Guanylyl Cyclase alpha 2兔多克隆抗体(ab42108)可与小鼠, 大鼠, 人样本反应并经WB, IHC实验严格验证,被5篇文献引用并得到1个独立的用户反馈。
购买我们的大鼠Guanylyl Cyclase alpha 1肽。Ab97987为合成肽并经过Blocking实验验证。Abcam提供免费的实验方案,操作技巧及专业的支持。中国80%以上现货。
Guanylate cyclase 2C, also known as guanylyl cyclase C (GC-C), intestinal guanylate cyclase, guanylate cyclase-C receptor, or the heat-stable enterotoxin receptor (hSTAR) is an enzyme that in humans is encoded by the GUCY2C gene. Guanylyl cyclase is an enzyme found in the luminal aspect of intestinal epithelium and dopamine neurons in the brain. The receptor has an extracellular ligand-binding domain, a single transmembrane region, a region with sequence similar to that of protein kinases, and a C-terminal guanylate cyclase domain. Tyrosine kinase activity mediates the GC-C signaling pathway within the cell. GC-C is a key receptor for heat-stable enterotoxins that are responsible for acute secretory diarrhea. Heat-stable enterotoxins are produced by pathogens such as Escherichia coli. Knockout mice deficient in the GC-C gene do not show secretory diarrhea on infection with E. coli, though they do with cholera toxin. This demonstrates the specificity of the GC-C receptor. Because GC-C is ...
TY - JOUR. T1 - Oxidation and loss of heme in soluble guanylyl cyclase from Manduca sexta. AU - Fritz, Bradley G.. AU - Hu, Xiaohui. AU - Brailey, Jacqueline L.. AU - Berry, Robert E.. AU - Walker, F. Ann. AU - Montfort, William R.. PY - 2011/7/5. Y1 - 2011/7/5. N2 - Oxidation and loss of heme in soluble guanylyl/guanylate cyclase (sGC), the nitric oxide receptor, is thought to be a major contributor to cardiovascular disease and is the target of compounds BAY 58-2667 and HMR1766. Using spectroelectrochemical titration, we found a truncated sGC to be highly stable in the ferrous state (234 mV) and to bind ferrous heme tightly even in the presence of NO, despite the NO-induced release of the proximal histidine. In contrast, oxidized sGC readily loses ferric heme to myoglobin (0.47 ± 0.02 h-1). Peroxynitrite, the presumed cellular oxidant, readily oxidizes sGC in 5 mM glutathione.. AB - Oxidation and loss of heme in soluble guanylyl/guanylate cyclase (sGC), the nitric oxide receptor, is thought ...
Little is known about the active site of guanylate cyclase, although it is assigned to a 239-amino acid region (catalytic domain).4 Since the catalytic domain of guanylate cyclase (GC-c) can be functionally expressed as a soluble protein in E coli, it, rather than the whole enzyme, may be an ideal system for studying the active site of guanylate cyclase. Using guanylate cyclase assay, we screened several PCR-cloned gene products of GC-c and identified a mutant that lacks enzyme activity. Results of cDNA sequencing revealed that Leu 817 is converted into an Arg residue in the mutant. Sequence comparison reveals that Leu 817 is conserved in the corresponding position of most known guanylate cyclases and adenylate cyclases. These results suggest that Leu 817 of guanylate cyclase may play an important functional or structural role.. GC-A has been reported to form oliogomers (dimer, tetramer, and possibly higher order oligomers) in the absence of ANF, and the extracellular receptor sequence has been ...
Background: Soluble guanylate cyclase (sGC) stimulation is an important signaling event in various cardioprotective pathways, with potential clinical applications in cardiac critical care and resuscitation. The sGCα subunit, which binds to the common sGCβ1 subunit, exists in 2 different isoforms, sGCα1 and sGCα2, but their relative physiological roles remain unknown.. Methods: We studied Langendorff-perfused isolated hearts of genetically engineered mice lacking functional sGCα1 (sGCα1KO mice), which is the predominant isoform in the heart. We subjected the hearts to 40 min of global ischemia and 1 hour of reperfusion, with or without ischemic preconditioning (IPC) to elicit cardioprotection.. Results: Deficiency of sGCα1 enhanced both inotropy and lusitropy in isolated hearts, indicating an important role for this isoform in regulating basal myocardial contractility. Surprisingly, cardioprotection by IPC led to a similar reduction in infarct size in both wild-type (WT) and sGCα1KO ...
Diabetes mellitus (DM) leads to the development of diabetic cardiomyopathy, which is associated with altered nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signalling. Cardioprotective effects of elevated intracellular cGMP-levels have been described in different heart diseases. In the current study we aimed at investigating the effects of pharmacological activation of sGC in diabetic cardiomyopathy. Type-1 DM was induced in rats by streptozotocin. Animals were treated either with the sGC activator cinaciguat (10 mg/kg/day) or with placebo orally for 8 weeks. Left ventricular (LV) pressure-volume (P-V) analysis was used to assess cardiac performance. Additionally, gene expression (qRT-PCR) and protein expression analysis (western blot) were performed. Cardiac structure, markers of fibrotic remodelling and DNA damage were examined by histology, immunohistochemistry and TUNEL assay, respectively. DM was associated with deteriorated cGMP signalling in the myocardium
Cyclic GMP is synthesized in endothelial cells following ANP activation of the particulate guanylate cyclase GC-A, and also after NO-dependent activation of the soluble guanylate cyclase. The relative contributions of ANP- and NO-modulated changes in cGMP-mediated pathways are incompletely understood. We designed duplex siRNA targeting constructs to knock down selected signaling proteins in bovine aortic endothelial cells (BAEC), and explored receptor-mediated changes in cGMP pathways. ANP activation of the GC-A receptor led to an increase in intracellular cGMP content (determined by EIA) that was rapid (,2min); dose-dependent (EC50 1 nM); and robust (600-fold increase; n=3-4; all p values ,0.001). By contrast, activation of soluble guanylate cyclase by nitric oxide agonists led only to a weak (,2-fold) transient increase in endothelial cell cGMP. Increases in cGMP lead to phosphorylation of the vasodilator-stimulated phosphoprotein (VASP). ANP markedly stimulated phosphorylation of VASP Ser239, ...
Co-activation of soluble and particulate guanylate cyclase by BAY 58-2667 and BNP enhances cardiorenal function in experimental heart failure. Boerrigter, Guido; Costello-Boerrigter, Lisa C.; Lapp, Harald; Stasch, Johannes-Peter; Burnett Jr., John C. // BMC Pharmacology;2005 Supplement 1, Vol. 5, pP5 An abstract of the article "Co-activation of soluble and particulate guanylate cyclase by BAY 58-2667 and BNP enhances cardiorenal function in experimental heart failure," by Guido Boerrigter, Lisa C Costello-Boerrigter and Harald Lapp is presented. ...
Guanylate cyclase activity of retinal rod outer segments was measured by an assay procedure that minimizes the technical problems caused by the high activity of cyclic nucleotide phosphodiesterase in neural tissue. Cyclase activity in rods is significantly higher than in brain. Moreover, activity is two-fold higher in dark-adapted rods than in light-bleached rods, a sensitivity that is lost when the preparation is treated with detergent. ...
As arterial stiffness is an import indicator of cardiovascular risks and mortality, we aimed at determining the role of NO-GC for aortic stiffness using general KO mice (GCKO) and smooth muscle-specific KO mice (SMC-GCKO) for NO-GC. Measurement of pulse wave velocity (PWV) was frequently used to determine aortic stiffness. We used magnetic resonance tomography (17.6 Tesla) for non-invasive measurement of local aortic PWV. PWV was calculated by simultaneously measuring of cross-sectional change and volume flow in a defined time. ...
The endothelial cell has a unique intrinsic feature: it produces a most potent vasopressor peptide hormone, endothelin (ET-1), yet it also contains a signaling system of an equally potent hypotensive...
Our previous research show a differential expression of nitric oxide (Zero) signaling elements in Ha sido cells and our recent research demonstrated a sophisticated differentiation of Ha sido cells into myocardial cells without donors and soluble guanylyl cyclase (sGC) activators. appearance from the sGC subunits NOS-1 and PKG proteins and mRNA amounts in a variety of individual cancers versions. As opposed to sGCα1 solid degrees of sGC β1 had been seen in OVCAR-3 (ovarian) and MDA-MB-468 (breasts) cancers cells which correlated well using the sGC activity R788 (Fostamatinib) and a proclaimed upsurge in cGMP amounts upon contact with the mix of a Simply no donor and R788 (Fostamatinib) a sGC activator. NOC-18 (DETA NONOate; NO donor) BAY41-2272 (3-(4-Amino-5-cyclopropylpyrimidin-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo[3 4 sGC activator) NOC-18+BAY41-2272 IBMX (3-Isobutyl-1-methylxanthine; phosphodiesterase inhibitor) and 8-bromo-cGMP (cGMP analog) triggered development inhibition and apoptosis in ...
Stasch J-P, Becker EM, Alonso-Alija C, Apeler H, Dembowsky K, Feurer A, Gerzer R, Minuth T, Perzborn E, Pleiss U, Schröder H, Schroeder W, Stahl E, Steinke W, Straub A and Schramm M. NO-independent regulatory site on soluble guanylate cyclase and therapeutic implications. Nature 410: 212-215 (2001 ...
annotations (the reliablity of the annotated protein expression using immunohistochemically (IH) stained on human tissues, the reliablity of the annotated protein expression in immunofluorescently (IF) stained human cell lines, tissue specificity (the distribution of antibody staining or protein expression in human cell types), cell line specificity (the distribution of RNA abundance in cell lines) and subcellular location (based on immunofluorescent staining of cell lines ...
Results sGC stimulation inhibited TGFβ-dependent fibroblast activation and collagen release. sGC knockout fibroblasts confirmed that the sGC is essential for the antifibrotic effects of BAY 41-2272. Furthermore, 8-Bromo-cGMP reduced TGFβ-dependent collagen release. While nuclear p-SMAD2 and 3 levels, SMAD reporter activity and transcription of classical TGFβ target genes remained unchanged, sGC stimulation blocked the phosphorylation of ERK. In vivo, sGC stimulation inhibited TGFβ-driven dermal fibrosis but did not change p-SMAD2 and 3 levels and TGFβ target gene expression, confirming that non-canonical TGFβ pathways mediate the antifibrotic sGC activity. ...
Guanylate cyclase was purified from rat liver supernatant. Electrophoresis under denaturing conditions revealed one major peptide of Mr approx. 69 000. On the basis of the Stokes radius (4.7 nm) and S20,w (6.4S), the calculated Mr value of the native enzyme was 133 000, i.e. it is apparently a homodimer. Kinetics of inactivation by diamide (which was reversible with dithiothreitol) suggested that oxidation of a single class of thiol sites was involved. In the absence of other additions, cyclase activity assayed with Mn2+ was over 7 times that assayed with Mg2+; maximal effects were observed with approx. 5 mM of each (with 1 mM-GTP). The purified enzyme was markedly activated by nitrosylhaemoglobin. Relative activation was much greater in assays with Mg2+ than with Mn2+, although maximal activities were similar. When assayed with Mg2+, the enzyme exhibited a single Km (0.35 mM) for GTP; with Mn2+, plots of 1/v versus 1/[S] were non-linear. Activator or nitrosylhaemoglobin increased Vmax, but did ...
To convert light into an electrical signal, vertebrate photoreceptors use an enzymatic transduction cascade to control the circulating current that flows into the cell through cGMP‐gated channels. The intracellular level of cGMP depends on the relative activities of light‐stimulated PDE and Ca2+‐dependent GC. The present study investigates the molecular mechanisms responsible for the Ca2+ regulation of cGMP synthesis. This issue has not been resolved and is complicated by the fact that rods contain two distinct particulate guanylate cyclases (GC1 and GC2) and two different Ca2+‐sensitive activators (GCAP1 and GCAP2).. The GCAPs are among the best characterized Ca2+ binding proteins of the calmodulin superfamily, many of which are specifically expressed in neurons. The genes encoding GCAP1 and GCAP2 are related evolutionarily. They were generated by ancient gene duplication/inversion events and share an identical gene structure. On the protein level, however, the two GCAPs share only ...
The effects of extracellularly applied 3′-5′ cyclic guanosine monophosphate (cGMP) on kainate responses from cultured cerebellar granule and Purkinje neurons were investigated using whole-cell and outside-out patch recording modes. Cerebellar granule cell responses to kainate were not homogeneous, nor were the effects of cGMP. Therefore, effects of cGMP are described for two groups of granule cells categorized on the basis of the underlying channel conductance estimated by variance analysis. Cells with high-noise kainate responses had average channel conductances of 5 to 7 picoseimens, whereas the average conductances of low-variance noise responses were 0.3 to 2.0 picoseimens. High-noise kainate responses were inhibited by externally applied cGMP (5-1000 μM) in a rapidly reversible and dose-dependent manner. IC50 values were estimated at ∼150 μM cGMP for 25 μM kainate and ∼500 μM cGMP for 100 μM kainate. Evidence that cGMP-mediated inhibition of high-noise kainate responses ...
Agonists of Guanylate Cyclase Useful for the Treatment of Hypercholesterolemia, Atherosclerosis, Coronary Heart Disease, Gallstone, Obesity and Other Cardiovascular Diseases - diagram, schematic, and image 69 ...
Right up until the late twentieth century, small was recognized with regards to the mode of action on the nitrate medicines beyond The reality that they appeared to cause vasodilatation by way of vascular smooth muscle mass leisure. Even so, in 1977 the pharmacologist Ferid Murad and colleagues [nine] showed that nitrate software induced stimulation of soluble guanylyl cyclase derived from rat liver and bovine tracheal easy muscle mass. In turn, this brought about a rise in the second messenger cGMP stages, which induced vascular rest. They suggested that the cGMP activation may possibly occur via NO because they had also discovered that NO by itself elevated guanylyl cyclase exercise [nine, ten ...
Nitric oxide regulates BP by binding the reduced heme iron (Fe2+) in soluble guanylyl cyclase (sGC) and relaxing vascular smooth muscle cells (SMCs). We previously showed that sGC heme iron reduction (Fe3+ → Fe2+) is modulated by cytochrome b5 reductase 3 (CYB5R3). However, the in vivo role of SMC CYB5R3 in BP regulation remains elusive. Here, we generated conditional smooth muscle cell-specific Cyb5r3 KO mice (SMC CYB5R3-KO) to test if SMC CYB5R3 loss affects systemic BP in normotension and hypertension via regulation of the sGC redox state. SMC CYB5R3-KO mice exhibited a 5.84-mmHg increase in BP and impaired acetylcholine-induced vasodilation in mesenteric arteries compared with controls. To drive sGC oxidation and elevate BP, we infused mice with angiotensin II. We found that SMC CYB5R3-KO mice exhibited a 14.75-mmHg BP increase, and mesenteric arteries had diminished nitric oxide-dependent vasodilation but increased responsiveness to sGC heme-independent activator BAY 58-2667 over ...
This paper is a collaboration with Dr. Wolfgang Baehr and two experts in guanylate cyclase enzymology, Dr. Alexander Dizhoor, and Dr. Kris Palczewski representing a long standing collaboration that has generated over fifty papers going back to 1994.. Continue reading "Enzymatic Properties and Regulation of the Native Isozymes of Retinal Membrane Guanylate Cyclase (RetGC) from Mouse Photoreceptors". ...
Guanylyl Cyclase beta 1 Antibodies available through Novus Biologicals. Browse our Guanylyl Cyclase beta 1 Antibody catalog backed by our Guarantee+.
Nitric oxide (NO) is a short-lived free radical gas that acts as a second messenger. The 3 enzymes responsible for NO biosynthesis are endothelial, induced, and neuronal nitric oxide synthases (eNOS, iNOS, and nNOS). These enzymes have different tissue distributions, activation mechanisms, and biological functions. eNOS signaling regulates blood pressure via vascular smooth muscle contractility and blood vessel vasodilation. nNOS signaling regulates skeletal muscle contractility and central and peripheral neurotransmission, as well as synaptic signaling and plasticity. NO generated by both eNOS and nNOS signal via soluble guanylate cyclases and protein kinase G. Macrophages increase iNOS transcription to enhance their cytotoxic function in response to endotoxins and cytokines via NFκB and other intracellular signaling pathways. Increased NO levels assist in killing or slowing the growth of invading microorganisms or neoplastic tissue by inhibiting DNA synthesis and inducing double-stranded DNA ...
Nitric oxide (NO) is a short-lived free radical gas that acts as a second messenger. The 3 enzymes responsible for NO biosynthesis are endothelial, induced, and neuronal nitric oxide synthases (eNOS, iNOS, and nNOS). These enzymes have different tissue distributions, activation mechanisms, and biological functions. eNOS signaling regulates blood pressure via vascular smooth muscle contractility and blood vessel vasodilation. nNOS signaling regulates skeletal muscle contractility and central and peripheral neurotransmission, as well as synaptic signaling and plasticity. NO generated by both eNOS and nNOS signal via soluble guanylate cyclases and protein kinase G. Macrophages increase iNOS transcription to enhance their cytotoxic function in response to endotoxins and cytokines via NFκB and other intracellular signaling pathways. Increased NO levels assist in killing or slowing the growth of invading microorganisms or neoplastic tissue by inhibiting DNA synthesis and inducing double-stranded DNA ...
Background Direct interaction between Red blood cells (RBCs) and platelets is known for a long time. The bleeding time is prolonged in anemic patients independent of their platelet count and could be corrected by transfusion of RBCs, which indicates that RBCs play an important role in hemostasis and platelet activation. However, in the last few years, opposing mechanisms of platelet inhibition by RBCs derived nitric oxide (NO) were proposed. The aim of our study was to identify whether RBCs could produce NO and activate soluble guanylate cyclase (sGC) in platelets. Methods To test whether RBCs could activate sGC under different conditions (whole blood, under hypoxia, or even loaded with NO), we used our well-established and highly sensitive models of NO-dependent sGC activation in platelets and activation of purified sGC. The activation of sGC was monitored by detecting the phosphorylation of Vasodilator Stimulated Phosphoprotein (VASPS239) by flow cytometry and Western blot. ANOVA followed by ...
When mixing any other medications while on any PDE5 inhibitor, it leads to health complications and adverse body reactions that cant be treated with regular over-the-counter meds. And though Levitra is the safest of the ED meds, its combination with riociguat has two sides: the first one triggers health issues when doses arent adjusted and the second one may treat the blood vessel conditions that are responsible for poor erections. What Is Riociguat? The drug belongs to the class of medications under the name soluble guanylate cyclase stimulators. What do […]. ...
The results of our study indicate that the integrity of epithelial cells isolated from the mucosa of the rat proximal small intestine is reduced upon exposure to high concentration of the NO donors, SNP and SNAP. This confirms the early findings of Lopez-Belmonte et al., (1993) demonstrating that release of high levels of NO,in vivo, in response to local infusions of NO donors induced gastric mucosal injury. Furthermore, Whittle (1993) and Teppermanet al., (1994) have shown that incubation of intestinal epithelial cells with high concentration of NO donors was also accompanied by an increase in the extent of cell injury.. NO stimulates the production of cGMP through a direct action on the soluble guanylate cyclase (see Moncada et al., 1991) and, in our study, both SNP and SNAP increased the levels of cGMP in intestinal epithelial cells. Similar increases in colonic cellular cGMP have been previously demonstrated in response to challenge by high concentrations of the NO donor, SNAP (Tepperman et ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
Dear Netters, Does anybody have/know of a decent antibody to guanylyl cyclase (sol or part)? If so, Id be mighty glad to hear from you! Thanks, Simon Penson. spenson at nature.Berkeley.EDU. -- Simon Penson Plant Biology UC Berkeley (510) 642 8064 ...
And Hutton, York, YO41 1LZ; and 2National Plant Protection Organisation, NematologyAnd Hutton, York, YO41 1LZ; and 2National Plant Protection Organisation,
Computational exploration of the binding mode of the heme-dependent activator YC-1 into the active catalytic site of soluble guanylate cyclase ...
Priciple functions of the kidneys are tubular reabsorption of important solutes and regulation of renal and systemic blood pressure. This work has been focused on parameters to control the tubulo-glomerular feedback and epithelial transport in the distal tubule and collecting duct system. The L-arginine-nitric oxide (NO)-system and components of the renal prostaglandin synthesis are thought to play major roles therein. Key-enzymes are NO-Synthase 1 (NOS1) and cyclooxygenase-2 (COX-2), both are localized in the macula densa and are regulated in dependence of the filtrate formation. The cell-specific role of further components in the signalling cascades remains unclear. For investigation we used histochemical and biochemical methods (immunohistochemistry, RT-PCR, in situ hybridisation, western blotting and specific cGMP measurements in tissue and cell extracts to localize the NO-receptor (soluble guanylyl cyclase, sGC), COX-1, COX-2 and the membranous prostaglandin E2-synthase (mPGES). Moreover we ...
The enzyme guanylate cyclase [EC 4.6.1.2] in response to increase nitric oxide (NO) converts GTP into cGMP which leads to smooth muscle relaxation (vasodilation) of the internal cushions of the helicine arteries resulting in creased blood flow. The action of Viagra prevents the degradation of this cGMP by cGMP phosphodiesterase keeping the increased blood flow rates high ...
Complete information for GUCY1B1 gene (Protein Coding), Guanylate Cyclase 1 Soluble Subunit Beta 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Genetic disruption of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene (Npr1) in mice exhibits high blood pressure, cardiac hypertrophy, fibrosis, and remodeling leading to congestive heart failure. The objective of this study was to determine the mechanisms regulating the development of fibrosis in Npr1 gene-disrupted mice hearts. The Npr1 null mutant (Npr1-/-, 0-copy), heterozygous (Npr1+/-, 1-copy), and wild-type (Npr1+/+, 2-copy) mice were administered by oral gavage with transforming growth factor-β1 (TGF- β1) receptor inhibitor GW788388 (1mg/kg/day) for 28 days. The heart tissues were isolated and used for quantification of fibrotic markers by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot analyses. Together, systolic blood pressure (SBP), heart weight-to-body weight (HW/BW) ratio, left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVEDS), and percent fractional shortening (FS) were ...
TY - JOUR. T1 - Cyclic stretch induces inducible nitric oxide synthase and soluble guanylate cyclase in pulmonary artery smooth muscle cells. AU - Shah, Monica R.. AU - Wedgwood, Stephen. AU - Czech, Lyubov. AU - Kim, Gina A.. AU - Lakshminrusimha, Satyanarayana. AU - Schumacker, Paul T.. AU - Steinhorn, Robin H. AU - Farrow, Kathryn N.. PY - 2013/2. Y1 - 2013/2. N2 - In the pulmonary vasculature, mechanical forces such as cyclic stretch induce changes in vascular signaling, tone and remodeling. Nitric oxide is a potent regulator of soluble guanylate cyclase (sGC), which drives cGMP production, causing vasorelaxation. Pulmonary artery smooth muscle cells (PASMCs) express inducible nitric oxide synthase (iNOS), and while iNOS expression increases during late gestation, little is known about how cyclic stretch impacts this pathway. In this study, PASMC were subjected to cyclic stretch of 20% amplitude and frequency of 1 Hz for 24 h and compared to control cells maintained under static conditions. ...
Purpose: : To explain on structural basis the principles of Ca2+-modulated ROS-GC1 phototransduction process. Methods: : Gene deletion analysis, living cell fluorescence, co-immunoprecipitation and molecular modeling. Results: : The coiled coil signaling helix domain has been perceived critical for the signaling integrity of all receptor membrane guanylate cyclases. The puzzle is whether it is also critical for photoreceptor ROS-GC1 modulation. The study demonstrates that the GCAP components of ROS-GC1 transduction system, GCAP1 and GCAP2, sense and transmit signals in divergent modes. The target domains of these GCAPs reside on the opposite sides of the core catalytic domain of ROS-GC1. In vivo analyses utilizing in situ living cells fluorescence show that the signaling helix of ROS-GC1 is not required for GCAPs binding to ROS-GC1. Enzymatic analyses of various deletion mutants demonstrate that GCAP2 signals activation of ROS-GC1 in the absence of the signaling helix, thus the helix is not ...
Purpose : Previous studies evaluating the impact of mutations in human retinal guanylyl cyclase (GUCY2D) known to be associated with Leber congenital amaurosis (LCA1) revealed wide heterogeneity in the biochemical properties of the affected cyclase - some of the mutations completely inactivated RetGC1 and some did not [1]. The purpose of this study was to test the mutant cyclase in vivo using AAV-mediated expression in mouse photoreceptors. Methods : The activities of LCA1-linked RetGC1 mutants and their abilities to bind GCAP and RD3 were assessed in vitro and in cyto, using cultured HEK293 cells expressing fluorescently labeled RetGC1, GCAP1 and RD3. AAV-mediated expression of human wild type, R1091x, and S248W RetGC1 [1] was evaluated in subretinally injected [2] RetGC1/RetGC2 double knockout (GCdKO) mice. ERG, immunofluorescence and biochemical properties of RetGC1s in the AAV-injected eyes were tested using the non-injected eyes as a control. Results : The R1091x and S248W RetGC1 retained ...
Bee venom and phospholipase A2 extracted from bee venom enhanced guanylate cyclase (E.C. 4.6.1.2) activity two- to threefold in rat liver, lung, heart, kidney, ileum, and cerebellum. Dose-response relationships revealed that bee venom at concentrations as low as 1 microgram per milliliter and phospholipase A2 at 1 microunit per milliliter caused a maximal enhancement of guanylate cyclase.. ...
Abstract: Treatment of rat cerebellar astrocyte-enriched primary cultures with dexamethasone enhances the nitric oxide-dependent cyclic GMP formation induced by noradrenaline in a time-(,6 h) and concentration-dependent manner (half-maximal effect at 1 nM). Stimulation of cyclic GMP formation by the calcium ionophore A23187 is similarly enhanced. In contrast, cyclic GMP accumulation in cells treated with lipopolysaccharide is inhibited by dexamethasone. The potentiating effect of dexamethasone is prevented by the protein synthesis inhibitor cycloheximide and is not due to increased soluble guanylate cyclase activity. Agonist stimulation of [3H]arginine to [3H]citrulline conversion is enhanced by dexamethasone in astrocytes but not in cerebellar granule cells. These results indicate that glucocorticoids may up-regulate astroglial calcium-dependent nitric oxide synthase while preventing expression of inducible nitric oxide synthase and are the first report of a differential long-term regulation of ...
The concentration of guanosine 3′,5′-monophosphate (cGMP) controls the response to light in the retina. Binding of cGMP to a plasma membrane cation channel maintains a small calcium flux. Light promotes the degradation of cGMP, allowing these cyclic nucleotide-gated channels to close, resulting in hyperpolarization and a fall in intracellular calcium concentration. Production of cGMP is intimately associated with this changing calcium concentration such that when calcium is high, guanylyl cyclase-activating proteins (GCAPs) inhibit guanylate cyclase (GC) activity, and when calcium is low, GCAPs activate GC activity. However, in vitro the responsiveness of GCAPs to calcium is outside the range of calcium concentrations present in the retina. Peshenko and Dizhoor report that the Mg2+ concentration sets the dynamic range of calcium concentrations over which GCAPs regulate GC activity in assays with recombinant GCAP and outer segment membranes or mouse retina homogenate. Tryptophan fluorescence ...
Total IgE and interferon-gamma production were measured in supernatants of these cultures. The signaling module motif is conserved in nearly all membrane guanylate cyclases and is believed to be critical in the signaling activities buy cialis canada online of all membrane guanylate cyclases. Patients were rated with the HAMD and the Montgomery-Asberg Depression Rating Scale (MADRS). In agreement with the previous studies, double-layered graphite flakes can be curled up to form the classical carbon nanotubes of 5 mg cialis over the counter at walmart different diameters. The abnormalities are evident in patients with first-episode schizophrenia and correlate more strongly with cognitive performance than with symptom severity. Although she received anti-tuberculosis treatment, the steroids caused an exacerbation of the tuberculosis, and after a massive hemoptysis in 1993, best orgasims viagra or cialis a right upper and middle lobectomy was performed. Altogether 24 papers were found using the ...
Buy our Recombinant Human Natriuretic peptides A protein. Ab114317 is a full length protein produced in Wheat germ and has been validated in WB, ELISA…
The endogenously produced gaseous molecule carbon monoxide is able to promote organ protection after ischemia-reperfusion injuries (IRI). The impact of carbon monoxide releasing molecules (CORM) regarding inflammation in neuronal tissues has not been studied in detail. In this investigation, we aimed to analyze the effects of the CORM ALF-186 on neuro-inflammation and hypothesized that the soluble guanylate cyclase (sGC) is playing a decisive role. Retinal ischemia-reperfusion injury was performed for 60 min in Sprague-Dawley rats. Thereafter, the CORM ALF-186 (10 mg/kg) in the presence or absence of the sGC inhibitor ODQ was injected via a tail vein. Retinal tissue was harvested 24 h later to analyze mRNA or protein expression of sGC-β1 subunit, transcription factors NF-κB and CREB, the inflammatory cytokines TNF-α and IL-6, as well as the heat shock proteins (HSP) HSP-70 and HSP-90. Immunohistochemistry was performed on frozen sections of the retina. The overall neuroprotective effect of ALF-186
Carbon monoxide (CO) inhibits human platelet aggregation triggered with threshold levels of agonists like arachidonate, ADP, collagen, thrombin, or the prostaglandin endoperoxide analogue U46619. This inhibition is counteracted by illumination with light above 400 nm indicating the involvement of a ferrous hemoprotein. An earlier suggestion that the mechanism of CO inhibition involves the cytochrome P450 protein thromboxane A2 synthase was ruled out as well as the involvement of the iron containing enzymes like cyclooxygenase or 12-lipoxygenase. In the presence of CO, no arachidonate was released from phospholipids, no increase of intracellular calcium levels was observed, and phospholipase C was not activated suggesting that the transducing mechanisms from the receptors to phospholipase C was effected in the presence of CO. cAMP levels were also unchanged but cGMP levels showed an increase of about 30%. By comparison with the guanylate cyclase stimulator nitroprusside, it was shown that such ...
This study was performed to investigate the regulatory mechanism of cerebral blood flow of adenosine A $_{2B}$ receptor agonist in the rats, and to define whether its mechanism is mediated by adenylate cyclase, guanylate cyclase and potassium channel. In pentobarbital-anesthetized, pancuronium-par...
Transmembrane GCs comprise extracellular as well as intracellular domains, suggesting that these enzymes function as receptors for specific ligands. In fact, most of them are activated by peptide ligands. The GC subtype GC‐G, however, is considered as an orphan receptor (Kuhn, 2009; Potter, 2011). Recently, it has been reported that the heterologously expressed intracellular cyclase domain of GC‐G is activated by bicarbonate (Chao et al, 2010). This observation is supported by the finding that in GG neurons from transgenic mice lacking functional expression of GC‐G, responsiveness to bicarbonate in calcium imaging experiments was dramatically reduced compared to GG neurons endowed with GC‐G (our unpublished observations). Yet, it is uncertain whether GC‐G indeed serves as a receptor for bicarbonate under physiological conditions. Toward the identification of stimuli activating GC‐G, it is important to note that previous studies in C. elegans indicated that several transmembrane GC ...
Kang, Y.-H., West, W. L. and George, M. (1983), Ultracytochemical localization of guanylate cyclase in the oviduct of estrogen-stimulated rat. Anat. Rec., 205: 251-262. doi: 10.1002/ar.1092050303 ...