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arginine methylation

Chu Shan Tan, Mun Fei Yam
Previous studies have demonstrated that 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (TMF) content in Orthosiphon stamineus fractions correlate with its vasorelaxation activity. Even with the availability of previous studies, there is still very little information on the vasorelaxation effect of TMF, and few scientific studies have been carried out. Therefore, the present study was designed to investigate the vasorelaxation activity and mechanism of action of the TMF. The vasorelaxation activity and the underlying mechanisms of TMF were evaluated on thoracic aortic rings isolated from Sprague Dawley rats...
March 19, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Fernando Francisco Borges Resende, Simoneide Souza Titze-de-Almeida, Ricardo Titze-de-Almeida
Astrocytic tumors, including astrocytomas and glioblastomas, are the most common type of primary brain tumors. Treatment for glioblastomas includes radiotherapy, chemotherapy with temozolomide (TMZ) and surgical ablation. Despite certain therapeutic advances, the survival time of patients is no longer than 12-14 months. Cancer cells overexpress the neuronal isoform of nitric oxide synthase (nNOS). In the present study, it was examined whether the nNOS enzyme serves a role in the damage of astrocytoma (U251MG and U138MG) and glioblastoma (U87MG) cells caused by TMZ...
April 2018: Oncology Letters
Kun Qian, Hao Hu, Hui Xu, Y George Zheng
Protein arginine methyltransferases (PRMTs) are crucial epigenetic regulators in eukaryotic organisms that serve as histone writers for chromatin remodeling. PRMTs also methylate a variety of non-histone protein substrates to modulate their function and activity. The development of potent PRMT inhibitors has become an emerging and imperative research area in the drug discovery field to provide novel therapeutic agents for treating diseases and as tools to investigate the biological functions of PRMTs. PRMT1 is the major type I enzyme that catalyzes the formation of asymmetric dimethyl arginine, and PRMT1 plays important regulatory roles in signal transduction, transcriptional activation, RNA splicing, and DNA repair...
2018: Signal Transduction and Targeted Therapy
Tom H Wright, Benjamin G Davis
Methods for installing natural and unnatural amino acids and their modifications into proteins in a benign and precise manner are highly sought-after in protein science. Here we describe a protocol for 'post-translational mutagenesis' that enables the programmed installation of protein side chains through the use of rapid, mild and operationally simple free-radical chemistry performed on recombinantly expressed and purified proteins. By introduction of protein dehydroalanine (Dha) residues (in this instance, from a unique cysteine residue introduced by site-directed mutagenesis) as free-radical trapping 'tags' for downstream modification, exquisite control over the site of subsequent modification is achieved...
October 2017: Nature Protocols
Scott K Ferguson, Julie W Harral, David I Pak, Katherine M Redinius, Kurt R Stenmark, Dominik J Schaer, Paul W Buehler, David C Irwin
Free hemoglobin (Hb) associated with hemolysis extravasates into vascular tissue and depletes nitric oxide (NO), which leads to impaired vascular function and could impair skeletal muscle metabolic control during exercise. We tested the hypothesis that: 1) free Hb would extravasate into skeletal muscle tissue, reducing the contracting skeletal muscle O2 delivery/O2 utilization ratio (microvascular PO2 , PO2 mv) to a similar extent as that observed following NO synthase (NOS) blockade, and 2) that the Hb scavenging protein haptoglobin (Hp) would prevent Hb extravasation and inhibit these skeletal muscle tissue effects...
March 8, 2018: Nitric Oxide: Biology and Chemistry
Zhongjian Cheng, Xinggui Shen, Xiaohua Jiang, Huimin Shan, Maria Cimini, Pu Fang, Yong Ji, Joon Young Park, Konstantinos Drosatos, Xiaofeng Yang, Christopher G Kevil, Raj Kishore, Hong Wang
Insufficient hydrogen sulfide (H2 S) has been implicated in Type 2 diabetic mellitus (T2DM) and hyperhomocysteinemia (HHcy)-related cardiovascular complications. We investigated the role of H2 S in T2DM and HHcy-induced endothelial dysfunction in small mesenteric artery (SMA) of db/db mice fed a high methionine (HM) diet. HM diet (8 weeks) induced HHcy in both T2DM db/db mice and non-diabetic db/+ mice (total plasma Hcy: 48.4 and 31.3 µM, respectively), and aggravated the impaired endothelium-derived hyperpolarization factor (EDHF)-induced endothelium-dependent relaxation to acetylcholine (ACh), determined by the presence of eNOS inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) and prostacyclin (PGI2 ) inhibitor indomethacin (INDO), in SMA from db/db mice but not that from db/+ mice...
February 14, 2018: Redox Biology
Hong-Qiang Chen, Ji Zhao, Yan Li, Li-Xiong He, Yu-Jing Huang, Wei-Qun Shu, Jia Cao, Wen-Bin Liu, Jin-Yi Liu
Microcystin (MC) is a cyclic heptapeptide compound which could lead to the development of hepatocellular carcinoma. However, the underlying epigenetic regulation mechanism is largely unknown. In this study, microcystin-LR (L: lysine, R: arginine, MC-LR) was used to induce the malignant transformation of human hepatocyte L02 cell line. The profile of gene expression, microRNA (miRNA) and DNA methylation were detected through high-throughput sequencing. Compared with control group, the expression of 826 genes and 187 miRNAs changed significantly in MC-LR treated group...
March 5, 2018: Toxicology Letters
David E Timm, Valorie Bowman, Russell Madsen, Charles Rauch
Protein arginine methyl transferase 5 (PRMT5) is a signaling protein and histone modifying enzyme that is important in many cellular processes, including regulation of eukaryotic gene transcription. Reported here is a 3.7 Å structure of PRMT5, solved in complex with regulatory binding subunit MEP50 (methylosome associated protein 50, WDR77, p44), by single particle (SP) cryo-Electron Microscopy (cryo-EM) using micrographs of particles that are visibly crowded and aggregated. Despite suboptimal micrograph appearance, this cryo-EM structure is in good agreement with previously reported crystal structures of the complex, which revealed a 450 kDa hetero-octameric assembly having internal D2 symmetry...
2018: PloS One
Keyun Wang, Mingliang Ye
Protein methylation is receiving increasing attention for its important role in regulating diverse biological processes, including epigenetic regulation of gene transcription, RNA processing, DNA damage repair, and signal transduction. Proteome level analysis of protein methylation requires the enrichment of various forms of methylated peptides. Unfortunately, immunoaffinity purification can only enrich a subset of them due to the lack of pan-specific antibodies. Chromatography-based methods, however, can enrich methylated peptides in a global manner...
February 21, 2018: Current Protocols in Protein Science
Carla Blum-Johnston, Richard B Thorpe, Chelsea Wee, Raechel Opsahl, Monica Romero, Samuel Murray, Alexander Brunelle, Quintin Blood, Rachael Wilson, Arlin B Blood, Lubo Zhang, Lawrence D Longo, William J Pearce, Sean M Wilson
Bradykinin-induced activation of the pulmonary endothelium triggers a rise in intracellular Ca2+ , which activates nitric oxide (NO)-dependent vasorelaxation. Chronic hypoxia is commonly associated with increased pulmonary vascular tone, which can cause pulmonary hypertension in responsive individuals. In the present study, we tested the hypothesis that long-term high altitude hypoxia (LTH) diminishes bradykinin-induced Ca2+ signals and inhibits eNOS, PGI2 and BKCa channels in sheep, which are moderately responsive to LTH, resulting in decreased pulmonary arterial vasorelaxation...
March 7, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Tracy Bell, Magali Araujo, Zaiming Luo, James Tomlinson, James Leiper, William J Welch, Christopher S Wilcox
BACKGROUND: Nitric oxide prevents hypertension yet paradoxically reduces proximal tubule Na+ reabsorption. Nitric oxide synthase is inhibited by asymmetric dimethylarginine (ADMA) that is metabolized by dimethylarginine dimethylaminohydrolase (DDAH) whose type 1 isoform is expressed abundantly in the PT. HYPOTHESIS: That ADMA generated by DDAH-1 fluid reabsorbtion (Jv) by the proximal tubule. METHODS: S2 segments of the PT were perfused in vivo to assess Jv...
March 7, 2018: American Journal of Physiology. Renal Physiology
Masakazu Kotoda, Tadahiko Ishiyama, Kazuha Mitsui, Sohei Hishiyama, Takashi Matsukawa
PURPOSE: Nicorandil has dual properties and acts as a nitric oxide donor and an ATP-sensitive potassium (KATP ) channel opener. Considering its pharmacological profile, nicorandil might exert protective effects on the brain as well as on the heart. The purpose of this study was to directly evaluate the effect of nicorandil on cerebral blood flow (CBF) in mice using a transcranial Doppler method. METHODS: Under general anesthesia, the nicorandil groups received a single-bolus intraperitoneal injection of the respective doses of nicorandil (1, 5, or 10 mg/kg), while the control group received vehicle only...
March 5, 2018: Journal of Anesthesia
Yongchul Lim, Suyeun Yu, Jung-A Yun, In-Gu Do, Lan Cho, Yang Hee Kim, Hee Cheol Kim
Protein arginine methylation is involved in cellular differentiation and proliferation. Recently, aberrant expression of protein arginine methyltransferases, which are responsible for the methylation reaction, has been reported in various types of cancer. However, there is no clear evidence regarding the prognostic value of abnormal PRMT6 expression in colorectal cancer or the effect of PRMT6 regulation on CRC cells. We investigated the expression patterns of PRMT6 in patients with stage II and III CRC. We detected nuclear expression of PRMT6 in 23...
February 6, 2018: Oncotarget
Dariusz Zakrzewicz, Miroslava Didiasova, Marcus Krüger, Benedetto Daniele Giaimo, Tilman Borggrefe, Maren Mieth, Andreas C Hocke, Anna Zakrzewicz, Liliana Schaefer, Klaus T Preissner, Malgorzata Wygrecka
OBJECTIVES: Enolase-1-dependent cell surface proteolysis plays an important role in cell invasion. Although enolase-1 (Eno-1), a glycolytic enzyme, has been found on the surface of various cells, the mechanism responsible for its exteriorization remains elusive. Here, we investigated the involvement of post-translational modifications (PTMs) of Eno-1 in its lipopolysaccharide (LPS)-triggered trafficking to the cell surface. RESULTS: We found that stimulation of human lung adenocarcinoma cells with LPS triggered the monomethylation of arginine 50 (R50me) within Eno-1...
March 1, 2018: Biochimica et Biophysica Acta
Soo Jin Yang, Hyun Ju Do, Youngae Jung, Geum-Sook Hwang, Min-Jeong Shin
The alpha-glucosidase inhibitor voglibose (VO) was recently reported to have a protective effect against weight gain as well as affect various metabolic changes related to food intake and gut-brain signaling. We hypothesized that VO prevents weight gain by altering neurometabolome profiles in the hypothalamus to reduce food intake. To test this hypothesis, we assessed metabolite profiles in the hypothalamus of standard diet- or high-fat (HF) diet-fed mice in the absence or presence of VO. In total, 29 male C57BL/6 mice were divided into 3 groups: (1) lean control, (2) HF, and (3) HF + VO...
March 1, 2018: Nutritional Neuroscience
Michael P Greenwood, Mingkwan Greenwood, Elena V Romanova, Andre S Mecawi, Alex Paterson, Olivera Sarenac, Nina Japundžić-Žigon, José Antunes-Rodrigues, Julian F R Paton, Jonathan V Sweedler, David Murphy
Elderly people exhibit a diminished capacity to cope with osmotic challenges such as dehydration. We have undertaken a detailed molecular analysis of arginine vasopressin (AVP) biosynthetic processes in the supraoptic nucleus (SON) of the hypothalamus and secretory activity in the posterior pituitary of adult (3 months) and aged (18 months) rats, to provide a comprehensive analysis of age-associated changes to the AVP system. By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, we identified differences in pituitary peptides, including AVP, in adult and aged rats under both basal and dehydrated states...
January 31, 2018: Neurobiology of Aging
Bailin Liu, Yanping Liu, Ruixiu Shi, Xueqin Feng, Xiang Li, Wenna Zhang, Jue Wu, Na Li, Xiuwen Zhou, Miao Sun, Zhice Xu
BACKGROUND/AIMS: Chronic hypoxia in utero could impair vascular functions in the offspring, underlying mechanisms are unclear. This study investigated functional alteration in large-conductance Ca2+-activated K+ (BK) channels in offspring mesenteric arteries following prenatal hypoxia. METHODS: Pregnant rats were exposed to normoxic control (21% O2, Con) or hypoxic (10.5% O2, Hy) conditions from gestational day 5 to 21, their 7-month-old adult male offspring were tested for blood pressure, vascular BK channel functions and expression using patch clamp and wire myograh technique, western blotting, and qRT-PCR...
February 21, 2018: Cellular Physiology and Biochemistry
Mark McEvoy, David C Harris, Arduino A Mangoni, Julia Z Sarant
OBJECTIVE: Age-related hearing loss is associated with endothelial dysfunction and increased cardiovascular risk, suggesting a vascular etiology. Methylarginines are endogenous nitric oxide synthase inhibitors that cause endothelial dysfunction and increase cardiovascular disease risk. This study is the first to examine the hypothesis that higher serum concentrations of methylarginines are associated with greater hearing loss prevalence. STUDY DESIGN/PATIENTS: Cross-sectional audiometric data on hearing levels, and serum methylarginines were collected from a population-based sample of 630 older community-dwelling adults...
February 23, 2018: Otology & Neurotology
Wataru Matsuura, Shinichi Harada, Keyue Liu, Masahiro Nishibori, Shogo Tokuyama
We have previously showed that spinal high-mobility group box-1 (HMGB1) plays an important role in the induction of central post-stroke pain (CPSP). It has been reported that HMGB1 exacerbates inflammation and pain via TLR4 or RAGE. Furthermore, the relationship between glial cells, such as microglia and astrocytes, involved in pain exacerbation and HMGB1 has also attracted attention. In this study, we investigated whether the interaction between spinal glial cells and HMGB1 signaling, including its receptors TLR4 or RAGE, is directly involved in the induction of CPSP...
February 21, 2018: Brain Research
Lifeng Huang, Zhihao Wang, Nithya Narayanan, Yanzhong Yang
DNA topoisomerase 3B (TOP3B) is unique among all mammalian topoisomerases for its dual activities that resolve both DNA and RNA topological entanglements to facilitate transcription and translation. However, the mechanism by which TOP3B activity is regulated is still elusive. Here, we have identified arginine methylation as an important post-translational modification (PTM) for TOP3B activity. Protein arginine methyltransferase (PRMT) 1, PRMT3 and PRMT6 all methylate TOP3B in vitro at its C-terminal arginine (R) and glycine (G)-rich motif...
February 19, 2018: Nucleic Acids Research
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