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https://www.readbyqxmd.com/read/28922657/methods-employed-in-cytofluorometric-assessment-of-eryptosis-the-suicidal-erythrocyte-death
#1
Mohamed Jemaà, Myriam Fezai, Rosi Bissinger, Florian Lang
Suicidal erythrocyte death or eryptosis contributes to or even accounts for anemia in a wide variety of clinical conditions, such as iron deficiency, dehydration, hyperphosphatemia, vitamin D excess, chronic kidney disease (CKD), hemolytic-uremic syndrome, diabetes, hepatic failure, malignancy, arteriitis, sepsis, fever, malaria, sickle-cell disease, beta-thalassemia, Hb-C and G6PD-deficiency, Wilsons disease, as well as advanced age. Moreover, eryptosis is triggered by a myriad of xenobiotics and endogenous substances including cytotoxic drugs and uremic toxins...
September 1, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28918326/a-surrogate-analyte-based-liquid-chromatography-tandem-mass-spectrometry-method-for-the-determination-of-endogenous-cyclic-nucleotides-in-rat-brain
#2
Jie Chen, Ali Tabatabaei, Doug Zook, Yan Wang, Anne Danks, Kathe Stauber
A robust high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) assay was developed and qualified for the measurement of cyclic nucleotides (cNTs) in rat brain tissue. Stable isotopically labeled 3',5'-cyclic adenosine-(13)C5 monophosphate ((13)C5-cAMP) and 3',5'-cyclic guanosine-(13)C,(15)N2 monophosphate ((13)C(15)N2-cGMP) were used as surrogate analytes to measure endogenous 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP). Pre-weighed frozen rat brain samples were rapidly homogenized in 0...
September 14, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28917840/both-nitric-oxide-and-nitrite-prevent-homocysteine-induced-endoplasmic-reticulum-stress-and-subsequent-apoptosis-via-cgmp-dependent-pathway-in-neuronal-cells
#3
Sun-Oh Jeong, Yong Son, Ju Hwan Lee, Seung Won Choi, Sung Hun Kim, Yong-Kwan Cheong, Hun-Taeg Chung, Hyun-Ock Pae
Growing evidence indicates that endoplasmic reticulum (ER) stress and/or ER stress-mediated apoptosis may play a role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. The present study investigated the effects of non-cytotoxic concentrations of nitric oxide (NO) and nitrite, a metabolite of NO, on ER stress and ER stress-mediated apoptosis in Neuro-2a cells exposed to homocysteine (Hcy), an endogenous ER stress inducer. Hcy induced ER stress, as confirmed by inositol-requiring enzyme 1α (IRE1α) phosphorylation and X-box-binding protein-1 (Xbp1) mRNA splicing as well as C/EBP homologous protein (CHOP) expression, and apoptosis, as verified by Annexin V-positive cells...
September 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28915270/the-single-cyclic-nucleotide-specific-phosphodiesterase-of-the-intestinal-parasite-giardia-lamblia-represents-a-potential-drug-target
#4
Stefan Kunz, Vreni Balmer, Geert Jan Sterk, Michael P Pollastri, Rob Leurs, Norbert Müller, Andrew Hemphill, Cornelia Spycher
BACKGROUND: Giardiasis is an intestinal infection correlated with poverty and poor drinking water quality, and treatment options are limited. According to the Center for Disease Control and Prevention, Giardia infections afflict nearly 33% of people in developing countries, and 2% of the adult population in the developed world. This study describes the single cyclic nucleotide-specific phosphodiesterase (PDE) of G. lamblia and assesses PDE inhibitors as a new generation of anti-giardial drugs...
September 15, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28914189/a-hopeful-prospect-of-riociguat-as-a-soluble-guanylate-cyclase-stimulator-for-management-of-pressure-ulcers
#5
Soha Azadi, Hajar Ashrafi, Amir Azadi
Pressure ulcer remains as a common problem, especially developed in disabled patients and hence, subjected to continuous pressure for prolonged periods of time. Most of the studies investigating the preventive and therapeutic approaches have focused on wound cleansing, dressing and supportive strategies , as well as pharmacological therapy including zinc sulphate, vitamin A or phenytoin. Despite such efforts, pressure ulcer continues to impair the life quality and expectancy. Thus involving in the paradigm shift in biomedical studies, the recent ones focus on biological signaling pathways involving nitric oxide (NO)- soluble guanylatecyclase (sGC)- cyclic guanosine monophosphate (cGMP) contributing in vasodilation, reperfusion and oxygen delivery...
September 15, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/28911813/functional-dynamics-in-cyclic-nucleotide-signaling-and-amyloid-inhibition
#6
REVIEW
Bryan VanSchouwen, Rashik Ahmed, Julijana Milojevic, Giuseppe Melacini
It is now established that understanding the molecular basis of biological function requires atomic resolution maps of both structure and dynamics. Here, we review several illustrative examples of functional dynamics selected from our work on cyclic nucleotide signaling and amyloid inhibition. Although fundamentally diverse, a central aspect common to both fields is that function can only be rationalized by considering dynamic equilibria between distinct states of the accessible free energy landscape. The dynamic exchange between ground and excited states of signaling proteins is essential to explain auto-inhibition and allosteric activation...
September 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28910498/phosphodiesterase-1a-inhibition-elicits-cgmp-dependent-relaxation-of-rat-mesenteric-arteries
#7
Makhala Michell Khammy, Thomas Dalsgaard, Peter Hjørringgaard Larsen, Claus Tornby Christoffersen, Dorte Clausen, Lars Kyhn Rasmussen, Lasse Folkersen, Morten Grunnet, Jan Kehler, Christian Aalkjaer, Jacob Nielsen
BACKGROUND AND PURPOSE: Phosphodiesterase 1 (PDE1), a subfamily of cyclic nucleotide phosphodiesterases consisting of three isoforms, PDE1A, PDE1B, and PDE1C, has been implicated in regulation of vascular tone. The PDE1 isoform(s) responsible for tone regulation is unknown. This study used isoform-preferring PDE1 inhibitors, Lu AF58027, Lu AF64196, Lu AF66896, and Lu AF67897, to investigate the relative contribution of PDE1 isoforms to regulation of vascular tone. EXPERIMENTAL APPROACH: In rat mesenteric arteries, expression and localisation of Pde1 isoforms were determined by qPCR and in situ hybridisation, and physiological impact of PDE1 inhibition were evaluated by isometric tension recordings...
September 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28904388/protective-efficacy-of-phosphodiesterase-1-inhibition-against-alpha-synuclein-toxicity-revealed-by-compound-screening-in-luhmes-cells
#8
Matthias Höllerhage, Claudia Moebius, Johannes Melms, Wei-Hua Chiu, Joachim N Goebel, Tasnim Chakroun, Thomas Koeglsperger, Wolfgang H Oertel, Thomas W Rösler, Marc Bickle, Günter U Höglinger
α-synuclein-induced neurotoxicity is a core pathogenic event in neurodegenerative synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. There is currently no disease-modifying therapy available for these diseases. We screened 1,600 FDA-approved drugs for their efficacy to protect LUHMES cells from degeneration induced by wild-type α-synuclein and identified dipyridamole, a non-selective phosphodiesterase inhibitor, as top hit. Systematic analysis of other phosphodiesterase inhibitors identified a specific phosphodiesterase 1 inhibitor as most potent to rescue from α-synuclein toxicity...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28904134/an-ant-plant-mutualism-through-the-lens-of-cgmp-dependent-kinase-genes
#9
Pierre-Jean G Malé, Kyle M Turner, Manjima Doha, Ina Anreiter, Aaron M Allen, Marla B Sokolowski, Megan E Frederickson
In plant-animal mutualisms, how an animal forages often determines how much benefit its plant partner receives. In many animals, foraging behaviour changes in response to foraging gene expression or activation of the cGMP-dependent protein kinase (PKG) that foraging encodes. Here, we show that this highly conserved molecular mechanism affects the outcome of a plant-animal mutualism. We studied the two PKG genes of Allomerus octoarticulatus, an Amazonian ant that defends the ant-plant Cordia nodosa against herbivores...
September 13, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28900772/clathrin-dependent-internalization-signaling-and-metabolic-processing-of-guanylyl-cyclase-natriuretic-peptide-receptor-a
#10
Naveen K Somanna, Indra Mani, Satyabha Tripathi, Kailash N Pandey
Cardiac hormones, atrial and brain natriuretic peptides (ANP and BNP), have pivotal roles in renal hemodynamics, neuroendocrine signaling, blood pressure regulation, and cardiovascular homeostasis. Binding of ANP and BNP to the guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) induces rapid internalization and trafficking of the receptor via endolysosomal compartments, with concurrent generation of cGMP. However, the mechanisms of the endocytotic processes of NPRA are not well understood. The present study, using (125)I-ANP binding assay and confocal microscopy, examined the function of dynamin in the internalization of NPRA in stably transfected human embryonic kidney-293 (HEK-293) cells...
September 12, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28899499/mechanisms-underlying-antiatherosclerotic-properties-of-an-enriched-fraction-obtained-from-ilex-paraguariensis-a-st-hil
#11
Patrícia Gonçalves Santiago, Francielly Mourão Gasparotto, Karimi Sater Gebara, Flavia Barbieri Bacha, Francislaine Aparecida Dos Reis Lívero, Maria Angélica Strapazon, Euclides Lara Cardozo Junior, Cândida Aparecida Leite Kassuya, Lauro Mera de Souza, Arquimedes Gasparotto Junior
BACKGROUND: Ilex paraguariensis A. St. Hil. var. paraguariensis (Aquifoliaceae) popularly known as 'mate' is an important species native to South America. Despite numerous studies showing significant antioxidant and lipid lowering properties, the antiatherosclerotic mechanisms of this species remain unknown. PURPOSE: To evaluate the possible antiatherosclerotic effects of a butanolic fraction (n-BFIP) obtained from I. paraguariensis and to investigate the molecular mechanisms involved in this activity...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28895923/st-producing-e-coli-oppose-carcinogen-induced-colorectal-tumorigenesis-in-mice
#12
Peng Li, Jieru E Lin, Adam E Snook, Scott A Waldman
There is a geographic inequality in the incidence of colorectal cancer, lowest in developing countries, and greatest in developed countries. This disparity suggests an environmental contribution to cancer resistance in endemic populations. Enterotoxigenic bacteria associated with diarrheal disease are prevalent in developing countries, including enterotoxigenic E. coli (ETEC) producing heat-stable enterotoxins (STs). STs are peptides that are structurally homologous to paracrine hormones that regulate the intestinal guanylyl cyclase C (GUCY2C) receptor...
September 12, 2017: Toxins
https://www.readbyqxmd.com/read/28895506/targeting-l-arginine-nitric-oxide-cgmp-pathway-in-pulmonary-arterial-hypertension
#13
Haiyang Tang, Rebecca R Vanderpool, Jian Wang, Jason X-J Yuan
No abstract text is available yet for this article.
July 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28894114/cinaciguat-ameliorates-glomerular-damage-by-reducing-erk1-2-activity-and-tgf-%C3%A3-expression-in-type-1-diabetic-rats
#14
Szabina Czirok, Lilla Fang, Tamás Radovits, Gábor Szabó, Gábor Szénási, László Rosivall, Béla Merkely, Gábor Kökény
Decreased soluble guanylate cyclase activity and cGMP levels in diabetic kidneys were shown to influence the progression of nephropathy. The regulatory effects of soluble guanylate cyclase activators on renal signaling pathways are still unknown, we therefore investigated the renal molecular effects of the soluble guanylate cyclase activator cinaciguat in type-1 diabetic (T1DM) rats. Male adult Sprague-Dawley rats were divided into 2 groups after induction of T1DM with 60 mg/kg streptozotocin: DM, untreated (DM, n = 8) and 2) DM + cinaciguat (10 mg/kg per os daily, DM-Cin, n = 8)...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28890382/in-vitro-genotoxicity-and-in-vivo-subchronic-evaluation-of-the-anti-inflammatory-pyrazole-compound-lqfm021
#15
Soraia Santa de Moura, Renato Ivan de Ávila, Lara Barroso Brito, Rhaul de Oliveira, Gisele Augusto Rodrigues de Oliveira, Francine Pazini, Ricardo Menegatti, Aline Carvalho Batista, Cesar Koppe Grisolia, Marize Campos Valadares
Scientific evidences have highlighted 5-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)-2H-tetrazole (LQFM021) as a promising anti-inflammatory, analgesic and antinociceptive agent due to its effects on peripheral opioid receptors associated with activation of the nitric oxide/cGMP/KATP pathway. Despite these important pharmacological findings, toxicity data of LQFM021 are scarce. Thus, this study investigated the in vitro genotoxicity of LQFM021 through cytokinesis-block micronucleus assay (OECD Nº 487/2014). Moreover, zebrafish model was used to assess the embryotoxicity potential of LQFM021 using fish embryo toxicity test (OECD Nº 236/2013) with extended exposure to evaluate subchronic larval development...
September 7, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28889285/identification-and-quantification-of-cyclic-di-guanosine-monophosphate-and-its-linear-metabolites-by-reversed-phase-lc-ms-ms
#16
Heike Bähre, Volkhard Kaever
Cyclic dinucleotides such as bis-(3',5')-cyclic dimeric guanosine monophosphate (3',3'-c-di-GMP) represent an important class of second messengers in bacteria and are involved in numerous (patho)physiological settings. Here, we describe a sensitive and specific quantification method for 3',3'-c-di-GMP by HPLC-coupled tandem mass spectrometry (LC-MS/MS). Additionally, linear 3',3'-c-di-GMP metabolites, i.e., 5'-phosphoguanylyl-3',5'-guanosine (pGpG) and 5'-guanosine monophosphate (5'-GMP), as well as cyclic guanosine monophosphate (3',5'-cGMP) and 3',3' c-di-GMP analogues (2',3'-c-di-GMP and 2',2'-c-di-GMP) can be simultaneously determined by this method...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28882822/both-nherf3-and-nherf2-are-necessary-for-multiple-aspects-of-acute-regulation-of-nhe3-by-elevated-ca-2-cgmp-and-lysophosphatidic-acid
#17
Leela Rani Avula, Tiane Chen, Olga Kovbasnjuk, Mark Donowitz
The intestinal epithelial brush border Na(+)/H(+) exchanger NHE3 accounts for a large component of intestinal Na absorption. NHE3 is regulated during digestion by signaling complexes on its C-terminus that include the four multi-PDZ domain containing NHERF family proteins. Because the roles of each NHERF appear to vary based on the cell model or intestinal segment studied and because of our recent finding that a NHERF3-NHERF2 heterodimer appears important for NHE3 regulation in Caco-2 cells, we examined the role of NHERF3 and NHERF2 in homozygous C57BL/6 NHERF2 and NHERF3 KO mouse jejunum...
September 7, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28880927/scf-kit-signaling-induces-endothelin-3-synthesis-and-secretion-thereby-activates-and-regulates-endothelin-b-receptor-for-generating-temporally-and-spatially-precise-nitric-oxide-to-modulate-scf-and-or-kit-expressing-cell-functions
#18
Lei L Chen, Jing Zhu, Jonathan Schumacher, Chongjuan Wei, Latha Ramdas, Victor G Prieto, Arnie Jimenez, Marco A Velasco, Sheryl R Tripp, Robert H I Andtbacka, Launce Gouw, George M Rodgers, Liansheng Zhang, Benjamin K Chan, Pamela B Cassidy, Robert S Benjamin, Sancy A Leachman, Marsha L Frazier
We demonstrate that SCF-KIT signaling induces synthesis and secretion of endothelin-3 (ET3) in human umbilical vein endothelial cells and melanoma cells in vitro, gastrointestinal stromal tumors, human sun-exposed skin, and myenteric plexus of human colon post-fasting in vivo. This is the first report of a physiological mechanism of ET3 induction. Integrating our finding with supporting data from literature leads us to discover a previously unreported pathway of nitric oxide (NO) generation derived from physiological endothelial NO synthase (eNOS) or neuronal NOS (nNOS) activation (referred to as the KIT-ET3-NO pathway)...
2017: PloS One
https://www.readbyqxmd.com/read/28880852/rna-sequencing-uncovers-molecular-mechanisms-underlying-pathological-complete-response-to-chemotherapy-in-patients-with-operable-breast-cancer
#19
Yongfeng Li, Xiaozhen Liu, Hongchao Tang, Hongjian Yang, Xuli Meng
BACKGROUND This study aimed to identify key genes contributing to pathological complete response (pCR) to chemotherapy by mRNA sequencing (RNA-seq). MATERIAL AND METHODS RNA was extracted from the frozen biopsy tissue of patients with pathological complete response and patients with non-pathological complete response. Sequencing was performed on the HiSeq2000 platform. Differentially expressed genes (DEGs) were identified between the pCR group and non-pCR (NpCR) group. Pathway enrichment analysis of DEGs was performed...
September 7, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28874749/structural-and-pharmacological-basis-for-the-induction-of-mitochondrial-biogenesis-by-formoterol-but-not-clenbuterol
#20
Robert B Cameron, Craig C Beeson, Rick G Schnellmann
Mitochondrial dysfunction is associated with numerous acute and chronic degenerative diseases. The beta-2 adrenergic receptor (β2AR) agonist formoterol induces mitochondrial biogenesis (MB), but other β2AR agonists, such as clenbuterol, do not. We sought to identify the MB signaling pathway of formoterol and the differences in signaling between these two ligands that result in the differential induction of MB. While formoterol and clenbuterol increased cAMP, only formoterol increased the phosphorylation of Akt and its downstream target eNOS...
September 5, 2017: Scientific Reports
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