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https://www.readbyqxmd.com/read/28434814/novel-protein-biomarkers-associated-with-coronary-artery-disease-in-statin-treated-patients-with-familial-hypercholesterolemia
#1
Sven Bos, Michael Phillips, Gerald F Watts, Adrie J M Verhoeven, Eric J G Sijbrands, Natalie C Ward
BACKGROUND: Familial hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipid metabolism. The incidence of coronary artery disease (CAD) varies among both treated and untreated FH patients. OBJECTIVE: The aim of the study was to utilize proteomics to identify novel protein biomarkers that differentiate genetically confirmed heterozygous patients with FH at high CAD risk from those at low CAD risk. METHODS: Sixty genetically confirmed FH patients were recruited and stratified into (1) asymptomatic FH with low atherosclerotic burden (FH, n = 20); (2) asymptomatic FH with high atherosclerotic burden (FH + Ca, n = 20); and (3) FH with previously confirmed symptomatic CAD (FH + CAD, n = 20)...
April 4, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28434780/total-chemical-synthesis-of-methylated-analogues-of-histone-3-revealed-kdm4d-as-a-potential-regulator-of-h3k79me3
#2
Muhammad Jbara, Noga Guttmann-Raviv, Suman Kumar Maity, Nabieh Ayoub, Ashraf Brik
Histone H3 methylation plays an important role in regulating gene expression. In histones in general, this mark is dynamically regulated via various demethylases, which found to control cell fate decisions as well as linked to several diseases, including neurological and cancer. Despite major progress in studying methylation mark at various positions in H3 histone proteins, less is known about the regulation of methylated H3 at Lys79. Methylation at this site is known to have direct cross-talk with monoubiquitination of histone H2B at positions Lys120 and 34, as well as with acetylated H3 at Lys9...
April 12, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28433418/binge-alcohol-alters-pnpla3-levels-in-liver-through-epigenetic-mechanism-involving-histone-h3-acetylation
#3
REVIEW
Ricardo J Restrepo, Robert W Lim, Ronald J Korthuis, Shivendra D Shukla
The human PNPLA3 (patatin-like phospholipase domain-containing 3) gene codes for a protein which is highly expressed in adipose tissue and liver, and is implicated in lipid homeostasis. While PNPLA3 protein contains regions homologous to functional lipolytic proteins, the regulation of its tissue expression is reflective of lipogenic genes. A naturally occurring genetic variant of PNPLA3 in humans has been linked to increased susceptibility to alcoholic liver disease. We have examined the modulatory effect of alcohol on PNPLA3 protein and mRNA expression as well as the association of its gene promoter with acetylated histone H3K9 by chromatin immunoprecipitation (ChIP) assay in rat hepatocytes in vitro, and in vivo in mouse and rat models of acute binge, chronic, and chronic followed by acute binge ethanol administration...
March 12, 2017: Alcohol
https://www.readbyqxmd.com/read/28432685/chiral-analysis-of-%C3%AE-diimine-ru-ii-and-fe-ii-complexes-by-capillary-electrophoresis-using-sulfated-cyclodextrins-as-stereoselectors
#4
Petra Sázelová, Dušan Koval, Lukáš Severa, Filip Teplý, Václav Kašička
Capillary electrophoresis (CE) using randomly highly sulfated α-, β-, and γ-cyclodextrins (S-α-CD, S-β-CD, S-γ-CD), sulfobutylether-β-CD (SBE-β-CD), single isomer (6-O-sulfo) α-, β-, and γ-CDs and their derivatives as stereoselectors was applied to chiral analysis of polypyridyl complexes of [Ru(bpy)3 ](2+) , [Ru(phen)3 ](2+) , and [Fe(phen)3 ](2+) (bpy = 2,2'-bipyridine; phen = 1,10 phenanthroline). The best separations of Δ- and Λ-enantiomers of the these complexes with high resolution (up to R1,2  = 7...
April 22, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28431339/novel-coumarin-and-quinolinone-based-polycycles-as-cell-division-cycle-25-a-and-c-phosphatases-inhibitors-induce-proliferation-arrest-and-apoptosis-in-cancer-cells
#5
Clemens Zwergel, Brigitte Czepukojc, Emilie Evain-Bana, Zhanjie Xu, Giulia Stazi, Mattia Mori, Alexandros Patsilinakos, Antonello Mai, Bruno Botta, Rino Ragno, Denise Bagrel, Gilbert Kirsch, Peter Meiser, Claus Jacob, Mathias Montenarh, Sergio Valente
Cell division cycle phosphatases CDC25 A, B and C are involved in modulating cell cycle processes and are found overexpressed in a large panel of cancer typology. Here, we describe the development of two novel quinone-polycycle series of CDC25A and C inhibitors on the one hand 1a-k, coumarin-based, and on the other 2a-g, quinolinone-based, which inhibit either enzymes up to a sub-micro molar level and at single-digit micro molar concentrations, respectively. When tested in six different cancer cell lines, compound 2c displayed the highest efficacy to arrest cell viability, showing in almost all cell lines sub-micro molar IC50 values, a profile even better than the reference compound NCS95397...
April 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28430635/unsuccessful-mitosis-in-multicellular-tumour-spheroids
#6
Annie Molla, Morgane Couvet, Jean-Luc Coll
Multicellular spheroids are very attractive models in oncology because they mimic the 3D organization of the tumour cells with their microenvironment. We show here using 3 different cell types (mammary TSA/pc, embryonic kidney Hek293 and cervical cancer HeLa), that when the cells are growing as spheroids the frequency of binucleated cells is augmented as occurs in some human tumours.We therefore describe mitosis in multicellular spheroids by following mitotic markers and by time-lapse experiments. Chromosomes alignment appears to be correct on the metaphasic plate and the passenger complex is well localized on centromere...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425976/prenatal-exposure-to-a-maternal-high-fat-diet-affects-histone-modification-of-cardiometabolic-genes-in-newborn-rats
#7
Bijaya Upadhyaya, Tricia Larsen, Shivon Barwari, Eli J Louwagie, Michelle L Baack, Moul Dey
Infants born to women with diabetes or obesity are exposed to excess circulating fuels during fetal heart development and are at higher risk of cardiac diseases. We have previously shown that late-gestation diabetes, especially in conjunction with a maternal high-fat (HF) diet, impairs cardiac functions in rat-offspring. This study investigated changes in genome-wide histone modifications in newborn hearts from rat-pups exposed to maternal diabetes and HF-diet. Chromatin-immunoprecipitation-sequencing revealed a differential peak distribution on gene promoters in exposed pups with respect to acetylation of lysines 9 and 14 and to trimethylation of lysines 4 and 27 in histone H3 (all, false discovery rate, FDR < 0...
April 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28425177/design-and-synthesis-of-c3-substituted-%C3%AE-carboline-based-histone-deacetylase-inhibitors-with-potent-antitumor-activities
#8
Yong Ling, Jiao Feng, Lin Luo, Jing Guo, Yanfu Peng, Tingting Wang, Xiang Ge, Qibing Xu, Xinyang Wang, Hong Dai, Yanan Zhang
A series of hydroxamic acid histone deacetylase (HDAC) inhibitors in which the β-carboline motif has been incorporated were designed and synthesized. The effect of substitution at the C3 amide on HDAC inhibition and antiproliferative activities was investigated. Most of these compounds were found to display significant HDAC inhibitory effects and good antiproliferative activity, with IC50 values in the low-micromolar range. In particular, the HDAC inhibition IC50 value of N-(2-(dimethylamino)ethyl)-N-(4-(hydroxylcarbamoyl)benzyl)-1-(4-methoxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxamide (9 h) is five-fold lower than that of suberoylanilide hydroxamic acid (SAHA, vorinostat)...
April 20, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28421257/histone-deacetylase-inhibitors-reverse-age-related-increases-in-side-effects-of-haloperidol-in-mice
#9
Janitza L Montalvo-Ortiz, Daniel W Fisher, Guadalupe Rodríguez, Deyu Fang, John G Csernansky, Hongxin Dong
BACKGROUND: Older patients can be especially susceptible to antipsychotic-induced side effects, and the pharmacodynamic mechanism underlying this phenomenon remains unclear. We hypothesized that age-related epigenetic alterations lead to decreased expression and functionality of the dopamine D2 receptor (D2R), contributing to this susceptibility. METHODS: In this study, we treated young (2-3 months old) and aged (22-24 months old) C57BL/6 mice with the D2R antagonist haloperidol (HAL) once a day for 14 days to evaluate HAL-induced motor side effects...
April 18, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28420800/setdb1-plays-an-essential-role-in-maintenance-of-gonocyte-survival-in-pigs
#10
Tian Tian Liu, Pengfei Zhang, Tian Jiao Li, Xiao Xu Chen, Zhen Shuo Zhu, Ying Hua Lyu, Xue Liang Li, Xiue Tian, Wen Xian Zeng
Histone methyltransferase SETDB1 suppresses gene expression and modulates heterochromatin formation through H3K9me2/3. Previous studies have revealed that SETDB1 catalyzes lysine 9 of histone H3 tri-methylation and plays essential roles in maintaining the survival of embryonic stem cells and spermatogonial stem cells in mice. However, the function of SETDB1 in porcine male germ cells remains unclear. The aim of the present study was to reveal the expression profile and function of SETDB1 in porcine germ cells...
April 18, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28420001/nicotinamide-n-methyltransferase-suppression-participates-in-nickel-induced-histone-h3-lysine9-dimethylation-in-beas-2b-cells
#11
Qian Li, Min-Di He, Lin Mao, Xue Wang, Yu-Lin Jiang, Min Li, Yong-Hui Lu, Zheng-Ping Yu, Zhou Zhou
BACKGROUND: Nickel compounds are well-established human carcinogens with weak mutagenic activity. Histone methylation has been proposed to play an important role in nickel-induced carcinogenesis. Nicotinamide N-methyltransferase (NNMT) decreases histone methylation in several cancer cells by altering the cellular ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). However, the role of NNMT in nickel-induced histone methylation remains unclear. METHODS: BEAS-2B cells were exposed to different concentrations of nickel chloride (NiCl2) for 72 h or 200 μM NiCl2 for different time periods...
April 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28419608/multiple-breath-hold-proton-spectroscopy-of-human-liver-at-3t-relaxation-times-and-concentrations-of-glycogen-choline-and-lipids
#12
Jan Weis, Joel Kullberg, Håkan Ahlström
PURPOSE: To evaluate the feasibility of an expiration multiple breath-hold (1) H-MRS technique to measure glycogen (Glycg), choline-containing compounds (CCC), and lipid relaxation times T1 , T2 , and their concentrations in normal human liver. MATERIALS AND METHODS: Thirty healthy volunteers were recruited. Experiments were performed at 3T. Multiple expiration breath-hold single-voxel point-resolved spectroscopy (PRESS) technique was used for localization. Water-suppressed spectra were used for the estimation of Glycg, CCC, lipid methylene (CH2 )n relaxation times and concentrations...
April 17, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28416018/detection-of-histone-h3-mutations-in-cerebrospinal-fluid-derived-tumor-dna-from-children-with-diffuse-midline-glioma
#13
Tina Y Huang, Andrea Piunti, Rishi R Lulla, Jin Qi, Craig M Horbinski, Tadanori Tomita, C David James, Ali Shilatifard, Amanda M Saratsis
Diffuse midline gliomas (including diffuse intrinsic pontine glioma, DIPG) are highly morbid glial neoplasms of the thalamus or brainstem that typically arise in young children and are not surgically resectable. These tumors are characterized by a high rate of histone H3 mutation, resulting in replacement of lysine 27 with methionine (K27M) in genes encoding H3 variants H3.3 (H3F3A) and H3.1 (HIST1H3B). Detection of these gain-of-function mutations has clinical utility, as they are associated with distinct tumor biology and clinical outcomes...
April 17, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28414027/arsenic-activates-the-expression-of-3%C3%AE-hsd-in-mouse-leydig-cells-through-repression-of-histone-h3k9-methylation
#14
Ambreen Alamdar, Guochen Xi, Qingyu Huang, Meiping Tian, Syed Ali Musstjab Akber Shah Eqani, Heqing Shen
Arsenic exposure has been associated with male reproductive dysfunction by disrupting steroidogenesis; however, the roles of epigenetic drivers, especially histone methylation in arsenic-induced steroidogenic toxicity remain not well documented. In this study, we investigated the role of histone H3 lysine 9 (H3K9) methylation in steroidogenesis disturbance in mouse Leydig cells (MLTC-1) due to arsenic exposure. Our results indicated that mRNA and protein expression levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) were both significantly up-regulated while the rest of key genes involved in steroidogenesis were down-regulated...
April 13, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28413956/structure-roles-and-inhibitors-of-a-mitotic-protein-kinase-haspin
#15
Katrin Kestav, Asko Uri, Darja Lavogina
Background Haspin (haploid germ cell-specific nuclear protein kinase) is an atypical serine/threonine-protein kinase that was for a long time considered an inactive pseudokinase due to low degree of structural homology of Haspin with the 'classical' protein kinases. However, the discovery of Haspin-catalyzed phosphorylation of histone H3 at Thr3 residue unveiled importance of Haspin in mitosis and provided yet another link between mitotic phosphorylation pathways and chromatin modifications. Results In this review of 111 publications, we have (1) briefly summarized catalytic properties and physiological roles of Haspin, (2) focussed on the architecture of Haspin and mechanisms behind its substrate recognition, (3) provided detailed insight into the advances in the development and characterization of Haspin-selective inhibitors, and (4) given overview of inhibitor scaffolds that despite targeting other protein kinases feature Haspin as a common off-target...
April 14, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28402630/benzo-isoquinoline-diones-as-potent-and-selective-inhibitors-of-brpf2-and-taf1-taf1l-bromodomains
#16
Léa Bouché, Clara D Christ, Stephan Siegel, Amaury E Fernández-Montalván, Simon J Holton, Oleg Fedorov, Antonius Ter Laak, Tatsuo Sugawara, Detlef Stöckigt, Cynthia Tallant, James M Bennett, Octovia P Monteiro, Laura Díaz-Sáez, Paulina Siejka, Julia Meier, Vera Puetter, Joerg Weiske, Susanne Müller, Kilian Veit Marcus Huber, Ingo V Hartung, Bernard Haendler
Bromodomains (BD) are readers of lysine acetylation marks present in numerous proteins associated with chromatin. Here we describe a dual inhibitor of the bromodomain and PHD finger (BRPF) family member BRPF2 and the TATA box binding protein-associated factors TAF1 and TAF1L. These proteins are found in large chromatin complexes and play important roles in transcription regulation. The substituted benzo-isoquinoline-dione series was identified by high-througput screening and subsequent structure-activity relationship optimization allowed generation of low nanomolar BRPF2 BD inhibitors with strong selectivity against BRPF1 and BRPF3 BDs...
April 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28402439/chromodomain-protein-cdyl-is-required-for-transmission-restoration-of-repressive-histone-marks
#17
Yongqing Liu, Shumeng Liu, Shuai Yuan, Huajing Yu, Yu Zhang, Xiaohan Yang, Guojia Xie, Zhe Chen, Wanjin Li, Bosen Xu, Luyang Sun, Yongfeng Shang, Jing Liang
Faithful transmission or restoration of epigenetic information such as repressive histone modifications through generations is critical for the maintenance of cell identity. We report here that chromodomain Y-like protein (CDYL), a chromodomain-containing transcription corepressor, is physically associated with chromatin assembly factor 1 (CAF-1) and the replicative helicase MCM complex. We showed that CDYL bridges CAF-1 and MCM, facilitating histone transfer and deposition during DNA replication. We demonstrated that CDYL recruits histone-modifying enzymes G9a, SETDB1, and EZH2 to replication forks, leading to the addition of H3K9me2/3 and H3K27me2/3 on newly deposited histone H3...
April 10, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28401334/h3-idh-wild-type-pediatric-glioblastoma-is-comprised-of-molecularly-and-prognostically-distinct-subtypes-with-associated-oncogenic-drivers
#18
Andrey Korshunov, Daniel Schrimpf, Marina Ryzhova, Dominik Sturm, Lukas Chavez, Volker Hovestadt, Tanvi Sharma, Antje Habel, Anna Burford, Chris Jones, Olga Zheludkova, Ella Kumirova, Christof M Kramm, Andrey Golanov, David Capper, Andreas von Deimling, Stefan M Pfister, David T W Jones
Pediatric glioblastoma (pedGBM) is an extremely aggressive pediatric brain tumor, accounting for ~6% of all central nervous system neoplasms in children. Approximately half of pedGBM harbor recurrent somatic mutations in histone 3 variants or, infrequently, IDH1/2. The remaining subset of pedGBM is highly heterogeneous, and displays a variety of genomic and epigenetic features. In the current study, we aimed to further stratify an H3-/IDH-wild type (wt) pedGBM cohort assessed through genome-wide molecular profiling...
April 11, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28401060/therapeutic-targeting-of-histone-modifications-in-adult-and-pediatric-high-grade-glioma
#19
REVIEW
Maria J Williams, Will G B Singleton, Stephen P Lowis, Karim Malik, Kathreena M Kurian
Recent exciting work partly through The Cancer Genome Atlas has implicated epigenetic mechanisms including histone modifications in the development of both pediatric and adult high-grade glioma (HGG). Histone lysine methylation has emerged as an important player in regulating gene expression and chromatin function. Lysine (K) 27 (K27) is a critical residue in all seven histone 3 variants and the subject of posttranslational histone modifications, as it can be both methylated and acetylated. In pediatric HGG, two critical single-point mutations occur in the H3F3A gene encoding the regulatory histone variant H3...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28394041/taming-silicon-congeners-of-co-and-co2-synthesis-of-monomeric-si-ii-and-si-iv-chalcogenide-complexes
#20
Alexander Burchert, Robert Müller, Shenglai Yao, Caspar Schattenberg, Yun Xiong, Martin Kaupp, Matthias Driess
The synthesis of the unprecedented monomeric Si(II) selenide complex (bis-NHC)Si=Se→GaCl3 2 (bis-NHC=bis-N heterocyclic carbene, H2 C[{NC(H)=C(H)N(Dipp)}C:]2 , Dipp=2,6-iPr2 C6 H3 ), bearing the elusive SiSe ligand as a heavy CO homologue by the reaction of the silylone-GaCl3 adduct (bis-NHC)Si→GaCl3 1 with elemental selenium in acetonitrile, is reported. The similar conversion of 1 with excess selenium conducted in THF afforded the SiSe2 complex (bis-NHC)Si(=Se)Se→GaCl3 3. Remarkably, the reaction of 1 with Te=P(nBu)3 as a gentle Te transfer reagent led to the isolation of the monomeric SiTe2 complex (bis-NHC)SiTe2 4, the first structurally characterized Lewis acid free heavy CO2 homologue complex...
April 10, 2017: Angewandte Chemie
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