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https://www.readbyqxmd.com/read/27882448/sirtuins-and-their-roles-in-brain-aging-and-neurodegenerative-disorders
#1
Henryk Jęśko, Przemysław Wencel, Robert P Strosznajder, Joanna B Strosznajder
Sirtuins (SIRT1-SIRT7) are unique histone deacetylases (HDACs) whose activity depends on NAD(+) levels and thus on the cellular metabolic status. SIRTs regulate energy metabolism and mitochondrial function. They orchestrate the stress response and damage repair. Through these functions sirtuins modulate the course of aging and affect neurodegenerative diseases. SIRTSs interact with multiple signaling proteins, transcription factors (TFs) and poly(ADP-ribose) polymerases (PARPs) another class of NAD(+)-dependent post-translational protein modifiers...
November 24, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27881643/inclusion-body-fusion-of-human-parainfluenza-virus-type-3-regulated-by-acetylated-%C3%AE-tubulin-enhances-viral-replication
#2
Shengwei Zhang, Yanliang Jiang, Qi Cheng, Zhong Yi, Yali Qin, Mingzhou Chen
: Viral inclusion bodies (IBs) or replication factories are unique structures generated by viral proteins together with some cellular proteins as a platform for efficient viral replication, but little is known about the mechanism underlying IB formation and fusion. Our previous study demonstrated that the interaction between the nucleoprotein (N) and phosphoprotein (P) of human parainfluenza virus type 3 (HPIV3), an enveloped virus of great medical impact, can form IBs. In this study, we found that small IBs can fuse with each other to form large IBs that enhance viral replication...
November 23, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27875273/sirt2-regulates-nuclear-envelope-reassembly-via-ankle2-deacetylation
#3
Tanja Kaufmann, Eva Kukolj, Andreas Brachner, Etienne Beltzung, Melania Bruno, Sebastian Kostrhon, Susanne Opravil, Otto Hudecz, Karl Mechtler, Graham Warren, Dea Slade
Sirtuin 2 (SIRT2) is an NAD-dependent deacetylase known to regulate microtubule dynamics and cell cycle progression. SIRT2 has also been implicated in the pathology of cancer, neurodegenerative diseases and progeria. Here we show that SIRT2 depletion or overexpression causes nuclear envelope reassembly defects. We link this phenotype to the recently identified regulator of nuclear envelope reassembly ANKLE2. ANKLE2 acetylation at K302 and phosphorylation at S662 are dynamically regulated throughout the cell cycle by SIRT2 and are essential for normal nuclear envelope reassembly...
November 14, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27833050/eicosapentaenoic-acid-regulates-brown-adipose-tissue-metabolism-in-high-fat-fed-mice-and-in-clonal-brown-adipocytes
#4
Mandana Pahlavani, Fitia Razafimanjato, Latha Ramalingam, Nishan S Kalupahana, Hanna Moussa, Shane Scoggin, Naima Moustaid-Moussa
Brown adipose tissue (BAT) plays a key role in energy expenditure through its specialized thermogenic function. Therefore, BAT activation may help prevent and/or treat obesity. Interestingly, subcutaneous white adipose tissue (WAT) also has the ability to differentiate into brown-like adipocytes and may potentially contribute to increased thermogenesis. We have previously reported that eicosapentaenoic acid (EPA) reduces high-fat (HF)-diet-induced obesity and insulin resistance in mice. Whether BAT mediates some of these beneficial effects of EPA has not been determined...
September 22, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27823629/javamide-i-o-methyl-ester-increases-p53-acetylation-and-induces-cell-death-via-activating-caspase-3-7-in-monocytic-thp-1-cells
#5
Jae B Park
BACKGROUND: Javamide-I and-II are phenolic amide compounds found in Coffea sp. Previous study suggested that javamide-II may be a potent compound with Sirt1/2 inhibition activity. PURPOSE: However, the effects of javamide-I and the its O-methyl ester on Sirt inhibition, p53 acetylation and cell death have not been investigated. METHODS: The isolation and synthesis of javamide-I and its O-methyl ester analogue were confirmed by NMR. Their potential effects on Sirt1/2/3, p53 acetylation and cell death were examined using sirt assay, silico analysis, Western blot, caspase 3/7 and apoptotic assay methods...
December 1, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27803663/environmental-enrichment-modified-epigenetic-mechanisms-in-samp8-mouse-hippocampus-by-reducing-oxidative-stress-and-inflammaging-and-achieving-neuroprotection
#6
Christian Griñan-Ferré, Dolors Puigoriol-Illamola, Verónica Palomera-Ávalos, David Pérez-Cáceres, Júlia Companys-Alemany, Antonio Camins, Daniel Ortuño-Sahagún, M Teresa Rodrigo, Mercè Pallàs
With the increase in life expectancy, aging and age-related cognitive impairments are becoming one of the most important issues for human health. At the same time, it has been shown that epigenetic mechanisms are emerging as universally important factors in life expectancy. The Senescence Accelerated Mouse P8 (SAMP8) strain exhibits age-related deterioration evidenced in learning and memory abilities and is a useful model of neurodegenerative disease. In SAMP8, Environmental Enrichment (EE) increased DNA-methylation levels (5-mC) and reduced hydroxymethylation levels (5-hmC), as well as increased histone H3 and H4 acetylation levels...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27796760/downregulation-of-nad-dependent-deacetylase-sirt2-protects-mouse-brain-against-ischemic-stroke
#7
Xiao Qiang Xie, Pei Zhang, Bo Tian, Xiao Qian Chen
Sirtuin 2 (SIRT2) is a member of NAD(+)-dependent protein deacetylases involved in a wide range of pathophysiological processes including myocardial injury, Parkinson's disease, and Huntington's disease. However, the direct implication of SIRT2 in ischemic stroke is still unclear. In the present study, we observed that SIRT2 protein was mainly expressed in the cytoplasm of neurons, but not in astrocyte and microglia. SIRT2 was upregulated in ischemic neurons in the oxygen-glucose deprivation cell model and in the transient middle cerebral artery occlusion (tMCAo) mouse model...
October 29, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27793977/acute-stimulation-of-glucose-influx-by-mitoenergetic-dysfunction-requires-lkb1-ampk-sirt2-and-mtor-raptor
#8
Dania C Liemburg-Apers, Jori A L Wagenaars, Jan A M Smeitink, Peter H G M Willems, Werner J H Koopman
Mitochondria play a central role in cellular energy production and their dysfunction can trigger a compensatory increase in glycolytic flux to sustain cellular ATP levels. Here we studied the mechanism of this homeostatic phenomenon in C2C12 myoblasts. Acute (30 min) mitoenergetic dysfunction induced by the mitochondrial inhibitors piericidin A and antimycin A, stimulated Glut1-mediated glucose uptake without altering Glut1 mRNA or plasma membrane levels. The serine/threonine liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK) played a central role in this stimulation...
October 28, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27785339/sirt2-plays-a-significant-role-in-maintaining-the-survival-and-energy-metabolism-of-piec-endothelial-cells
#9
Jie Zhang, Caixia Wang, Hui Nie, Danhong Wu, Weihai Ying
SIRT2, a member of the sirtuin (SIRT1-7) family, is a tubulin deacetylase. It has been reported that SIRT2 mediates cellular stress responses and is highly expressed in vascular endothelial cells, while its roles in cell survival and energy metabolism of endothelial cells remain unknown. In the current study, we tested our hypothesis that SIRT2 plays an important role in the cell survival and energy metabolism of endothelial cells, using a porcine vascular endothelial cell line (PIEC) as a cellular model. Our study showed that both SIRT2 inhibitor AGK2 and SIRT2 siRNA led to a significant reduction of the cell survival of PIEC cells...
2016: International Journal of Physiology, Pathophysiology and Pharmacology
https://www.readbyqxmd.com/read/27783945/the-sirt2-deacetylase-stabilizes-slug-to-control-malignancy-of-basal-like-breast-cancer
#10
Wenhui Zhou, Thomas K Ni, Ania Wronski, Benjamin Glass, Adam Skibinski, Andrew Beck, Charlotte Kuperwasser
Overabundance of Slug protein is common in human cancer and represents an important determinant underlying the aggressiveness of basal-like breast cancer (BLBC). Despite its importance, this transcription factor is rarely mutated in BLBC, and the mechanism of its deregulation in cancer remains unknown. Here, we report that Slug undergoes acetylation-dependent protein degradation and identify the deacetylase SIRT2 as a key mediator of this post-translational mechanism. SIRT2 inhibition rapidly destabilizes Slug, whereas SIRT2 overexpression extends Slug stability...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27762282/application-of-targeted-mass-spectrometry-for-the-quantification-of-sirtuins-in-the-central-nervous-system
#11
T Jayasena, A Poljak, N Braidy, L Zhong, B Rowlands, J Muenchhoff, R Grant, G Smythe, C Teo, M Raftery, P Sachdev
Sirtuin proteins have a variety of intracellular targets, thereby regulating multiple biological pathways including neurodegeneration. However, relatively little is currently known about the role or expression of the 7 mammalian sirtuins in the central nervous system. Western blotting, PCR and ELISA are the main techniques currently used to measure sirtuin levels. To achieve sufficient sensitivity and selectivity in a multiplex-format, a targeted mass spectrometric assay was developed and validated for the quantification of all seven mammalian sirtuins (SIRT1-7)...
October 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27725455/identification-of-a-selective-sirt2-inhibitor-and-its-anti-breast-cancer-activity
#12
Asad Ali Shah, Akihiro Ito, Akiko Nakata, Minoru Yoshida
SIRT2 is a member of the human sirtuin family of proteins and possesses nicotinamide adenine dinucleotide (NAD)-dependent lysine deacetylase activity. SIRT2 has been involved in various cellular processes including gene transcription, genome constancy, and the cell cycle. In addition, SIRT2 is deeply implicated in diverse diseases including cancer. In this study, we identified a small molecule inhibitor of SIRT2 with a structure different from known SIRT2 inhibitors by screening from a chemical library. The hit compound showed a high selectivity toward SIRT2 as it only inhibited SIRT2, and not other sirtuins including SIRT1 and SIRT3 or zinc-dependent histone deacetylases (HDACs) including HDAC1 and HDAC6, in vitro...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27711253/hspb1-enhances-sirt2-mediated-g6pd-activation-and-promotes-glioma-cell-proliferation
#13
Hongxing Ye, Hongguang Huang, Fei Cao, Mantao Chen, Xiujue Zheng, Renya Zhan
Heat shock proteins belong to a conserved protein family and are involved in multiple cellular processes. Heat shock protein 27 (Hsp27), also known as heat HSPB1, participates in cellular responses to not only heat shock, but also oxidative or chemical stresses. However, the contribution of HSPB1 to anti-oxidative response remains unclear. Here, we show that HSPB1 activates G6PD in response to oxidative stress or DNA damage. HSPB1 enhances the binding between G6PD and SIRT2, leading to deacetylation and activation of G6PD...
2016: PloS One
https://www.readbyqxmd.com/read/27697532/pep-1-sirt2-induced-matrix-metalloproteinase-1-and-13-modulates-type-ii-collagen-expression-via-erk-signaling-in-rabbit-articular-chondrocytes
#14
Seong-Hui Eo, Soo Young Choi, Song Ja Kim
Matrix metalloproteinases (MMPs) are critical for the degradation of the extracellular matrix (ECM), which includes cartilage-specific collagen types I, II and XI. We previously found that PEP-1-sirtuin (SIRT)2 could induce dedifferentiation of articular chondrocytes; however, the underlying mechanisms remains unclear. We addressed this in the present study by examining the association between PEP-1-SIRT2 and the expression of MMP-1 and MMP-13 and type II collagen in rabbit articular chondrocytes. We found that PEP-1-SIRT2 increased MMP-1 and -13 expression in a dose- and time-dependent manner, as determined by western blotting...
November 1, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27687219/resistance-training-and-redox-homeostasis-correlation-with-age-associated-genomic-changes
#15
Ivan Dimauro, Mattia Scalabrin, Cristina Fantini, Elisa Grazioli, Maria Reyes Beltran Valls, Neri Mercatelli, Attilio Parisi, Stefania Sabatini, Luigi Di Luigi, Daniela Caporossi
Regular physical activity is effective as prevention and treatment for different chronic conditions related to the ageing processes. In fact, a sedentary lifestyle has been linked to a worsening of cellular ageing biomarkers such as telomere length (TL) and/or specific epigenetic changes (e.g. DNA methylation), with increase of the propensity to aging-related diseases and premature death. Extending our previous findings, we aimed to test the hypothesis that 12 weeks of low frequency, moderate intensity, explosive-type resistance training (EMRT) may attenuate age-associated genomic changes...
September 21, 2016: Redox Biology
https://www.readbyqxmd.com/read/27637077/sirt2-deletion-enhances-kras-induced-tumorigenesis-in-vivo-by-regulating-k147-acetylation-status
#16
Ha Yong Song, Marco Biancucci, Hong-Jun Kang, Carol O'Callaghan, Seong-Hoon Park, Daniel R Principe, Haiyan Jiang, Yufan Yan, Karla Fullner Satchell, Kirtee Raparia, David Gius, Athanassios Vassilopoulos
The observation that cellular transformation depends on breaching a crucial KRAS activity threshold, along with the finding that only a small percentage of cellsharboring KRAS mutations are transformed, support the idea that additional, not fully uncovered, regulatory mechanisms may contribute to KRAS activation. Here we report that KrasG12D mice lacking Sirt2 show an aggressive tumorigenic phenotype as compared to KrasG12D mice. This phenotype includes increased proliferation, KRAS acetylation, and activation of RAS downstream signaling markers...
September 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27628218/a-novel-role-for-sirt3-in-regulating-mediators-involved-in-the-terminal-pathways-of-human-labor-and-delivery
#17
Ratana Lim, Gillian Barker, Ramkumar Menon, Martha Lappas
Preterm birth remains the major cause of neonatal mortality and morbidity, mediated largely by an inflammatory process. The sirtuin (SIRT) family of cellular regulators have been implicated as key inhibitors of inflammation. We have previously reported a role for SIRT1, SIRT2 and SIRT6 in regulating inflammation-induced pro-labor mediators. In this study, we determined the effect of term labor and pro-inflammatory cytokines on SIRT3, SIRT4, SIRT5 and SIRT7 expression in human myometrium. Functional studies were also employed to investigate the effect of siRNA knockdown of SIRTs in regulating inflammation-induced pro-labor mediators...
September 14, 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/27610633/sirt2-reverses-4-oxononanoyl-lysine-modification-on-histones
#18
Jing Jin, Bin He, Xiaoyu Zhang, Hening Lin, Yi Wang
Post-translational modifications (PTMs) regulate numerous proteins and are important for many biological processes. Lysine 4-oxononanoylation (4-ONylation) is a newly discovered histone PTM that prevents nucleosome assembly under oxidative stress. Whether there are cellular enzymes that remove 4-ONyl from histones remains unknown, which hampers the further investigation of the cellular function of this PTM. Here, we report that mammalian SIRT2 can remove 4-ONyl from histones and other proteins in live cells...
September 28, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27586085/sirt2-activates-g6pd-to-enhance-nadph-production-and-promote-leukaemia-cell-proliferation
#19
Shuang-Nian Xu, Tian-Shi Wang, Xi Li, Yi-Ping Wang
Like most other types of cancer cells, leukaemia cells undergo metabolic reprogramming to support rapid proliferation through enhancing biosynthetic processes. Pentose phosphate pathway (PPP) plays a pivotal role in meeting the anabolic demands for cancer cells. However, the molecular mechanism by which PPP contributes to leukaemia remains elusive. Here, we report that leukaemia cell proliferation is dependent on the oxidative branch of PPP, in particular the first and rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD)...
September 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27542094/fluorescence-probe-for-imaging-sirtuin-activity-in-living-cells-based-on-one-step-cleavage-of-dabcyl-quencher
#20
Mitsuyasu Kawaguchi, Shohei Ikegawa, Naoya Ieda, Hidehiko Nakagawa
Sirtuins (SIRTs) are a family of NAD+-dependent histone deacetylases. In mammals, dysfunction of SIRTs is associated with age-related metabolic diseases and cancers, so SIRT modulators are considered attractive therapeutic targets. However, current screening methodologies are problematic, and no tools are available for imaging endogenous SIRT activity in living cells. In this work, we present a series of simple and highly sensitive novel SIRT activity probes. Fluorescence of these probes is activated by SIRT-mediated hydrolytic release of a 4-(4-dimethylaminophenylazo)benzoyl (Dabcyl)-based FRET quencher moiety from the -amino group of lysine in a histone H3K9-derived nonapeptide bearing a C-terminal fluorophore...
August 19, 2016: Chembiochem: a European Journal of Chemical Biology
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