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https://www.readbyqxmd.com/read/28416444/the-pharmacology-of-voltage-gated-sodium-channel-activators
#1
REVIEW
Jennifer R Deuis, Alexander Mueller, Mathilde R Israel, Irina Vetter
Toxins and venom components that target voltage-gated sodium (NaV) channels have evolved numerous times due to the importance of this class of ion channels in the normal physiological function of peripheral and central neurons as well as cardiac and skeletal muscle. NaV channel activators in particular have been isolated from the venom of spiders, wasps, snakes, scorpions, cone snails and sea anemone and are also produced by plants, bacteria and algae. These compounds have provided key insight into the molecular structure, function and pathophysiological roles of NaV channels and are important tools due to their at times exquisite subtype-selectivity...
April 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28414035/bothrops-jararaca-venom-gland-secretory-cells-in-culture-effects-of-noradrenaline-on-toxin-production-and-secretion
#2
Luciana Godoy Viana, Richard Hemmi Valente, Cíntia Scucuglia Heluany, Andreia Souza-Imberg, Milene Schmidt Luna, Jonas Perales, Norma Yamanouye
Primary culture of snake venom gland secretory cells could be a good model to study the mechanism(s) of toxin(s) production. These cells can produce and secrete venom to the medium with a hemorrhagic activity comparable to that induced by venom collected from snakes. Production of new venom is triggered by the sympathetic outflow, through the release of noradrenaline, but the importance of this neurotransmitter on toxin synthesis has not been addressed. This work led to the identification and comparison of the toxin panel produced by cultured secretory cells, during a 12-day time-course analysis, as well as to the effects of noradrenaline on the process...
April 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28392982/comparative-venom-gland-transcriptomics-of-naja-kaouthia-monocled-cobra-from-malaysia-and-thailand-elucidating-geographical-venom-variation-and-insights-into-sequence-novelty
#3
Kae Yi Tan, Choo Hock Tan, Lawan Chanhome, Nget Hong Tan
BACKGROUND: The monocled cobra (Naja kaouthia) is a medically important venomous snake in Southeast Asia. Its venom has been shown to vary geographically in relation to venom composition and neurotoxic activity, indicating vast diversity of the toxin genes within the species. To investigate the polygenic trait of the venom and its locale-specific variation, we profiled and compared the venom gland transcriptomes of N. kaouthia from Malaysia (NK-M) and Thailand (NK-T) applying next-generation sequencing (NGS) technology...
2017: PeerJ
https://www.readbyqxmd.com/read/28390830/bmajpla2-ii-a-basic-lys49-phospholipase-a2-homologue-from-bothrops-marajoensis-snake-venom-with-parasiticidal-potential
#4
Amy N Grabner, Jorge Alfonso, Anderson M Kayano, Leandro S Moreira-Dill, Ana Paula de A Dos Santos, Cleópatra A S Caldeira, Juliana C Sobrinho, Ana Gómez, Fernando P Grabner, Fabio F Cardoso, Juliana Pavan Zuliani, Marcos R M Fontes, Daniel C Pimenta, Celeste Vega Gómez, Carolina B G Teles, Andreimar M Soares, Leonardo A Calderon
Snake venoms contain various proteins, especially phospholipases A2 (PLA2s), which present potential applications in diverse areas of health and medicine. In this study, a new basic PLA2 from Bothrops marajoensis with parasiticidal activity was purified and characterized biochemically and biologically. B. marajoensis venom was fractionated through cation exchange followed by reverse phase chromatographies. The isolated toxin, BmajPLA2-II, was structurally characterized with MALDI-TOF (Matrix-assisted laser desorption/ionization-time of flight) mass spectrometry, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), followed by two-dimensional electrophoresis, partial amino acid sequencing, an enzymatic activity assay, circular dichroism, and dynamic light scattering assays...
April 5, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28380330/to-stress-or-not-to-stress-physiological-responses-to-tetrodotoxin-in-resistant-gartersnakes-vary-by-sex
#5
Lorin A Neuman-Lee, Edmund D Brodie, Tyler Hansen, Edmund D Brodie, Susannah S French
The activation of the hypothalamic pituitary adrenal (HPA) axis is one of the most important physiological processes in coping with any deviation in an organism's homeostasis. This activation and the secretion of glucocorticoids, such as corticosterone, allow organisms to cope with perturbations and return to optimal physiological functioning as quickly as possible. In this study, we examined the HPA axis activation in Common gartersnakes (Thamnophis sirtalis) as a response to a natural toxin, tetrodotoxin (TTX)...
April 2, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28347742/corticosteroid-responses-of-snakes-to-toxins-from-toads-bufadienolides-and-plants-cardenolides-reflect-differences-in-dietary-specializations
#6
Shabnam Mohammadi, Susannah S French, Lorin A Neuman-Lee, Susan L Durham, Yosuke Kojima, Akira Mori, Edmund D Brodie, Alan H Savitzky
Toads are chemically defended by cardiotonic steroids known as bufadienolides. Resistance to the acute effects of bufadienolides in snakes that prey on toads is conferred by target-site insensitivity of the toxin's target enzyme, the Na(+)/K(+)-ATPase. Previous studies have focused largely on the molecular mechanisms of resistance but have not investigated the physiological mechanisms or consequences of exposure to the toxins. Adrenal enlargement in snakes often is associated with specialization on a diet of toads...
March 24, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28344595/alpha-type-phospholipase-a2-inhibitors-from-snake-blood
#7
REVIEW
Norival A Santos-Filho, Claudia T Santos
It is of popular and scientific knowledge that toxins from snake venom (among them the PLA2 and myotoxins) are neutralized by various compounds, such as antibodies and proteins purified from animal blood. Venomous and nonvenomous snakes have PLA2 inhibitory proteins, called PLIs, in their blood serum. One hypothesis that could explain the presence of these PLIs in the serum of venomous snakes would be self-protection against the enzymes of their own venom, which eventually could reach the circulatory system...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28335411/how-the-cobra-got-its-flesh-eating-venom-cytotoxicity-as-a-defensive-innovation-and-its-co-evolution-with-hooding-aposematic-marking-and-spitting
#8
Nadya Panagides, Timothy N W Jackson, Maria P Ikonomopoulou, Kevin Arbuckle, Rudolf Pretzler, Daryl C Yang, Syed A Ali, Ivan Koludarov, James Dobson, Brittany Sanker, Angelique Asselin, Renan C Santana, Iwan Hendrikx, Harold van der Ploeg, Jeremie Tai-A-Pin, Romilly van den Bergh, Harald M I Kerkkamp, Freek J Vonk, Arno Naude, Morné A Strydom, Louis Jacobsz, Nathan Dunstan, Marc Jaeger, Wayne C Hodgson, John Miles, Bryan G Fry
The cytotoxicity of the venom of 25 species of Old World elapid snake was tested and compared with the morphological and behavioural adaptations of hooding and spitting. We determined that, contrary to previous assumptions, the venoms of spitting species are not consistently more cytotoxic than those of closely related non-spitting species. While this correlation between spitting and non-spitting was found among African cobras, it was not present among Asian cobras. On the other hand, a consistent positive correlation was observed between cytotoxicity and utilisation of the defensive hooding display that cobras are famous for...
March 13, 2017: Toxins
https://www.readbyqxmd.com/read/28327300/rbaltmip-a-recombinant-alpha-type-myotoxin-inhibitor-from-bothrops-alternatus-rhinocerophis-alternatus-snake-as-a-potential-candidate-to-complement-the-antivenom-therapy
#9
Norival A Santos-Filho, Tiago S Sousa, Johara Boldrini-França, Ludier K Santos-Silva, Danilo L Menaldo, Flávio Henrique-Silva, Adélia C O Cintra, Helen J Laure, Carla C N Mamede, Fábio Oliveira, Thalita B Riul, Marcelo Dias-Baruffi, José C Rosa, Suely V Sampaio
Phospholipase A2 inhibitors (PLIs) are important targets in the search and development of new drugs. This study aimed at evaluating the potential of an alpha-type phospholipase A2 inhibitor from Bothrops alternatus (Rhinocerophis alternatus) snake in its recombinant form (rBaltMIP) to complement the conventional antivenom therapy. Biochemical experiments showed that rBaltMIP presented pI 5.8 and molecular masses of ∼21 kDa by SDS-PAGE and 19.57 kDa by MALDI/TOF MS. After tryptic peptides sequencing, the results were compared with other PLIs available in databases, showing 100% identity between rBaltMIP and its native inhibitor BaltMIP and from 92% to 96% identity with other inhibitors...
December 15, 2016: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28326549/the-three-finger-toxin-fold-a-multifunctional-structural-scaffold-able-to-modulate-cholinergic-functions
#10
REVIEW
Pascal Kessler, Pascale Marchot, Marcela Silva, Denis Servent
Three-finger fold toxins are miniproteins frequently found in Elapidae snake venoms. This fold is characterized by three distinct loops rich in β-strands and emerging from a dense, globular core reticulated by four highly conserved disulfide bridges. The number and diversity of receptors, channels, and enzymes identified as targets of three-finger fold toxins is increasing continuously. Such manifold diversity highlights the specific adaptability of this fold for generating pleiotropic functions. Although this toxin superfamily disturbs many biological functions by interacting with a large diversity of molecular targets, the most significant target is the cholinergic system...
March 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28302413/characterization-of-daboia-russelii-and-naja-naja-venom-neutralizing-ability-of-an-undocumented-indigenous-medication-in-sri-lanka
#11
Madhushika M Silva, Sampath S Seneviratne, Devaka K Weerakoon, Charitha L Goonasekara
BACKGROUND: Indigenous medicinal practice in Sri Lanka talks about powerful compounds extracted from native plants for treating venomous snake bites which are hardly documented in literature but are used by the indigenous doctors for thousand years. OBJECTIVE: We screened the neutralizing ability of a herbal preparation practiced in indigenous medicine of Sri Lanka, consisting of Sansevieria cylindrica, Jatropha podagrica and Citrus aurantiifolia, for its ability to neutralize venom toxins of Naja naja (Common Cobra) and Daboia russelii (Russell's viper)...
January 2017: Journal of Ayurveda and Integrative Medicine
https://www.readbyqxmd.com/read/28289430/envenoming-by-viridovipera-stejnegeri-snake-a-patient-with-liver-cirrhosis-presenting-disruption-of-hemostatic-balance
#12
Chih-Ying Chien, Shu-Chen Liao, Chien-Hung Liao, Ting-Shuo Huang, Yu-Hsien Chen
BACKGROUND: In most cases of envenoming by the green habu Viridovipera stejnegeri in Taiwan coagulopathy is not observed. CASE PRESENTATION: Herein, we describe the case of a patient with liver cirrhosis who developed venom-induced consumptive coagulopathy after V. stejnegeri bite. Laboratory investigation revealed the following: prothrombin time > 100 s (international normalized ratio > 10), activated partial thromboplastin time > 100 s, fibrinogen < 50 mg/dL, and fibrin degradation product > 80 μg/mL...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28288817/animal-venoms-as-antimicrobial-agents
#13
REVIEW
Ramar Perumal Samy, Bradley G Stiles, Octavio L Franco, Gautam Sethi, Lina H K Lim
Hospitals are breeding grounds for many life-threatening bacteria worldwide. Clinically associated gram-positive bacteria such as Staphylococcus aureus/methicillin-resistant S. aureus and many others increase the risk of severe mortality and morbidity. The failure of antibiotics to kill various pathogens due to bacterial resistance highlights the urgent need to develop novel, potent, and less toxic agents from natural sources against various infectious agents. Currently, several promising classes of natural molecules from snake (terrestrial and sea), scorpion, spider, honey bee and wasp venoms hold promise as rich sources of chemotherapeutics against infectious pathogens...
March 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28275208/understanding-the-snake-venom-metalloproteinases-an-interview-with-jay-fox-and-jos%C3%A3-mar%C3%A3-a-guti%C3%A3-rrez
#14
EDITORIAL
Jay W Fox, José María Gutiérrez
Jay W. Fox and José María Gutiérrez recently finished editing a Special Issue on the topic "Snake Venom Metalloproteinases" in Toxins. The Special Issue covers a wide range of topics, including the molecular evolution and structure of snake venom metalloproteinases (SVMPs), the mechanisms involved in the generation of diversity of SVMPs, the mechanism of action of SVMPs, and their role in the pathophysiology of envenomings, with implications for improving the therapy of envenomings. In this interview, we discussed with Jay W...
January 16, 2017: Toxins
https://www.readbyqxmd.com/read/28265084/lys49-myotoxin-from-the-brazilian-lancehead-pit-viper-elicits-pain-through-regulated-atp-release
#15
Chuchu Zhang, Katalin F Medzihradszky, Elda E Sánchez, Allan I Basbaum, David Julius
Pain-producing animal venoms contain evolutionarily honed toxins that can be exploited to study and manipulate somatosensory and nociceptive signaling pathways. From a functional screen, we have identified a secreted phospholipase A2 (sPLA2)-like protein, BomoTx, from the Brazilian lancehead pit viper (Bothrops moojeni). BomoTx is closely related to a group of Lys49 myotoxins that have been shown to promote ATP release from myotubes through an unknown mechanism. Here we show that BomoTx excites a cohort of sensory neurons via ATP release and consequent activation of P2X2 and/or P2X3 purinergic receptors...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28264436/toxin-fused-with-sumo-tag-a-new-expression-vector-strategy-to-obtain-recombinant-venom-toxins-with-easy-tag-removal-inside-the-bacteria
#16
Lhiri H A L Shimokawa-Falcão, Maria C Caporrino, Katia C Barbaro, Maisa S Della-Casa, Geraldo S Magalhães
Many animal toxins may target the same molecules that need to be controlled in certain pathologies; therefore, some toxins have led to the formulation of drugs that are presently used, and many other drugs are still under development. Nevertheless, collecting sufficient toxins from the original source might be a limiting factor in studying their biological activities. Thus, molecular biology techniques have been applied in order to obtain large amounts of recombinant toxins into Escherichia coli. However, most animal toxins are difficult to express in this system, which results in insoluble, misfolded, or unstable proteins...
February 27, 2017: Toxins
https://www.readbyqxmd.com/read/28263888/combined-venomics-antivenomics-and-venom-gland-transcriptome-analysis-of-the-monocoled-cobra-naja-kaouthia-from-china
#17
Ning Xu, Hong-Yan Zhao, Yin Yin, Shan-Shan Shen, Lin-Lin Shan, Chuan-Xi Chen, Yan-Xia Zhang, Jian-Fang Gao, Xiang Ji
We conducted an omics-analysis of the venom of Naja kaouthia from China. Proteomics analysis revealed six protein families [three-finger toxins (3-FTx), phospholipase A2 (PLA2), nerve growth factor, snake venom metalloproteinase (SVMP), cysteine-rich secretory protein and ohanin], and venom-gland transcriptomics analysis revealed 28 protein families from 79 unigenes. 3-FTx (56.5% in proteome/82.0% in transcriptome) and PLA2 (26.9%/13.6%) were identified as the most abundant families in venom proteome and venom-gland transcriptome...
March 3, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28249773/toad-toxin-resistant-snake-thamnophis-elegans-expresses-high-levels-of-mutant-na-k-atpase-mrna-in-cardiac-muscle
#18
Shabnam Mohammadi, Alan H Savitzky, Jennifer Lohr, Susanne Dobler
Toads are chemically defended by bufadienolides, which are lethal to most predators. These toxins exert their lethal effects by binding to and disabling the Na(+)/K(+)-ATPases of cell membranes. Many species of snakes exhibit resistance to the effects of bufadienolides due to target-site insensitivity of the Na(+)/K(+)-ATPase. Mutations that confer resistance have previously been identified in ATP1a3, the gene that codes for the Na(+)/K(+)-ATPase α-3 paralog. We have found that this mutant gene is expressed at a significantly elevated level in heart tissue compared to gut, kidney, and liver of the bufadienolide-resistant snake, Thamnophis elegans...
May 30, 2017: Gene
https://www.readbyqxmd.com/read/28245079/hemorrhagic-metalloproteinase-cc-hsm-iii-isolated-from-cerastes-cerastes-venom-purification-and-biochemical-characterization
#19
Wafa Tachoua, Hinda Boukhalfa-Abib, Fatima Laraba-Djebari
Snake venom metalloproteinases are the most abundant toxins in Viperidae venoms. In this study, a new hemorrhagin, Cc HSM-III (66 kDa), was purified from Cerastes cerastes venom by gel filtration, ion exchange, and reversed-phase high-performance liquid chromatographies. The analysis of Cc HSM-III by liquid chromatography with a tandem mass spectrometry revealed 32 peptides sharing a homology with P-III metalloproteinases from Echis ocellatus snake venom. Cc HSM-III displays hemorrhagic activity with a minimal hemorrhagic dose of 5 μg, which is abolished by ethylene diamine tetracetic acid but not by phenylmethylsulfonyl fluoride...
February 28, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28240232/venomics-of-tropidolaemus-wagleri-the-sexually-dimorphic-temple-pit-viper-unveiling-a-deeply-conserved-atypical-toxin-arsenal
#20
Choo Hock Tan, Kae Yi Tan, Michelle Khai Khun Yap, Nget Hong Tan
Tropidolaemus wagleri (temple pit viper) is a medically important snake in Southeast Asia. It displays distinct sexual dimorphism and prey specificity, however its venomics and inter-sex venom variation have not been thoroughly investigated. Applying reverse-phase HPLC, we demonstrated that the venom profiles were not significantly affected by sex and geographical locality (Peninsular Malaya, insular Penang, insular Sumatra) of the snakes. Essentially, venoms of both sexes share comparable intravenous median lethal dose (LD50) (0...
February 27, 2017: Scientific Reports
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