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https://www.readbyqxmd.com/read/28088387/sirt2-mediated-antitumour-effects-of-shikonin-on-metastatic-colorectal-cancer
#1
Li-Li Zhang, Lin Zhan, Yong-Dong Jin, Zhen-Li Min, Can Wei, Qiang Wang, Ya-Jun Chen, Qing-Ming Wu, Xia-Min Hu, Qiong Yuan
SIRT2 is involved in the development of a variety of cancers. Shikonin is a natural compound that is known to have antitumour effects. This study aims to assess the effects of shikonin on the development and metastatic progression of colorectal cancer (CRC) through regulation of SIRT2 expression and whether this effect is related to the phosphorylation of extracellular signal-regulated kinases (ERKs). The results demonstrated that SIRT2 is downregulated in CRC biopsy samples (n = 31) compared with the adjacent non-cancerous tissues (ANCT, n = 26)...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28078537/sirt2-mediated-foxo3a-deacetylation-drives-its-nuclear-translocation-triggering-fasl-induced-cell-apoptosis-during-renal-ischemia-reperfusion
#2
Yan Wang, Yu Mu, Xiaorui Zhou, Huaixue Ji, Xing Gao, Wen Wen Cai, Qiuhua Guan, Tie Xu
We have found that Fas/FasL-mediated "extrinsic" pathway promoted cell apoptosis induced by renal ischemic injury. This study is to elucidate the upstream mechanism regulating FasL-induced extrinsic pathway during renal ischemia/reperfusion. Results demonstrated that when SIRT2 was activated by renal ischemia/reperfusion, activated SIRT2 could bind to and deacetylate FOXO3a, promoting FOXO3a nuclear translocation which resulted in an increase of nuclear FOXO3a along with FasL expression and activation of caspase8 and caspase3, triggering cell apoptosis during renal ischemia/reperfusion...
January 11, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28073696/spop-promotes-sirt2-degradation-and-suppresses-non-small-cell-lung-cancer-cell-growth
#3
Jie Luo, Yu-Chen Bao, Xian-Xiu Ji, Bin Chen, Qin-Fang Deng, Song-Wen Zhou
SIRT2 is a NAD-dependent deacetylase and inhibition of SIRT2 has a broad anticancer activity. Here we report that SPOP binds to SIRT2 and mediates its degradation by the 26S proteasome, which can be blocked by MG132 treatment. We also found that the levels of SPOP significantly decreased, while the levels of SIRT2 significantly increased in non-small cell lung cancer (NSCLC) cell lines, compared to normal bronchial epithelial cell line and NSCLC specimens, compared to the paired non-tumor lung tissue. Furthermore, SPOP can suppress NSCLC cell growth...
January 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28068403/normalisation-against-circadian-and-age-related-disturbances-enables-robust-detection-of-gene-expression-changes-in-liver-of-aged-mice
#4
Sara S Fonseca Costa, Daniel Wegmann, Jürgen A Ripperger
The expression of some genes is affected by age. To detect such age-related changes, their expression levels are related to constant marker genes. However, transcriptional noise increasing with advancing age renders difficult the identification of real age-related changes because it may affect the marker genes as well. Here, we report a selection procedure for genes appropriate to normalise the mouse liver transcriptome under various conditions including age. These genes were chosen from an initial set of 16 candidate genes defined based on a RNA-sequencing experiment and published literature...
2017: PloS One
https://www.readbyqxmd.com/read/28061480/co-ordinated-overexpression-of-sirt1-and-stat3-is-associated-with-poor-survival-outcome-in-gastric-cancer-patients
#5
Shu Zhang, Shuling Huang, Chao Deng, Yu Cao, Jun Yang, Guangxia Chen, Bin Zhang, Chaoqin Duan, Jiong Shi, Bo Kong, Helmut Friess, Nanyi Zhao, Chen Huang, Xiaoli Huang, Lei Wang, Xiaoping Zou
In many gastric cancer patients, the disease is diagnosed in an advanced stage and therefore the mortality levels are high. Because there is a need to identify novel early diagnostic and prognostic biomarkers, we tested whether SIRT1 and STAT3 are good candidates. Towards this, we used patient tissues representing different stages of gastric cancer including gastric pre-cancerous lesions, early gastric cancer, and advanced gastric cancer, and probed SIRT1, STAT3 and phosphorylated STAT3 (pSTAT3) levels using immunohistochemistry...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28053616/sirtuin-2-inhibition-affects-hippocampal-functions-and-sodium-butyrate-ameliorates-the-reduction-in-novel-object-memory-cell-proliferation-and-neuroblast-differentiation
#6
Hyo Young Jung, Dae Young Yoo, Jong Whi Kim, Dae Won Kim, Jung Hoon Choi, Jin Young Chung, Moo-Ho Won, Yeo Sung Yoon, In Koo Hwang
We investigated the effects of the sirtuin-2 (SIRT2) inhibitor AK-7 on novel object memory, cell proliferation, and neuroblast differentiation in the dentate gyrus. In addition, we also observed the relationships with sodium butyrate, a histone deacetylase inhibitor, on the hippocampal functions. To investigate the effects of AK-7 on hippocampal functions, 10-week-old C57BL/6 mice were daily injected intraperitoneally with 20 mg/kg AK-7 alone or in combination with subcutaneous administration of 300 mg/kg sodium butyrate, a histone deacetylase inhibitor, for 21 days...
December 2016: Laboratory Animal Research
https://www.readbyqxmd.com/read/28053092/histone-acetyltransferase-pcaf-is-required-for-all-trans-retinoic-acid-induced-granulocytic-differentiation-in-leukemia-cells
#7
Yoshitaka Sunami, Marito Araki, Shin Kan, Akihiro Ito, Yumi Hironaka, Misa Imai, Soji Morishita, Akimichi Ohsaka, Norio Komatsu
Differentiation therapy with all-trans retinoic acid (ATRA) improves the treatment outcome of acute promyelocytic leukemia (APL); however, the molecular mechanism by which ATRA induces granulocytic differentiation remains unclear. We previously reported that the inhibition of the NAD-dependent histone deacetylase (HDAC) SIRT2 induces granulocytic differentiation in leukemia cells, suggesting the involvement of protein acetylation in ATRA-induced leukemia cell differentiation. Herein, we showed that p300/CREB-binding protein-associated factor (PCAF), a histone acetyltransferase (HAT), is a prerequisite for ATRA-induced granulocytic differentiation in leukemia cells...
January 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27990725/structural-basis-of-sirtuin-6-activation-by-synthetic-small-molecules
#8
Weijie You, Dante Rotili, Tie-Mei Li, Christian Kambach, Marat Meleshin, Mike Schutkowski, Katrin F Chua, Antonello Mai, Clemens Steegborn
Sirtuins are protein deacylases regulating metabolism and stress responses, and are implicated in aging-related diseases. Small molecule activators for the human sirtuins Sirt1-7 are sought as chemical tools and potential therapeutics, such as for cancer. Activators are available for Sirt1 and exploit its unique N-terminus, whereas drug-like activators for Sirt2-7 are lacking. We synthesized and screened pyrrolo[1,2-a]quinoxaline derivatives, yielding the first synthetic Sirt6 activators. Biochemical assays show direct, substrate-independent compound binding to the Sirt6 catalytic core and potent activation of Sirt6-dependent deacetylation of peptide substrates and complete nucleosomes...
December 19, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27933951/identification-of-the-binding-site-of-chroman-4-one-based-sirtuin-2-selective-inhibitors-using-photoaffinity-labeling-in-combination-with-tandem-mass-spectrometry
#9
Tina Seifert, Marcus Malo, Johan Lengqvist, Carina Sihlbom, Elina M Jarho, Kristina Luthman
Photoaffinity labeling (PAL) was used to identify the binding site of chroman-4-one-based SIRT2-selective inhibitors. The photoactive diazirine 4, a potent SIRT2 inhibitor, was subjected to detailed photochemical characterization. In PAL experiments with SIRT2, a tryptic peptide originating from the covalent attachment of photoactivated 4 was identified. The peptide covers both the active site of SIRT2 and the proposed binding site of chroman-4-one-based inhibitors. A high-power LED was used as source for the monochromatic UV light enabling rapid photoactivation...
December 8, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27909079/ampk-and-sirt2-control-compensatory-glucose-uptake
#10
(no author information available yet)
No abstract text is available yet for this article.
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27882448/sirtuins-and-their-roles-in-brain-aging-and-neurodegenerative-disorders
#11
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
#12
Shengwei Zhang, Yanliang Jiang, Qi Cheng, Yi Zhong, 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 with 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...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27875273/sirt2-regulates-nuclear-envelope-reassembly-through-ankle2-deacetylation
#13
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...
December 15, 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
#14
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...
January 2017: 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
#15
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
#16
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
#17
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-upon-mitoenergetic-dysfunction-requires-lkb1-ampk-sirt2-and-mtor-raptor
#18
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 (also known as SLC2A1) mRNA or plasma membrane levels. The serine/threonine liver kinase B1 (LKB1; also known as STK11) and AMP-activated protein kinase (AMPK) played a central role in this stimulation...
December 1, 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
#19
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
#20
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
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