• Cyclic GMP-AMP synthase (cGAS, cGAMP synthase), belonging to the nucleotidyltransferase family, is a cytosolic DNA sensor that activates a type-I interferon response. (wikipedia.org)
  • cGAS recognizes the pathogenic DNA in the cytosol and then synthesizes 2′3′-cyclic GMP-AMP (2′3′cGAMP). (frontiersin.org)
  • As the second messenger, cGAMP activates STING and induces the following cascade to produce type I interferon (IFN-I) to protect against infections. (frontiersin.org)
  • The models of most immune evasion during innate immune responses are conserved, including altering the post-transcriptional modifications (PTMs) of vital proteins to inactivate or degrade these components, eluding DNA sensing from PRRs, decreasing cyclic GMP-AMP (cGAMP) cellular abundance, and modifying metabolism approach in host cells ( Eaglesham and Kranzusch, 2020 ). (frontiersin.org)
  • Upon binding of dsDNA, cGAS produces a cyclic di-nucleotide molecule, cGAMP. (monash.edu)
  • STING (Stimulator of Interferon Genes) is then activated by cGAMP to produce key immune mediators, such as interferons (IFNs) and pro-inflammatory cytokines to elicit a protective anti-viral immune response. (monash.edu)
  • Cyclic GMP-AMP synthase (cGAS) senses foreign DNA to produce 2'3′-cyclic GMP-AMP (2'3′-cGAMP). (knoblauchpublishing.com)
  • cGAS is activated upon binding of cytosolic DNA and produces cGAMP and then activates STING (Stimulator of Interferon Genes) [4]. (gw786034inhibitor.com)
  • cGLR1 is activated by dsRNA to produce the novel CDN 3'2'-cGAMP whereas cGLR2 produces a combination of 2'3'-cGAMP and 3'2' cGAMP in response to a yet unidentified stimulus. (cnrs.fr)
  • In mammals, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide (CDN) 2'3'-cGAMP in response to cytosolic DNA and this triggers an antiviral immune response. (cnrs.fr)
  • cGAS signals by synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING). (ox.ac.uk)
  • We show that cGAMP is incorporated into viral particles, including lentivirus and herpesvirus virions, when these are produced in cGAS-expressing cells. (ox.ac.uk)
  • The Transcreener cGAMP cGAS Assay directly detects cyclic GMP-AMP (cGAMP), the product of a cGAS reaction, allowing researchers to monitor cGAS activity with simple, mix-and-read fluorescent detection. (labbulletin.com)
  • cGAS triggers this response to cytoplasmic DNA by producing the dinucleotide second messenger cGAMP, which activates the stimulator of interferon genes (STING) receptor leading to a type I interferon response. (labbulletin.com)
  • The Transcreener cGAS cGAMP FP Assay is a biochemical activity assay that measures the cGAMP produced by the cGAS enzyme. (bellbrooklabs.com)
  • i) Cyclic AMP-GMP (Bacterial cGAMP) signaling: Using an in vitro biosensor assay, we discovered a cyclic AMP-GMP (cGAMP)-sensing riboswitch class, which was highlighted by Science Signaling as a Signaling Breakthrough of the Year . (utah.edu)
  • ii) Mammalian cGAMP signaling: The enzyme cyclic GMP-AMP synthase (cGAS) was discovered to be the innate immune sensor for cytosolic DNA, which may result from microbial infection or other pathophysiological conditions. (utah.edu)
  • Upon binding double-stranded DNA, cGAS produces the signaling molecule cGAMP, which activates the receptor protein, stimulator of interferon genes (STING). (utah.edu)
  • The aim of the present study was to compare microvessel responses to hypercapnic and isocapnic acidosis in hyperoxia-injured lungs and to assess the role of constitutive and inducible forms of nitric oxide synthase (NOS) and cyclo-oxygenase (COX). (ersjournals.com)
  • The nitric oxide produced by ecNOS attenuated COX‐1 activity in injured arterioles and venules, but carbon dioxide enhanced it, leading to paradoxical dilatation of these microvessels under hypercapnic conditions with ecNOS inhibition. (ersjournals.com)
  • Constitutive, but not inducible, isoforms of cyclo-oxygenase and nitric oxide synthase play an important role in abnormal microvessel responses to carbon dioxide and hydrogen ions in hyperoxia-injured lungs. (ersjournals.com)
  • However, these previous studies did not determine the relative contributions of COX (COX‐1 and COX‐2) and nitric oxide synthase (NOS) isoforms (endothelial constitutive (ecNOS) and inducible NOS (iNOS)) to the abnormal acinar microvessel response to HA 4 , 7 . (ersjournals.com)
  • REACTIVE oxygen intermediates modulate skeletal muscle contraction1,2, but little is known about the role of nitric oxide (NO). Here we show that rat skeletal muscle expresses neuronal-type NO synthase and that activity varies among several respiratory and limb muscles. (typeset.io)
  • A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. (bvsalud.org)
  • Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. (bvsalud.org)
  • Cyclic GMP (cGMP), produced in response to either nitric oxide (NO) or certain peptides, controls important neuronal functions. (nova.edu)
  • The benefits of L-arginine may be accounted for its role as the precursor of nitric oxide (NO). NO is produced by all tissues of the body and plays very important roles in the cardiovascular system, immune system and nervous system. (herbstoreusa.com)
  • NO is formed from L-arginine via the enzyme nitric oxide synthase or synthetase (NOS), and the effects of NO are mainly mediated by 3,'5' -cyclic guanylate or cyclic GMP. (herbstoreusa.com)
  • There are three isoforms of the NO synthesizing enzyme nitric oxide synthase (NOS): neuronal (nNOS), endothelial (eNOS), and inducible nitric oxide synthase (iNOS), each one involved with specific events in the brain. (frontiersin.org)
  • Diagram showing the synthetic pathway responsible for nitric oxide (NO) production from arginine and O 2 and catalyzed by the enzyme nitric oxide synthase (NOS). (frontiersin.org)
  • BACKGROUND AND PURPOSE: 8-Nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP), formed nitric oxide (NO)-dependently, is a physiological second messenger, yet little is known about its role in the pathophysiology of vascular diseases. (elsevierpure.com)
  • In primates, including humans, the L -arginine-nitric oxide-guanylyl cyclase-cyclic guanosine monophosphate (cGMP) pathway is the key mechanism of penile erection (Figure 1). (trochetadalafil.com)
  • Nitric oxide (NO) is produced from oxygen and L -arginine under the control of nitric oxide synthase (NOS). (trochetadalafil.com)
  • Increasing evidence has suggested the possibility that the activation of N-methyl-D-aspartate (NMDA) receptors modulates spinal nociceptive transmission via a nitric oxide (NO)/cyclic guanosine 3',5'-monophosphate (cGMP) pathway. (silverchair.com)
  • 1 Nitric oxide synthase (NOS) is a Ca 2+ /calmodulin-dependent enzyme that is stimulated by the activation of NMDA receptors and synthesizes nitric oxide (NO) from L-arginine. (silverchair.com)
  • We find that these cells contain exclusively neuronal NO synthase (nNOS) isoforms as well as both NO- (soluble guanylyl cyclase, sGC) and natriuretic peptide- (natriuretic peptide receptor-A, NPR-A) responsive cGMP-producing enzymes. (nova.edu)
  • 10 μM), 8-nitro-cGMP produced relaxation of the phenylephrine-contracted aortas from C57BL/6, db/+ and db/db mice. (elsevierpure.com)
  • The first is by activation of guanylate cyclase, which promotes the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP). (trochetadalafil.com)
  • Cyclic GMP activates cGMP-dependent protein kinase (PKG), which in turn phosphorylates several proteins. (trochetadalafil.com)
  • Conversely, either NO or cGMP analogs paired with one-train tetanization produced late-phase potentiation, and the cGMP-induced potentiation was blocked by inhibitors of protein or RNA synthesis and an inhibitor of PKG, but not by an inhibitor of PKA. (jneurosci.org)
  • 2,3 NO increases cyclic guanosine 3′,5′-monophosphate (cGMP) through the activation of soluble guanylate cyclase (sGC). (silverchair.com)
  • 7,8 Intrathecal administration of either an NO donor or a membrane-permeable cGMP analog enhances neuropathic pain-related behavior 9,10 and produces hyperalgesia. (silverchair.com)
  • 2005 ). cAMP and cGMP are hydrolyzed by phosphodiesterase (PDE) enzymes, and inhibitors of PDEs (PDE-Is) produce cognition-enhancing effects in animal models of cognition. (springer.com)
  • Several dinucleotide cyclases, including cyclic GMP-AMP synthase, and their involvement in STING-mediated immunity have been extensively studied. (unav.edu)
  • Our publication in PLoS Pathogens (2014) demonstrated that infection of conventional DCs with MVA, leads to the induction of type I IFN production that is dependent on the cytosolic DNA sensor cGAS (cyclic GMP-AMP synthase) and its adaptor STING (stimulator of IFN genes). (mskcc.org)
  • Cyclic GMP-AMP synthase (cGAS) is a signaling protein in the innate immune system that senses DNA floating in a cell and can activate a molecular pathway to fight off the invader. (scienceboard.net)
  • IMPORTANCE Recent studies provided important insight into our understanding of the role of c-di-GMP signaling and the regulation of enteric biofilms. (knoblauchpublishing.com)
  • Despite an improved understanding of how c-di-GMP signaling regulates S. Typhimurium biofilms, the processes that affect the intracellular c-di-GMP levels and the formation of multicellular communities in vivo during infections remain unknown. (knoblauchpublishing.com)
  • The Hammond lab has a dual focus on engineering nucleic acids as programmable tools for molecular imaging and gene control, and on understanding the chemistry and biology of cyclic dinucleotides as signaling molecules in bacteria and mammalian cells. (utah.edu)
  • Cyclic dinucleotides are an emerging class of intracellular signaling molecules with diverse roles in bacteria and with newfound roles in innate immunity in mammalian cells. (utah.edu)
  • We have analyzed the activity of cyclic di-GMP and cyclic di-AMP signaling enzymes using in vivo biosensor assays. (utah.edu)
  • Cyclic nucleotide signaling can be initiated by two general mechanisms. (pancreapedia.org)
  • Cyclic nucleotides, like other nucleotides, are composed of three functional groups: a ribose sugar, a nitrogenous base, and a single phosphate group. (pancreapedia.org)
  • A cyclic nucleotide, unlike other nucleotides, has a cyclic bond arrangement between the ribose sugar and the phosphate group. (pancreapedia.org)
  • There are two main groups of cyclic nucleotides: the canonical or well-established and the non-canonical or unknown-function cyclic nucleotides. (pancreapedia.org)
  • The two well-established cyclic nucleotides are adenosine-3',5'-cyclic monophosphate (cyclic AMP) and guanine-3',5'-cyclic monophosphate (cyclic GMP). (pancreapedia.org)
  • The non-canonical cyclic nucleotides include the purines inosine-3',5'-cyclic monophosphate (cyclic IMP), xanthosine-3',5'-cyclic monophosphate (cyclic XMP) and the pyrimidines cytidine-3',5'-cyclic monophosphate (cyclic cCMP), uridine-3',5'-cyclic monophosphate (cyclic UMP), and thymidine-3',5'-cyclic monophosphate (cTMP) (145). (pancreapedia.org)
  • An overview of the non-canonical cyclic nucleotides is provided in Section V. (pancreapedia.org)
  • Cyclic nucleotides form when the phosphate group of the molecule of nucleotide triphosphate (ATP or GTP) is attacked by the 3' hydroxyl group of the ribose, forming a cyclic 3',5'-phosphate ester with release of pyrophosphate. (pancreapedia.org)
  • This cyclic conformation allows cyclic nucleotides to bind to proteins to which other nucleotides cannot. (pancreapedia.org)
  • In bacteria, these enzymes synthesize a range of cyclic oligonucleotide and have recently emerged as important regulators of phage infections6-8. (cnrs.fr)
  • The Transcreener UDP 2 Glycosyltransferase Assay is a single step, homogenous, fluorescent assay for the detection and screening of UDP-producing enzymes. (bellbrooklabs.com)
  • Researchers at BellBrook Labs have developed a high throughput screening (HTS) compatible biochemical assay to discover and advance small molecule modulators for the target cyclic GMP-AMP synthase (cGAS). (labbulletin.com)
  • An inhibitor of NO synthase blocked L-LTP induced by three-train tetanization and reduced L-LTP induced by four-train tetanization, whereas an inhibitor of PKA was more effective in blocking four-train L-LTP than three-train L-LTP. (jneurosci.org)
  • The authors have examined the effects of an NO synthase inhibitor and a soluble guanylate cyclase inhibitor on the concentrations of NO metabolites (NO2-/NO3-) and glutamate in the cerebrospinal fluid after intrathecal perfusion of NMDA, concomitantly observing pain-related behavior (scratching, biting, and vocalization) in unanesthetized, free-moving rats using an intrathecal microdialysis method. (silverchair.com)
  • An NO synthase inhibitor, N(G)-monomethyl-L-arginine acetate, at a dose that completely blocked the increase in NO2-/NO3-, inhibited both the NMDA-induced pain-related behavior and the increase in glutamate concentration. (silverchair.com)
  • A specific inhibitor of cyclic GMP dependent protein kinase, Rp-8pCPT-cGMPS, partially inhibited the effect of dinitrosyl-iron-thiosulfate on neurogenic vasoconstriction, but not on [ 3 H]noradrenaline release. (biomedcentral.com)
  • The cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) pathway is a critical defender to sense various pathogens and trigger innate immunity of mammalian cells. (frontiersin.org)
  • Top panel: a simplified map of the adenovirus serotype 5 genome showing the early genes (E1-E4) and the region from which the major late transcript is produced. (genemedi.com)
  • TREX1 −/− macrophages did not exhibit significant augmented ability to produce proinflammatory cytokines compared with normal macrophages following exposure to STING-dependent activators, but rather appeared chronically stimulated by genomic DNA. (aai.org)
  • Adjuvants formulated with a TLR9 agonist, CpG-2722, with various cyclic dinucleotides (CDNs) that are STING agonists increased germinal center B cell response and elicited humoral immune responses in immunized mice. (ijbs.com)
  • Cyclic GMP-AMP synthase (cGAS) detects cytosolic DNA during virus infection and induces an antiviral state. (ox.ac.uk)
  • Given that three out of the four known cyclic dinucleotides were discovered in the past decade, much remains to be explored about their chemistry and biology. (utah.edu)
  • To study these chemical signals, our lab has developed fluorescent biosensors for each of the known cyclic dinucleotides. (utah.edu)
  • We also recently developed the first bioluminescent sensor for measuring cyclic dinucleotides in complex settings (Nat Chem Biol Research Highlight , JGI Science Highlight ). (utah.edu)
  • our result provides the first evidence that this enzyme class can make alternative cyclic dinucleotides to cyclic di-GMP (Berkeley news story) . (utah.edu)
  • synthesized by GGDEF domain-containing diguanylate cyclases and degraded by HD-GYP domain-containing phosphodiesterases (PDEs) to 2 GMP or by EAL domain-containing PDE-As to 5′-phosphoguanylyl-(3′,5′)-guanosine (pGpG). (knoblauchpublishing.com)
  • Laboratory-produced, purified proteins serve as key tools for countless research endeavors. (adelecordner.com)
  • With over 10000 full-length human proteins produced in human cells, origene offers a wide range of high quality human protein products. (adelecordner.com)
  • Recombinant proteins have been produced for over 30 years. (adelecordner.com)
  • It is shown that rat skeletal muscle expresses neuronal-type NO synthase and that activity varies among several respiratory and limb muscles, and that two physiological functions of NO in skeletal muscle are supported. (typeset.io)
  • Endothelial NO synthase (eNOS) uncoupling and superoxide were tested by Western blot and dihydroethidium fluorescence respectively. (elsevierpure.com)
  • The major sensor of cytosolic double stranded (ds)DNA is the enzyme cGAS (cyclic GMP-AMP synthase). (monash.edu)
  • Among PRRs, cyclic GMP-AMP synthase (cGAS) is a recently identified DNA sensor, which plays a pivotal role in recognizing cytosolic DNA [3]. (gw786034inhibitor.com)
  • The compound is toxic and mutagenic and will react in vivo with secondary or tertiary amines thereby producing highly carcinogenic nitrosamines. (lookformedical.com)
  • Ammonia incorporation in animals occurs through the actions of glutamate dehydrogenase and glutamine synthase. (medmuv.com)
  • Intrathecal perfusion of NMDA produced pain-related behavior and increased glutamate and NO2-/NO3-concentrations in a dose-dependent manner. (silverchair.com)
  • A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. (lookformedical.com)
  • Reduced nitrogen enters the human body as dietary free amino acids, protein, and the ammonia produced by intestinal tract bacteria. (medmuv.com)
  • During virus infection, the specific immune signals produced from infected cells are important for dictating the recruitment and activation of innate or adaptive immune cells that are required to fight virus infection. (nature.com)
  • Dendritic cells obtained from wt mice and infected in vitro with Ad vector containing AdrA wt, but not mut, had increased activation markers and produced large amounts of several immunostimulatory cytokines. (unav.edu)
  • A cyclase enzyme (lyase) catalyzes the formation of the cyclic nucleotide from its nucleotide triphosphate precursor ( Figure 1 ). (pancreapedia.org)
  • Because HIV-1 is an RNA virus, it produces very little DNA and scientists were stumped as to how cGAS and the innate immune system are able to detect it -- until now. (scienceboard.net)
  • A model complex, dinitrosyl-iron-thiosulfate (at 1-10 μM) produced a concentration-dependent enhancement of electrical field stimulated [ 3 H]noradrenaline release (up to 2 fold). (biomedcentral.com)
  • SARS-CoV-2 primarily spreads among people through aerosols and respiratory droplets produced from coughs, sneezes, or exhaling [ 1 - 3 ]. (ijbs.com)
  • Active, full-length Mouse Cyclic GMP-AMP synthase enzyme, His-tagged protein expressed and purified from E.coli. (bellbrooklabs.com)