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https://www.readbyqxmd.com/read/28188285/rna-binding-protein-quaking-stabilizes-sirt2-mrna-during-oligodendroglial-differentiation
#1
Merlin P Thangaraj, Kendra L Furber, Jotham K Gan, Shaoping Ji, Larhonda Sobchishin, J Ronald Doucette, Adil J Nazarali
Myelination is controlled by timely expression of genes involved in the differentiation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes (OLs). Sirtuin 2 (SIRT2), a NAD+-dependent deacetylase, plays a critical role in OL differentiation by promoting both arborization and downstream expression of myelin specific genes. However, the mechanisms involved in regulating SIRT2 expression during OL development are largely unknown. The RNA binding protein Quaking (QKI) plays an important role in myelination by post-transcriptionally regulating the expression of several myelin specific genes...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28185898/sirt2-inhibition-modulate-glutamate-and-serotonin-systems-in-the-prefrontal-cortex-and-induces-antidepressant-like-action
#2
Mercedes Erburu, Irene Muñoz-Cobo, Teresa Diaz-Perdigon, Paolo Mellini, Takayoshi Suzuki, Elena Puerta, Rosa M Tordera
Growing evidence suggests that changes in histone acetylation in specific sites of the chromatin modulate neuronal plasticity and contribute to antidepressant-like action. Sirtuin 2 (SIRT2) is a class III NAD(+)-dependent histone deacetylase involved in transcriptional repression of genes regulating synaptic plasticity. Importantly, a key role for the glutamate system in prefrontal cortex (PFC) synaptic plasticity changes induced by antidepressants has been suggested. Here, we asked whether SIRT2 could be a pharmacological target for depression therapy...
February 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28166441/expression-profile-of-sirt2-in-human-melanoma-and-implications-for-sirtuin-based-chemotherapy
#3
Melissa Jean Wilking-Busch, Mary Ann Ndiaye, Wei Huang, Nihal Ahmad
Melanoma is cancer of melanin-containing melanocyte cells. This neoplasm is one of the most deadly forms of skin cancer, and currently available therapeutic options are insufficient in significantly improve outcomes for many patients. Therefore, novel targets are required to effectively manage this neoplasm. Several sirtuins have previously been found to be upregulated in melanoma, so in this study, the expression profile of SIRT2 was determined. Employing a tissue microarray containing benign nevi, primary melanomas, and lymph node metastases, we have found that the tissue from lymph node metastases appears to have a significant upregulation of SIRT2 relative to primary tumors across the nuclear, cytoplasmic, and whole cell data...
February 6, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28135086/thienopyrimidinone-based-sirtuin-2-sirt2-selective-inhibitors-bind-in-the-ligand-induced-selectivity-pocket
#4
Sandeep Sundriyal, Sébastien Moniot, Zimam Mahmud, Shang Yao, Paolo Di Fruscia, Christopher R Reynolds, David T Dexter, Michael J E Sternberg, Eric W-F Lam, Clemens Steegborn, Matthew J Fuchter
Sirtuins (SIRTs) are NAD-dependent deacylases, known to be involved in a variety of pathophysiological processes and thus remain promising therapeutic targets for further validation. Previously, we reported a novel thienopyrimidinone SIRT2 inhibitor with good potency and excellent selectivity for SIRT2. Herein, we report an extensive SAR study of this chemical series and identify the key pharmacophoric elements and physiochemical properties that underpin the excellent activity observed. New analogues have been identified with submicromolar SIRT2 inhibtory activity and good to excellent SIRT2 subtype-selectivity...
February 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28127057/sirtinol-promotes-pepck1-degradation-and-inhibits-gluconeogenesis-by-inhibiting-deacetylase-sirt2
#5
Mingming Zhang, Yida Pan, Robert G Dorfman, Yuyao Yin, Qian Zhou, Shan Huang, Jie Liu, Shimin Zhao
Phosphoenolpyruvate carboxykinase 1 (PEPCK1) is the critical enzyme for gluconeogenesis and is linked with type II diabetes. Previous studies have found that SIRT2, a deacetylase, plays an important role in deacetylating PEPCK1 and little is known about the anti-diabetic activity of SIRT2 inhibitors. In this study, we investigated the anti-diabetic effects of sirtinol, a SIRT2 inhibitor, on cell gluconeogenesis in vivo and in vitro. Immunoblotting analysis revealed that sirtinol significantly decreased the protein level of PEPCK1, and was accompanied by the hyperacetylation of PEPCK1 as well as decreased glucose output in a dose-dependent manner...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28103679/histone-ketoamide-adduction-by-4-oxo-2-nonenal-is-a-reversible-posttranslational-modification-regulated-by-sirt2
#6
LETTER
Yiwen Cui, Xin Li, Jianwei Lin, Quan Hao, Xiang David Li
Lipid-derived electrophiles (LDEs) directly modify proteins to modulate cellular signaling pathways in response to oxidative stress. One such LDE, 4-oxo-2-nonenal (4-ONE), has recently been found to target histones and interfere with histone assembly into nucleosomes. Unlike other LDEs that preferentially modify cysteine via nucleophilic Michael addition, 4-ONE reacts with histone lysine residues to form a new histone modification, gamma-oxononanoylation (Kgon). However, it remains unclear whether Kgon can cause irreversible damage or be regulated by enzymes "erasing" this nonenzymatic modification...
20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28088387/sirt2-mediated-antitumor-effects-of-shikonin-on-metastatic-colorectal-cancer
#7
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 antitumor 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 12, 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
#8
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
#9
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
#10
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
#11
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
#12
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-p300-creb-binding-protein-associated-factor-pcaf-is-required-for-all-trans-retinoic-acid-induced-granulocytic-differentiation-in-leukemia-cells
#13
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 show that p300/CREB-binding protein-associated factor (PCAF), a histone acetyltransferase (HAT), is a prerequisite for ATRA-induced granulocytic differentiation in leukemia cells...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27990725/structural-basis-of-sirtuin-6-activation-by-synthetic-small-molecules
#14
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
#15
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
#16
(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
#17
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
#18
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
#19
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
#20
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
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