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arginine methylation

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https://www.readbyqxmd.com/read/28408866/post-translational-modifications-and-protein-quality-control-in-motor-neuron-and-polyglutamine-diseases
#1
REVIEW
Fabio Sambataro, Maria Pennuto
Neurodegenerative diseases, including motor neuron and polyglutamine (polyQ) diseases, are a broad class of neurological disorders. These diseases are characterized by neuronal dysfunction and death, and by the accumulation of toxic aggregation-prone proteins in the forms of inclusions and micro-aggregates. Protein quality control is a cellular mechanism to reduce the burden of accumulation of misfolded proteins, a function that results from the coordinated actions of chaperones and degradation systems, such as the ubiquitin-proteasome system (UPS) and autophagy-lysosomal degradation system...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28406400/the-rnf168-paralog-rnf169-defines-a-new-class-of-ubiquitylated-histone-reader-involved-in-the-response-to-dna-damage
#2
Julianne Kitevski-LeBlanc, Amélie Fradet-Turcotte, Predrag Kukic, Marcus D Wilson, Guillem Portella, Tairan Yuwen, Stephanie Panier, Shili Duan, Marella D Canny, Hugo van Ingen, Cheryl H Arrowsmith, John L Rubinstein, Michele Vendruscolo, Daniel Durocher, Lewis E Kay
Site-specific histone ubiquitylation plays a central role in orchestrating the response to DNA double-strand breaks (DSBs). DSBs elicit a cascade of events controlled by the ubiquitin ligase RNF168, which promotes the accumulation of repair factors such as 53BP1 and BRCA1 on the chromatin flanking the break site. RNF168 also promotes its own accumulation, and that of its paralog RNF169, but how they recognize ubiquitylated chromatin is unknown. Using methyl-TROSY solution NMR spectroscopy and molecular dynamics simulations, we present an atomic resolution model of human RNF169 binding to a ubiquitylated nucleosome, and validate it by electron cryomicroscopy...
April 13, 2017: ELife
https://www.readbyqxmd.com/read/28403791/multimeric-system-of-rgd-grafted-pmma-nanoparticles-as-a-targeted-drug-delivery-system-for-paclitaxel
#3
Gibbens-Bandala Brenda Vianey, Ocampo-García Blanca Eli, Ferro-Flores Guillermina, Morales-Avila Enrique, Ancira-Cortez Alejandra, Jaimes-Aguirre Laura
BACKGROUND: Polymer-based nanoparticles as drug-delivery systems offer new therapeutic opportunities. Among them, ligand-mediated targeting, which increases selectivity and efficacy, allows controllable drug delivery. The aim of the this research was to prepare and characterize poly(methyl methacrylate) (PMMA) nanoparticles grafted with the -Arginine, Glycine, Aspartic Acid (RGD)- peptide sequence as a promising smart drug delivery system for Paclitaxel (PTX), directed at the sites of integrin receptor overexpression...
April 7, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28397890/discovery-and-optimization-of-selective-inhibitors-of-protein-arginine-methyltransferase-5-by-docking-based-virtual-screening
#4
Yan Ye, Bidong Zhang, Ruifeng Mao, Chenhua Zhang, Yulan Wang, Jing Xing, Yu-Chih Liu, Xiaomin Luo, Hong Ding, Yaxi Yang, Bing Zhou, Hualiang Jiang, Kaixian Chen, Cheng Luo, Mingyue Zheng
Protein arginine methyltransferase 5 (PRMT5) is a type II PRMT enzyme critical for diverse cellular processes and different types of cancers. Many efforts have been made to discover novel scaffold PRMT5 inhibitors. Herein, we report the discovery of DC_P33 as a hit compound of PRMT5 inhibitor, identified by molecular docking based virtual screening and (3)H-labeled radioactive methylation assays. Structure-activity relationship (SAR) analysis was performed on the analogs of DC_P33 and then structural modifications were done to improve its activity...
April 11, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28392442/protein-arginine-methylation-of-npl3-promotes-splicing-of-the-sus1-intron-harboring-non-consensus-5-splice-site-and-branch-site
#5
Bhavana Muddukrishna, Christopher A Jackson, Michael C Yu
Protein arginine methylation occurs on spliceosomal components and spliceosome-associated proteins, but how this modification contributes to their function in pre-mRNA splicing remains sparse. Here we provide evidence that protein arginine methylation of the yeast SR-/hnRNP-like protein Npl3 plays a role in facilitating efficient splicing of the SUS1 intron that harbors a non-consensus 5' splice site and branch site. In yeast cells lacking the major protein arginine methyltransferase HMT1, we observed a change in the co-transcriptional recruitment of the U1 snRNP subunit Snp1 and Npl3 to pre-mRNAs harboring both consensus (ECM33 and ASC1) and non-consensus (SUS1) 5' splice site and branch site...
April 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28392261/bound-waters-mediate-binding-of-diverse-substrates-to-a-ubiquitin-ligase
#6
Juliana Muñoz-Escobar, Edna Matta-Camacho, Cordelia Cho, Guennadi Kozlov, Kalle Gehring
The N-end rule pathway controls the half-life of proteins based on their N-terminal residue. Positively charged type 1 N-degrons are recognized by a negatively charged pocket on the Zn finger named the UBR box. Here, we show that the UBR box is rigid, but bound water molecules in the pocket provide the structural plasticity required to bind different positively charged amino acids. Ultra-high-resolution crystal structures of arginine, histidine, and methylated arginine reveal that water molecules mediate the binding of N-degron peptides...
March 27, 2017: Structure
https://www.readbyqxmd.com/read/28391290/role-of-nitric-oxide-synthase-on-blood-pressure-regulation-and-vascular-function-in-pregnant-rats-on-a-high-fat-diet
#7
Ana C Palei, Frank T Spradley, Joey P Granger
BACKGROUND: While obesity is a leading risk factor for preeclampsia, the mechanisms whereby obese women are more susceptible to pregnancy-induced hypertension are unclear. As high-fat diet (HFD) is an important contributor to the development of obesity, we tested the hypothesis that pregnant rats on HFD have hypertension and endothelial dysfunction due to reduced nitric oxide synthase (NOS). METHODS: Twelve-week-old Sprague-Dawley female rats were fed normal diet (ND, 13% fat kcal) or HFD (40% fat kcal) for 9 weeks...
March 1, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28384243/neuropeptide-s-reduces-duodenal-bicarbonate-secretion-and-ethanol-induced-increases-in-duodenal-motility-in-rats
#8
Wan Salman Wan Saudi, Markus Sjöblom
Alcohol disrupts the intestinal mucosal barrier by inducing metabolic and functional changes in epithelial cells. Recently, we showed that neuropeptide S (NPS) decreases duodenal motility and increases mucosal paracellular permeability, suggesting a role of NPS in the pathogenesis of disorders and dysfunctions in the small intestine. The aim of the present study was to investigate the effects of NPS on ethanol- and HCl-induced changes of duodenal mucosal barrier function and motility. Rats were anaesthetized with thiobarbiturate, and a 30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ...
2017: PloS One
https://www.readbyqxmd.com/read/28382930/highly-selective-inhibition-of-histone-demethylases-by-de-novo-macrocyclic-peptides
#9
Akane Kawamura, Martin Münzel, Tatsuya Kojima, Clarence Yapp, Bhaskar Bhushan, Yuki Goto, Anthony Tumber, Takayuki Katoh, Oliver N F King, Toby Passioura, Louise J Walport, Stephanie B Hatch, Sarah Madden, Susanne Müller, Paul E Brennan, Rasheduzzaman Chowdhury, Richard J Hopkinson, Hiroaki Suga, Christopher J Schofield
The JmjC histone demethylases (KDMs) are linked to tumour cell proliferation and are current cancer targets; however, very few highly selective inhibitors for these are available. Here we report cyclic peptide inhibitors of the KDM4A-C with selectivity over other KDMs/2OG oxygenases, including closely related KDM4D/E isoforms. Crystal structures and biochemical analyses of one of the inhibitors (CP2) with KDM4A reveals that CP2 binds differently to, but competes with, histone substrates in the active site. Substitution of the active site binding arginine of CP2 to N-ɛ-trimethyl-lysine or methylated arginine results in cyclic peptide substrates, indicating that KDM4s may act on non-histone substrates...
April 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28376377/combined-oral-contraceptive-and-nitric-oxide-synthesis-inhibition-synergistically-causes-cardiac-hypertrophy-and-exacerbates-insulin-resistance-in-female-rats
#10
Lawrence A Olatunji, Kehinde S Olaniyi, Taofeek O Usman, Bilikis A Abolarinwa, Caleb J Achile, In-Kyeom Kim
Combined oral contraceptive (COC) use or inhibition of nitric oxide (NO) synthesis has been shown to cause hypertension and insulin resistance. However, the concomitant effects of COC and NO deficiency on the heart and glucose regulation are not well known. We therefore hypothesized that COC treatment during NO deficiency would lead to the development of cardiac hypertrophy that is associated with aggravated glucose deregulation, pro-inflammatory and pro-fibrotic biomarkers. Eight-week-old female Wistar rats were randomly allotted into control, NO deficient (N(G)-nitro-l-arginine methyl ester: L-NAME; 20...
March 20, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28369032/bidirectional-regulatory-effects-of-dexmedetomidine-on-porcine-coronary-tone-in-vitro
#11
Shu-Zhi Zhou, Zhi-Ming Li, Xue-Ru Liu, Jun Zhou, Xiao-Qiu Tan, Yan Yang, Ji-Cheng Wei
BACKGROUND Studies in vivo have shown that dexmedetomidine (DEX) could protect the myocardium and modulate the coronary blood flow. This study aimed to investigate the direct and concentration-dependent effects of DEX on the tone of porcine coronary artery in vitro and the underlying mechanisms. MATERIAL AND METHODS Distal branches of the porcine anterior descending coronary arteries were dissected and cut into 3-5 mm rings. The tones of coronary rings in response to cumulative DEX were measured using the PowerLab system...
April 3, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28367100/padi4-epigenetically-suppresses-p21-transcription-and-inhibits-cell-apoptosis-in-fibroblast-like-synoviocytes-from-rheumatoid-arthritis-patients
#12
Lieying Fan, Ming Zong, Ruhan Gong, Dongyi He, Niu Li, Li Shan Sun, Qin Ye, Shanshan Yu
Rheumatoid arthritis (RA) is characterized by synovial lining hyperplasia, which involves abnormal growth of fibroblast-like synoviocytes (FLSs). This study aimed to investigate the function and molecular mechanism of peptidylarginine deiminase type 4 (PADI4) in FLSs isolated from RA patients (RA-FLSs). FLSs were isolated from RA patients and transfected with small interfering RNAs (siRNAs) or PADI4 overexpression plasmid. FLSs were treated by Adriamycin (ADR) to induce apoptosis, and apoptotic cells were detected by flow cytometry...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28364192/protein-arginine-methylation-a-prominent-modification-and-its-demethylation
#13
REVIEW
Juste Wesche, Sarah Kühn, Benedikt M Kessler, Maayan Salton, Alexander Wolf
Arginine methylation of histones is one mechanism of epigenetic regulation in eukaryotic cells. Methylarginines can also be found in non-histone proteins involved in various different processes in a cell. An enzyme family of nine protein arginine methyltransferases catalyses the addition of methyl groups on arginines of histone and non-histone proteins, resulting in either mono- or dimethylated-arginine residues. The reversibility of histone modifications is an essential feature of epigenetic regulation to respond to changes in environmental factors, signalling events, or metabolic alterations...
March 31, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28358054/argininosuccinate-synthase-1-deficiency-enhances-the-cell-sensitivity-to-arginine-through-decreased-deptor-expression-in-endometrial-cancer
#14
Kenji Ohshima, Satoshi Nojima, Shinichiro Tahara, Masako Kurashige, Yumiko Hori, Kohei Hagiwara, Daisuke Okuzaki, Shinya Oki, Naoki Wada, Jun-Ichiro Ikeda, Yoshikatsu Kanai, Eiichi Morii
Argininosuccinate synthetase 1 (ASS1) is a rate-limiting enzyme in arginine biosynthesis. Although ASS1 expression levels are often reduced in several tumors and low ASS1 expression can be a poor prognostic factor, the underlying mechanism has not been elucidated. In this study, we reveal a novel association between ASS1 and migration/invasion of endometrial tumors via regulation of mechanistic target of rapamycin complex (mTORC) 1 signaling. ASS1-knockout cells showed enhanced migration and invasion in response to arginine following arginine starvation...
March 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28346137/histone-gene-replacement-reveals-a-post-transcriptional-role-for-h3k36-in-maintaining-metazoan-transcriptome-fidelity
#15
Michael P Meers, Telmo Henriques, Christopher A Lavender, Daniel J McKay, Brian D Strahl, Robert J Duronio, Karen Adelman, A Gregory Matera
Histone H3 lysine 36 methylation (H3K36me) is thought to participate in a host of co-transcriptional regulatory events. To study the function of this residue independent from the enzymes that modify it, we used a 'histone replacement' system in Drosophila to generate a non-modifiable H3K36 lysine-to-arginine (H3K36R) mutant. We observed global dysregulation of mRNA levels in H3K36R animals that correlates with the incidence of H3K36me3. Similar to previous studies, we found that mutation of H3K36 also resulted in H4 hyperacetylation...
March 27, 2017: ELife
https://www.readbyqxmd.com/read/28341346/stimulation-of-%C3%AE-opioid-receptors-dilates-retinal-arterioles-by-neuronal-nitric-oxide-synthase-derived-nitric-oxide-in-rats
#16
Eriko Someya, Asami Mori, Kenji Sakamoto, Kunio Ishii, Tsutomu Nakahara
Opioids contribute to the regulation of cerebral vascular tone. The purpose of this study was to examine the effects of herkinorin, a non-opioid μ-opioid receptor agonist derived from salvinorin A, on blood vessels in the rat retina and to investigate the mechanism underlying the herkinorin-induced retinal vasodilatory response. Ocular fundus images were captured using an original high-resolution digital fundus camera in vivo. The retinal vascular responses were evaluated by measuring the diameter of retinal arterioles in the fundus images...
March 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28337643/recombinant-heat-shock-protein-27-hsp27-hspb1-protects-against-cadmium-induced-oxidative-stress-and-toxicity-in-human-cervical-cancer-cells
#17
Daiana G Alvarez-Olmedo, Veronica S Biaggio, Geremy A Koumbadinga, Nidia N Gómez, Chunhua Shi, Daniel R Ciocca, Zarah Batulan, Mariel A Fanelli, Edward R O'Brien
Cadmium (Cd) is a carcinogen with several well-described toxicological effects in humans, but its molecular mechanisms are still not fully understood. Overexpression of heat shock protein 27 (HSP27/HSPB1)-a multifunctional protein chaperone-has been shown to protect cells from oxidative damage and apoptosis triggered by Cd exposure. The aims of this work were to investigate the potential use of extracellular recombinant HSP27 to prevent/counteract Cd-induced cellular toxicity and to evaluate if peroxynitrite was involved in the development of Cd-induced toxicity...
March 24, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28330993/transition-state-mimics-are-valuable-mechanistic-probes-for-structural-studies-with-the-arginine-methyltransferase-carm1
#18
Matthijs J van Haren, Nils Marechal, Nathalie Troffer-Charlier, Agostino Cianciulli, Gianluca Sbardella, Jean Cavarelli, Nathaniel I Martin
Coactivator associated arginine methyltransferase 1 (CARM1) is a member of the protein arginine methyltransferase (PRMT) family and methylates a range of proteins in eukaryotic cells. Overexpression of CARM1 is implicated in a number of cancers, and it is therefore seen as a potential therapeutic target. Peptide sequences derived from the well-defined CARM1 substrate poly(A)-binding protein 1 (PABP1) were covalently linked to an adenosine moiety as in the AdoMet cofactor to generate transition state mimics...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28330868/protein-arginine-methyltransferase-1-modulates-innate-immune-responses-through-regulation-of-peroxisome-proliferator-activated-receptor-gamma-dependent-macrophage-differentiation
#19
Irina Tikhanovich, Jie Zhao, Jody Olson, Abby Adams, Ryan Taylor, Brian Bridges, Laurie Marshall, Benjamin Roberts, Steven A Weinman
Arginine methylation is a common posttranslational modification that has been shown to regulate both gene expression and extranuclear signaling events. We recently reported defects in Protein Arginine Methyltransferase 1 (PRMT1) activity and arginine methylation in the livers of cirrhosis patients with a history of recurrent infections. To examine the role of PRMT1 in innate immune responses in vivo, we created a cell type specific knockout mouse model. We showed that myeloid specific PRMT1 knockout mice demonstrate higher proinflammatory cytokine production and a lower survival rate after cecal ligation and puncture...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28325791/individual-variations-in-nitric-oxide-synthase-dependent-sweating-in-young-and-older-males-during-exercise-in-the-heat-role-of-aerobic-power
#20
Tatsuro Amano, Naoto Fujii, Jeffrey C Louie, Robert D Meade, Glen P Kenny
We evaluated the association between aerobic power (defined by peak oxygen consumption; VO2peak) and the contribution of nitric oxide synthase (NOS) to the sweating response in young and older individuals during exercise in the heat. Data from 44 young (24 ± 1 years) and 48 older (61 ± 2 years) males with mean VO2peak of 47.8 ± 2.4 (range, 28.0-62.3) and 39.1 ± 2.3 (range, 26.4-55.7) mLO2 kg(-1) min(-1), respectively, were compiled from our prior studies. Participants performed two 15- to 30-min bouts of exercise at a fixed rate of metabolic heat production of 400 or 500 W, each separated by 15-20 min recovery in the heat (35°C, relative humidity of 20%)...
March 2017: Physiological Reports
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