). Proliferating cells exhibit a cancer-like metabolic switch where mitochondrial glucose oxidation is suppressed, whereas glycolysis is up-regulated as the major source of adenosine triphosphate production. This multifactorial mitochondrial suppression leads to inhibition of apoptosis and downstream signaling promoting proliferation...
October 25, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29064820/identification-of-polymorphisms-in-cancer-patients-that-differentially-affect-survival-with-age
#13
Aoife Doherty, Yelena Kernogitski, Alexander M Kulminski, João Pedro de Magalhães
The World Health Organization predicts that the proportion of the world's population over 60 will almost double from 12% to 22% between 2015 and 2050. Ageing is the biggest risk factor for cancer, which is a leading cause of deaths worldwide. Unfortunately, research describing how genetic variants affect cancer progression commonly neglects to account for the ageing process. Herein is the first systematic analysis that combines a large longitudinal data set with a targeted candidate gene approach to examine the effect of genetic variation on survival as a function of age in cancer patients...
October 20, 2017: Aging
https://www.readbyqxmd.com/read/29063982/role-of-beta-adrenergic-receptors-and-sirtuin-signaling-in-the-heart-during-aging-heart-failure-and-adaptation-to-stress
#14
REVIEW
Regina Celia Spadari, Claudia Cavadas, Ana Elisa T Saturi de Carvalho, Daniela Ortolani, Andre Luiz de Moura, Paula Frizera Vassalo
In the heart, catecholamine effects occur by activation of beta-adrenergic receptors (β-ARs), mainly the beta 1 (β1-AR) and beta 2 (β2-AR) subtypes, both of which couple to the Gs protein that activates the adenylyl cyclase signaling pathway. The β2-ARs can also couple to the Gi protein that counterbalances the effect of the Gs protein on cyclic adenosine monophosphate production and activates the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway. In several cardiovascular disorders, including heart failure, as well as in aging and in animal models of environmental stress, a reduction in the β1/β2-AR ratio and activation of the β2-AR-Gi-PI3K-Akt signaling pathway have been observed...
October 24, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29059204/alterations-of-sirtuins-in-mitochondrial-cytochrome-c-oxidase-deficiency
#15
Arne Björn Potthast, Theresa Heuer, Simone Johanna Warneke, Anibh Martin Das
BACKGROUND: Sirtuins are NAD+ dependent deacetylases, which regulate mitochondrial energy metabolism as well as cellular response to stress. The NAD/NADH-system plays a crucial role in oxidative phosphorylation linking sirtuins and the mitochondrial respiratory chain. Furthermore, sirtuins are able to directly deacetylate and activate different complexes of the respiratory chain. This prompted us to analyse sirtuin levels in skin fibroblasts from patients with cytochrome c-oxidase (COX) deficiency and to test the impact of different pharmaceutical activators of sirtuins (SRT1720, paeonol) to modulate sirtuins and possibly respiratory chain enzymes in patient cells in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/29042548/human-mesenchymal-stromal-cells-transplanted-into-mice-stimulate-renal-tubular-cells-and-enhance-mitochondrial-function
#16
Luca Perico, Marina Morigi, Cinzia Rota, Matteo Breno, Caterina Mele, Marina Noris, Martino Introna, Chiara Capelli, Lorena Longaretti, Daniela Rottoli, Sara Conti, Daniela Corna, Giuseppe Remuzzi, Ariela Benigni
Mesenchymal stromal cells (MSCs) are renoprotective and drive regeneration following injury, although cellular targets of such an effect are still ill-defined. Here, we show that human umbilical cord (UC)-MSCs transplanted into mice stimulate tubular cells to regain mitochondrial mass and function, associated with enhanced microtubule-rich projections that appear to mediate mitochondrial trafficking to create a reparative dialogue among adjacent tubular cells. Treatment with UC-MSCs in mice with cisplatin-induced acute kidney injury (AKI) regulates mitochondrial biogenesis in proximal tubuli by enhancing PGC1α expression, NAD(+) biosynthesis and Sirtuin 3 (SIRT3) activity, thus fostering antioxidant defenses and ATP production...
October 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29032377/microrna-210-modulates-the-cellular-energy-metabolism-shift-during-h2o2-induced-oxidative-stress-by-repressing-iscu-in-h9c2-cardiomyocytes
#17
Wei Sun, Lei Zhao, Xianjing Song, Jichang Zhang, Yue Xing, Ning Liu, Youyou Yan, Zhibo Li, Yang Lu, Junduo Wu, Longbo Li, Yanlong Xiao, Xin Tian, Tianyi Li, Yinuo Guan, Yiran Wang, Bin Liu
BACKGROUND/AIMS: The myocardial energy metabolism shift is one of the most important pathological features of ischemic heart disease (IHD). Although several microRNAs (miRs) are involved in the regulation of myocardial energy metabolism, their exact effects and underlying mechanisms remain unclear. The aim of this study was to investigate whether microRNA(miR-210) regulates the energy metabolism shift during oxidative stress in H9c2 cardiomyocytes. METHODS: Cell survival was analyzed via CCK assay...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29031725/intestinal-sirt3-overexpression-in-mice-improves-whole-body-glucose-homeostasis-independent-of-body-weight
#18
Deepti Ramachandran, Rosmarie Clara, Shahana Fedele, Junmin Hu, Endre Lackzo, Jing-Yi Huang, Eric Verdin, Wolfgang Langhans, Abdelhak Mansouri
OBJECTIVE: Intestinal metabolism might play a greater role in regulating whole body metabolism than previously believed. We aimed to enhance enterocyte metabolism in mice and investigate if it plays a role in diet-induced obesity (DIO) and its comorbidities. METHODS: Using the cre-loxP system, we overexpressed the mitochondrial NAD(+) dependent protein deacetylase SIRT3 in enterocytes of mice (iSIRT3 mice). We chronically fed iSIRT3 mice and floxed-SIRT3 control (S3fl) mice a low-fat, control diet (CD) or a high-fat diet (HFD) and then phenotyped the mice...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29030272/impact-of-fasting-followed-by-short-term-exposure-to-interleukin-6-on-cytochrome-p450-mrna-in-mice
#19
Martin Krøyer Rasmussen, Lærke Bertholdt, Anders Gudiksen, Henriette Pilegaard, Jakob G Knudsen
The gene expression of the cytochrome P450 (CYP) enzyme family is regulated by numerous factors. Fasting has been shown to induce increased hepatic CYP mRNA in both humans and animals. However, the coordinated regulation of CYP, CYP-regulating transcription factors, and transcriptional co-factors in the liver linking energy metabolism to detoxification has never been investigated. Interleukin-6 (IL-6) has been suggested to be released during fasting and has been shown to regulate CYP expression. The present study investigated the hepatic mRNA content of selected CYP, AhR, CAR, PXR and PPARα in mice fasted for 18h and subsequently exposed to IL-6...
October 10, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28989580/luteolin-and-fisetin-suppress-oxidative-stress-by-modulating-sirtuins-and-forkhead-box-o3a-expression-under-in-vitro-diabetic-conditions
#20
Arang Kim, Wooje Lee, Jung-Mi Yun
BACKGROUND/OBJECTIVE: Chronic hyperglycemia induces oxidative stress via accumulation of reactive oxygen species (ROS) and contributes to diabetic complications. Hyperglycemia induces mitochondrial superoxide anion production through the increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This study aimed to determine whether fisetin and luteolin treatments suppress the oxidative stress by modulating the expression of sirtuins (SIRTs) and forkhead box O3a (FOXO3a) under hyperglycemic conditions in human monocytes...
October 2017: Nutrition Research and Practice
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