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https://www.readbyqxmd.com/read/29900525/norepinephrine-upregulates-volume-regulated-chloride-current-by-pka-independent-camp-epac-pathway-in-human-atrial-myocytes
#1
Guo-Sheng Xiao, Yan-Hui Zhang, Yan Wang, Hai-Ying Sun, Clive M Baumgarten, Gui-Rong Li
BACKGROUND AND PURPOSE: Adrenergic regulation of cell volume-regulated chloride current (ICl.vol ) is species-dependent. The present study investigates the mechanism underlying adrenergic regulation of ICl.vol in human atrial myocytes. EXPERIMENTAL APPROACH: A conventional whole-cell patch voltage-clamp technique was utilized to record membrane current in human atrial myocytes. ICl.vol was evoked by hyposmotic bath solution (0.6-times isosmotic, 0.6T). KEY RESULTS: ICl...
June 13, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29896202/nitric-oxide-generated-by-tumor-associated-macrophages-is-responsible-for-cancer-resistance-to-cisplatin-and-correlated-with-syntaxin-4-and-acid-sphingomyelinase-inhibition
#2
Cristiana Perrotta, Davide Cervia, Ilaria Di Renzo, Claudia Moscheni, Maria Teresa Bassi, Lara Campana, Cristina Martelli, Elisabetta Catalani, Matteo Giovarelli, Silvia Zecchini, Marco Coazzoli, Annalisa Capobianco, Luisa Ottobrini, Giovanni Lucignani, Patrizia Rosa, Patrizia Rovere-Querini, Clara De Palma, Emilio Clementi
Tumor microenvironment is fundamental for cancer progression and chemoresistance. Among stromal cells tumor-associated macrophages (TAMs) represent the largest population of infiltrating inflammatory cells in malignant tumors, promoting their growth, invasion, and immune evasion. M2-polarized TAMs are endowed with the nitric oxide (NO)-generating enzyme inducible nitric oxide synthase (iNOS). NO has divergent effects on tumors, since it can either stimulate tumor cells growth or promote their death depending on the source of it; likewise the role of iNOS in cancer differs depending on the cell type...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29885334/compartmentalized-cyclic-nucleotides-have-opposing-effects-on-regulation-of-hypertrophic-phospholipase-c%C3%AE%C2%B5-signaling-in-cardiac-myocytes
#3
Craig A Nash, Loren M Brown, Sundeep Malik, Xiaodong Cheng, Alan V Smrcka
In cardiac myocytes activation of an exchange factor activated by cAMP (Epac) leads to activation of phospholipase Cε (PLCε)-dependent hydrolysis of phosphatidylinositol 4-phosphate (PI4P) in the Golgi apparatus a process critical for development of cardiac hypertrophy. Here we show that β-adrenergic receptor (βAR) stimulation does not stimulate this pathway in the presence of the broad spectrum phosphodiesterase (PDE) inhibitor IBMX, but selective PDE3 inhibition revealed βAR-dependent PI4P depletion...
June 6, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29872396/trpc5-enos-axis-negatively-regulates-atp-induced-cardiomyocyte-hypertrophy
#4
Caroline Sunggip, Kakeru Shimoda, Sayaka Oda, Tomohiro Tanaka, Kazuhiro Nishiyama, Supachoke Mangmool, Akiyuki Nishimura, Takuro Numaga-Tomita, Motohiro Nishida
Cardiac hypertrophy, induced by neurohumoral factors, including angiotensin II and endothelin-1, is a major predisposing factor for heart failure. These ligands can induce hypertrophic growth of neonatal rat cardiomyocytes (NRCMs) mainly through Ca2+ -dependent calcineurin/nuclear factor of activated T cell (NFAT) signaling pathways activated by diacylglycerol-activated transient receptor potential canonical 3 and 6 (TRPC3/6) heteromultimer channels. Although extracellular nucleotide, adenosine 5'-triphosphate (ATP), is also known as most potent Ca2+ -mobilizing ligand that acts on purinergic receptors, ATP never induces cardiomyocyte hypertrophy...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29859189/%C3%AE-3-adrenergic-receptor-activation-induces-tgf%C3%AE-1-expression-in-cardiomyocytes-via-the-pkg-jnk-c-jun-pathway
#5
Zhongcheng Xu, Jimin Wu, Junzhou Xin, Yenan Feng, Guomin Hu, Jing Shen, Mingzhe Li, Youyi Zhang, Han Xiao, Li Wang
In heart failure, the expression of cardiac β3 -adrenergic receptors (β3 -ARs) increases. However, the precise role of β3 -AR signaling within cardiomyocytes remains unclear. Transforming growth factor β1 (TGFβ1) is a crucial cytokine mediating the cardiac remodeling that plays a causal role in the progression of heart failure. Here, we set out to determine the effect of β3 -AR activation on TGFβ1 expression in rat cardiomyocytes and examine the underlying mechanism. The selective β3 -AR agonist BRL37344 induced an increase in TGFβ1 expression and the phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun in β3 -AR-overexpressing cardiomyocytes...
May 30, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29845318/egl-4-modulates-electroconvulsive-seizure-duration-in-c-elegans
#6
Monica G Risley, Stephanie P Kelly, Justin Minnerly, Kailiang Jia, Ken Dawson-Scully
Increased neuronal excitability causes seizures with debilitating symptoms. Effective and noninvasive treatments are limited for easing symptoms, partially due to the complexity of the disorder and lack of knowledge of specific molecular faults. An unexplored, novel target for seizure therapeutics is the cGMP/protein kinase G (PKG) pathway, which targets downstream K+ channels, a mechanism similar to Retigabine, a recently FDA-approved antiepileptic drug. Our results demonstrate that increased PKG activity decreased seizure duration in C...
May 30, 2018: Invertebrate Neuroscience: IN
https://www.readbyqxmd.com/read/29798846/contribution-of-a-natural-polymorphism-protein-kinase-g-modulates-electroconvulsive-seizure-recovery-in-d-melanogaster
#7
Stephanie P Kelly, Monica G Risley, Leonor E Miranda, Ken Dawson-Scully
Drosophila melanogaster is a well-characterized model for neurological disorders and is widely used for investigating causes of altered neuronal excitability leading to seizure-like behavior. One method used to analyze behavioral output of neuronal perturbance is recording the time to locomotor recovery from an electroconvulsive shock. Based on this behavior, we sought to quantify seizure susceptibility in larval D. melanogaster with differences in the enzymatic activity levels of a major protein, cGMP-dependent protein kinase (PKG)...
May 24, 2018: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29773995/hypoxia-reoxygenation-of-rat-renal-arteries-impairs-vasorelaxation-via-modulation-of-endothelium-independent-sgc-cgmp-pkg-signaling
#8
Diana Braun, Christa Zollbrecht, Stefanie Dietze, Rudolf Schubert, Stefan Golz, Holger Summer, Pontus B Persson, Mattias Carlström, Marion Ludwig, Andreas Patzak
Ischemia/reperfusion injury holds a key position in many pathological conditions such as acute kidney injury and in the transition to chronic stages of renal damage. We hypothesized that besides a reported disproportional activation of vasoconstrictor response, hypoxia/reoxygenation (H/R) adversely affects endothelial dilatory systems and impairs relaxation in renal arteries. Rat renal interlobar arteries were studied under isometric conditions. Hypoxia was induced by application of 95% N2 , 5% CO2 for 60 min to the bath solution, followed by a 10 min period of reoxygenation (95% O2 , 5% CO2 )...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29771541/plasmodial-kinase-inhibitors-license-to-cure
#9
Diego Gonzalez Cabrera, André Horatscheck, Colin Rylott Wilson, Gregory S Basarab, Charles J Eyermann, Kelly Chibale
Advances in the genetics, function and stage-specificity of Plasmodium kinases has driven robust efforts to identify targets for the design of antimalarial therapies. Reverse genomics following phenotypic screening against Plasmodia or related parasites has uncovered vulnerable kinase targets including PI4K, PKG and GSK-3, an approach bolstered by access to human disease-directed kinase libraries. Alternatively, screening compound libraries against Plasmodium kinases has successfully led to inhibitors with antiplasmodial activity...
May 17, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29769318/structural-basis-for-selective-inhibition-of-human-pkg-i%C3%AE-by-the-balanol-like-compound-n46
#10
Liying Qin, Banumathi Sankaran, Sahar Aminzai, Darren Casteel, Choel Kim
Activation of PKG Iα in nociceptive neurons induces a long-term hyperexcitability that causes chronic pain. Recently, a derivative of the fungal metabolite balanol, N46, has been reported to inhibit PKG Iα with high potency and selectivity and attenuates thermal hyperalgesia and osteoarthritic pain. Here, we determined co-crystal structures of the PKG Iα C-domain and cAMP-dependent protein kinase (PKA) Cα, each bound with N46, at 1.98 Å and 2.65 Å, respectively. N46 binds the active site with its external phenyl ring specifically interacting with the glycine-rich loop and the αC helix...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29766323/cgmp-at-the-centre-of-attention-emerging-strategies-for-activating-the-cardioprotective-pkg-pathway
#11
REVIEW
Min Park, Peter Sandner, Thomas Krieg
The nitric oxide (NO)-protein kinase G (PKG) pathway has been known for some time to be an important target for cardioprotection against ischaemia/reperfusion injury and heart failure. While many approaches for reducing infarct size in patients have failed in the past, the advent of novel drugs that modulate cGMP and its downstream targets shows very promising results in recent preclinical and clinical studies. Here, we review main aspects of the NO-PKG pathway in light of recent drug development and summarise potential cardioprotective strategies in which cGMP is the main player...
May 15, 2018: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29760016/diabetes-induced-cardiomyocyte-passive-stiffening-is-caused-by-impaired-insulin-dependent-titin-modification-and-can-be-modulated-by-neuregulin-1
#12
Anna-Eliane Hopf, Christian Andresen, Sebastian Kötter, Malgorzata Isic, Kamila Ulrich, Senem Sahin, Sabine Bongardt, Wilhelm Roell, Felicitas Drove, Nina Scheerer, Leni Vandekerckhove, Gilles W De Keulenaer, Nazha Hamdani, Wolfgang A Linke, Martina Krüger
<u>Rationale:</u> Increased titin-dependent cardiomyocyte tension is a hallmark of heart failure with preserved ejection fraction (HFpEF) associated with type-2 diabetes mellitus (T2DM). However, the insulin-related signaling pathways that modify titin-based cardiomyocyte tension, thereby contributing to modulation of diastolic function, are largely unknown. <u>Objective:</u> We aimed to determine how impaired insulin signaling affects titin expression and phosphorylation and thus increases passive cardiomyocyte tension, and whether metformin or neuregulin-1 can correct disturbed titin modifications and increased titin-based stiffness...
May 14, 2018: Circulation Research
https://www.readbyqxmd.com/read/29753142/heme-oxygenase-1-inhibits-spring-viremia-of-carp-virus-replication-through-carbon-monoxide-mediated-cyclic-gmp-protein-kinase-g-signaling-pathway
#13
Cong Li, Lijuan Li, Ling Jin, Junfa Yuan
Spring viremia of carp virus (SVCV) is the etiological agent of spring viremia of carp (SVC) and causes mass mortality in common carp (Cyprinus carpio). Currently, no effective treatments or commercial vaccines against SVCV are available. Heme oxygenase-1 (HO-1), an enzyme that catalyzes the degradation of heme to produce carbon monoxide (CO), biliverdin and ferrous iron (Fe2+), exerts anti-oxidant, antiinflammatory and anti-apoptotic properties. Previous studies demonstrated that nuclear factor-erythroid 2 related factor 2 (Nrf2) functions as an important upstream regulator of HO-1 and exhibits robust activity against SVCV infection...
May 9, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29748710/critical-role-of-angiotensin-ii-type-2-receptors-in-the-control-of-mitochondrial-and-cardiac-function-in-angiotensin-ii-preconditioned-rat-hearts
#14
Rebeca E Nuñez, Sabzali Javadov, Nelson Escobales
Angiotensin II preconditioning (APC) involves an angiotensin II type 1 receptor (AT1-R)-dependent translocation of PKCε and survival kinases to the mitochondria leading to cardioprotection after ischemia-reperfusion (IR). However, the role that mitochondrial AT1-Rs and angiotensin II type 2 receptors (AT2-Rs) play in APC is unknown. We investigated whether pretreatment of Langendorff-perfused rat hearts with losartan (L, AT1-R blocker), PD 123,319 (PD, AT2-R blocker), or their combination (L + PD) affects mitochondrial AT1-R, AT2-R, PKCε, PKCδ, Akt, PKG-1, MAPKs (ERK1/2, JNK, p38), mitochondrial respiration, cardiac function, and infarct size (IS)...
May 10, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29747747/tiger-nut-and-walnut-extracts-modulate-extracellular-metabolism-of-atp-and-adenosine-through-the-nos-cgmp-pkg-signalling-pathway-in-kidney-slices
#15
Ayodeji A Olabiyi, Fabiano B Carvalho, Nathieli B Bottari, Vera M Morsch, Ademir F Morel, Ganiyu Oboh, Maria Rosa Schetinger
BACKGROUND: Tiger nut (Cyperus esculentus L.) and walnut (Tetracarpidium conophorum Müll. Arg.) have been reportedly used in the treatment of inflammatory diseases such as atherosclerosis, prevent heart attack and improve blood circulation, reduce serum cholesterol level as well as inhibit oxidation reactions. PURPOSE: This study investigated the effect of tiger nut and walnut hydro-alcoholic extracts on extracellular metabolism of ATP through the NOS/cGMP/PKG signaling pathway induced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) in kidney slices...
April 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29742029/nitric-oxide-augments-single-persistent-na-channel-currents-via-the-cgmp-pkg-signaling-pathway-in-kenyon-cells-isolated-from-the-cricket-mushroom-bodies
#16
Mariko Ikeda, Masami Yoshino
The nitric oxide (NO)/cyclic GMP signaling pathway has been suggested to be important in the formation of olfactory memory in insects. However, the molecular targets of the NO signaling cascade in the central neurons associated with olfactory learning and memory have not been fully analyzed. In this study, we investigated the effects of NO donors on single voltage-dependent Na+ channels in intrinsic neurons, called Kenyon cells, in the mushroom bodies in the brain of the cricket. Step depolarization on cell-attached patch membranes induces single-channel currents with fast-activating and -inactivating brief openings at the beginning of the voltage steps followed by more persistently recurring brief openings all along the 150-ms pulses...
May 9, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29736011/s-nitrosylation-of-nos-pathway-mediators-in-the-penis-contributes-to-cavernous-nerve-injury-induced-erectile-dysfunction
#17
Biljana Musicki, Anil K Bhunia, Serkan Karakus, Arthur L Burnett
cGMP-independent nitric oxide (NO) signaling occurs via S-nitrosylation. We evaluated whether aberrant S-nitrosylation operates in the penis under conditions of cavernous nerve injury and targets proteins involved in regulating erectile function. Adult male Sprague-Dawley rats underwent bilateral cavernous nerve crush injury (BCNI) or sham surgery. Rats were given a denitrosylation agent N-acetylcysteine (NAC, 300 mg/kg/day) or vehicle in drinking water starting 2 days before BCNI and continuing for 2 weeks following surgery...
May 8, 2018: International Journal of Impotence Research
https://www.readbyqxmd.com/read/29727215/acute-stimulation-of-the-soluble-guanylate-cyclase-does-not-impact-on-left-ventricular-capacitance-in-normal-and-hypertrophied-porcine-hearts-in-vivo
#18
Alessio Alogna, Michael Schwarzl, Martin Manninger, Nazha Hamdani, Birgit Zirngast, Benjamin Kloth, Paul Steendijk, Jochen Verderber, David Zweiker, Dirk Westermann, Stefan Blankenberg, Heinrich Maechler, Carsten Tschöpe, Wolfgang A Linke, Gunther Marsche, Burkert M Pieske, Heiner Post
Experimental data indicate that stimulation of the nitric oxide (NO) - soluble guanylate cyclase (sGC) - cyclic guanosine monophosphate (cGMP) - protein kinase G (PKG) pathway can increase left ventricular (LV) capacitance via phosphorylation of the myofilamental protein titin. We aimed to test whether acute pharmacological sGC stimulation with BAY 41-8543 would increase LV capacitance via titin phosphorylation in healthy and deoxycorticosteroneacetate (DOCA)-induced hypertensive pigs. Nine healthy, landrace pigs and seven pigs with DOCA-induced hypertension and LV concentric hypertrophy were acutely instrumented to measure LV end-diastolic pressure-volume-relationships (EDPVR) at baseline and during intravenous infusion of BAY 41-8543 (1 and 3 μg/kg/min for 30 min, respectively)...
May 4, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29723849/the-mechanism-of-action-of-zingerone-in-the-pacemaker-potentials-of-interstitial-cells-of-cajal-isolated-from-murine-small-intestine
#19
Jung Nam Kim, Hyun Jung Kim, Iksung Kim, Yun Tai Kim, Byung Joo Kim
BACKGROUND/AIMS: Zingerone, a major component found in ginger root, is clinically effective for the treatment of various diseases. Interstitial cells of Cajal (ICCs) are the pacemaker cells responsible for slow waves in the gastrointestinal (GI) tract. We investigated the effects of zingerone on the pacemaker potentials of ICCs to assess its mechanisms of action and its potential as a treatment for GI tract motility disorder. METHODS: We isolated ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs...
April 28, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29722134/a-novel-pde9-inhibitor-wyq-c36d-ameliorates-corticosterone-induced-neurotoxicity-and-depression-like-behaviors-by-cgmp-creb-related-signaling
#20
Xian-Feng Huang, Wen-Tao Jiang, Li Liu, Fang-Chen Song, Xia Zhu, Gui-Lan Shi, Shu-Ming Ding, Heng-Ming Ke, Wei Wang, James M O'Donnell, Han-Ting Zhang, Hai-Bin Luo, Yi-Qian Wan, Guo-Qiang Song, Ying Xu
BACKGROUND: Major depressive disorder (MDD) is a mental disease characterized by depressed mood, lifetime anxiety, and deficits of learning and memory. Inhibition of phosphodiesterase 9 (PDE9) has been reported to improve rodent cognitive and memory function. However, the role of PDE9 in MDD, in particular its manifestations of depression and anxiety, has not been investigated. METHODS: We examined the protective effects of WYQ-C36D (C36D), a novel PDE9 inhibitor, against corticosterone-induced cytotoxicity, pCREB/CREB and BDNF expression by cell viability, and immunoblot assays in HT-22 cells...
May 2, 2018: CNS Neuroscience & Therapeutics
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