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https://www.readbyqxmd.com/read/28722423/generation-of-a-cgmp-indicator-with-an-expanded-dynamic-range-by-optimization-of-amino-acid-linkers-between-a-fluorescent-protein-and-pde5%C3%AE
#1
Shogo Matsuda, Kazuki Harada, Motoki Ito, Mai Takizawa, Devina Wongso, Takashi Tsuboi, Tetsuya Kitaguchi
Here we describe the development of a single fluorescent protein (FP)-based cGMP indicator, Green cGull, based on the cGMP binding domain from mouse phosphodiesterase 5α. The dynamic range of Green cGull was enhanced to a 7.5-fold fluorescence change upon cGMP binding by optimization of the amino acid linkers between the cGMP binding domain and FP. Green cGull has excitation and emission peaks at 498 and 522 nm, respectively, and specifically responds to cGMP in a dose-dependent manner. Live cell imaging analysis revealed that addition of a nitric oxide (NO) donor induced different cGMP kinetics and was cell-type dependent...
January 27, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28719717/audiometry-results-and-teoae-and-dpoae-amplitudes-in-men-taking-a-phosphodiesterase-type-5-inhibitor-for-erectile-dysfunction
#2
Sertan Öntepeli, Nuray Bayar Muluk, Devrim Tuğlu, Timuçin Şipal
We conducted a prospective study of transient evoked otoacoustic emissions (TEOAEs) and distortion-product otoacoustic emissions (DPOAEs) in men who were taking an oral phosphodiesterase type 5 (PDE5) inhibitor for erectile dysfunction. Our study group was made up of 30 men (60 ears), aged 34 to 60 years (mean: 50.9). They were randomly divided into three groups; 10 men were given sildenafil (Viagra) at 50 mg twice a week, 10 were given tadalafil (Cialis) at 20 mg twice a week, and 10 were given vardenafil (Levitra) at 20 mg twice a week...
July 2017: Ear, Nose, & Throat Journal
https://www.readbyqxmd.com/read/28717838/the-triterpenoid-alpha-beta-amyrin-prevents-the-impaired-aortic-vascular-reactivity-in-high-fat-diet-induced-obese-mice
#3
Flávia Almeida Santos, Karine Maria Martins Bezerra Carvalho, Francisco José Batista-Lima, Paulo Iury Gomes Nunes, Ana Flávia Seraine Custódio Viana, Armenio André de Carvalho Almeida da Silva, Said Gonçalves da Cruz Fonseca, Mariana Helena Chaves, Vietla Satyanarayana Rao, Pedro Jorge Caldas Magalhães, Teresinha Silva de Brito
To characterize the protective effects of the triterpenoid mixture alpha, beta-amyrin (AMY, 20 mg/kg, during 15 days) on the reactivity of isolated aorta of high-fat diet (HFD)-induced obese mice. Male Swiss mice were fed with HFD or normal diet (ND) for 15 weeks. Contractions of thoracic aorta in response to KCl or phenylephrine (PHE) and relaxation by acetylcholine (ACh) or sodium nitroprusside (SNP) were analyzed. HFD-fed mice developed hyperglycemia, hyperlipidemia, and significant body weight gain, parameters prevented by AMY treatment...
July 17, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28717180/a-three-mirnas-signature-predicts-survival-in-cervical-cancer-using-bioinformatics-analysis
#4
Bin Liang, Yunhui Li, Tianjiao Wang
Growing evidences showed that a large number of miRNAs were abnormally expressed in cervical cancer tissues and played irreplaceable roles in tumorigenesis, progression and metastasis. The aim of the present study was to identify the differential miRNAs expression between cervical cancer and normal cervical tissues by analyzing the high-throughput miRNA data downloaded from TCGA database. Additionally, we evaluated the prognostic values of the differentially expressed miRNAs and constructed a three-miRNA signature that could effectively predict patient survival...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716951/a-calcium-diacylglycerol-stimulated-protein-kinase-c-c-elegans-pkc-2-links-thermal-signals-to-learned-behavior-by-acting-in-a-sensory-neuron-and-intestinal-cells
#5
Marianne Land, Charles S Rubin
Ca(2+) and diacylglycerol (DAG) activated protein kinase C (cPKC) promotes learning and behavioral plasticity. However, knowledge of in vivo regulation and exact functions of cPKCs that affect behavior is limited. We show that PKC-2, a C. elegans cPKC, is essential for a complex behavior, thermotaxis. C. elegans memorizes a nutrient-associated cultivation temperature (Tc) and migrates along Tc within a 17-25°C gradient. pkc-2 gene disruption abrogated thermotaxis; a PKC-2 transgene, driven by endogenous pkc-2 promoters, restored thermotaxis behavior in pkc-2(-/-) animals...
July 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28705908/importance-of-kynurenine-in-pulmonary-hypertension
#6
Bence M Nagy, Chandran Nagaraj, Andreas Meinitzer, Neha Sharma, Rita Papp, Vasile Foris, Bahil Ghanim, Grazyna Kwapiszewska, Gabor Kovacs, Walter Klepetko, Thomas R Pieber, Harald Mangge, Horst Olschewski, Andrea Oslchewski
The tryptophan metabolite kynurenine is significantly increased in pulmonary arterial hyper-tension (PAH) patients, and it is a potent vasodilator of systemic arteries. Our aim was to in-vestigate the role of kynurenine in the pulmonary circulation. Serum tryptophan, kynurenine and kynurenic-acid levels were measured in 20 idiopathic PAH (IPAH) patients, 20 healthy controls and 20 patients with chronic lung disease or meta-bolic syndrome without-PH. Laser-dissected pulmonary arteries from IPAH and control lungs were tested for the expression of IDO, the rate-limiting enzyme for the conversion from tryptophan to kynurenine...
July 13, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28705807/augmentation-of-cgmp-pkg-pathway-and-colonic-motility-by-hydrogen-sulfide
#7
Ancy D Nalli, Sayak Bhattacharya, Hongxia Wang, Derek M Kendig, John R Grider, Karnam S Murthy
Hydrogen sulfide (H2S), like nitric oxide (NO), causes smooth muscle relaxation, but unlike NO, does not stimulate soluble guanylyl cyclase (sGC) activity and generate cGMP. The aim of this study was to investigate the interplay between NO and H2S in colonic smooth muscle. In colonic smooth muscle from rabbit, mouse and human, L-cysteine, substrate of cystathionine-γ-lyase (CSE), or NaHS, an H2S donor, inhibited phosphodiesterase 5 (PDE5) activity and augmented the increase in cGMP levels, IP3 receptor phosphorylation at Ser(1756) (measured as a proxy for PKG activation), and muscle relaxation in response to NO donor, s-nitrosoglutathione (GSNO), suggesting augmentation of cGMP/PKG pathway by H2S...
July 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28703960/antioxidative-properties-of-milk-protein-preparations-fermented-by-polish-strains-of-lactobacillus-helveticus
#8
Katarzyna W Skrzypczak, Waldemar Z Gustaw, Ewa D Jabłońska-Ryś, Monika Michalak-Majewska, Aneta Sławińska, Wojciech P Radzki, Klaudia M Gustaw, Adam D Waśko
BACKGROUND: The increasing significance of food products containing substances with antioxidative activi- ties is currently being observed. This is mainly due to the fact that pathogenic changes underlying some diseases are related to the carcinogenic effects of free radicals. Antioxidative compounds play an important role in supporting and enhancing the body’s defense mechanisms, which is useful in preventing some civili- zation diseases. Unfortunately, it has been already proved that some synthetic antioxidants pose a potential risk in vivo...
April 2017: Acta Scientiarum Polonorum. Technologia Alimentaria
https://www.readbyqxmd.com/read/28700735/molecular-mechanisms-by-which-casein-glycomacropeptide-maintains-internal-homeostasis-in-mice-with-experimental-ulcerative-colitis
#9
Yongbo Cui, Chenchen Zhu, Zhu Ming, Jiangming Cao, Yali Yan, Pei Zhao, Guangchang Pang, Zixin Deng, Yi Yao, Qingsen Chen
OBJECTIVES: The aim of this study was to elucidate the molecular mechanisms by which food-derived casein glycomacropeptide (CGMP) maintains internal homeostasis in the intestinal mucosa and to investigate the effects of CGMP on the intestinal mucosal immunological barrier and related signal transduction pathways. METHODS: In this study, a famoxadone (OXZ)-induced mouse experimental ulcerative colitis (UC) model was built. The experimental UC mice were intragastrically administered milk-derived CGMP for four consecutive days...
2017: PloS One
https://www.readbyqxmd.com/read/28700469/microarray-analysis-of-copy-number-variations-and-gene-expression-profiles-in-prostate-cancer
#10
Yuping Han, Xuefei Jin, Hongyan Li, Kaichen Wang, Ji Gao, Lide Song, Yanting Lv
BACKGROUND: This study aimed to identify potential prostate cancer (PC)-related variations in gene expression profiles. METHODS: Microarray data from the GSE21032 dataset that contained the whole-transcript and exon-level expression profile (GSE21034) and Agilent 244K array-comparative genomic hybridization data (GSE21035) were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and copy-number variations (CNVs) were identified between PC and normal tissue samples...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28698456/combining-nmr-spectroscopy-and-chemometrics-to-monitor-structural-features-of-crude-hep-arin
#11
Lucio Mauri, Maria Marinozzi, Giulia Mazzini, Richard E Kolinski, Michael Karfunkle, David A Keire, Marco Guerrini
Because of the complexity and global nature of the heparin supply chain, the control of heparin quality during manufacturing steps is essential to ensure the safety of the final active pharmaceutical ingredient (API). For this reason, there is a need to develop consistent analytical methods able to assess the quality of heparin early in production (i.e., as the crude heparin before it is purified to API under cGMP conditions). Although a number of analytical techniques have been applied to characterize heparin APIs, few of them have been applied for crude heparin structure and composition analyses...
July 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28697992/pde3-inhibition-by-c-type-natriuretic-peptide-induced-cgmp-enhances-camp-mediated-signaling-in-both-non-failing-and-failing-hearts
#12
Silja Meier, Kjetil Wessel Andressen, Jan Magnus Aronsen, Ivar Sjaastad, Karina Hougen, Tor Skomedal, Jan-Bjørn Osnes, Eirik Qvigstad, Finn Olav Levy, Lise Román Moltzau
We have previously shown that the natriuretic peptide receptor B (NPR-B) agonist C-type natriuretic peptide (CNP) enhances cyclic adenosine 3´,5´-monophosphate (cAMP)-mediated signaling in failing hearts, through cyclic guanosine 3´,5´-monophosphate (cGMP)-mediated phosphodiesterase (PDE) 3 inhibition. As several signaling pathways are importantly changed in failing hearts, it could not be taken for granted that this crosstalk would be the same in non-failing hearts. Thus, we wanted to clarify to which extent this effect of CNP occurred also in non-failing hearts...
July 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28692698/nitric-oxide-attenuates-overexpression-of-gi%C3%AE-proteins-in-vascular-smooth-muscle-cells-from-shr-role-of-ros-and-ros-mediated-signaling
#13
Oli Sarkar, Yuan Li, Madhu B Anand-Srivastava
Vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit decreased levels of nitric oxide (NO) that may be responsible for the overexpression of Giα proteins that has been shown as a contributing factor for the pathogenesis of hypertension in SHR. The present study was undertaken to investigate if increasing the intracellular levels of NO by NO donor S-Nitroso-N-acetyl-DL-penicillamine (SNAP) could attenuate the enhanced expression of Giα proteins in VSMC from SHR and explore the underlying mechanisms responsible for this response...
2017: PloS One
https://www.readbyqxmd.com/read/28690194/examining-a-role-for-pkg-i%C3%AE-oxidation-in-the-pathogenesis-of-cardiovascular-dysfunction-during-diet-induced-obesity
#14
Olena Rudyk, Philip Eaton
BACKGROUND: Protein kinase G (PKG) Iα is the end-effector kinase that mediates nitric oxide (NO)-dependent and oxidant-dependent vasorelaxation to maintain blood pressure during health. A hallmark of cardiovascular disease is attenuated NO production, which in part is caused by NO Synthase (NOS) uncoupling, which in turn increases oxidative stress because of superoxide generation. NOS uncoupling promotes PKG Iα oxidation to the interprotein disulfide state, likely mediated by superoxide-derived hydrogen peroxide, and because the NO-cyclic guanosine monophosphate (cGMP) pathway otherwise negatively regulates oxidation of the kinase to its active disulfide dimeric state...
July 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28688901/microrna-155-regulates-arsenite-induced-malignant-transformation-by-targeting-nrf2-mediated-oxidative-damage-in-human-bronchial-epithelial-cells
#15
Chengzhi Chen, Xuejun Jiang, Shiyan Gu, Zunzhen Zhang
Arsenite is a well-documented human lung carcinogen but the detailed mechanisms of carcinogenesis remain unclear. In this study, human bronchial epithelial (16-HBE) cells were continuously exposed to 2.5μM arsenite for about 13 weeks to induce the phenotypes of malignant transformation. Our results showed that Nrf2 expression was gradually decreased whereas no significant change was observed on NF-κB activation with increased time of arsenite exposure. To test the roles of Nrf2-meidtaed oxidative damage in the arsenite-induced malignant transformation, we compared the levels of cGMP, PKG and oxidative damage-related indicators between arsenic-transformed cells and control cells...
July 6, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28679626/the-bradykinin-bk-cgmp-pkg-pathway-augments-insulin-sensitivity-via-upregulation-of-mapk-phosphatase-5-and-inhibition-of-jun-kinase-jnk
#16
Maria E Frigolet, Garry Thomas, Kristin Beard, Huogen Lu, Lijiang Liu, I George Fantus
Bradykinin (BK) promotes insulin sensitivity and glucose uptake in adipocytes and other cell types. We demonstrated that in rat adipocytes BK enhances insulin-stimulated glucose transport via endothelial nitric oxide synthase (eNOS), nitric oxide (NO) generation, and decreased activity of the mitogen activated protein kinase (MAPK), JNK (c-Jun-N-terminal kinase). In endothelial cells, NO increases soluble guanylate cyclase (sGC) activity which in turn, activates protein kinase G (PKG) by increasing cGMP levels...
July 5, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28673898/platelet-derived-factor-v-is-a-critical-mediator-of-arterial-thrombosis
#17
Meiping Ren, Rong Li, Ni Chen, Ningbo Pang, Yongjie Li, Xin Deng, Liqun Wang, Mao Luo, Yan Liu, Haiyan Hao, Yong Liu, Hongmin Sun, Jianbo Wu
BACKGROUND: Coagulation factor V (FV) plays a key role in hemostasis, is present in plasma and platelets, and has both pro- and anticoagulant properties; however, the contribution of platelet-derived FV to arterial thrombosis remains undetermined. METHODS AND RESULTS: Using transgenic mice with various levels of FV gene expression that was restricted to the plasma or platelets, the roles of platelet FV were evaluated in the regulation of arterial thrombosis and platelet activation...
July 3, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28671970/cardioprotective-effects-of-pkg-activation-by-soluble-gc-activator-bay-60-2770-in-ischemia-reperfusion-injured-rat-hearts
#18
Kyung Hye Lee, So-Ra Lee, Haneul Cho, Jong Shin Woo, Jung Hee Kang, Yun-Mi Jeong, Xian Wu Cheng, Woo-Shik Kim, Weon Kim
Soluble guanylate cyclase (sGC) has been suggested as a therapeutic target for cardiac ischemia-reperfusion (IR) injury. Until now, the molecular mechanism of BAY 60-2770, a sGC activator, in cardiac IR injury has not been assessed. To identify the cardioprotective effects of BAY 60-2770 in IR-injured rat hearts, IR injury was established by occlusion of LAD for 40 min and reperfusion for 7 days, and the effects of BAY 60-2770 on myocardial protection were assessed by echocardiography and TTC staining. 5 nM and 5 μM of BAY 60-2770 were perfused into isolated rat hearts in a Langendorff system...
2017: PloS One
https://www.readbyqxmd.com/read/28668721/pde2-at-the-crossway-between-camp-and-cgmp-signalling-in-the-heart
#19
REVIEW
Silvio Weber, Miriam Zeller, Kaomei Guan, Frank Wunder, Michael Wagner, Ali El-Armouche
The cyclic nucleotides cAMP and cGMP are central second messengers in cardiac cells and critical regulators of cardiac physiology as well as pathophysiology. Consequently, subcellular compartmentalization allows for spatiotemporal control of cAMP/cGMP metabolism and subsequent regulation of their respective effector kinases PKA or PKG is most important for cardiac function in health and disease. While acute cAMP-mediated signalling is a mandatory prerequisite for the physiological fight-or-flight response, sustained activation of this pathway may lead to the progression of heart failure...
June 28, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28660304/differences-in-the-renal-antifibrotic-cgmp-cgki-dependent-signaling-of-serelaxin-zaprinast-and-their-combination
#20
Veronika Wetzl, Elisabeth Schinner, Frieder Kees, Lothar Faerber, Jens Schlossmann
Renal fibrosis is an important factor for end-stage renal failure. However, only few therapeutic options for its treatment are established. Zaprinast, a phosphodiesterase 5 inhibitor, and serelaxin, the recombinant form of the naturally occurring hormone relaxin, are differently acting modulators of cyclic guanosine monophosphate (cGMP) signaling. Both agents enhance cGMP availability in kidney tissue. These substances alone or in combination might interfere with the development of kidney fibrosis. Therefore, we compared the effects of combination therapy with the effects of monotherapy on renal fibrosis...
June 28, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
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