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https://www.readbyqxmd.com/read/28087360/the-synthetic-peptide-pnpp-19-induces-peripheral-antinociception-via-activation-of-no-cgmp-katp-pathway-role-of-enos-and-nnos
#1
A C N Freitas, G Silva, D F Pacheco, V Lemos, I D G Duarte, M E de Lima
BACKGROUND AND PURPOSE: The peptide PnPP-19, derived from the spider toxin PnTx2-6, potentiates erectile function by activating the nitrergic system. Since NO has been studied as an antinociceptive molecule and PnPP-19 is known to induce peripheral antinociception, we intended to evaluate whether PnPP-19 could induce peripheral antinociception through activation of this pathway. EXPERIMENTAL APPROACH: Nociceptive thresholds were measured by paw pressure test. PGE2 (2 μg/paw) was administered intraplantarly together with PnPP-19 and inhibitors/blockers of NOS, guanylyl cyclase and KATP channels...
January 10, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28073499/physiological-and-transcriptional-responses-to-inorganic-nutrition-in-a-tropical-pacific-strain-of-alexandrium-minutum-implications-for-the-saxitoxin-genes-and-toxin-production
#2
Kieng Soon Hii, Po Teen Lim, Nyuk Fong Kon, Yoshinobu Takata, Gires Usup, Chui Pin Leaw
Saxitoxins (STXs) constitute a family of potent sodium channel blocking toxins, causative agents of paralytic shellfish poisoning (PSP), and are produced by several species of marine dinoflagellates and cyanobacteria. Two STX-core genes, sxtA and sxtG, have been well elucidated in Alexandrium but the expression of these genes under various nutritional modes in tropical species remains unclear. This study investigates the physiological responses of a tropical Pacific strain of Alexandrium minutum growing with nitrate or ammonium, and with various nitrogen to phosphorus (N:P) supply ratios...
June 2016: Harmful Algae
https://www.readbyqxmd.com/read/28065753/the-roles-of-conserved-aromatic-residues-tyr5-and-tyr42-in-interaction-of-scorpion-toxin-bmk-agp-sypu1-with-human-nav1-7
#3
Xiangxue Meng, Yijia Xu, Fangyang Wang, Mingyi Zhao, Xue Hou, Yuanyuan Ma, Yao Jin, Yanfeng Liu, Yongbo Song, Jinghai Zhang
Scorpion toxins are invaluable source of therapeutic leads and pharmacological tools which produce influence on the voltage gated sodium channels. In the previous study, our group has reported BmK AGP-SYPU1 (64 amino acids), one scorpion toxin with both potential α-type and β-type scorpion characteristics and analgesic activity in vivo, act as an activator to hNav1.4 and hNav1.5. Additionally, conserved aromatic amino acids Tyr5 and Tyr42 played important roles in bioactivity of BmK AGP-SYPU1 on hNav1.4 and hNav1...
January 5, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28063984/protein-toxins-of-the-echis-coloratus-viper-venom-directly-activate-trpv1
#4
Matan Geron, Rakesh Kumar, Henry Matzner, Adi Lahiani, Galit Gincberg, Gadi Cohen, Philip Lazarovici, Avi Priel
BACKGROUND: Peptide and protein toxins are essential tools to dissect and probe the biology of their target receptors. Venoms target vital physiological processes to evoke pain. Snake venoms contain various factors with the ability to evoke, enhance and sustain pain sensation. While a number of venom-derived toxins were shown to directly target TRPV1 channels expressed on somatosensory nerve terminals to evoke pain response, such toxins were yet to be identified in snake venoms. METHODS: We screened Echis coloratus saw-scaled viper venom's protein fractions isolated by reversed phase HPLC for their ability to activate TRPV1 channels...
January 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28060274/gap-junctional-intercellular-communication-a-functional-biomarker-to-assess-adverse-effects-of-toxicants-and-toxins-and-health-benefits-of-natural-products
#5
Brad L Upham, Iva Sovadinová, Pavel Babica
This protocol describes a scalpel loading-fluorescent dye transfer (SL-DT) technique that measures intercellular communication through gap junction channels, which is a major intercellular process by which tissue homeostasis is maintained. Interruption of gap junctional intercellular communication (GJIC) by toxicants, toxins, drugs, etc. has been linked to numerous adverse health effects. Many genetic-based human diseases have been linked to mutations in gap junction genes. The SL-DT technique is a simple functional assay for the simultaneous assessment of GJIC in a large population of cells...
December 25, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28041976/moving-pieces-in-a-cryptomic-puzzle-cryptide-from-tityus-serrulatus-ts3-nav-toxin-as-potential-agonist-of-muscarinic-receptors
#6
Cibele Rocha-Resende, Nádia Miricéia Leão, Maria Elena de Lima, Robson Augusto Santos, Adriano Monteiro de Castro Pimenta, Thiago Verano-Braga
Cryptome is as a subset of a given proteome containing bioactive cryptides embedded in larger peptides or proteins. We pinpointed a striking sequence similarity between two peptides from the Tityus serrulatus venom: Ts10 (KKDGYPVEYDRAY) and the N-terminal of Ts3 (KKDGYPVEYDNCAY). Ts3 (former Tityustoxin or TsIV) is an α-neurotoxin acting on voltage-gated sodium channels while Ts10 (former Peptide T) is a bradykinin-potentiating peptide and was originally reported as inhibitor of the angiotensin-converting enzyme (ACEi)...
December 29, 2016: Peptides
https://www.readbyqxmd.com/read/28035974/a-novel-toxin-from-haplopelma-lividum-selectively-inhibits-the-nav1-8-channel-and-possesses-potent-analgesic-efficacy
#7
Ping Meng, Honggang Huang, Gan Wang, Shilong Yang, Qiuming Lu, Jingze Liu, Ren Lai, Mingqiang Rong
Spider venoms are a complex mixture of peptides with a large number of neurotoxins targeting ion channels. Although thousands of peptide toxins have been identified from venoms of numerous species of spiders, many unknown species urgently need to be investigated. In this study, a novel sodium channel inhibitor, µ-TRTX-Hl1a, was identified from the venom of Haplopelma lividum. It contained eight cysteines and formed a conserved cysteine pattern of ICK motif. µ-TRTX-Hl1a inhibited the TTX-resistant (TTX-r) sodium channel current rather than the TTX-sensitive (TTX-s) sodium channel current...
December 26, 2016: Toxins
https://www.readbyqxmd.com/read/28025487/indoxyl-sulfate-as-a-mediator-involved-in-dysregulation-of-pulmonary-aquaporin-5-in-acute-lung-injury-caused-by-acute-kidney-injury
#8
Nozomi Yabuuchi, Masataka Sagata, Chika Saigo, Go Yoneda, Yuko Yamamoto, Yui Nomura, Kazuhiko Nishi, Rika Fujino, Hirofumi Jono, Hideyuki Saito
High mortality of acute kidney injury (AKI) is associated with acute lung injury (ALI), which is a typical complication of AKI. Although it is suggested that dysregulation of lung salt and water channels following AKI plays a pivotal role in ALI, the mechanism of its dysregulation has not been elucidated. Here, we examined the involvement of a typical oxidative stress-inducing uremic toxin, indoxyl sulfate (IS), in the dysregulation of the pulmonary predominant water channel, aquaporin 5 (AQP-5), in bilateral nephrectomy (BNx)-induced AKI model rats...
December 23, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27999995/lipid-glycosylation-a-primer-for-histochemists-and-cell-biologists
#9
REVIEW
Jürgen Kopitz
Glycolipids are glycoconjugates that are predominantly found on the extracellular surface of cells ranging from bacteria to men. In bacteria and plants, glycoglycerolipids represent the main glycolipid species. Ceramides as carrier for glycans, termed glycosphingolipids (GSLs), are characteristic for vertebrates and insects. The glycan part is involved in a variety of biological activities including cell adhesion and initiation of signaling. Most of these functions rest on two basic principles: (1) GSLs spontaneously contribute to organize lipid rafts in biological membranes, thereby forming functional complexes ('glycosynapses') with receptor proteins and ion channels and (2) their glycans are bound by receptors like galectins (protein-glycan recognition) or cognate glycans (glycan-glycan recognition)...
December 20, 2016: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/27999389/transcriptome-analysis-to-understand-the-toxicity-of-latrodectus-tredecimguttatus-eggs
#10
Dehong Xu, Xianchun Wang
Latrodectus tredecimguttatus is a kind of highly venomous black widow spider, with toxicity coming from not only venomous glands but also other parts of its body as well as newborn spiderlings and eggs. Up to date, although L. tredecimguttatus eggs have been demonstrated to be rich in proteinaceous toxins, there is no systematic investigation on such active components at transcriptome level. In this study, we performed a high-throughput transcriptome sequencing of L. tredecimguttatus eggs with Illumina sequencing technology...
December 20, 2016: Toxins
https://www.readbyqxmd.com/read/27996025/in-vitro-synthesis-of-a-major-facilitator-transporter-for-specific-active-transport-across-droplet-interface-bilayers
#11
Heather E Findlay, Nicola J Harris, Paula J Booth
Nature encapsulates reactions within membrane-bound compartments, affording sequential and spatial control over biochemical reactions. Droplet Interface Bilayers are evolving into a valuable platform to mimic this key biological feature in artificial systems. A major issue is manipulating flow across synthetic bilayers. Droplet Interface Bilayers must be functionalised, with seminal work using membrane-inserting toxins, ion channels and pumps illustrating the potential. Specific transport of biomolecules, and notably transport against a concentration gradient, across these bilayers has yet to be demonstrated...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27993565/acylation-of-the-bordetella-pertussis-cyaa-hemolysin-functional-implications-for-efficient-membrane-insertion-and-pore-formation
#12
Kanungsuk Meetum, Chompounoot Imtong, Gerd Katzenmeier, Chanan Angsuthanasombat
Previously, the ~130-kDa CyaA-hemolysin domain (CyaA-Hly) from Bordetella pertussis co-expressed with CyaC-acyltransferase in Escherichia coli was demonstrated to be palmitoylated at Lys(983) and thus activated its hemolytic activity against target erythrocytes. Here, we report the functional importance of Lys(983)-palmitoylation for membrane insertion and pore formation of CyaA-Hly. Intrinsic fluorescence emissions of both non-acylated CyaA-Hly (NA/CyaA-Hly) and CyaA-Hly were indistinguishable, suggesting no severe conformational change upon acylation at Lys(983)...
December 18, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27976413/medicinal-chemistry-pharmacology-and-clinical-implications-of-trpv1-receptor-antagonists
#13
REVIEW
Mojgan Aghazadeh Tabrizi, Pier Giovanni Baraldi, Stefania Baraldi, Stefania Gessi, Stefania Merighi, Pier Andrea Borea
Transient receptor potential vanilloid 1 (TRPV1) is an ion channel expressed on sensory neurons triggering an influx of cations. TRPV1 receptors function as homotetramers responsive to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Its phosphorylation increases sensitivity to both chemical and thermal stimuli, while desensitization involves a calcium-dependent mechanism resulting in receptor dephosphorylation. TRPV1 functions as a sensor of noxious stimuli and may represent a target to avoid pain and injury...
December 15, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27960031/functional-studies-of-sodium-channels-from-target-to-compound-identification
#14
Daniel Bertrand, Bruno Biton, Thomas Licher, Jean-Marie Chambard, Christophe Lanneau, Michel Partiseti, Isabel A Lefevre
Over the last six decades, voltage-gated sodium (Nav ) channels have attracted a great deal of scientific and pharmaceutical interest, driving fundamental advances in both biology and technology. The structure and physiological function of these channels have been extensively studied; clinical and genetic data have uncovered their implication in diseases such as epilepsy, arrhythmias, and pain, bringing them into focus as current and future drug targets. While different techniques have been established to record the activity of Nav channels, proper determination of their properties still presents serious challenges, depending upon the experimental conditions and the desired subtype of channel to be characterized...
December 13, 2016: Current Protocols in Pharmacology
https://www.readbyqxmd.com/read/27941686/venom-gland-transcriptomic-and-proteomic-analyses-of-the-enigmatic-scorpion-superstitionia-donensis-scorpiones-superstitioniidae-with-insights-on-the-evolution-of-its-venom-components
#15
Carlos E Santibáñez-López, Jimena I Cid-Uribe, Cesar V F Batista, Ernesto Ortiz, Lourival D Possani
Venom gland transcriptomic and proteomic analyses have improved our knowledge on the diversity of the heterogeneous components present in scorpion venoms. However, most of these studies have focused on species from the family Buthidae. To gain insights into the molecular diversity of the venom components of scorpions belonging to the family Superstitioniidae, one of the neglected scorpion families, we performed a transcriptomic and proteomic analyses for the species Superstitionia donensis. The total mRNA extracted from the venom glands of two specimens was subjected to massive sequencing by the Illumina protocol, and a total of 219,073 transcripts were generated...
December 9, 2016: Toxins
https://www.readbyqxmd.com/read/27932254/investigating-possible-biological-targets-of-bj-crp-the-first-cysteine-rich-secretory-protein-crisp-isolated-from-bothrops-jararaca-snake-venom
#16
Marina E Lodovicho, Tássia R Costa, Carolina P Bernardes, Danilo L Menaldo, Karina F Zoccal, Sante E Carone, José C Rosa, Manuela B Pucca, Felipe A Cerni, Eliane C Arantes, Jan Tytgat, Lúcia H Faccioli, Luciana S Pereira-Crott, Suely V Sampaio
Cysteine-rich secretory proteins (CRISPs) are commonly described as part of the protein content of snake venoms, nevertheless, so far, little is known about their biological targets and functions. Our study describes the isolation and characterization of Bj-CRP, the first CRISP isolated from Bothrops jararaca snake venom, also aiming at the identification of possible targets for its actions. Bj-CRP was purified using three chromatographic steps (Sephacryl S-200, Source 15Q and C18) and showed to be an acidic protein of 24...
January 4, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/27929417/atp-release-from-human-airway-epithelial-cells-exposed-to-staphylococcus-aureus-alpha-toxin
#17
Romina Baaske, Mandy Richter, Nils Möller, Sabine Ziesemer, Ina Eiffler, Christian Müller, Jan-Peter Hildebrandt
Airway epithelial cells reduce cytosolic ATP content in response to treatment with S. aureus alpha-toxin (hemolysin A, Hla). This study was undertaken to investigate whether this is due to attenuated ATP generation or to release of ATP from the cytosol and extracellular ATP degradation by ecto-enzymes. Exposure of cells to rHla did result in mitochondrial calcium uptake and a moderate decline in mitochondrial membrane potential, indicating that ATP regeneration may have been attenuated. In addition, ATP may have left the cells through transmembrane pores formed by the toxin or through endogenous release channels (e...
December 6, 2016: Toxins
https://www.readbyqxmd.com/read/27929062/an-oxygen-sensitive-toxin-antitoxin-system
#18
Oriol Marimon, João M C Teixeira, Tiago N Cordeiro, Valerie W C Soo, Thammajun L Wood, Maxim Mayzel, Irene Amata, Jesús García, Ainara Morera, Marina Gay, Marta Vilaseca, Vladislav Yu Orekhov, Thomas K Wood, Miquel Pons
The Hha and TomB proteins from Escherichia coli form an oxygen-dependent toxin-antitoxin (TA) system. Here we show that YmoB, the Yersinia orthologue of TomB, and its single cysteine variant [C117S]YmoB can replace TomB as antitoxins in E. coli. In contrast to other TA systems, [C117S]YmoB transiently interacts with Hha (rather than forming a stable complex) and enhances the spontaneous oxidation of the Hha conserved cysteine residue to a -SOxH-containing species (sulfenic, sulfinic or sulfonic acid), which destabilizes the toxin...
December 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27919210/three-dimensional-modelling-of-the-voltage-gated-sodium-ion-channel-from-anopheles-gambiae-reveals-spatial-clustering-of-evolutionarily-conserved-acidic-residues-at-the-extracellular-sites
#19
Rithvik S Vinekar, Ramanathan Sowdhamini
The eukaryotic voltage-gated sodium channel(e-Nav) is a large asymmetric transmembrane protein with important functions concerning neurological function. No structure has been resolved at high resolution for this protein. A homology model of the transmembrane and extracellular regions of an Anopheles gambiae para-like channel with emphasis on the pore entrance has been constructed, based upon the templates provided by a prokaryotic sodium channel and a potassium two-pore channel. The latter provides a template for the extracellular regions, which are located above the entrance to the pore, which is likely to open at a side of a dome formed by these loops...
December 5, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/27916464/subtype-specific-block-of-voltage-gated-k-channels-by-%C3%AE-conopeptides
#20
Enrico Leipold, Florian Ullrich, Markus Thiele, Alesia A Tietze, Heinrich Terlau, Diana Imhof, Stefan H Heinemann
The neurotoxic cone snail peptide μ-GIIIA specifically blocks skeletal muscle voltage-gated sodium (NaV1.4) channels. The related conopeptides μ-PIIIA and μ-SIIIA, however, exhibit a wider activity spectrum by also inhibiting the neuronal NaV channels NaV1.2 and NaV1.7. Here we demonstrate that those μ-conopeptides with a broader target range also antagonize select subtypes of voltage-gated potassium channels of the KV1 family: μ-PIIIA and μ-SIIIA inhibited KV1.1 and KV1.6 channels in the nanomolar range, while being inactive on subtypes KV1...
January 22, 2017: Biochemical and Biophysical Research Communications
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