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https://www.readbyqxmd.com/read/29660457/a-lectin-fraction-from-green-seaweed-caulerpa-cupressoides-inhibits-inflammatory-nociception-in-the-temporomandibular-joint-of-rats-dependent-from-peripheral-mechanisms
#1
Renata Line da Conceição Rivanor, Danielle Rocha Do Val, Natássia Albuquerque Ribeiro, Felipe Dantas Silveira, Ellen Lima de Assis, Álvaro Xavier Franco, Lorena Vasconcelos Vieira, Ismael Nilo Lino de Queiroz, Hellíada Vasconcelos Chaves, Mirna Marques Bezerra, Norma Maria Barros Benevides
Temporomandibular disorders are the second most common cause of orofacial pain mediated by inflammatory compounds, which in many cases leads to chronic orofacial pain. This study assessed the antinociceptive and anti-inflammatory effects of a lectin from the green seaweed Caulerpa cupressoides (CcL) on hypernociception inflammatory in TMJ of rats and investigated the involvement of different mechanisms. Rats received i.v. CcL 30 min prior to injection of flogistic agentes or 0.9% saline into the left TMJ...
April 13, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29649180/establishing-a-split-luciferase-assay-for-proteinkinase-g-pkg-interaction-studies
#2
Andrea Schramm, Philip Mueller-Thuemen, Timo Littmann, Manuela Harloff, Takeaki Ozawa, Jens Schlossmann
Nitric oxide (NO/cyclic guanosine monophosphate (cGMP)-regulated cellular mechanisms are involved in a variety of (patho-) physiological processes. One of the main effector molecules in this system, proteinkinase G (PKG), serves as a molecular switch by phosphorylating different target proteins and thereby turning them on or off. To date, only a few interaction partners of PKG have been described although the identification of protein-protein interactions (PPI) is indispensable for the understanding of cellular processes and diseases...
April 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29617357/cyclic-guanosine-monophosphate-cgmp-dependent-protein-kinase-ii-blocks-epidermal-growth-factor-egf-epidermal-growth-factor-receptor-egfr-induced-biological-effects-on-osteosarcoma-cells
#3
Dapeng Li, Ye Hua, Lu Jiang, Yonghui Huang, Jiawei Yue, Yan Wu, Yongchang Chen
BACKGROUND The present work was performed to detect the potential inhibitory effect of cyclic guanosine monophosphate (cGMP)-dependent protein kinase II (PKG II) on epidermal growth factor (EGF) receptor-induced biological activity and related signal cascades in osteosarcoma cells. MATERIAL AND METHODS We transfected the osteosarcoma MG-63 cell line with an adenoviral vector encoding PKG II cDNA (Ad-PKGII) and incubated the transfected cells with 250 μM 8-pCPT-cGMP to activate the PKG II. We stimulated the MG-63 cells with100 ng/ml EGF, and then detected their proliferation using a CCK-8 assay...
April 4, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29610853/a-novel-selective-soluble-guanylate-cyclase-activator-mgv354-lowers-intraocular-pressure-in-preclinical-models-following-topical-ocular-dosing
#4
Ganesh Prasanna, Luciana Ferrara, Christopher Adams, Takeru Ehara, Byron Li, Louis Yang, Chuanxi Xiang, Christopher Thow Hing Ng, Sean Kim, Christopher Towler, Todd Topley, Cale McAllister, Malay Ghosh, Ronald Newton, Rebecca Stacy, Dennis S Rice, Muneto Mogi
Purpose: The nitric oxide/soluble guanylate cyclase/protein kinase G (NO/sGC/PKG) is known to be involved in the regulation of intraocular pressure (IOP) and may be dysregulated in glaucoma. The purpose is to demonstrate that the sGC activator MGV354 lowers IOP in a monkey model of glaucoma and could be considered as a possible new clinical drug candidate. Methods: Changes to cGMP were assessed in primary human trabecular meshwork (hNTM) cells and binding studies were conducted using human sGC full-length protein...
April 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29604206/from-molecules-to-patients-exploring-the-therapeutic-role-of-soluble-guanylate-cyclase-stimulators
#5
Peter Sandner
Nitric Oxide (NO) signaling represents one of the major regulatory pathways for cardiovascular function. After the discovery of NO, awarded with the Nobel Prize in 1998, this signaling cascade was stepwise clarified. We now have a good understanding of NO production and NO downstream targets such as the soluble guanylyl cyclases (sGCs) which catalyze cGMP production. Based on the important role of NO-signaling in the cardiovascular system, intense research and development efforts are currently ongoing to fully exploit the therapeutic potential of cGMP increase...
March 1, 2018: Biological Chemistry
https://www.readbyqxmd.com/read/29602907/an-n-terminally-truncated-form-of-cyclic-gmp-dependent-protein-kinase-i%C3%AE-pkg-i%C3%AE-is-monomeric-autoinhibited-and-provides-a-model-for-activation
#6
Thomas M Moon, Jessica L Sheehe, Praveena Nukareddy, Lydia W Nausch, Jessica Wohlfahrt, Dwight E Matthews, Donald K Blumenthal, Wolfgang R Dostmann
The type I cGMP-dependent protein kinases serve essential physiological functions, including smooth muscle relaxation, cardiac remodeling, and platelet aggregation. These enzymes form homodimers through their N-terminal dimerization domains, a feature implicated in regulating their cooperative activation. Previous investigations into the activation mechanisms of PKG I isoforms have been largely influenced by structures of the cAMP-dependent protein kinase (PKA). Here, we examined PKG Iα activation by cGMP and cAMP by engineering a monomeric form that lacks N-terminal residues 1-53 (Δ53)...
March 30, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29590153/mechanisms-for-type-ii-vitellogenesis-inhibiting-hormone-suppression-of-vitellogenin-transcription-in-shrimp-hepatopancreas-crosstalk-of-gc-cgmp-pathway-with-different-mapk-dependent-cascades
#7
Ting Chen, Chunhua Ren, Xiao Jiang, Lvping Zhang, Hongmei Li, Wen Huang, Chaoqun Hu
Vitellogenesis is the process of yolk formation via accumulating vitellin (Vn) with nutrients in the oocytes. Expression of vitellogenin (Vg), the precursor of Vn, is one of the indicators for the start of vitellogenesis. In Pacific white shrimp (Litopenaeus vannamei), the type-II vitellogenesis-inhibiting hormone (VIH-2) effectively suppresses hepatopancreatic Vg mRNA expression. In this study, we demonstrate the increasing transcript levels of hepatopancreatic Vg during L. vannamei ovarian development, suggesting that the hepatopancreas-derived Vg/Vn may also contribute to vitellogenesis in this species...
2018: PloS One
https://www.readbyqxmd.com/read/29584705/particulate-guanylyl-cyclase-a-cgmp-signaling-pathway-in-the-kidney-physiologic-and-therapeutic-indications
#8
REVIEW
Yang Chen, John C Burnett
The particulate guanylyl cyclase A (pGC-A)/cGMP pathway plays important roles in regulating renal physiological function and as well as in counteracting pathophysiological conditions. Naturally occurring peptide pGC-A activators consist of atrial natriuretic peptide (ANP), b-type NP (BNP), and urodilatin (URO). These activators bind and activate pGC-A, generating the second messenger cyclic 3',5' guanosine monophosphate (cGMP). Cyclic GMP binds to downstream pathway effector molecules including protein kinase G (PKG), cGMP-gated ion channels, and phosphodiesterases (PDEs)...
March 27, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29577868/regulation-of-smooth-muscle-myosin-light-chain-phosphatase-by-multi-site-phosphorylation-of-the-myosin-targeting-subunit-mypt1
#9
Michael P Walsh, Justin A MacDonald
Smooth muscle contraction is triggered primarily by activation of Ca2+/calmodulin-dependent myosin light chain kinase leading to phosphorylation of the regulatory light chains of myosin II. Numerous contractile stimuli also induce inhibition of myosin light chain phosphatase thereby prolonging the contractile response. The phosphatase is a trimeric enzyme containing a catalytic subunit, a regulatory, myosin-binding subunit (MYPT1) and a third subunit of uncertain function. MYPT1 is phosphorylated at multiple sites by several kinases, which regulate phosphatase activity, protein-protein interactions and subcellular localization...
March 26, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29566761/the-expression-profile-of-human-peripheral-blood-mononuclear-cell-mirna-is-altered-by-antibody-dependent-enhancement-of-infection-with-dengue-virus-serotype-3
#10
Liming Jiang, Qiangming Sun
BACKGROUND: Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection has been identified as the main risk factor for severe dengue disease, although the underlying mechanisms leading to severe dengue fever remain unclear. MicroRNAs (miRNAs) participate in numerous pathological and biological processes, including host responses to viral infections. METHOD: Here, we aimed to investigate the differences in miRNA expression patterns in human peripheral blood mononuclear cells (PBMCs) infected with DENV-3 and DENV-3-ADE at various time points employing high-throughput sequencing...
March 22, 2018: Virology Journal
https://www.readbyqxmd.com/read/29565464/comprehensive-analysis-of-differential-expression-profiles-of-mrnas-and-lncrnas-and-identification-of-a-14-lncrna-prognostic-signature-for-patients-with-colon-adenocarcinoma
#11
Yanwei Xing, Zhiwei Zhao, Yuekun Zhu, Liangliang Zhao, Anlong Zhu, Daxun Piao
The objective of this study was to identify potentially significant genes and long non-coding RNAs (lncRNAs) in colon cancer for a panel of lncRNA signatures that could be used as prognostic markers for colon adenocarcinoma (COAD) based on the data from The Cancer Genome Atlas (TCGA). RNA-seq V2 exon data of COAD were downloaded from the TCGA data portal for 285 tumor samples and 41 normal tissue samples adjacent to tumors. Differentially expressed mRNAs and lncRNAs were identified. A functional enrichment analysis of differentially expressed mRNAs was performed, followed by protein-protein interaction (PPI) network construction and significant module selection...
May 2018: Oncology Reports
https://www.readbyqxmd.com/read/29563296/new-threats-of-h7n9-influenza-virus-the-spread-and-evolution-of-highly-and-low-pathogenic-variants-with-high-genomic-diversity-in-wave-five
#12
Chuansong Quan, Weifeng Shi, Yang Yang, Yongchun Yang, Xiaoqing Liu, Wen Xu, Hong Li, Juan Li, Qianli Wang, Zhou Tong, Gary Wong, Cheng Zhang, Sufang Ma, Zhenghai Ma, Guanghua Fu, Zewu Zhang, Yu Huang, Houhui Song, Liuqing Yang, William J Liu, Yingxia Liu, Wenjun Liu, George F Gao, Yuhai Bi
H7N9 virus has caused five infection waves since it emerged in 2013. The highest number of human cases was seen in Wave Five; however, the underlying reasons have not been thoroughly elucidated. In this study, the geographical distribution, phylogeny and genetic evolution of 240 H7N9 viruses in Wave Five, including 35 new isolates from patients and poultry in nine provinces, were comprehensively analyzed together with strains from first four waves. Geographical distribution analysis displayed the newly-emerging highly pathogenic (HP) and low pathogenic (LP) H7N9 viruses were co-circulating, causing human and poultry infections across China...
March 21, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29550521/effects-of-the-no-soluble-guanylate-cyclase-cgmp-system-on-the-functions-of-human-platelets
#13
REVIEW
Stephanie Makhoul, Elena Walter, Oliver Pagel, Ulrich Walter, Albert Sickmann, Stepan Gambaryan, Albert Smolenski, René P Zahedi, Kerstin Jurk
Platelets are circulating sentinels of vascular integrity and are activated, inhibited, or modulated by multiple hormones, vasoactive substances or drugs. Endothelium- or drug-derived NO strongly inhibits platelet activation via activation of the soluble guanylate cyclase (sGC) and cGMP elevation, often in synergy with cAMP-elevation by prostacyclin. However, the molecular mechanisms and diversity of cGMP effects in platelets are poorly understood and sometimes controversial. Recently, we established the quantitative human platelet proteome, the iloprost/prostacyclin/cAMP/protein kinase A (PKA)-regulated phosphoproteome, and the interactions of the ADP- and iloprost/prostacyclin-affected phosphoproteome...
March 14, 2018: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29550336/endothelium-derived-hyperpolarizing-factor-and-protein-kinase-g-i%C3%AE-activation-h-2-o-2-versus-s-nitrosothiols
#14
Paula K Bautista-Niño, Marien van der Stel, Wendy W Batenburg, René de Vries, Anton J M Roks, A H Jan Danser
Protein kinase G (PKG) Iα mediates the cyclic guanosine monophosphate-mediated vasodilatory effects induced by NO. Endothelium-derived hyperpolarizing factors (EDHFs), like H2 O2 can activate PKGIα in a cyclic guanosine monophosphate-independent manner, but whether this is true for all EDHFs (e.g., S-nitrosothiols) is unknown. Here, we investigated the contribution of PKGIα to bradykinin-, H2 O2 -, L-S-nitrosocysteine-, and light-induced relaxation in porcine coronary arteries, making use of the fact that thioredoxin reductase inhibition with auranofin or 1-chloro-2,4-dinitrobenzene potentiates PKGIα...
March 14, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29546540/cardiac-unloading-by-lvad-support-differentially-influences-components-of-the-cgmp-pkg-signaling-pathway-in-ischemic-and-dilated-cardiomyopathy
#15
Sven Persoon, Michael Paulus, Stephan Hirt, Carsten Jungbauer, Alexander Dietl, Andreas Luchner, Christof Schmid, Lars S Maier, Christoph Birner
Implantation of left ventricular assist devices (LVADs) as bridge to transplant in end-stage heart failure allows for analyzing reverse remodeling processes of the supported heart. Whether this therapy influences the cGMP-PKG signaling pathway, which is currently under thorough investigation for developing new heart failure therapeutics, is unknown. In fourteen end-stage heart failure patients (8 with dilated cardiomyopathy, DCM; 6 with ischemic cardiomyopathy, ICM) tissue specimens of left ventricles were collected at LVAD implantation and afterwards at receiver heart explantation, respectively...
March 15, 2018: Heart and Vessels
https://www.readbyqxmd.com/read/29545395/prevention-of-pkg-1%C3%AE-oxidation-suppresses-antihypertrophic-antifibrotic-effects-from-pde5-inhibition-but-not-sgc-stimulation
#16
Taishi Nakamura, Guangshuo Zhu, Mark J Ranek, Kristen Kokkonen-Simon, Manling Zhang, Grace E Kim, Kenichi Tsujita, David A Kass
BACKGROUND: Stimulation of sGC (soluble guanylate cyclase) or inhibition of PDE5 (phosphodiesterase type 5) activates PKG (protein kinase G)-1α to counteract cardiac hypertrophy and failure. PKG1α acts within localized intracellular domains; however, its oxidation at cysteine 42, linking homomonomers, alters this localization, impairing suppression of pathological cardiac stress. Because PDE5 and sGC reside in separate microdomains, we speculated that PKG1α oxidation might also differentially influence the effects from their pharmacological modulation...
March 2018: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29540815/computational-methods-for-estimating-molecular-system-from-membrane-potential-recordings-in-nerve-growth-cone
#17
Tatsuya Yamada, Makoto Nishiyama, Shigeyuki Oba, Henri Claver Jimbo, Kazushi Ikeda, Shin Ishii, Kyonsoo Hong, Yuichi Sakumura
Biological cells express intracellular biomolecular information to the extracellular environment as various physical responses. We show a novel computational approach to estimate intracellular biomolecular pathways from growth cone electrophysiological responses. Previously, it was shown that cGMP signaling regulates membrane potential (MP) shifts that control the growth cone turning direction during neuronal development. We present here an integrated deterministic mathematical model and Bayesian reversed-engineering framework that enables estimation of the molecular signaling pathway from electrical recordings and considers both the system uncertainty and cell-to-cell variability...
March 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29534509/effects-of-nitric-oxide-on-voltage-gated-k%C3%A2-%C2%BA-currents-in-human-cardiac-fibroblasts-through-the-protein-kinase-g-and-protein-kinase-a-pathways-but-not-through-s-nitrosylation
#18
Hyemi Bae, Jeongyoon Choi, Young-Won Kim, Donghee Lee, Jung-Ha Kim, Jae-Hong Ko, Hyoweon Bang, Taeho Kim, Inja Lim
This study investigated the expression of voltage-gated K⁺ (KV ) channels in human cardiac fibroblasts (HCFs), and the effect of nitric oxide (NO) on the KV currents, and the underlying phosphorylation mechanisms. In reverse transcription polymerase chain reaction, two types of KV channels were detected in HCFs: delayed rectifier K⁺ channel and transient outward K⁺ channel. In whole-cell patch-clamp technique, delayed rectifier K⁺ current (IK ) exhibited fast activation and slow inactivation, while transient outward K⁺ current (Ito ) showed fast activation and inactivation kinetics...
March 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29518656/copper-induced-activation-of-trp-channels-promotes-extracellular-calcium-entry-and-activation-of-camk-pka-pkc-pkg-and-cblpk-leading-to-increased-expression-of-antioxidant-enzymes-in-ectocarpus-siliculosus
#19
Alberto González, Claudio A Sáez, Bernardo Morales, Alejandra Moenne
The existence of functional Transient Receptor Potential (TRP) channels was analyzed in Ectocarpus siliculosus using agonists of human TRPs and specific antagonists of TRPA1, TRPC5, TRPM8 and TRPV; intracellular calcium was detected for 60 min. Increases in intracellular calcium were observed at 13, 29, 39 and 50-52 min, which appeared to be mediated by the activation of TRPM8/V1 at 13 min, TRPV1 at 29 min, TRPA1/V1 at 39 min and TRPA1/C5 at 50-52 min. In addition, intracellular calcium increases appear to be due to extracellular calcium entry, not requiring protein kinase activation...
March 2, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29517905/neutron-crystallography-detects-differences-in-protein-dynamics-structure-of-pkg-ii-cyclic-nucleotide-binding-domain-in-complex-with-an-activator
#20
Oksana O Gerlits, James C Campbell, Matthew P Blakeley, Choel Kim, Andrey Y Kovalevsky
As one of main receptors of a second messenger, cGMP, cGMP-dependent protein kinase (PKG) isoforms I and II regu-late distinct physiological processes. Design of isoform specific activators is thus of great biomedical importance and requires detailed structural information on PKG isoforms bound with activators, including accurate positions of hydrogen atoms and description of hydrogen bonding and water architecture. Here, we determined a 2.2 Å room-temperature joint X-ray/neutron (XN) structure of the human PKG II carboxyl cyclic nucleotide binding (CNB-B) domain bound with a potent PKG II activator, 8-pCPT-cGMP...
March 8, 2018: Biochemistry
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