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https://www.readbyqxmd.com/read/28239389/harnessing-evolutionary-toxins-for-signaling-reactive-oxygen-species-nitric-oxide-and-hydrogen-sulfide-in-plant-cell-regulation
#1
John T Hancock
During the early periods of evolution, as well as in niche environments today, organisms have had to learn to tolerate the presence of many reactive compounds, such as reactive oxygen species, nitric oxide, and hydrogen sulfide. It is now known that such compounds are instrumental in the signaling processes in plant cells. There are enzymes which can make them, while downstream of their signaling pathways are coming to light. These include the production of cGMP, the activation of MAP kinases and transcription factors, and the modification of thiol groups on many proteins...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28238802/phoneutria-nigriventer-spider-toxin-tx2-6-induces-priapism-in-mice-even-after-cavernosal-denervation
#2
Katherine Garcia Ravelli, Adriana de Toledo Ramos, Luana Baracho Gonçalves, Fábio Carlos Magnoli, Lanfranco Ranieri Paolo Troncone
The Phoneutria nigriventer spider toxin Tx2-6 causes priapism in humans and mice. This toxin produces a delay in Sodium channel inactivation, generalized vascular congestion and death by respiratory failure. NO-Synthase inhibitors seem to abolish toxin-induced priapism. The understanding of the ultimate molecular mechanism involved in toxin-induced priapism may shed light on aspects of erectile function/dysfunction. This study investigates if cavernosal denervation can abolish the toxin-induced priapism. Surgical cavernosal nerve excision/denervation was performed in mice and confirmed by infertility, histological assessment of fibrosis and immunohistochemical staining for synaptophysin...
February 24, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28230071/probing-the-molecular-mechanism-of-human-soluble-guanylate-cyclase-activation-by-no-in-vitro-and-in-vivo
#3
Jie Pan, Hong Yuan, Xiaoxue Zhang, Huijuan Zhang, Qiming Xu, Yajun Zhou, Li Tan, Shingo Nagawa, Zhong-Xian Huang, Xiangshi Tan
Soluble guanylate cyclase (sGC) is a heme-containing metalloprotein in NO-sGC-cGMP signaling. NO binds to the heme of sGC to catalyze the synthesis of the second messenger cGMP, which plays a critical role in several physiological processes. However, the molecular mechanism for sGC to mediate the NO signaling remains unclear. Here fluorophore FlAsH-EDT2 and fluorescent proteins were employed to study the NO-induced sGC activation. FlAsH-EDT2 labeling study revealed that NO binding to the H-NOX domain of sGC increased the distance between H-NOX and PAS domain and the separation between H-NOX and coiled-coil domain...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229930/atrial-natriuretic-peptide-a-novel-mediator-for-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-in-16hbe-14o-and-a549-cells
#4
Shuyuan Chu, Xiufeng Zhang, Yabing Sun, Yuanyuan Yu, Yaxi Liang, Ming Jiang, Jianwei Huang, Libing Ma
Atrial natriuretic peptide (ANP) is increasingly expressed on airway and inhibits pulmonary arterial remodeling. However, the role of ANP in remodeling of respiratory system is still unclear. The role of ANP on airway remodeling and the possible mechanism was explored in this study. Both human bronchial epithelial 16HBE-14o cells and alveolar epithelial A549 cells were stimulated by TGF-β1, ANP, cGMP inhibitor, PKG inhibitor, and cGMP analogue. The expressions of epithelial markers, mesenchymal markers, and Smad3 were assessed by quantitative real-time PCR and western blotting...
February 13, 2017: Peptides
https://www.readbyqxmd.com/read/28228615/levels-of-cyclic-amp-and-cyclic-gmp-in-porcine-oocyte-cumulus-complexes-and-cumulus-free-oocytes-derived-from-small-and-middle-follicles-during-the-first-24-hour-period-of-in-vitro-maturation
#5
Yuichi Okudaira, Takuya Wakai, Hiroaki Funahashi
The objective of this study was to compare the cAMP and cGMP levels in cumulus-oocyte complexes (COCs) derived from the middle follicles (MFs, 3-6 mm in diameter) and small follicles (SFs, 1-3 mm in diameter) of pre-pubertal gilts during the first 24-h period of maturation in vitro (IVM). Both cAMP and cGMP levels in MF- and SF-derived oocytes did not change during this period. Although the cAMP levels increased in the COCs at 10 and 20 h after the start of IVM, the levels of cAMP were significantly higher in MF-derived COCs than in SF-derived COCs at 20 h after the start of IVM...
February 23, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28218740/maresin1-stimulates-alveolar-fluid-clearance-through-the-alveolar-epithelial-sodium-channel-na-k-atpase-via-the-alx-pi3k-nedd4-2-pathway
#6
Jun-Li Zhang, Xiao-Jun Zhuo, Jing Lin, Ling-Chun Luo, Wei-Yang Ying, Xiang Xie, Hua-Wei Zhang, Jing-Xiang Yang, Dan Li, Fang Gao Smith, Sheng-Wei Jin
Maresin1 (MaR1) is a new docosahexaenoic acid-derived pro-resolving agent that promotes the resolution of inflammation. In this study, we sought to investigate the effect and underlining mechanisms of MaR1 in modulating alveolar fluid clearance (AFC) on LPS-induced acute lung injury. MaR1 was injected intravenously or administered by instillation (200 ng/kg) 8 h after LPS (14 mg/kg) administration and AFC was measured in live rats. In primary rat alveolar type II epithelial cells, MaR1 (100 nM) was added to the culture medium with lipopolysaccharide for 6 h...
February 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28218702/phytochemical-study-of-tapirira-guianensis-leaves-guided-by-vasodilatory-and-antioxidant-activities
#7
Amélia M G Rodrigues, Denise O Guimarães, Tatiana U P Konno, Luzineide W Tinoco, Thiago Barth, Fernando A Aguiar, Norberto P Lopes, Ivana C R Leal, Juliana M Raimundo, Michelle F Muzitano
The aim of this research was to perform a phytochemical study of the methanol leaves extract of T. guianensis (MET) guided by vasodilatory and antioxidant activities. The chemical profile of MET and the ethyl acetate fraction (EA fraction) was determined by HPLC-UV-MS and EA fraction guided fractionation by reverse-phase chromatography. The vasorelaxant effects of MET, fractions, sub-fractions and constituents were assessed on rat aorta pre-contracted with phenylephrine. Antioxidant activity was evaluated by using a DPPH assay...
February 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28218456/endothelial-cells-inhibit-the-angiotensin-ii-induced-phenotypic-modulation-of-rat-vascular-fibroblasts
#8
Xu Jia-Ying, Chang Nen-Bin, Li Tao, Jiang Rui, Sun Xiao-Lei, He Yan-Zheng, Jiang Jun
PURPOSE: The phenotypic modulation of vascular adventitial fibroblasts plays an important role in vascular remodeling. Evidence have shown that endothelial cells and adventitial fibroblasts interact under certain conditions. In this study, we investigated the influence of endothelial cells on the phenotypic modulation of adventitial fibroblasts. METHODS: Endothelial cells and adventitial fibroblasts from rat thoracic aorta were cultivated in a co-culture system and adventitial fibroblasts were induced with angiotensin II (Ang II)...
February 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28217374/plecanatide-mediated-activation-of-guanylate-cyclase-c-suppresses-inflammation-induced-colorectal-carcinogenesis-in-apc-min-fccc-mice
#9
Wen-Chi L Chang, Shet Masih, Anusha Thadi, Viren Patwa, Apoorva Joshi, Harry S Cooper, Vaseem A Palejwala, Margie L Clapper, Kunwar Shailubhai
AIM: To evaluate the effect of orally administered plecanatide on colorectal dysplasia in Apc(+/Min-FCCC) mice with dextran sodium sulfate (DSS)-induced inflammation. METHODS: Inflammation driven colorectal carcinogenesis was induced in Apc(+/Min-FCCC) mice by administering DSS in their drinking water. Mice were fed a diet supplemented with plecanatide (0-20 ppm) and its effect on the multiplicity of histopathologically confirmed polypoid, flat and indeterminate dysplasia was evaluated...
February 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28216314/visual-working-memory-requires-permissive-and-instructive-no-cgmp-signaling-at-presynapses-in-the-drosophila-central-brain
#10
Sara Kuntz, Burkhard Poeck, Roland Strauss
The gaseous second messenger nitric oxide (NO) has been shown to regulate memory formation by activating retrograde signaling cascades from post- to presynapse that involve cyclic guanosine monophosphate (cGMP) production to induce synaptic plasticity and transcriptional changes. In this study, we analyzed the role of NO in the formation of a visual working memory that lasts only a few seconds. This memory is encoded in a subset of ring neurons that form the ellipsoid body in the Drosophila brain. Using genetic and pharmacological manipulations, we show that NO signaling is required for cGMP-mediated CREB activation, leading to the expression of competence factors like the synaptic homer protein...
February 8, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28216026/cyclic-nucleotide-imaging-and-cardiovascular-disease
#11
REVIEW
Filip Berisha, Viacheslav O Nikolaev
The universal second messengers cyclic nucleotides 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) play central roles in cardiovascular function and disease. They act in discrete, functionally relevant subcellular microdomains which regulate, for example, calcium cycling and excitation-contraction coupling. Such localized cAMP and cGMP signals have been difficult to measure using conventional biochemical techniques. Recent years have witnessed the advent of live cell imaging techniques which allow visualization of these functionally relevant second messengers with unprecedented spatial and temporal resolution at cellular, subcellular and tissue levels...
February 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28213937/targeting-phosphodiesterase-5-as-a-therapeutic-option-against-myocardial-ischemia-reperfusion-injury-and-in-treating-heart-failure
#12
REVIEW
Sevil Korkmaz-Icöz, Tamás Radovits, Gábor Szabó
Phosphodiesterase type 5 (PDE5) selectively hydrolyses the second messenger cyclic 3´-5´guanosine monophosphate (cGMP) into 5'-GMP, thereby regulating its intracellular concentrations. Dysregulation of the cGMP-dependent pathway plays a significant role in various cardiovascular diseases. Therefore, its modulation by drugs, such as PDE5 inhibitors, may represent an effective therapeutic approach. There are currently four PDE5 inhibitors available for the treatment of erectile dysfunction: sildenafil, vardenafil, tadalafil, and avanafil...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28213625/8-nitro-cgmp-a-novel-protein-reactive-cnmp-and-its-emerging-roles-in-autophagy
#13
Hirokazu Arimoto, Daiki Takahashi
Nitric oxide (NO) raises the intracellular 3',5'-cyclic guanosine monophosphate (cGMP) level through the activation of soluble guanylate cyclase and, in the presence of reactive oxygen species (ROS), reacts with biomolecules to produce nitrated cGMP derivatives. 8-Nitro-cGMP was the first endogenous cGMP derivative discovered in mammalian cells (2007) and was later found in plant cells. Among the six nitrogen atoms in this molecule, the one in the nitro group (NO2) comes from NO. This chapter asserts that this newly found cGMP is undoubtedly one of the major physiological cNMPs...
February 18, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28211938/establishment-and-validation-of-a-microfluidic-capillary-gel-electrophoresis-platform-method-for-purity-analysis-of-therapeutic-monoclonal-antibodies
#14
Michael T Smith, Shu Zhang, Troy Adams, Byron DiPaolo, Jennifer Dally
Capillary and microfluidic chip electrophoresis technologies are heavily utilized for development, characterization, release, and stability testing of biopharmaceuticals. Within the biopharmaceutical industry, CE-SDS and M-CGE are commonly used for purity determination by separation and quantitation of size-based variants. M-CGE is used primarily as a R&D tool for product and process development, while cGMP release and stability testing applications are commonly reserved for CE-SDS. This paper describes the establishment of a M-CGE platform method to be used for R&D and cGMP applications, including release and stability testing, for monoclonal antibodies...
February 17, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28211580/inhibition-of-pde5a1-guanosine-cyclic-monophosphate-cgmp-hydrolysing-activity-by-sildenafil-analogues-that-inhibit-cellular-cgmp-efflux
#15
Anna Subbotina, Aina W Ravna, Roy A Lysaa, Ruben Abagyan, Ryszard Bugno, Georg Sager
OBJECTIVES: To determine the ability of 11 sildenafil analogues to discriminate between cyclic nucleotide phosphodiesterases (cnPDEs) and to characterise their inhibitory potencies (Ki values) of PDE5A1-dependent guanosine cyclic monophosphate (cGMP) hydrolysis. METHODS: Sildenafil analogues were identified by virtual ligand screening (VLS) and screened for their ability to inhibit adenosine cyclic monophosphate (cAMP) hydrolysis by PDE1A1, PDE1B1, PDE2A1, PDE3A, PDE10A1 and PDE10A2, and cGMP hydrolysis by PDE5A, PDE6C, PDE9A2 for a low (1 nm) and high concentration (10 μm)...
February 17, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28210757/sildenafil-a-phosphodiesterase-type-5-inhibitor-downregulates-osteopontin-in-human-peripheral-blood-mononuclear-cells
#16
Beata Kaleta, Agnieszka Boguska
The aim of this study was to investigate the ability of sildenafil to regulate osteopontin (OPN) gene and protein in peripheral blood mononuclear cells (PBMCs) from healthy blood donors. OPN is expressed by a wide variety of cell types, including immune cells. OPN functions are linked to various physiological and pathological conditions. Sildenafil is a selective inhibitor of type 5 phosphodiesterase. Sildenafil has recently been found to have immunomodulatory effects in animal models and in studies performed in humans...
February 16, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28204955/inactivation-of-non-canonical-cyclic-nucleotides-hydrolysis-and-transport
#17
Erich H Schneider, Roland Seifert
This chapter addresses cNMP hydrolysis by phosphodiesterases (PDEs) and export by multidrug resistance associated proteins (MRPs). Both mechanisms are well-established for the canonical cNMPs, cAMP, and cGMP. Increasing evidence shows that non-canonical cNMPs (specifically cCMP, cUMP) are also PDE and MRP substrates. Hydrolysis of cUMP is achieved by PDE 3A, 3B, and 9A, which possibly explains the cUMP-degrading activities previously reported for heart, adipose tissue, and brain. Regarding cCMP, the only known "conventional" (class I) PDE that hydrolyzes cCMP is PDE7A...
February 16, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28198469/garp2-accelerates-retinal-degeneration-in-rod-cgmp-gated-cation-channel-%C3%AE-subunit-knockout-mice
#18
Marci L DeRamus, Delores A Stacks, Youwen Zhang, Carrie E Huisingh, Gerald McGwin, Steven J Pittler
The Cngb1 locus-encoded β-subunit of rod cGMP-gated cation channel and associated glutamic acid rich proteins (GARPs) are required for phototransduction, disk morphogenesis, and rod structural integrity. To probe individual protein structure/function of the GARPs, we have characterized several transgenic mouse lines selectively restoring GARPs on a Cngb1 knockout (X1(-/-)) mouse background. Optical coherence tomography (OCT), light and transmission electron microscopy (TEM), and electroretinography (ERG) were used to analyze 6 genotypes including WT at three and ten weeks postnatal...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28185305/cgmp-production-of-the-radiopharmaceutical-18-f-mk-6240-for-pet-imaging-of-human-neurofibrillary-tangles
#19
Thomas Lee Collier, Daniel L Yokell, Eli Livni, Peter A Rice, Sofie Celen, Kim Serdons, Ramesh Neelamegam, Guy Bormans, Dawn Harris, Abbas Walji, Eric D Hostetler, Idriss Bennacef, Neil Vasdev
Fluorine-18 labelled 6-(fluoro)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([(18) F]MK-6240) is a novel potent and selective PET radiopharmaceutical for detecting human neurofibrillary tangles, which are made up of aggregated tau protein. Herein, we report the fully automated two-step radiosynthesis of [(18) F]MK-6240 using a commercially available radiosynthesis module, GE Healthcare Tracerlab(TM) FXFN . Nucleophilic fluorination of the 5-diBoc-6-nitro precursor with potassium cryptand [(18) F]fluoride (K[(18) F]/K222 ) was carried out by conventional heating, followed by acid deprotection and semi-preparative HPLC under isocratic conditions...
February 9, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28181008/ccmp-and-cump-across-the-tree-of-life-from-ccmp-and-cump-generators-to-ccmp-and-cump-regulated-cell-functions
#20
Roland Seifert
The cyclic purine nucleotides cAMP and cGMP are well-established second messenger molecules that are generated by distinct nucleotidyl cyclases (NCs) and regulate numerous cell functions via specific effector molecules. In contrast, the existence of the cyclic pyrimidine nucleotides cCMP and cUMP has been controversial for many years. The development of highly specific and sensitive mass spectrometry methods has enabled the unequivocal detection and quantitation of cCMP and cUMP in biological systems. These cNMPs occur broadly in numerous mammalian cell lines and primary cells...
February 9, 2017: Handbook of Experimental Pharmacology
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