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arginine methylation

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https://www.readbyqxmd.com/read/28087667/prmt5-selective-inhibitors-suppress-inflammatory-t-cell-responses-and-experimental-autoimmune-encephalomyelitis
#1
Lindsay M Webb, Stephanie A Amici, Kyle A Jablonski, Himanshu Savardekar, Amanda R Panfil, Linsen Li, Wei Zhou, Kevin Peine, Vrajesh Karkhanis, Eric M Bachelder, Kristy M Ainslie, Patrick L Green, Chenglong Li, Robert A Baiocchi, Mireia Guerau-de-Arellano
In the autoimmune disease multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), expansion of pathogenic, myelin-specific Th1 cell populations drives active disease; selectively targeting this process may be the basis for a new therapeutic approach. Previous studies have hinted at a role for protein arginine methylation in immune responses, including T cell-mediated autoimmunity and EAE. However, a conclusive role for the protein arginine methyltransferase (PRMT) enzymes that catalyze these reactions has been lacking...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087254/anti-diabetic-drug-metformin-dilates-retinal-blood-vessels-through-activation-of-amp-activated-protein-kinase-in-rats
#2
Asami Mori, Eriko Ishikawa, Tomoyo Amano, Kenji Sakamoto, Tsutomu Nakahara
The aim of this study was to examine whether metformin, a biguanide anti-hyperglycemic drug, dilates retinal blood vessels in rats. Ocular fundus images were captured with an original high-resolution digital fundus camera in vivo and diameters of retinal blood vessels were measured. Both systemic blood pressure and heart rate were continuously recorded. Metformin (0.01-0.3mg/kg/min) increased diameters of retinal blood vessels in a dose-dependent manner. This retinal vasodilator effect of metformin was abolished by compound C, an inhibitor of AMP-activated protein kinase (AMPK), and N(G)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide (NO) synthase...
January 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28074910/myosin-phosphatase-and-rhoa-activated-kinase-modulate-arginine-methylation-by-the-regulation-of-protein-arginine-methyltransferase-5-in-hepatocellular-carcinoma-cells
#3
Adrienn Sipos, Judit Iván, Bálint Bécsi, Zsuzsanna Darula, István Tamás, Dániel Horváth, Katalin F Medzihradszky, Ferenc Erdődi, Beáta Lontay
Myosin phosphatase (MP) holoenzyme is a protein phosphatase-1 (PP1) type Ser/Thr specific enzyme that consists of a PP1 catalytic (PP1c) and a myosin phosphatase target subunit-1 (MYPT1). MYPT1 is an ubiquitously expressed isoform and it targets PP1c to its substrates. We identified the protein arginine methyltransferase 5 (PRMT5) enzyme of the methylosome complex as a MYPT1-binding protein uncovering the nuclear MYPT1-interactome of hepatocellular carcinoma cells. It is shown that PRMT5 is regulated by phosphorylation at Thr80 by RhoA-associated protein kinase and MP...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28061334/arginine-methylation-the-coming-of-age
#4
REVIEW
Roméo S Blanc, Stéphane Richard
Arginine methylation is a common post-translational modification functioning as an epigenetic regulator of transcription and playing key roles in pre-mRNA splicing, DNA damage signaling, mRNA translation, cell signaling, and cell fate decision. Recently, a wealth of studies using transgenic mouse models and selective PRMT inhibitors helped define physiological roles for protein arginine methyltransferases (PRMTs) linking them to diseases such as cancer and metabolic, neurodegenerative, and muscular disorders...
January 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28054274/nicorandil-improves-post-fatigue-tension-in-slow-skeletal-muscle-fibers-by-modulating-glutathione-redox-state
#5
E Sánchez-Duarte, X Trujillo, C Cortés-Rojo, A Saavedra-Molina, G Camargo, L Hernández, M Huerta, R Montoya-Pérez
Fatigue is a phenomenon in which force reduction has been linked to impairment of several biochemical processes. In skeletal muscle, the ATP-sensitive potassium channels (KATP) are actively involved in myoprotection against metabolic stress. They are present in sarcolemma and mitochondria (mitoKATP channels). K(+) channel openers like nicorandil has been recognized for their ability to protect skeletal muscle from ischemia-reperfusion injury, however, the effects of nicorandil on fatigue in slow skeletal muscle fibers has not been explored, being the aim of this study...
January 4, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28050775/neuroprotective-efficacy-of-mitochondrial-antioxidant-mitoq-in-suppressing-peroxynitrite-mediated-mitochondrial-dysfunction-inflicted-by-lead-toxicity-in-the-rat-brain
#6
Arpan Kumar Maiti, Nimai Chandra Saha, Sunil S More, Ashish Kumar Panigrahi, Goutam Paul
Lead (Pb) is one of the most pollutant metals that accumulate in the brain mitochondria disrupting mitochondrial structure and function. Though oxidative stress mediated by reactive oxygen species remains the most accepted mechanism of Pb neurotoxicity, some reports suggest the involvement of nitric oxide ((•)NO) and reactive nitrogen species in Pb-induced neurotoxicity. But the impact of Pb neurotoxicity on mitochondrial respiratory enzyme complexes remains unknown with no relevant report highlighting the involvement of peroxynitrite (ONOO(-)) in it...
January 3, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28043171/the-story-of-protein-arginine-methylation-characterization-regulation-and-function
#7
Chao Peng, Catherine Cl Wong
Arginine methylation is an important post-translational modification (PTM) in cells, which is catalyzed by a group of protein arginine methyltransferases (PRMTs). It plays significant roles in diverse cellular processes and various diseases. Misregulation and aberrant expression of PRMTs can provide potential biomarkers and therapeutic targets for drug discovery. Areas covered: Herein, we review the arginine methylation literature and summarize the methodologies for the characterization of this modification, as well as describe the recent insights into arginine methyltransferases and their biological functions in diseases...
January 5, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28042453/design-and-synthesis-of-selective-small-molecule-inhibitors-of-coactivator-associated-arginine-methyltransferase-1-carm1
#8
H Ü Kaniskan, M S Eram, J Liu, D Smil, M L Martini, Y Shen, V Santhakumar, P J Brown, C Arrowsmith, M Vedadi, J Jin
Coactivator-associated arginine methyltransferase 1 (CARM1) is a type I protein arginine methyltransferase (PRMT) that catalyzes the conversion of arginine into monomethylarginine (MMA) and further into asymmetric dimethylarginine (ADMA). CARM1 methylates histone 3 arginines 17 and 26, as well as numerous non-histone proteins including CBP/p300, SRC-3, NCOA2, PABP1, and SAP49, while also functioning as a coactivator for various proteins that have been linked to cancer such as p53, NF-κβ, β-catenin, E2F1 and steroid hormone receptor ERα...
September 1, 2016: MedChemComm
https://www.readbyqxmd.com/read/28041850/lipid-sorting-specificity-encoded-in-k-ras-membrane-anchor-regulates-signal-output
#9
Yong Zhou, Priyanka Prakash, Hong Liang, Kwang-Jin Cho, Alemayehu A Gorfe, John F Hancock
K-Ras is targeted to the plasma membrane by a C-terminal membrane anchor that comprises a farnesyl-cysteine-methyl-ester and a polybasic domain. We used quantitative spatial imaging and atomistic molecular dynamics simulations to examine molecular details of K-Ras plasma membrane binding. We found that the K-Ras anchor binds selected plasma membrane anionic lipids with defined head groups and lipid side chains. The precise amino acid sequence and prenyl group define a combinatorial code for lipid binding that extends beyond simple electrostatics; within this code lysine and arginine residues are non-equivalent and prenyl chain length modifies nascent polybasic domain lipid preferences...
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28040796/role-of-rpl39-in-metaplastic-breast-cancer
#10
Bhuvanesh Dave, Daniel D Gonzalez, Zhi-Bin Liu, Xiaoxian Li, Helen Wong, Sergio Granados, Nadeer E Ezzedine, Douglas H Sieglaff, Joe E Ensor, Kathy D Miller, Milan Radovich, Agda KarinaEtrovic, Steven S Gross, Olivier Elemento, Gordon B Mills, Michael Z Gilcrease, Jenny C Chang
BACKGROUND: Metaplastic breast cancer is one of the most therapeutically challenging forms of breast cancer because of its highly heterogeneous and chemoresistant nature. We have previously demonstrated that ribosomal protein L39 (RPL39) and its gain-of-function mutation A14V have oncogenic activity in triple-negative breast cancer and this activity may be mediated through inducible nitric oxide synthase (iNOS). The function of RPL39 and A14V in other breast cancer subtypes is currently unknown...
June 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28040436/fam98a-associates-with-ddx1-c14orf166-fam98b-in-a-novel-complex-involved-in-colorectal-cancer-progression
#11
Khondker Ayesha Akter, Mohammed A Mansour, Toshinori Hyodo, Takeshi Senga
Protein Arginine Methyl Transferase 1 (PRMT1) is deemed to be a potential oncogenic protein considering its overexpression in several malignancies including colorectal cancer. However, the molecular pathogenesis regarding PRMT1 overexpression and overall poor patient survival involved in this devastating and life threatening cancer remains obscured. In our previous study, we have identified FAM98A as a novel substrate of PRMT1 and also identified its role in ovarian cancer progression. Here, we showed that the two structural homologs FAM98A and FAM98B included in a novel complex with DDX1 and C14orf166 are required for PRMT1 expression...
December 28, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28025466/deterioration-of-epithelium-mediated-mechanisms-in-diabetic-antigen-sensitized-airways-of-guinea-pigs
#12
Saidullah Bano, Omanwar Swati, Muralidhar Kambadur, Fahim Mohammad
BACKGROUND: The onset of diabetes causes disruption of respiratory epithelial mediators. The present study investigates whether diabetes modifies the epithelium mediated bronchial responses in hyper-reactive airway smooth muscle (ASM) primarily through nitric oxide (NO), cyclooxygenase (COX), and epithelium derived hyperpolarizing factor (EpDHF) pathways. METHODS: Experimental model of guinea pigs having hyper-reactive airways with or without diabetes were developed...
2016: Journal of Smooth Muscle Research, Nihon Heikatsukin Gakkai Kikanshi
https://www.readbyqxmd.com/read/28006762/h2s-attenuates-lps-induced-acute-lung-injury-by-reducing-oxidative-nitrative-stress-and-inflammation
#13
Hong-Xia Zhang, Shu-Juan Liu, Xiao-Lu Tang, Guo-Li Duan, Xin Ni, Xiao-Yan Zhu, Yu-Jian Liu, Chang-Nan Wang
BACKGROUND: Hydrogen sulfide (H2S), known as the third endogenous gaseous transmitter, has received increasing attention because of its diverse effects, including angiogenesis, vascular relaxation and myocardial protection.We aimed to investigate the role of H2S in oxidative/nitrative stress and inflammation in acute lung injury (ALI) induced by endotoxemia. METHODS: Male ICR mice were divided in six groups: (1) Control group; (2) GYY4137treatment group; (3) L-NAME treatment group; (4) lipopolysaccharide (LPS) treatment group; (5) LPS with GYY4137 treatment group; and (6) LPS with L-NAME treatment group...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28005704/the-antioxidant-effects-of-green-tea-reduces-blood-pressure-and-sympathoexcitation-in-an-experimental-model-of-hypertension
#14
Michelle L Garcia, Roberto B Pontes, Erika E Nishi, Flávia K Ibuki, Vanessa Oliveira, Alexandra C H Sawaya, Patrícia O Carvalho, Fernando N Nogueira, Maria do Carmo Franco, Ruy R Campos, Lila M Oyama, Cássia T Bergamaschi
BACKGROUND: Oxidative stress is a key mediator in the maintenance of sympathoexcitation and hypertension in human and experimental models. Green tea is widely known to be potent antioxidant. OBJECTIVE: We aimed to evaluate the effects of green tea in a model of hypertension. METHODS: Hypertension was induced by the nitric oxide synthase inhibitor [N-nitro-L-arginine-methyl-ester (L-NAME); 20 mg/kg per day, orally, for 2 weeks] in male Wistar rats...
February 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28000775/structural-basis-of-the-substrate-preference-towards-cmp-for-a-thymidylate-synthase-mila-involved-in-mildiomycin-biosynthesis
#15
Gong Zhao, Cheng Chen, Wei Xiong, Tuling Gao, Zixin Deng, Geng Wu, Xinyi He
Modified pyrimidine monophosphates such as methyl dCMP (mdCMP), hydroxymethyl dUMP (hmdUMP) and hmdCMP in some phages are synthesized by a large group of enzymes termed as thymidylate synthases (TS). Thymidylate is a nucleotide required for DNA synthesis and thus TS is an important drug target. In the biosynthetic pathway of the nucleoside fungicide mildiomycin isolated from Streptomyces rimofaciens ZJU5119, a cytidylate (CMP) hydroxymethylase, MilA, catalyzes the conversion of CMP into 5'-hydroxymethyl CMP (hmCMP) with an efficiency (kcat/KM) of 5-fold faster than for deoxycytidylate (dCMP)...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27999187/targeting-the-pro-angiogenic-forms-of-vegf-or-inhibiting-their-expression-as-anti-cancer-strategies
#16
Mélanie Guyot, Caroline Hilmi, Damien Ambrosetti, Marco Merlano, Cristiana Lo Nigro, Jérôme Durivault, Renaud Grépin, Gilles Pagès
Tumor growth relies on oxygen and blood supply depending on neo-vascularization. This process is mediated by the Vascular Endothelial Growth Factor (VEGF) in many tumors. This paradigm has led to the development of specific therapeutic approaches targeting VEGF or its receptors. Despite their promising effects, these strategies have not improved overall survival of patients suffering from different cancers compared to standard therapies. We hypothesized that the existence of anti-angiogenic forms of VEGF VEGFxxxb which are still present in many tumors limit the therapeutic effects of the anti-VEGF antibodies bevacizumab/Avastin (BVZ)...
December 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27998975/the-major-protein-arginine-methyltransferase-in-trypanosoma-brucei-functions-as-an-enzyme-prozyme-complex
#17
Lucie Kafkova, Erik W Debler, John C Fisk, Kanishk Jain, Steven G Clarke, Laurie K Read
Prozymes are catalytically inactive enzyme paralogs that dramatically stimulate the function of weakly active enzymes through complex formation. The two prozymes described to date reside in the polyamine biosynthesis pathway of the human parasite, Trypanosoma brucei, an early branching eukaryote that lacks transcriptional regulation and regulates proteome through posttranscriptional and posttranslational means. Arginine methylation is a common posttranslational modification in eukaryotes catalyzed by protein arginine methyltransferases (PRMTs) that are typically thought to function as homodimers...
December 20, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27995418/the-effects-of-sildenafil-citrate-on-urinary-podocin-and-nephrin-mrna-expression-in-an-l-name-model-of-pre-eclampsia
#18
Sooraj Baijnath, Saravanakumar Murugesan, Irene Mackraj, Prem Gathiram, Jagidesa Moodley
We investigated the effects of sildenafil citrate (SC) on podocyturia in N (ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME) model of pre-eclampsia (PE). One hundred and twenty Sprague-Dawley rats (SDR) were divided into five groups like pregnant control (PC), early-onset PE (EOPE), late-onset PE(LOPE), early and late-onset PE with SC-treated groups [EOPE (SC); LOPE (SC)]. PE was induced in SDR by oral administration of L-NAME in drinking water for 4-8 days for EOPE and 8-14 day for LOPE. The blood pressure, urine volume and total urine protein were increased in EOPE and LOPE groups when compared to PC, and all the above parameters decreased in EOPE (SC) and LOPE (SC) groups when compared to EOPE and LOPE groups, respectively...
December 19, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27993397/hydrodynamic-sample-injection-into-short-electrophoretic-capillary-in-systems-with-a-flow-gating-interface
#19
František Opekar, Petr Tůma
An electrophoretic apparatus with a flow-gating interface has been developed, enabling hydrodynamic sequence injection of the sample into the separation capillary from the liquid flow by underpressure generated in the outlet electrophoretic vessel. The properties of the apparatus were tested on an artificial sample of an equimolar mixture of 100μM potassium and sodium ions and arginine. The repeatability of the injection of the tested ions expressed as RSD (in%) for the peak area, peak height and migration time was in the range 0...
January 13, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/27993120/in-vitro-vasorelaxant-effect-of-artemisia-herba-alba-asso-in-spontaneously-hypertensive-rats
#20
Zeggwah Naoufel, Morad Hebi, Muhammad Ajebli, Jean B Michel, Muhammad Eddouks
BACKGROUND: The present study aims to evaluate the in vitro vasorelaxant effect of Artemisia herba alba (Ah) aqueous extract. METHOD: Aortic rings were isolated from spontaneously hypertensive rats and incubated in aqueous Ah extract at the following doses: 3, 5, 10 and 20 mg/ml. Incubation of aqueous Ah extract for 30 minutes produced a significant shift of the dose response curve to Norepinephrine (NE) (10-8 to 10-5 M) (p<0.001). RESULTS: Endothelium ablation significantly reduced the vasorelaxant effect of aqueous Ah extract (p<0...
December 15, 2016: Cardiovascular & Hematological Agents in Medicinal Chemistry
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