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https://www.readbyqxmd.com/read/28533215/inhibition-of-hdac3-prevents-diabetic-cardiomyopathy-in-ove26-mice-via-epigenetic-regulation-of-dusp5-erk1-2-pathway
#1
Zheng Xu, Qian Tong, Zhiguo Zhang, Shudong Wang, Yang Zheng, Qiuju Liu, Lingbo Qian, Shao-Yu Chen, Jian Sun, Lu Cai
Inhibition of total histone deacetylases (HDACs) was phenomenally associated with the prevention of diabetic cardiomyopathy (DCM). However, which specific HDAC plays the key role in DCM remains unclear. The present study was designed to determine whether DCM can be prevented by specific inhibition of HDAC3 and to elucidate the mechanisms by which inhibition of HDAC3 prevent DCM. Type 1 diabetes OVE26 and age-matched wild-type mice were given the selective HDAC3 inhibitor RGFP966 or vehicle for 3 months. These mice were then sacrificed immediately or 3 months later for cardiac function and pathological examination...
May 22, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28532786/fluxomic-evidence-for-impaired-contribution-of-short-chain-acyl-coa-dehydrogenase-to-mitochondrial-palmitate-%C3%AE-oxidation-in-symptomatic-patients-with-acads-gene-susceptibility-variants
#2
Anne-Frédérique Dessein, Monique Fontaine, Marie Joncquel Chevalier Curt, Gilbert Briand, Claire Sechter, Karine Mention-Mulliez, Dries Dobbelaere, Claire Douillard, Arnaud Lacour, Isabelle Redonnet-Vernhet, Delphine Lamireau, Magalie Barth, Marie-Christine Minot-Myhié, Alice Kuster, Pascale de Lonlay, Niels Gregersen, Cécile Acquaviva, Christine Vianey-Saban, Joseph Vamecq
BACKGROUND: Despite ACADS (acyl-CoA dehydrogenase, short-chain) gene susceptibility variants (c.511C>T and c.625G>A) are considered to be non-pathogenic, encoded proteins are known to exhibit altered kinetics. Whether or not, they might affect overall fatty acid β-oxidation still remains, however, unclear. METHODS: De novo biosynthesis of acylcarnitines by whole blood samples incubated with deuterated palmitate (16-(2)H3,15-(2)H2-palmitate) is suitable as a fluxomic exploration to distinguish between normal and disrupted β-oxidation, abnormal profiles and ratios of acylcarnitines with different chain-lengths being indicative of the site for enzymatic blockade...
May 19, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28531371/wing-1-of-protein-hop2-is-as-important-as-helix-3-in-dna-binding-by-md-simulation
#3
Hem Moktan, Donghua H Zhou
The repair of programmed DNA double-strand breaks through recombination is required for proper association and disjunction of the meiotic homologous chromosomes. Meiosis specific protein HOP2 plays essential roles in recombination by promoting recombinase activities. The N-terminal domain of HOP2 interacts with DNA through helix 3 (H3) and wing 1 (W1). Mutations in wing 1 (Y65A/K67A/Q68A) slightly weakened the binding but mutations in helices 2 and 3 (Q30A/K44A/K49A) nearly abolished the binding. To better understand such differential effects at atomic level, molecular dynamics simulations were employed...
May 20, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28529042/optimization-and-biological-evaluation-of-2-aminobenzothiazole-derivatives-as-aurora-b-kinase-inhibitors
#4
Eun Lee, Ying An, Junhee Kwon, Keun Il Kim, Raok Jeon
A strong relationship between abnormal functions of Aurora kinases and tumorigenesis has been reported for decades. Consequently, Aurora kinases serve as potential targets for anticancer agents. Here, we identified aminobenzothiazole derivatives as novel inhibitors of Aurora B kinase through bioisosteric replacement of the previous inhibitors, aminobenzoxazole derivatives. Most of the urea-linked aminobenzothiazole derivatives showed potent and selective inhibitory activity against Aurora B kinase over Aurora A kinase...
April 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28521864/insulin-induced-inhibition-of-gluconeogenesis-genes-including-glutamic-pyruvic-transaminase-2-is-associated-with-reduced-histone-acetylation-in-a-human-liver-cell-line
#5
Kazue Honma, Michiko Kamikubo, Kazuki Mochizuki, Toshinao Goda
OBJECTIVES: Hepatic glutamic pyruvic transaminase (GPT; also known as alanine aminotransferase) is a gluconeogenesis enzyme that catalyzes conversions between alanine and pyruvic acid. It is also used as a blood biomarker for hepatic damage. In this study, we investigated whether insulin regulates GPT expression, as it does for other gluconeogenesis genes, and if this involves the epigenetic modification of histone acetylation. METHODS: Human liver-derived HepG2 cells were cultured with 0...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28513992/immunoregulatory-protein-b7-h3-promotes-growth-and-decreases-sensitivity-to-therapy-in-metastatic-melanoma-cells
#6
Karine Flem-Karlsen, Christina Tekle, Yvonne Andersson, Kjersti Flatmark, Øystein Fodstad, Caroline E Nunes-Xavier
B7-H3 (CD276) belongs to the B7-family of immunoregulatory proteins, and has been implicated in cancer progression and metastasis. In this study, we found that metastatic melanoma cells with knockdown expression of B7-H3 showed modest decrease in proliferation and glycolytic capacity, and were more sensitive to dacarbazine (DTIC) chemotherapy and small-molecule inhibitors targeting MAP kinase (MAPK)- and AKT/mTOR-pathways: vemurafenib (PLX4032; BRAF inhibitor), binimetinib (MEK-162; MEK inhibitor), everolimus (RAD001; mTOR inhibitor) and triciribidine (API-2; AKT inhibitor)...
May 17, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28513171/ni-ii-complexes-of-the-redox-active-bis-2-aminophenyl-dipyrrin-structural-spectroscopic-and-theoretical-characterization-of-three-members-of-an-electron-transfer-series
#7
Jules Moutet, Christian Philouze, Amaury du Moulinet d'Hardemare, Nicolas Leconte, Fabrice Thomas
The sterically hindered bis(2-aminophenyl)dipyrrin ligand H3(N)L was prepared. X-ray diffraction discloses a bifurcated hydrogen bonding network involving the dipyrrin and one aniline ring. The reaction of H3(N)L with one equivalent of nickel(II) in the air produces a paramagnetic neutral complex, which absorbs intensively in the Vis-NIR region. Its electron paramagnetic resonance spectrum displays resonances at g1 = 2.033, g2 = 2.008, and g3 = 1.962 that are reminiscent of an (S = 1/2) system having a predominant organic radical character...
May 17, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28512107/divergent-requirements-for-ezh1-in-heart-development-versus-regeneration
#8
Shanshan Ai, Xianhong Yu, Yumei Li, Yong Peng, Chen Li, Yanzhu Yue, Ge Tao, Chuan-Yun Li, William T Pu, Aibin He
Rationale: Polycomb repressive complex 2 (PRC2) is a major epigenetic repressor that deposits methylation on histone H3 on lysine 27 (H3K27me) and controls differentiation and function of many cells, including cardiac myocytes. EZH1 and EZH2 are two alternative catalytic subunits with partial functional redundancy. The relative roles of EZH1 and EZH2 in heart development and regeneration are unknown. Objective: We compared the roles of EZH1 versus EZH2 in heart development and neonatal heart regeneration. Methods and Results: Heart development was normal in Ezh1(-/-) (E1KO) and Ezh2(f/f)::cTNT(-Cre) (E2KO) embryos...
May 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28511916/pre-treatment-with-amitriptyline-causes-epigenetic-up-regulation-of-neuroprotection-associated-genes-and-has-anti-apoptotic-effects-in-mouse-neuronal-cells
#9
Nguyen Quoc Vuong Tran, An Nghia Nguyen, Kyoko Takabe, Zentaro Yamagata, Kunio Miyake
Antidepressants, such as imipramine and fluoxetine, are known to alter gene expression patterns by inducing changes in the epigenetic status of neuronal cells. There is also some evidence for the anti-apoptotic effect of various groups of antidepressants; however, this effect is complicated and cell-type dependent. Antidepressants of the tricyclic group, in particular amitriptyline, have been suggested to be beneficial in the treatment of neurodegenerative disorders. We examined whether amitriptyline exerts an anti-apoptotic effect via epigenetic mechanisms...
May 13, 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/28511912/inhibition-of-kdm4a-activity-as-a-strategy-to-suppress-interleukin-6-production-and-attenuate-colitis-induction
#10
Kazuhiro Ishiguro, Osamu Watanabe, Masanao Nakamura, Takeshi Yamamura, Masanobu Matsushita, Hidemi Goto, Yoshiki Hirooka
4-Chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) functions as a hapten and fluoresces upon binding to proteins. Therefore, fluorescence visualization of hapten-proteins is a feature of the colitis induced by NBD-Cl. Using this colitis model, we located activated fibroblasts in the vicinity of hapten-proteins upon colitis induction and observed interleukin (IL)-6 production in the activated fibroblasts. We screened herbal ingredients using primary fibroblasts stimulated with tumor necrosis factor α (TNF-α) and found the suppressive action of Atractylodin on IL-6 production...
May 13, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28509866/hdac8-prevents-anthrax-lethal-toxin-induced-cell-cycle-arrest-through-silencing-pten-in-human-monocytic-thp-1-cells
#11
Soon-Duck Ha, Woohyun Cho, Sung Ouk Kim
Anthrax lethal toxin (LeTx) is a cytotoxic virulence factor that causes cell cycle arrest and cell death in various cell types. However, susceptibility to the cytotoxic effects varies depending on cell types. In proliferating monocytes, LeTx has only transient cytotoxic effects due to activation of the phosphoinositide 3-kinase (PI3K)-AKT-mediated adaptive responses. To date, the mechanism of LeTx in activating PI3K-AKT signaling axis is unknown. This study shows that the histone deacetylase 8 (HDAC8) is involved in activating PI3K-AKT signaling axis through down-regulating the phosphatase and tensin homolog 1 (PTEN) in human monocytic THP-1 cells...
May 16, 2017: Toxins
https://www.readbyqxmd.com/read/28508865/an-allosteric-site-in-the-t-cell-receptor-c%C3%AE-domain-plays-a-critical-signalling-role
#12
Kannan Natarajan, Andrew C McShan, Jiansheng Jiang, Vlad K Kumirov, Rui Wang, Huaying Zhao, Peter Schuck, Mulualem E Tilahun, Lisa F Boyd, Jinfa Ying, Ad Bax, David H Margulies, Nikolaos G Sgourakis
The molecular mechanism through which the interaction of a clonotypic αβ T-cell receptor (TCR) with a peptide-loaded major histocompatibility complex (p/MHC) leads to T-cell activation is not yet fully understood. Here we exploit a high-affinity TCR (B4.2.3) to examine the structural changes that accompany binding to its p/MHC ligand (P18-I10/H2-D(d)). In addition to conformational changes in complementarity-determining regions (CDRs) of the TCR seen in comparison of unliganded and bound X-ray structures, NMR characterization of the TCR β-chain dynamics reveals significant chemical shift effects in sites removed from the MHC-binding site...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28505000/h3f3a-histone-3-3-g34w-immunohistochemistry-a-reliable-marker-defining-benign-and-malignant-giant-cell-tumor-of-bone
#13
Fernanda Amary, Fitim Berisha, Hongtao Ye, Manu Gupta, Alice Gutteridge, Daniel Baumhoer, Rebecca Gibbons, Roberto Tirabosco, Paul O'Donnell, Adrienne M Flanagan
Giant cell tumor of bone (GCTB) is a locally aggressive subarticular tumor. Having recently reported that H3.3 G34W mutations are characteristic of this tumor type, we have now investigated the sensitivity and specificity of the anti-histone H3.3 G34W rabbit monoclonal antibody in a wide variety of tumors including histologic mimics of GCTB to assess its value as a diagnostic marker. We also determined the incidence of H3.3 G34 mutations in primary malignant bone tumors as assessed by genotype and H3.3 G34W immunostaining...
May 12, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28501482/ciproxifan-improves-cholinergic-transmission-attenuates-neuroinflammation-and-oxidative-stress-but-does-not-reduce-amyloid-level-in-transgenic-mice
#14
Vasudevan Mani, Siti Murnirah Jaafar, Nur Syamimi Mohd Azahan, Kalavathy Ramasamy, Siong Meng Lim, Long Chiau Ming, Abu Bakar Abdul Majeed
AIM: The present study is aimed to investigate the ability of ciproxifan, a histamine H3 receptor antagonist to inhibit β-amyloid (Aβ)-induced neurotoxicity in SK-N-SH cells and APP transgenic mouse model. MATERIALS AND METHODS: In vitro studies was designed to evaluate the neuroprotective effects of ciproxifan in Aβ25-35 - induced SK-N-SH cells. For the in vivo study, ciproxifan (1 and 3mg/kg, i.p.) was administrated to transgenic mice for 15days and behaviour was assessed using the radial arm maze (RAM)...
May 10, 2017: Life Sciences
https://www.readbyqxmd.com/read/28501130/collateral-artery-pathways-of-the-femoral-and-popliteal-artery
#15
Rombout R Kruse, Denise E Doomernik, Kasper V Maltha, Jan G M Kooloos, Tamas L Kozicz, Michel M P J Reijnen
BACKGROUND: The role of collateral artery circulation in the lower limb is under debate but clinically relevant, particularly when using covered stents for occlusive disease. Covered stents seem to outperform nitinol stents in extensive disease, but collaterals could be essential in case of acute thrombosis. In the present study, we describe the collateral pathways of the deep and superficial femoral artery (DFA, SFA) and the popliteal artery (PA), observed in human cadavers. METHODS: Ten fresh frozen cadaver legs were selected...
May 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28498016/accelerated-vernalization-response-by-an-altered-phd-finger-protein-in-arabidopsis
#16
Dong-Hwan Kim, Sibum Sung
Vernalization is a response to the winter cold to acquire the competence to flower in next spring. VERNALIZATION INSENSITIVE 3 (VIN3) is a PHD-finger protein that binds to modified histones in vitro. VIN3 is induced by long-term cold and is necessary for Polycomb Repression Complex 2 (PRC2)-mediated tri-methylation of Histone H3 Lysine 27 (H3K27me3) at the FLC locus in Arabidopsis. An alteration in the PHD-finger domain of VIN3 changes the binding specificity of the PHD-finger domain of VIN3 in vitro and results in an accelerated vernalization response in vivo...
May 12, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28497965/residues-of-alpha-helix-h3-determine-distinctive-features-of-transforming-growth-factor-%C3%AE-3
#17
Shahid M Nayeem, Francesco Oteri, Marc Baaden, Shashank Deep
Transforming growth factors (TGF-βs) are proteins that regulate cell growth by binding to their receptors. TGF-βs are disulfide-linked homo-dimers of 112-residue monomers. Three subtypes of TGF-β are known to be present in human namely TGF-β1, TGF-β2 and TGF-β3. The isoforms are highly similar in terms of their sequences (Figure 1), with TGF-β2 and TGF-β3 sharing 92 % similarity, TGF-β1 and TGF-β3 sharing 87%, and TGF-β1 and TGF-β2 sharing 86%(1). Monomers of TGF-βs are structurally homologous...
May 12, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28490912/update-on-the-treatment-of-narcolepsy-clinical-efficacy-of-pitolisant
#18
REVIEW
Michael W Calik
Narcolepsy is a neurological disease that affects 1 in 2,000 individuals and is characterized by excessive daytime sleepiness (EDS). In 60-70% of individuals with narcolepsy, it is also characterized by cataplexy or a sudden loss of muscle tone that is triggered by positive or negative emotions. Narcolepsy decreases the quality of life of the afflicted individuals. Currently used drugs treat EDS alone (modafinil/armodafinil, methylphenidate, and amphetamine), cataplexy alone ("off-label" use of antidepressants), or both EDS and cataplexy (sodium oxybate)...
2017: Nature and Science of Sleep
https://www.readbyqxmd.com/read/28485406/inducing-a-long-term-potentiation-in-the-dentate-gyrus-is-sufficient-to-produce-rapid-antidepressant-like-effects
#19
A Kanzari, C Bourcier-Lucas, A Freyssin, D N Abrous, N Haddjeri, G Lucas
Recent hypotheses propose that one prerequisite to obtain a rapid antidepressant (AD) effect would reside in processes of synaptic reinforcement occurring within the dentate gyrus (DG) of the hippocampus independently from neurogenesis. However, to date no relationship has been established between an increased DG synaptic plasticity, and rapid AD-like action. To the best of our knowledge, this study shows for the first time that inducing a long-term potentiation (LTP) within the DG by stimulating the perforant pathway (PP) is sufficient to induce such effects...
May 9, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28483375/mechanisms-regulating-prc2-recruitment-and-enzymatic-activity
#20
REVIEW
Daniel Holoch, Raphaël Margueron
Polycomb repressive complex 2 (PRC2) and its histone H3 lysine-27 methylation activity are crucial for multicellular development by virtue of their role in maintaining transcriptional repression patterns. The recruitment and enzymatic activity of PRC2 are controlled by a series of intricate mechanisms whose molecular details have been emerging at a rapid pace. Recent studies have uncovered intriguing modes of PRC2 regulation by facultative PRC2 subunits, PRC1, and specific features of the chromatin environment...
May 5, 2017: Trends in Biochemical Sciences
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