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https://www.readbyqxmd.com/read/28894448/sirtuin-2-deficiency-increases-bacterial-phagocytosis-by-macrophages-and-protects-from-chronic-staphylococcal-infection
#1
Eleonora Ciarlo, Tytti Heinonen, Charlotte Théroude, Jacobus Herderschee, Matteo Mombelli, Jérôme Lugrin, Marc Pfefferlé, Beatrice Tyrrell, Sarah Lensch, Hans Acha-Orbea, Didier Le Roy, Johan Auwerx, Thierry Roger
Sirtuin 2 (SIRT2) is one of the seven members of the family of NAD(+)-dependent histone deacetylases. Sirtuins target histones and non-histone proteins according to their subcellular localization, influencing various biological processes. SIRT2 resides mainly in the cytoplasm and regulates cytoskeleton dynamics, cell cycle, and metabolic pathways. As such, SIRT2 has been implicated in the pathogenesis of neurodegenerative, metabolic, oncologic, and chronic inflammatory disorders. This motivated the development of SIRT2-directed therapies for clinical purposes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28891317/the-role-of-sirtuins-in-antioxidant-and-redox-signaling
#2
Chandra K Singh, Gagan Chhabra, Mary Ndiaye, Liz Mariely Garcia-Peterson, Nicholas John Mack, Nihal Ahmad
SIGNIFICANCE: Antioxidant and redox signaling (ARS) events are regulated by critical molecules that modulate antioxidants, reactive oxygen or nitrogen species (ROS/RNS) and/or oxidative stress within the cell. Imbalances in these molecules can disturb cellular functions to become pathogenic. Sirtuins serve as important regulators of ARS in cells. Recent Advances: Sirtuins (SIRTs 1-7) are a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases with the ability to deacetylate histone and non-histone targets...
September 11, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28882678/rna-interference-mediated-knockdown-of-sirt1-and-or-sirt2-in-melanoma-identification-of-downstream-targets-by-large-scale-proteomics-analysis
#3
Melissa J Wilking-Busch, Mary A Ndiaye, Xiaoqi Liu, Nihal Ahmad
Melanoma is the most notorious and fatal of all skin cancers and the existing treatment options have not been proven to effectively manage this neoplasm, especially the metastatic disease. Sirtuin (SIRT) proteins have been shown to be differentially expressed in melanoma. We have shown that SIRTs 1 and 2 were overexpressed in melanoma and inhibition of SIRT1 imparts anti-proliferative responses in human melanoma cells. To elucidate the impact of SIRT 1 and/or 2 in melanoma, we created stable knockdowns of SIRTs 1, 2, and their combination using shRNA mediated RNA interference in A375 human melanoma cells...
September 4, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28857557/genetically-encoded-fluorescent-probe-for-detecting-sirtuins-in-living-cells
#4
Weimin Xuan, Anzhi Yao, Peter G Schultz
Sirtuins are NAD(+) dependent protein deacetylases, which are involved in many biological processes. We now report a novel genetically encoded fluorescent probe (EGFP-K85AcK) that responds to sirtuins in living cells. The probe design exploits a lysyl residue in EGFP that is essential for chromophore maturation, and is also an efficient deacetylation substrate for sirtuins. Analysis of activity in Escherichia coli ΔcobB revealed that the probe can respond to various human sirtuins, including SIRT1, SIRT2, SIRT3 and SIRT5...
August 31, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28828594/does-sirt2-regulate-cholesterol-biosynthesis-during-oligodendroglial-differentiation-in-vitro-and-in-vivo
#5
Merlin P Thangaraj, Kendra L Furber, LaRhonda Sobchishin, Shaoping Ji, J Ronald Doucette, Adil J Nazarali
Sirtuin2 (SIRT2) is a deacetylase enzyme predominantly expressed in myelinating glia of the central nervous system (CNS). We have previously demonstrated that Sirt2 expression enhances oligodendrocyte (OL) differentiation and arborization in vitro, but the molecular targets of SIRT2 in OLs remain speculative. SIRT2 has been implicated in cholesterol biosynthesis by promoting the nuclear translocation of sterol regulatory element binding protein (SREBP)-2. We investigated this further in CNS myelination by examining the role of Sirt2 in cholesterol biosynthesis in vivo and in vitro employing Sirt2 (-/-) mice, primary OL cells and CG4-OL cells...
August 21, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28819643/membrane-localization-of-acetylated-cnk1-mediates-a-positive-feedback-on-raf-erk-signaling
#6
Adrian Fischer, Wignand W D Mühlhäuser, Bettina Warscheid, Gerald Radziwill
Spatiotemporal control is a common mechanism that modulates activity and function of signal transducers in the signaling network. We identified acetylation of CNK1 (connector enhancer of kinase suppressor of Ras-1) as a late step in the activation of CNK1 signaling, accompanied with prolonged stimulation of extracellular signal-regulated kinase (ERK). We identified the acetyltransferase CREB (cyclic adenosine 3',5'-monophosphate response element-binding protein)-binding protein and the deacetylase SIRT2 (sirtuin type 2) as novel binding partners of CNK1, modulating the acetylation state of CNK1...
August 2017: Science Advances
https://www.readbyqxmd.com/read/28819322/nampt-enzyme-activity-regulates-catabolic-gene-expression-in-gingival-fibroblasts-during-periodontitis
#7
Ka Hyon Park, Duck-Kyu Kim, Yun Hyun Huh, Gyuseok Lee, Su-Hyeon Lee, Yunkyung Hong, Sun-Hun Kim, Min-Suk Kook, Jeong-Tae Koh, Jang-Soo Chun, Shee Eun Lee, Je-Hwang Ryu
Periodontal disease is one of the most prevalent chronic disorders worldwide. It is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss. Here, we focused on the role of adipokines, which are locally expressed by periodontal tissues, in the regulation of catabolic gene expression leading to periodontal inflammation. The expression of the nicotinamide phosphoribosyltransferase (NAMPT) adipokine was dramatically increased in inflamed human and mouse gingival tissues...
August 18, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28808139/differential-expression-of-sirtuin-2-and-adipocyte-maturation-restriction-an-adaptation-process-during-hypoxia-in-fish
#8
Padmini Ekambaram, Parimala Parasuraman
Sirtuins have received widespread attention due to their diverse physiological role in metabolism. Among sirtuins, SIRT2 is more abundant in adipocytes and exerts effects on adipocyte differentiation, a process which involves conversion of preadipocytes to mature adipocytes orchestrated by adipokines and adipogenic transcription factors. Grey mullet (Mugil cephalus) was chosen as a study organism due to its excellent service as a biomonitor. Adipocytes isolated from natural field conditions were termed as field-hypoxic (Ennore) and -normoxic (Kovalam) based on dissolved oxygen (DO) level in the estuary...
September 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28805748/synthesis-and-evaluation-of-novel-benzofuran-derivatives-as-selective-sirt2-inhibitors
#9
Yumei Zhou, Huaqing Cui, Xiaoming Yu, Tao Peng, Gang Wang, Xiaoxue Wen, Yunbo Sun, Shuchen Liu, Shouguo Zhang, Liming Hu, Lin Wang
A series of benzofuran derivatives were designed and synthesized, and their inhibitory activites were measured against the SIRT1-3. The enzymatic assay showed that all the compounds showed certain anti-SIRT2 activity and selective over SIRT1 and SIRT3 with IC50 (half maximal inhibitory concentration) values at the micromolar level. The preliminary structure-activity relationships were analyzed and the binding features of compound 7e (IC50 3.81 µM) was predicted using the CDOCKER program. The results of this research could provide informative guidance for further optimizing benzofuran derivatives as potent SIRT2 inhibitors...
August 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28793258/crucial-roles-for-sirt2-and-ampa-receptor-acetylation-in-synaptic-plasticity-and-memory
#10
Guan Wang, Shaomin Li, James Gilbert, Howard J Gritton, Zemin Wang, Zhangyuan Li, Xue Han, Dennis J Selkoe, Heng-Ye Man
AMPA receptors (AMPARs) mediate fast excitatory synaptic transmission and are crucial for synaptic plasticity, learning, and memory. However, the molecular control of AMPAR stability and its neurophysiological significance remain unclear. Here, we report that AMPARs are subject to lysine acetylation at their C termini. Acetylation reduces AMPAR internalization and degradation, leading to increased cell-surface localization and prolonged receptor half-life. Through competition for the same lysine residues, acetylation intensity is inversely related to the levels of AMPAR ubiquitination...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28776959/development-of-substrate-derived-sirtuin-inhibitors-with-potential-anticancer-activity
#11
Nora Kuhlmann, Constance Chollet, Linda Baldus, Ines Neundorf, Michael Lammers
RhoGDIα is a key regulator of Rho proteins, coordinating their GTP/GDP and membrane/cytosol cycle. Recently, it was demonstrated by quantitative mass spectrometry that RhoGDIα is heavily targeted by post-translational lysine acetylation. For one site in its N-terminal domain, namely K52, we reported earlier that acetylation completely switches off RhoGDIα function. Herein we show that K52-acetylated RhoGDIα is specifically deacetylated by the sirtuin deacetylase Sirt2. We show that acetylation at K52 decelerates cervical cancer cell proliferation, suggesting RhoGDIα acetylation to be a promising therapeutic target...
August 4, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28767699/molecular-evolutionary-patterns-of-nad-sirtuin-aging-signaling-pathway-across-taxa
#12
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/28756638/structure-based-discovery-of-new-selective-small-molecule-sirtuin-5-inhibitors
#13
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, six compounds displayed marked inhibitory activities against SIRT5. For the hit compound 19, a series of newly 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/28753589/differential-expression-of-tubulin-acetylase-and-deacetylase-between-the-damaged-central-and-peripheral-branch-of-dorsal-root-ganglion-neurons
#14
Zhiyi Fu, Jiangang Shi
BACKGROUND The differences between the peripheral and central branches of the dorsal root ganglion (DRG) have not been fully elucidated. This study aimed to explore the expression of tubulin post-translational modifications (acetylation and deacetylation) between damaged peripheral and central branches of DRG neurons. MATERIAL AND METHODS Fifty Sprague-Dawley rats were randomly assigned to five groups with 10 rats in each group. These five groups consisted of spinal nerve ligation (SNL) at 24 hour and 48 hour, and cauda equina compression (CEC) at 24 hour and 48 hour, and a sham group...
July 28, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28707980/extranuclear-sirtuins-and-metabolic-stress
#15
Mahmoud-Sobhy Elkhwanky, Jukka Hakkola
SIGNIFICANCE: Extranuclear sirtuins in cytosol (SIRT2) and mitochondria (SIRT3, SIRT4, and SIRT5) are key regulators of metabolic enzymes and the antioxidative defense mechanisms. They play an important role in the adjustment of metabolic pathways in alterations of the nutritional status. Recent Advances: Recent studies have shown that in addition to lysine deacetylation, sirtuins catalyze several different lysine deacylation reactions, removal of lipid modifications, and adenosine diphosphate-ribosylation...
August 11, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28683850/suppression-of-sirt2-and-altered-acetylation-status-of-human-pluripotent-stem-cells-possible-link-to-metabolic-switch-during-reprogramming
#16
Ok-Seon Kwon, Min-Joon Han, Hyuk-Jin Cha
Primed human pluripotent stem cells (hPSCs) are highly dependent on glycolysis rather than oxidative phosphorylation, which is similar to the metabolic switch that occurs in cancer cells. However, the molecular mechanisms that underlie this metabolic reprogramming in hPSCs and its relevance to pluripotency remain unclear. Cha et al. (2017) recently revealed that downregulation of SIRT2 by miR-200c enhances acetylation of glycolytic enzymes and glycolysis, which in turn facilitates cellular reprogramming, suggesting that SIRT2 is a key enzyme linking the metabolic switch and pluripotency in hPSCs...
July 7, 2017: BMB Reports
https://www.readbyqxmd.com/read/28638677/changes-in-sirtuin-2-and-sirtuin-3-mrna-expressions-in-rheumatoid-arthritis
#17
Murat Kara, Servet Yolbaş, Cem Şahin, Süleyman Serdar Koca
OBJECTIVE: Sirtuins (SIRTs) play a prominent role in metabolism, apoptosis, aging, inflammation, and epigenetics. Inflammation, apoptosis, and epigenetics are pathogenic issues in rheumatoid arthritis (RA). This study aimed to evaluate SIRT2 and SIRT3 mRNA expressions in patients with RA. MATERIAL AND METHODS: Fifty-four patients with RA and 26 healthy controls were enrolled. Disease activity was determined using the disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) (score of >2...
June 2017: European Journal of Rheumatology
https://www.readbyqxmd.com/read/28634568/sirtuin-2-protects-neural-cells-from-oxidative-stress-and-is-elevated-in-neurodegeneration
#18
Preeti Singh, Peter S Hanson, Christopher M Morris
Sirtuins are highly conserved lysine deacetylases involved in ageing, energy production, and lifespan extension. The mammalian SIRT2 has been implicated in Parkinson's disease (PD) where studies suggest SIRT2 promotes neurodegeneration. We therefore evaluated the effects of SIRT2 manipulation in toxin treated SH-SY5Y cells and determined the expression and activity of SIRT2 in postmortem brain tissue from patients with PD. SH-SY5Y viability in response to oxidative stress induced by diquat or rotenone was measured following SIRT2 overexpression or inhibition of deacetylase activity, along with α-synuclein aggregation...
2017: Parkinson's Disease
https://www.readbyqxmd.com/read/28628306/lysine-deacetylation-by-hdac6-regulates-the-kinase-activity-of-akt-in-human-neural-progenitor-cells
#19
Jonathan Iaconelli, Jasmin Lalonde, Bradley Watmuff, Bangyan Liu, Ralph Mazitschek, Stephen J Haggarty, Rakesh Karmacharya
The AKT family of serine-threonine kinases functions downstream of phosphatidylinositol 3-kinase (PI3K) to transmit signals by direct phosphorylation of a number of targets, including the mammalian target of rapamycin (mTOR), glycogen synthase kinase 3β (GSK3β), and β-catenin. AKT binds to phosphatidylinositol (3,4,5)-triphosphate (PIP3) generated by PI3K activation, which results in its membrane localization and subsequent activation through phosphorylation by phosphoinositide-dependent protein kinase 1 (PDK1)...
July 10, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28602396/mycoplasma-fermentans-deacetylase-promotes-mammalian-cell-stress-tolerance
#20
Qingzhou Cheng, Lijuan Wu, Rongfu Tu, Jun Wu, Wenqian Kang, Tong Su, Runlei Du, Wenbin Liu
Mycoplasma fermentans is a pathogenic bacterium that infects humans and has potential pathogenic roles in respiratory, genital and rheumatoid diseases. NAD(+)-dependent deacetylase is involved in a wide range of pathophysiological processes and our studies have demonstrated that expression of mycoplasmal deacetylase in mammalian cells inhibits proliferation but promotes anti-starvation stress tolerance. Furthermore, mycoplasmal deacetylase is involved in cellular anti-oxidation, which correlates with changes in the proapoptotic proteins BIK, p21 and BIM...
August 2017: Microbiological Research
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