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Wayne Clarence Hodgson - One of the best experts on this subject based on the ideXlab platform.
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isolation and pharmacological characterization of α elapitoxin ot1a a short chain postsynaptic Neurotoxin from the venom of the western desert taipan oxyuranus temporalis
Toxins, 2016Co-Authors: Carmel M Barber, Muhamad Rusdi Ahmad Rusmili, Wayne Clarence HodgsonAbstract:Taipans (Oxyuranus spp.) are elapids with highly potent venoms containing presynaptic (β) and postsynaptic (α) Neurotoxins. O. temporalis (Western Desert taipan), a newly discovered member of this genus, has been shown to possess venom which displays marked in vitro neurotoxicity. No components have been isolated from this venom. We describe the characterization of α-elapitoxin-Ot1a (α-EPTX-Ot1a; 6712 Da), a short-chain postsynaptic Neurotoxin, which accounts for approximately 30% of O. temporalis venom. α-Elapitoxin-Ot1a (0.1–1 µM) produced concentration-dependent inhibition of indirect-twitches, and abolished contractile responses to exogenous acetylcholine and carbachol, in the chick biventer cervicis nerve-muscle preparation. The inhibition of indirect twitches by α-elapitoxin-Ot1a (1 µM) was not reversed by washing the tissue. Prior addition of taipan antivenom (10 U/mL) delayed the neurotoxic effects of α-elapitoxin-Ot1a (1 µM) and markedly attenuated the neurotoxic effects of α-elapitoxin-Ot1a (0.1 µM). α-Elapitoxin-Ot1a displayed pseudo-irreversible antagonism of concentration-response curves to carbachol with a pA2 value of 8.02 ± 0.05. De novo sequencing revealed the main sequence of the short-chain postsynaptic Neurotoxin (i.e., α-elapitoxin-Ot1a) as well as three other isoforms found in O. temporalis venom. α-Elapitoxin-Ot1a shows high sequence similarity (i.e., >87%) with other taipan short-chain postsynaptic Neurotoxins.
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inhibition of presynaptic Neurotoxins in taipan venom by suramin
Neurotoxicity Research, 2014Co-Authors: Sanjaya Kuruppu, Janeyuth Chaisakul, Ian A Smith, Wayne Clarence HodgsonAbstract:Taipans are amongst the most venomous snakes in the world, and neurotoxicity is a major life-threatening symptom of envenoming by these snakes. Three species of taipans exist, and the venom from each species contains a presynaptic Neurotoxin which accounts for much of the neurotoxicity observed following human envenoming. The high cost of antivenom used to treat neurotoxicity has resulted in the need to develop alternative but effective therapies. Therefore, in this study, we examined the ability of the P2Y receptor antagonist suramin to prevent the in vitro neurotoxic effects of the three presynaptic Neurotoxins in taipan venoms: taipoxin, paradoxin and cannitoxin. Toxins were purchased from commercial sources or purified in house, using multiple steps of gel filtration chromatography. All three toxins (11 nM) inhibited nerve-mediated twitches in the chick biventer cervicis nerve–muscle preparation within 300 min. The presence of suramin (0.3 mM) completely blocked the taipoxin and cannitoxin-mediated inhibition of nerve-mediated twitches within the course of the experiment (P < 0.0001). However, paradoxin induced a 32 % decrease in twitch height even in the presence of suramin within 360 min. This was significantly different compared to toxin alone (P < 0.0001). We also examined the effect of suramin on the neurotoxic effects of textilotoxin and the products of phospholipase A2 action. Each toxin alone or in the presence of suramin failed to inhibit the responses to exogenous agonists ACh, CCh or KCl. Our results warrant clinical studies aimed determining the efficacy of suramin in preventing the onset of neurotoxicity following taipan envenoming.
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intersexual variations in the pharmacological properties of coremiocnemis tropix araneae theraphosidae spider venom
Toxicon, 2009Co-Authors: Volker Herzig, Wayne Clarence HodgsonAbstract:Abstract This study aimed to determine the biochemical, insecticidal and neurotoxic properties of venom from both sexes of the Australian spider Coremiocnemis tropix (Araneae, Theraphosidae). Insecticidal properties were tested in crickets, while in vitro neurotoxicity was determined in an avian skeletal muscle preparation. Some intersexual differences in venom composition were identified by rp-HPLC and by LC–MS, but the majority of components were found in venoms of both sexes. Injecting the venom into crickets revealed that venom from male specimens was slightly more potent, while female venom induced more prominent effects in the chick biventer cervicis nerve–muscle preparation. The results from the chick assay suggest the presence of at least two vertebrate-active Neurotoxins. A pre-synaptic Neurotoxin may explain the reversible inhibition of muscle twitches and the unaffected response to nicotinic agonists at medium concentrations of female and medium to high concentrations of male venom. In addition, the presence of a Neurotoxin that blocks post-synaptic nicotinic receptors might explain the irreversible inhibition of muscle twitches and the reduced response to nicotinic agonists at high concentrations (5–10 μg/ml) of venom from female specimens only.
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isolation and pharmacological characterization of cannitoxin a presynaptic Neurotoxin from the venom of the papuan taipan oxyuranus scutellatus canni
Journal of Pharmacology and Experimental Therapeutics, 2005Co-Authors: Sanjaya Kuruppu, Ian A Smith, Shane Reeve, Yajnavalka Banerjee, Manjunatha R Kini, Wayne Clarence HodgsonAbstract:The Papuan taipan ( Oxyuranus scutellatus canni ) is widely distributed throughout much of Papua New Guinea. Although neurotoxicity is a major symptom of envenomation, no Neurotoxins have been isolated from this venom. Using a series of size exclusion chromatography steps, we report the isolation of cannitoxin, a presynaptic Neurotoxin (44,848 Da) that represents approximately 16% of the whole venom. The toxin displayed high phospholipase A2 (PLA2) activity (330 ± 5 μmol/min/mg) and caused concentration-dependent (11–66 nM) inhibition of indirect (0.2 ms; 0.1 Hz; supramaximal V) twitches of the chick biventer cervicis nerve-muscle preparation without effecting nicotinic receptor agonists. Prior addition of CSL Taipan antivenom (5 U/ml) or inhibition of phospholipase A2 activity by incubation with 4-bromophenacyl bromide prevented the inhibition of twitches. Cannitoxin is composed of three different subunits, α, β, and γ, with the possibility of two β isomers. However, only the α subunit displayed in vitro neurotoxic activity of its own. Thus, cannitoxin is similar in structure and pharmacology to taipoxin, which has been isolated from the closely related Australian species O. scutellatus scutellatus (coastal taipan).
Steve Sorota - One of the best experts on this subject based on the ideXlab platform.
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Cobra (Naja spp. ) Nicotinic Acetylcholine Receptor Exhibits Resistance to Erabu Sea Snake (Laticauda semifasciata) Short-Chain α-Neurotoxin
Journal of Molecular Evolution, 2004Co-Authors: Zoltan Takacs, Kirk C. Wilhelmsen, Steve SorotaAbstract:Snake α-neutotoxins of Elapidae venoms are grouped into two structural classes, short-chain and long-chain α-neutotoxins. While these two classes share many chemical and biological characteristics, there are also distinct dissimilarities between them, including their binding site on the nicotinic acetylcholine receptor (nAChR), specificity among species of Chordata, and the associated pharmacological effects. In the present study we test the hypothesis that structural motifs that evolved to confer natural resistance against conspecific long-chain α-Neurotoxins in Elapidae snakes also interfere with the biological action of short-chain α-Neurotoxins. We expressed functional nAChRs that contains segments or single residues of the Elapidae nAChR ligand binding domain and tested the effect of short-chain α-Neurotoxin erabutoxin-a (ETX-a) from the Erabu sea snake Laticauda semifasciata on the acetylcholine-induced currents as measured by two-microelectrode voltage clamp. Our results show that the Elapidae nAChR α subunit segment T^154–L^208 ligand binding domain has an inhibitory effect on the pharmacological action of ETX-a. This effect is primarily attributed to the presence of glycosylation at position N^189. If the glycosylation is removed from the T^154–L^208 segment, the nAChR will be inhibited, however, to a lesser extent than seen in the mouse. This effect correlates with the variations in α-Neurotoxin sensitivity of different species and, importantly, reflects the evolutionary conservation of the binding site on the nAChR polypeptide backbone per se. Phylogenetic analysis of α-Neurotoxin resistance suggests that α-Neurotoxin-resistant nAChR evolved first, which permitted the evolution of snake venom α-Neurotoxins. A model describing α-Neurotoxin resistance in Elapidae snakes is presented.
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Snake α-Neurotoxin Binding Site on the Egyptian Cobra (Naja haje) Nicotinic Acetylcholine Receptor Is Conserved
Molecular biology and evolution, 2001Co-Authors: Zoltan Takacs, Kirk C. Wilhelmsen, Steve SorotaAbstract:Evolutionary success requires that animal venoms are targeted against phylogenetically conserved molecular structures of fundamental physiological processes. Species producing venoms must be resistant to their action. Venoms of Elapidae snakes (e.g., cobras, kraits) contain alpha-Neurotoxins, represented by alpha-bungarotoxin (alpha-BTX) targeted against the nicotinic acetylcholine receptor (nAChR) of the neuromuscular junction. The model which presumes that cobras (Naja spp., Elapidae) have lost their binding site for conspecific alpha-Neurotoxins because of the unique amino acid substitutions in their nAChR polypeptide backbone per se is incompatible with the evolutionary theory that (1) the molecular motifs forming the alpha-Neurotoxin target site on the nAChR are fundamental for receptor structure and/or function, and (2) the alpha-Neurotoxin target site is conserved among Chordata lineages. To test the hypothesis that the alpha-Neurotoxin binding site is conserved in Elapidae snakes and to identify the mechanism of resistance against conspecific alpha-Neurotoxins, we cloned the ligand binding domain of the Egyptian cobra (Naja haje) nAChR alpha subunit. When expressed as part of a functional Naja/mouse chimeric nAChR in Xenopus oocytes, this domain confers resistance against alpha-BTX but does not alter responses induced by the natural ligand acetylcholine. Further mutational analysis of the Naja/mouse nAChR demonstrated that an N-glycosylation signal in the ligand binding domain that is unique to N. haje is responsible for alpha-BTX resistance. However, when the N-glycosylation signal is eliminated, the nAChR containing the N. haje sequence is inhibited by alpha-BTX with a potency that is comparable to that in mammals. We conclude that the binding site for conspecific alpha-Neurotoxin in Elapidae snakes is conserved in the nAChR ligand binding domain polypeptide backbone per se. This conclusion supports the hypothesis that animal toxins are targeted against evolutionarily conserved molecular motifs. Such conservation also calls for a revision of the present model of the alpha-BTX binding site. The approach described here can be used to identify the mechanism of resistance against conspecific venoms in other species and to characterize toxin-receptor coevolution.
Qian Yang - One of the best experts on this subject based on the ideXlab platform.
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destabilization of survival factor mef2d mrna by Neurotoxin in models of parkinson s disease
Journal of Neurochemistry, 2014Co-Authors: Bao Wang, Linna Su, Fangfang Lu, Chen Li, Qian YangAbstract:: Progressive loss of dopaminergic (DA) neurons in the substantial nigra pars compacta (SNc) is an important pathological feature in Parkinson's disease (PD). Loss of transcription factor myocyte enhancer factor 2D (MEF2D), a key neuronal survival factor, has been shown to underlie the loss of DA neurons in SNc and the pathogenic process of PD. It is known that PD-associated Neurotoxins reduce the level of MEF2D protein to trigger neuronal death. Although Neurotoxins clearly destabilize MEF2D by post-translational mechanisms, it is not known whether regulation of MEF2D mRNA contributes to Neurotoxin-induced decrease in MEF2D protein. In this work, we showed that MPP(+), the toxic metabolite of MPTP, caused a significant decrease in the half-life and total level of MEF2D mRNA in a DA neuronal cell line, SN4741 cells. Quantitative PCR analysis of the SNc DA neurons captured by immune-laser capture microdissection showed that exposure to MPTP led to a marked reduction in the level of MEF2D mRNA in SNc DA neurons compared to controls. Down-regulation of MEF2D mRNA alone reduced the viability of SN4741 cells and sensitized the cells to MPP(+)-induced toxicity. These results suggest that destabilization and reduction in MEF2D mRNA is in part responsible for Neurotoxin-induced decrease in MEF2D protein and neuronal viability. Myocyte enhancer factor 2D (MEF2D) plays an important role in neuronal survival. How MEF2D mRNA is deregulated under toxic stress is unclear. We found that PD-associated Neurotoxins destabilize MEF2D mRNA and reduce its level in vitro and in vivo. Reduction in MEF2D mRNA is sufficient to sensitize model cells to Neurotoxin-induced toxicity, suggesting that destabilization of MEF2D mRNA is part of the mechanism by which Neurotoxins trigger deregulation of neuronal survival.
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destabilization of survival factor mef2d mrna by Neurotoxin in models of parkinson s disease
Journal of Neurochemistry, 2014Co-Authors: Bao Wang, Linna Su, Fangfang Lu, Chen Li, Qian YangAbstract:: Progressive loss of dopaminergic (DA) neurons in the substantial nigra pars compacta (SNc) is an important pathological feature in Parkinson's disease (PD). Loss of transcription factor myocyte enhancer factor 2D (MEF2D), a key neuronal survival factor, has been shown to underlie the loss of DA neurons in SNc and the pathogenic process of PD. It is known that PD-associated Neurotoxins reduce the level of MEF2D protein to trigger neuronal death. Although Neurotoxins clearly destabilize MEF2D by post-translational mechanisms, it is not known whether regulation of MEF2D mRNA contributes to Neurotoxin-induced decrease in MEF2D protein. In this work, we showed that MPP(+), the toxic metabolite of MPTP, caused a significant decrease in the half-life and total level of MEF2D mRNA in a DA neuronal cell line, SN4741 cells. Quantitative PCR analysis of the SNc DA neurons captured by immune-laser capture microdissection showed that exposure to MPTP led to a marked reduction in the level of MEF2D mRNA in SNc DA neurons compared to controls. Down-regulation of MEF2D mRNA alone reduced the viability of SN4741 cells and sensitized the cells to MPP(+)-induced toxicity. These results suggest that destabilization and reduction in MEF2D mRNA is in part responsible for Neurotoxin-induced decrease in MEF2D protein and neuronal viability. Myocyte enhancer factor 2D (MEF2D) plays an important role in neuronal survival. How MEF2D mRNA is deregulated under toxic stress is unclear. We found that PD-associated Neurotoxins destabilize MEF2D mRNA and reduce its level in vitro and in vivo. Reduction in MEF2D mRNA is sufficient to sensitize model cells to Neurotoxin-induced toxicity, suggesting that destabilization of MEF2D mRNA is part of the mechanism by which Neurotoxins trigger deregulation of neuronal survival.
Cesare Montecucco - One of the best experts on this subject based on the ideXlab platform.
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Detection of Clostridium tetani Neurotoxins Inhibited In Vivo by Botulinum Antitoxin B: Potential for Misleading Mouse Test Results in Food Controls
MDPI AG, 2018Co-Authors: Luca Bano, Elena Tonon, Ilenia Drigo, Marco Pirazzini, Angela Guolo, Giovanni Farina, Fabrizio Agnoletti, Cesare MontecuccoAbstract:The presence of botulinum Neurotoxin-producing Clostridia (BPC) in food sources is a public health concern. In favorable environmental conditions, BPC can produce botulinum Neurotoxins (BoNTs) outside or inside the vertebrate host, leading to intoxications or toxico-infectious forms of botulism, respectively. BPC in food are almost invariably detected either by PCR protocols targeted at the known Neurotoxin-encoding genes, or by the mouse test to assay for the presence of BoNTs in the supernatants of enrichment broths inoculated with the tested food sample. The sample is considered positive for BPC when the supernatant contains toxic substances that are lethal to mice, heat-labile and neutralized in vivo by appropriate polyclonal antibodies raised against purified BoNTs of different serotypes. Here, we report the detection in a food sample of a Clostridium tetani strain that produces tetanus Neurotoxins (TeNTs) with the above-mentioned characteristics: lethal for mice, heat-labile and neutralized by botulinum antitoxin type B. Notably, neutralization occurred with two different commercially available type B antitoxins, but not with type A, C, D, E and F antitoxins. Although TeNT and BoNT fold very similarly, evidence that antitoxin B antiserum can neutralize the neurotoxic effect of TeNT in vivo has not been documented before. The presence of C. tetani strains in food can produce misleading results in BPC detection using the mouse test
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presynaptic receptor arrays for clostridial Neurotoxins
Trends in Microbiology, 2004Co-Authors: Cesare Montecucco, Ornella Rossetto, Giampietro SchiavoAbstract:Tetanus and botulinum Neurotoxins act at femtomolar concentrations and are specific for the presynaptic membrane of neurons. Their mode of binding is still poorly defined. The exceptional potency and specificity of these Neurotoxins raise unprecedented questions about the nature of their receptor(s) and the mode of their membrane binding. We propose a presynaptic binding process for tetanus and botulinum Neurotoxins based on a capture step performed by an antenna, consisting of a lipid- or a protein-linked oligosaccharide, which brings about a very large membrane concentration effect; this is followed by additional interactions with arrays of receptor molecules, arranged in membrane microdomains, which render the Neurotoxin binding practically irreversible and triggers endocytosis.
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functional characterisation of tetanus and botulinum Neurotoxins binding domains
Journal of Cell Science, 1999Co-Authors: Giovanna Lalli, Judit Herreros, Shona L Osborne, Ornella Rossetto, Cesare Montecucco, Giampietro SchiavoAbstract:Tetanus and botulinum Neurotoxins constitute a family of bacterial protein toxins responsible for two deadly syndromes in humans (tetanus and botulism, respectively). They bind with high affinity to neurons wherein they cause a complete inhibition of evoked neurotransmitter release. Here we report on the cloning, expression and use of the recombinant fragments of the heavy chains of tetanus Neurotoxin and botulinum Neurotoxin serotypes A, B and E as tools to study the neurospecific binding of the holotoxins. We found that the recombinant 50 kDa carboxy-terminal domains of tetanus and botulinum Neurotoxins alone are responsible for the specific binding and internalisation into spinal cord cells in culture. Moreover, we provide evidence that the recombinant fragments block the internalization of the parental holotoxins in a dose-dependent manner, as determined by following the Neurotoxin-dependent cleavage of their targets VAMP/synaptobrevin and SNAP-25. In addition, the recombinant binding fragments cause a significant delay in the paralysis induced by the corresponding holotoxin on the mouse phrenic nerve-hemidiaphragm preparation. Taken together, these results show that the carboxy-terminal domain of tetanus and botulinum Neurotoxins is necessary and sufficient for the binding and internalisation of these proteins in neurons and open the possibility to use them as tools for the functional characterisation of the intracellular transport of clostridial Neurotoxins.
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structural determinants of the specificity for synaptic vesicle associated membrane protein synaptobrevin of tetanus and botulinum type b and g Neurotoxins
Journal of Biological Chemistry, 1996Co-Authors: Rossella Pellizzari, Clifford C. Shone, Ornella Rossetto, Luisa Lozzi, Silvia Giovedi, Eric A Johnson, Cesare MontecuccoAbstract:Abstract Tetanus and botulinum Neurotoxins type B and G are zinc-endopeptidases of remarkable specificity. They recognize and cleave a synaptic vesicle-associated membrane protein (VAMP)/synaptobrevin, an essential protein component of the vesicle docking and fusion apparatus. VAMP contains two copies of a nine-residue motif, also present in SNAP-25 (synaptosomal-associated protein of 25 kDa) and syntaxin, the two other substrates of clostridial Neurotoxins. This motif was suggested to be a determinant of the target specificity of Neurotoxins. Antibodies raised against this motif cross-react among VAMP, SNAP-25, and syntaxin and inhibit the proteolytic activity of the Neurotoxins. Moreover, the various Neurotoxins cross-inhibit each other's proteolytic action. The role of the three negatively charged residues of the motif in Neurotoxin recognition was probed by site-directed mutagenesis. Substitution of acidic residues in both copies of the VAMP motif indicate that the first one is involved in tetanus Neurotoxin recognition, whereas the second one is implicated in binding botulinum B and G Neurotoxins. These results suggest that the two copies of the motif have a tandem association in the VAMP molecule.
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structure and function of tetanus and botulinum Neurotoxins
Quarterly Reviews of Biophysics, 1995Co-Authors: Cesare Montecucco, Giampietro SchiavoAbstract:Tetanus and botulinum Neurotoxins are produced by Clostridia and cause the neuroparalytic syndromes of tetanus and botulism. Tetanus Neurotoxin acts mainly at the CNS synapse, while the seven botulinum Neurotoxins act peripherally. Clostridial Neurotoxins share a similar mechanism of cell intoxication: they block the release of neurotransmitters. They are composed of two disulfide-linked polypeptide chains. The larger subunit is responsible for neurospecific binding and cell penetration. Reduction releases the smaller chain in the neuronal cytosol, where it displays its zinc-endopeptidase activity specific for protein components of the neuroexocytosis apparatus. Tetanus Neurotoxin and botulinum Neurotoxins B, D, F and G recognize specifically VAMP/ synaptobrevin. This integral protein of the synaptic vesicle membrane is cleaved at single peptide bonds, which differ for each Neurotoxin. Botulinum A, and E Neurotoxins recognize and cleave specifically SNAP-25, a protein of the presynaptic membrane, at two different sites within the carboxyl-terminus. Botulinum Neurotoxin type C cleaves syntaxin, another protein of the nerve plasmalemma. These results indicate that VAMP, SNAP-25 and syntaxin play a central role in neuroexocytosis. These three proteins are conserved from yeast to humans and are essential in a variety of docking and fusion events in every cell. Tetanus and botulinum Neurotoxins form a new group of zinc-endopeptidases with characteristic sequence, mode of zinc coordination, mechanism of activation and target recognition. They will be of great value in the unravelling of the mechanisms of exocytosis and endocytosis, as they are in the clinical treatment of dystonias.
Nget Hong Tan - One of the best experts on this subject based on the ideXlab platform.
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venomics of the beaked sea snake hydrophis schistosus a minimalist toxin arsenal and its cross neutralization by heterologous antivenoms
Journal of Proteomics, 2015Co-Authors: Choo Hock Tan, Kae Yi Tan, Sin Ee Lim, Nget Hong TanAbstract:The venom proteome of Hydrophis schistosus (syn: Enhydrina schistosa) captured in Malaysian waters was investigated using reverse-phase HPLC, SDS-PAGE and high-resolution liquid chromatography-tandem mass spectrometry. The findings revealed a minimalist profile with only 18 venom proteins. These proteins belong to 5 toxin families: three-finger toxin (3FTx), phospholipase A2 (PLA2), cysteine-rich secretory protein (CRISP), snake venom metalloprotease (SVMP) and L-amino acid oxidase (LAAO). The 3FTxs (3 short Neurotoxins and 4 long Neurotoxins) constitute 70.5% of total venom protein, 55.8% being short Neurotoxins and 14.7% long Neurotoxins. The PLA2 family consists of four basic (21.4%) and three acidic (6.1%) isoforms. The minor proteins include one CRISP (1.3%), two SVMPs (0.5%) and one LAAO (0.2%). This is the first report of the presence of long Neurotoxins, CRISP and LAAO in H. schistosus venom. The Neurotoxins and the basic PLA2 are highly lethal in mice with an intravenous median lethal dose of <0.2 μg/g. Cross-neutralization by heterologous elapid antivenoms (Naja kaouthia monovalent antivenom and Neuro polyvalent antivenom) was moderate against the long Neurotoxin and basic PLA2, but weak against the short Neurotoxin, indicating that the latter is the limiting factor to be overcome for improving the antivenom cross-neutralization efficacy.
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proteomic characterization of venom of the medically important southeast asian naja sumatrana equatorial spitting cobra
Acta Tropica, 2014Co-Authors: Michelle Khai Khun Yap, Kae Yi Tan, Shin Yee Fung, Nget Hong TanAbstract:The proteome of Naja sumatrana (Equatorial spitting cobra) venom was investigated by shotgun analysis and a combination of ion-exchange chromatography and reverse phase HPLC. Shotgun analysis revealed the presence of 39 proteins in the venom while the chromatographic approach identified 37 venom proteins. The results indicated that, like other Asiatic cobra venoms, N. sumatrana contains large number of three finger toxins and phospholipases A2, which together constitute 92.1% by weight of venom protein. However, only eight of the toxins can be considered as major venom toxins. These include two phospholipases A2, three Neurotoxins (two long Neurotoxins and a short Neurotoxin) and three cardiotoxins. The eight major toxins have relative abundance of 1.6–27.2% venom proteins and together account for 89.8% (by weight) of total venom protein. Other venom proteins identified include Zn-metalloproteinase-disintegrin, Thaicobrin, CRISP, natriuretic peptide, complement depleting factors, cobra venom factors, venom nerve growth factor and cobra serum albumin. The proteome of N. sumatrana venom is similar to proteome of other Asiatic cobra venoms but differs from that of African spitting cobra venom. Our results confirm that the main toxic action of N. sumatrana venom is neurotoxic but the large amount of cardiotoxins and phospholipases A2 are likely to contribute significantly to the overall pathophysiological action of the venom. The differences in toxin distribution between N. sumatrana venom and African spitting cobra venoms suggest possible differences in the pathophysiological actions of N. sumatrana venom and the African spitting cobra venoms, and explain why antivenom raised against Asiatic cobra venom is not effective against African spitting cobra venoms.
