1,304 results match your criteria sgc activation


THE sGC STIMULATOR OLINCIGUAT ATTENUATES INFLAMMATION, VASO-OCCLUSION AND NEPHROPATHY IN MOUSE MODELS OF SICKLE CELL DISEASE.

Br J Pharmacol 2021 Apr 17. Epub 2021 Apr 17.

Cyclerion Therapeutics Inc., 301 Binney Street, Cambridge, MA, 02142, USA.

Background And Purpose: Reduced nitric oxide (NO) bioavailability, a hallmark of sickle cell disease (SCD), contributes to intravascular inflammation, vasoconstriction, vaso-occlusion, and organ damage observed in SCD patients. Soluble guanylyl cyclase (sGC) catalyzes synthesis of cyclic guanosine monophosphate (cGMP) in response to NO. cGMP amplifying agents, including NO donors and phosphodiesterase 9 inhibitors, alleviate tumor necrosis factor alpha (TNFα)-induced inflammation in wild-type C57BL/6 mice and in "humanized" mouse models of SCD. Read More

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Involvement of nNOS, and α1, α2, β1, and β2 Subunits of Soluble Guanylyl Cyclase Genes Expression in Anticonvulsant Effect of Sumatriptan on Pentylenetetrazole-Induced Seizure in Mice.

Iran J Pharm Res 2020 ;19(4):181-192

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Epileptic seizure is phenomenon of abnormal synchronous neuronal discharge of a set of neurons in brain as a result of neuronal excitation. Evidence shows the nitric oxide (NO) involvement in neuronal excitability. Moreover, the role of cyclic guanosine monophosphate (cGMP) activation in seizure pathogenesis is well-established. Read More

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January 2020

Spatial learning and memory deficits induced by prenatal glucocorticoid exposure depend on hippocampal CRHR1 and CXCL5 signaling in rats.

J Neuroinflammation 2021 Apr 2;18(1):85. Epub 2021 Apr 2.

Department of Gynecology and Obstetrics and Research Center for Molecular Metabolomics, Xiangya Hospital Central South University, Changsha, 410008, China.

Background: Prenatal synthetic glucocorticoid (sGC) exposure increases the susceptibility to cognitive and affective disorders in postnatal life. We previously demonstrated that prenatal sGC exposure results in an increase in corticotropin-releasing hormone (CRH) receptor type 1 (CRHR1) expression in the hippocampus of rats, and CRHR1 is involved in synapse formation via regulation of C-X-C chemokine ligand 5 (CXCL5) in hippocampus. We sought to investigate that the roles of CRHR1 and CXCL5 in learning and memory impairment caused by prenatal sGC exposure. Read More

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Distinct Pharmacological Properties of Gaseous CO and CO-Releasing Molecule in Human Platelets.

Int J Mol Sci 2021 Mar 30;22(7). Epub 2021 Mar 30.

Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, (JCET), Bobrzynskiego 14, 30-348 Krakow, Poland.

Carbon monoxide (CO)-gaseous or released by CO-RMs-both possess antiplatelet properties; however, it remains uncertain whether the mechanisms involved are the same. Here, we characterise the involvement of soluble guanylate cyclase (sGC) in the effects of CO-delivered by gaseous CO-saturated buffer (CO) and generated by CORM-A1-on platelet aggregation and energy metabolism, as well as on vasodilatation in aorta, using light transmission aggregometry, Seahorse XFe technique, and wire myography, respectively. ODQ completely prevented the inhibitory effect of CO on platelet aggregation, but did not modify antiplatelet effect of CORM-A1. Read More

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Targeted Delivery of Soluble Guanylate Cyclase (sGC) Activator Cinaciguat to Renal Mesangial Cells via Virus-Mimetic Nanoparticles Potentiates Anti-Fibrotic Effects by cGMP-Mediated Suppression of the TGF-β Pathway.

Int J Mol Sci 2021 Mar 4;22(5). Epub 2021 Mar 4.

Department of Pharmaceutical Technology, University of Regensburg, 93053 Regensburg, Germany.

Diabetic nephropathy (DN) ranks among the most detrimental long-term effects of diabetes, affecting more than 30% of all patients. Within the diseased kidney, intraglomerular mesangial cells play a key role in facilitating the pro-fibrotic turnover of extracellular matrix components and a progredient glomerular hyperproliferation. These pathological effects are in part caused by an impaired functionality of soluble guanylate cyclase (sGC) and a consequentially reduced synthesis of anti-fibrotic messenger 3',5'-cyclic guanosine monophosphate (cGMP). Read More

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Mechanistic role of antioxidants in rescuing delayed gastric emptying in high fat diet induced diabetic female mice.

Biomed Pharmacother 2021 May 22;137:111370. Epub 2021 Feb 22.

Department of ODS & Research, School of Dentistry, Meharry Medical College, Nashville, TN, USA. Electronic address:

Diabetic gastroparesis (DG) exhibits delayed gastric emptying (GE) due to impaired gastric non-adrenergic, non-cholinergic (NANC) relaxation. These defects are due to loss or reduction of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that causes reduced expression and/or dimerization of neuronal nitric oxide synthase alpha (nNOSα) gene expression and function. We investigated the effect of potent Nrf2 activators (cinnamaldehyde [CNM] & curcumin [CUR]) on GE in obesity-induced diabetic female mice. Read More

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Compensatory combination of mTOR and TrxR inhibitors to cause oxidative stress and regression of tumors.

Theranostics 2021 25;11(9):4335-4350. Epub 2021 Feb 25.

The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou 325035, China.

Cancer is a leading cause of death worldwide. Extensive research over decades has led to the development of therapies that inhibit oncogenic signaling pathways. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in the development of many cancers. Read More

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February 2021

Structure and activation mechanism of the human liver-type glutaminase GLS2.

Biochimie 2021 Mar 18;185:96-104. Epub 2021 Mar 18.

Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, Sao Paulo, Zip Code, 13083-970, Brazil; Sao Carlos Institute of Physics, University of Sao Paulo, Sao Carlos, SP, Zip Code, 13563-120, Brazil. Electronic address:

Cancer cells exhibit an altered metabolic phenotype, consuming higher levels of the amino acid glutamine. This metabolic reprogramming depends on increased mitochondrial glutaminase activity to convert glutamine to glutamate, an essential precursor for bioenergetic and biosynthetic processes in cells. Mammals encode the kidney-type (GLS) and liver-type (GLS2) glutaminase isozymes. Read More

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Violet LED induces vasodilation in rat aortic rings by soluble guanylate cyclase-dependent mechanism and increases SOD activity.

Lasers Med Sci 2021 Mar 18. Epub 2021 Mar 18.

Department of Physiological Sciences, Federal University of São Carlos, São Carlos, SP, Brazil.

We found several studies that have used the aortic rings as an experimental model, mainly for the testing of new drugs or new therapies that try to reverse or prevent endothelial dysfunction or characterize its mechanism of action in a biological system, creating the knowledge necessary to obtain the treatment of those several diseases, where many of these treatments involve photobiomodulation therapies. We also found numerous wavelengths represented by different colors of LASER or LED in which frequently, the mechanism of action in biological systems is unknown. This study has as main objective to investigate the effects of the Violet LED Light (405 nm) by using isolated aortic rings, looking for nitric oxide (NO) release, and evaluating if Violet LED Light can modulate the superoxide dismutase (SOD) activity. Read More

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Cisplatin-induced activation and functional modulation of satellite glial cells lead to cytokine-mediated modulation of sensory neuron excitability.

Exp Neurol 2021 Mar 14;341:113695. Epub 2021 Mar 14.

Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, Hufelandstr. 55, 45147 Essen, Germany.

Cisplatin plays an essential role in the treatment of various cancers. Cisplatin exhibits high efficacy, but it often leads to severe neurotoxic side effects, such as chemotherapy-induced polyneuropathy (CIPN). The pathophysiology of CIPN is not fully understood. Read More

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The DpdtbA induced EMT inhibition in gastric cancer cell lines was through ferritinophagy-mediated activation of p53 and PHD2/hif-1α pathway.

J Inorg Biochem 2021 May 4;218:111413. Epub 2021 Mar 4.

College of Basic Medical Science, Xinxiang Medical University, Xinxiang, Henan, PR China; School of Pharmacy, Sanquan College of Xinxiang Medical University, Xinxiang 453003, Henan, PR China. Electronic address:

Previous studies have shown that epithelial-mesenchymal transition (EMT) involves reactive oxygen species (ROS) production, but how ferritinophagy-mediated ROS production affects EMT status remains obscure. 2,2'-di-pyridylketone hydrazone dithiocarbamate s-butyric acid (DpdtbA), an iron chelator, exhibited interesting antitumor activities against gastric and esophageal cancer cells. As an extension of our previous research, in this paper we presented the effect of DpdtbA on EMT regulation of gastric cancer lines (SGC-7901 and MGC-803) in both normoxic and hypoxic conditions. Read More

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Primary cilia regulate gastric cancer-induced bone loss via cilia/Wnt/β-catenin signaling pathway.

Aging (Albany NY) 2021 03 9;13(6):8989-9010. Epub 2021 Mar 9.

Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.

Cancer-associated bone disease is a frequent occurrence in cancer patients and is associated with pain, bone fragility, loss, and fractures. However, whether primary or non-bone metastatic gastric cancer induces bone loss remains unclear. Here, we collected clinical evidence of bone loss by analyzing serum and X-rays of 25 non-bone metastatic gastric cancer patients. Read More

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Activation of soluble guanylyl cyclase signalling with cinaciguat improves impaired kidney function in diabetic mice.

Br J Pharmacol 2021 Mar 2. Epub 2021 Mar 2.

Institute of Pharmacy, Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.

Background And Purpose: Diabetic nephropathy is the leading cause for end-stage renal disease worldwide. Until now, there is no specific therapy available. Standard treatment with inhibitors of the renin-angiotensin system just slows down progression. Read More

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How do neurons in sensory ganglia communicate with satellite glial cells?

Brain Res 2021 Jun 22;1760:147384. Epub 2021 Feb 22.

Laboratory of Experimental Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem 91240, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Israel. Electronic address:

Neurons and satellite glial cells (SGCs) in sensory ganglia maintain bidirectional communications that are believed to be largely mediated by chemical messengers. Nerve injury leads to SGC activation, which was proposed to be mediated by nitric oxide (NO) released from active neurons, but evidence for this is lacking. Here we tested the idea that increased neuronal firing is a major factor in NO release. Read More

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C-type natriuretic peptide-induced relaxation through cGMP-dependent protein kinase and SERCA activation is impaired in two kidney-one clip rat aorta.

Life Sci 2021 May 18;272:119223. Epub 2021 Feb 18.

Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Department of Physics and Chemistry, Ribeirão Preto, SP, Brazil.

Aims: Hypertension underlies endothelial dysfunction, and activation of vasorelaxation signaling with low dependence on nitric oxide (NO) represents a good alternative for vascular modulation. C-type natriuretic peptide (CNP) causes relaxation by increasing cyclic guanosine 3',5'-monophosphate (cGMP) or Gi-protein activation through its natriuretic peptide receptor-B or -C, respectively. We have hypothesized that CNP could exerts its effects and could overcome endothelial dysfunction in two kidney-one clip (2K-1C) hypertensive rat aorta. Read More

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CBP Bromodomain Inhibition Rescues Mice From Lethal Sepsis Through Blocking HMGB1-Mediated Inflammatory Responses.

Front Immunol 2020 2;11:625542. Epub 2021 Feb 2.

Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China.

CREB binding protein (CBP), a transcriptional coactivator and acetyltransferase, is involved in the pathogenesis of inflammation-related diseases. High mobility group box-1 protein (HMGB1) is a critical mediator of lethal sepsis, which has prompted investigation for the development of new treatment for inflammation. Here, we report that the potent and selective inhibition of CBP bromodomain by SGC-CBP30 blocks HMGB1-mediated inflammatory responses and . Read More

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February 2021

Disease-specific platelet signaling defects in idiopathic pulmonary arterial hypertension.

Am J Physiol Lung Cell Mol Physiol 2021 05 17;320(5):L739-L749. Epub 2021 Feb 17.

Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.

Idiopathic pulmonary arterial hypertension (IPAH) is a rapidly progressive disease with several treatment options. Long-term mortality remains high with great heterogeneity in treatment response. Even though most of the pathology of IPAH is observed in the lung, there is systemic involvement. Read More

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Higher susceptibility to heme oxidation and lower protein stability of the rare αC517Yβ sGC variant associated with moyamoya syndrome.

Biochem Pharmacol 2021 Apr 8;186:114459. Epub 2021 Feb 8.

University of Texas Health Science Center, McGovern Medical School, Department of Internal Medicine, Division of Cardiology, United States. Electronic address:

NO sensitive soluble guanylyl cyclase (sGC) plays a key role in mediating physiological functions of NO. Genetic alterations of the GUCY1A3 gene, coding for the α1 subunit of sGC, are associated with several cardiovascular dysfunctions. A rare sGC variant with Cys517 → Tyr substitution in the α1subunit, has been associated with moyamoya disease and achalasia. Read More

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A recursive molecular docking coupled with energy-based pose-rescoring and MD simulations to identify sGC βH-NOX allosteric modulators for cardiovascular dysfunctions.

J Biomol Struct Dyn 2021 Feb 1:1-23. Epub 2021 Feb 1.

Department of Biostatistics and Medical Informatics, Acibadem M. A. A. University, Istanbul, Turkey.

Modulating the activity of human soluble guanylate cyclase (sGC) through allosteric regulation of the βH-NOX domain has been considered as an immediate treatment for cardiovascular disorder (CVDs). Currently available βH-NOX domain-specific agonists including cinaciguat are unable to deal with the conundrum raised due to oxidative stress in the case of CVDs and their associated comorbidities. Therefore, the idea of investigating novel compounds for allosteric regulation of sGC activation has been rekindled to circumvent CVDs. Read More

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February 2021

Astragalin Alleviates Neuropathic Pain by Suppressing P2X4-Mediated Signaling in the Dorsal Root Ganglia of Rats.

Front Neurosci 2020 11;14:570831. Epub 2021 Jan 11.

Department of Physiology, Medical School of Nanchang University, Nanchang, China.

Neurologic damage often leads to neuropathic pain, for which there are no effective treatments owing to its complex pathogenesis. The purinergic receptor P2X4 is closely associated with neuropathic pain. Astragalin (AST), a compound that is used in traditional Chinese medicine, has protective effects against allergic dermatitis and neuronal injury, but its mechanism of action is not well understood. Read More

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January 2021

GHR is involved in gastric cell growth and apoptosis via PI3K/AKT signalling.

J Cell Mol Med 2021 Mar 25;25(5):2450-2458. Epub 2021 Jan 25.

Department of Radiology, Affiliated Hospital 2 of Nantong University, Nantong, China.

Growth hormone receptor (GHR), the cognate receptor of growth hormone (GH), is a membrane bound receptor that belongs to the class I cytokine receptor superfamily. GH binding GHR induces cell differentiation and maturation, initiates the anabolism inside the cells and promotes cell proliferation. Recently, GHR has been reported to be associated with various types of cancer. Read More

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Inflammation in the Human Periodontium Induces Downregulation of the α- and β-Subunits of the sGC in Cementoclasts.

Int J Mol Sci 2021 Jan 7;22(2). Epub 2021 Jan 7.

Department of Periodontology and Operative Dentistry, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.

Nitric oxide (NO) binds to soluble guanylyl cyclase (sGC), activates it in a reduced oxidized heme iron state, and generates cyclic Guanosine Monophosphate (cGMP), which results in vasodilatation and inhibition of osteoclast activity. In inflammation, sGC is oxidized and becomes insensitive to NO. NO- and heme-independent activation of sGC requires protein expression of the α- and β-subunits. Read More

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January 2021

An inherent dysfunction in soluble guanylyl cyclase is present in the airway of severe asthmatics and is associated with aberrant redox enzyme expression and compromised NO-cGMP signaling.

Redox Biol 2021 02 13;39:101832. Epub 2020 Dec 13.

Department of Inflammation and Immunity, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH, 44195, USA. Electronic address:

A subset of asthmatics develop a severe form of the disease whose etiology involves airway inflammation along with inherent drivers that remain ill-defined. To address this, we studied human airway smooth muscle cells (HASMC), whose relaxation drives airway bronchodilation and whose dysfunction contributes to airway obstruction and hypersensitivity in severe asthma. Because HASMC relaxation can be driven by the NO-soluble guanylyl cyclase (sGC)-cGMP signaling pathway, we questioned if HASMC from severe asthma donors might possess inherent defects in their sGC or in redox enzymes that support sGC function. Read More

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February 2021

The Gamma-glutamyltransferase gene of Helicobacter pylori can promote gastric carcinogenesis by activating Wnt signal pathway through up-regulating TET1.

Life Sci 2021 Feb 5;267:118921. Epub 2021 Jan 5.

Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address:

Aims: Helicobacter pylori (Hp) infection plays an important role in the development of gastric cancer. Hp can secrete gamma-glutamyltransferase (GGT), however, the impact of GGT of Hp on the human gastric cells is not clear. Although it has been demonstrated that ten-eleven translocation 1 (TET1) is overexpressed in gastric cancer, the relationship between the GGT of Hp and TET1 has not been studied. Read More

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February 2021

Role of soluble guanylyl cyclase in renal afferent and efferent arterioles.

Am J Physiol Renal Physiol 2021 02 28;320(2):F193-F202. Epub 2020 Dec 28.

Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Renal arteriolar tone depends considerably on the dilatory action of nitric oxide (NO) via activation of soluble guanylyl cyclase (sGC) and cGMP action. NO deficiency and hypoxia/reoxygenation are important pathophysiological factors in the development of acute kidney injury. It was hypothesized that the NO-sGC-cGMP system functions differently in renal afferent arterioles (AA) compared with efferent arterioles (EA) and that the sGC activator cinaciguat differentially dilates these arterioles. Read More

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February 2021

Stimulation of soluble guanylyl cyclase (sGC) by riociguat attenuates heart failure and pathological cardiac remodelling.

Br J Pharmacol 2020 Nov 28. Epub 2020 Nov 28.

Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.

Background And Purpose: Heart failure is associated with an impaired NO-soluble guanylyl cyclase (sGC)-cGMP pathway and its augmentation is thought to be beneficial for its therapy. We hypothesized that stimulation of sGC by the sGC stimulator riociguat prevents pathological cardiac remodelling and heart failure in response to chronic pressure overload.

Experimental Approach: Transverse aortic constriction or sham surgery was performed in C57BL/6N mice. Read More

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November 2020

Indoxyl sulfate induces ROS production via the aryl hydrocarbon receptor-NADPH oxidase pathway and inactivates NO in vascular tissues.

Life Sci 2021 Jan 21;265:118807. Epub 2020 Nov 21.

Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. Electronic address:

Aims: The uremic toxin indoxyl sulfate (IS) was reported to be the cause of cardiovascular disease associated with chronic kidney disease. Therefore, we evaluated the direct influences of IS on vascular function, focusing on the superoxide anion (O) and nitric oxide (NO)/soluble guanylate cyclase (sGC) pathways.

Main Methods: Isolated rat thoracic aortas with and without vascular endothelium were incubated with IS for 4 h in a physiological solution. Read More

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January 2021

Induces Cell Proliferation in Cardia Adenocarcinoma via PI3K/AKT Signaling Pathway.

Onco Targets Ther 2020 4;13:11315-11326. Epub 2020 Nov 4.

Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, People's Republic of China.

Purpose: Previous studies have shown that non-SMC condensin I complex subunit G () overexpression is correlated to poor prognosis of multiple cancer types. Herein, we explored the underlying mechanism of -mediated cardia adenocarcinoma (CA) proliferation and cell cycle regulation.

Methods: The protein profiling technology was used to analyze the gene expression in 20 CA and adjacent tissue samples. Read More

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November 2020

Subgenual cingulate connectivity and hippocampal activation are related to MST therapeutic and adverse effects.

Transl Psychiatry 2020 11 10;10(1):392. Epub 2020 Nov 10.

Department of Psychiatry, Faculty of Health, University of California San Diego, La Jolla, CA, 92093-0603, USA.

Aberrant connectivity between the dorsolateral prefrontal cortex (DLPFC) and the subgenual cingulate cortex (SGC) has been linked to the pathophysiology of depression. Indirect evidence also links hippocampal activation to the cognitive side effects of seizure treatments. Magnetic seizure therapy (MST) is a novel treatment for patients with treatment resistant depression (TRD). Read More

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November 2020

circCUL2 regulates gastric cancer malignant transformation and cisplatin resistance by modulating autophagy activation via miR-142-3p/ROCK2.

Mol Cancer 2020 11 5;19(1):156. Epub 2020 Nov 5.

Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Circular RNAs (circRNAs) are a class of noncoding RNAs (ncRNAs) and can modulate gene expression by binding to miRNAs; further, circRNAs have been shown to participate in several pathological processes. However, the expression and biological function of circCUL2 in gastric cancer (GC) remains largely unknown.

Methods: circRNA microarrays and quantitative real-time PCR (qRT-PCR) were used to identify differentially expressed circRNAs in GC tissues and cell lines. Read More

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November 2020