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naja kaouthia

Anjana Silva, Wayne C Hodgson, Geoffrey K Isbister
There is limited information on the cross-neutralisation of neurotoxic venoms with antivenoms. Cross-neutralisation of the in vitro neurotoxicity of four Asian and four Australian snake venoms, four post-synaptic neurotoxins (α-bungarotoxin, α-elapitoxin-Nk2a, α-elapitoxin-Ppr1 and α-scutoxin; 100 nM) and one pre-synaptic neurotoxin (taipoxin; 100 nM) was studied with five antivenoms: Thai cobra antivenom (TCAV), death adder antivenom (DAAV), Thai neuro polyvalent antivenom (TNPAV), Indian Polyvalent antivenom (IPAV) and Australian polyvalent antivenom (APAV)...
October 18, 2016: Toxins
Tanmoy Bhowmik, Antony Gomes
BACKGROUND: Gold nanoparticle (GNP) and snake venom protein toxin NKCT1 was conjugated as stated earlier (Bhowmik et al., 2013). The aim of this study was to explore the caspase dependent apoptotic pathway and autophagy inducing ability of gold nanoparticles tagged snake venom protein toxin NKCT1 (GNP-NKCT1) in human leukemic U937 and K562 cell line. METHODS: GNP-NKCT1 induced apoptosis in U937 and K562 cell line were assessed through mitochondrial membrane potential assay, ROS generation assay, caspase 3 pathways and western blotting...
October 2016: Toxicon: Official Journal of the International Society on Toxinology
Ekaterina N Lyukmanova, Mikhail A Shulepko, Zakhar O Shenkarev, Igor E Kasheverov, Anton O Chugunov, Dmitrii S Kulbatskii, Mikhail Yu Myshkin, Yuri N Utkin, Roman G Efremov, Victor I Tsetlin, Alexander S Arseniev, Mikhail P Kirpichnikov, Dmitry A Dolgikh
'Three-finger' toxin WTX from Naja kaouthia interacts with nicotinic and muscarinic acetylcholine receptors (nAChRs and mAChRs). Mutagenesis and competition experiments with (125)I-α-bungarotoxin revealed that Arg31 and Arg32 residues from the WTX loop II are important for binding to Torpedo californica and human α7 nAChRs. Computer modeling suggested that loop II occupies the orthosteric binding site at α7 nAChR. The similar toxin interface was previously described as a major determinant of allosteric interactions with mAChRs...
September 1, 2016: Toxicon: Official Journal of the International Society on Toxinology
Cassandra M Modahl, Ashis K Mukherjee, Stephen P Mackessy
Venoms of snakes of the family Elapidae (cobras, kraits, mambas, and relatives) are predominantly composed of numerous phospholipases A2 (PLA2s) and three-finger toxins (3FTxs), some of which are lethal while others are not significantly toxic. Currently, the only identified prey-specific toxins are several nonconventional 3FTxs, and given the large diversity of 3FTxs within Monocled Cobra (Naja kaouthia) venom, it was hypothesized that several 3FTxs, previously found to be non-toxic or weakly toxic 3FTxs in murine models, could potentially be toxic towards non-murine prey...
September 1, 2016: Toxicon: Official Journal of the International Society on Toxinology
Kae Yi Tan, Choo Hock Tan, Shin Yee Fung, Nget Hong Tan
Antivenom neutralization against cobra venoms is generally low in potency, presumably due to poor toxin-specific immunoreactivity. This study aimed to investigate the effectiveness of two elapid antivenoms to neutralize the principal toxins purified from the venoms of the Thai monocled cobra (Naja kaouthia, Nk-T) and the Malaysian beaked sea snake (Hydrophis schistosus, Hs-M). In mice, N. kaouthia Monovalent Antivenom (NKMAV) neutralization against Nk-T long neurotoxin (LNTX) and cytotoxin was moderate (potency of 2...
April 2016: Toxins
Kae Yi Tan, Choo Hock Tan, Si Mui Sim, Shin Yee Fung, Nget Hong Tan
The Southeast Asian monocled cobras (Naja kaouthia) exhibit geographical variations in their venom proteomes, especially on the composition of neurotoxins. This study compared the neuromuscular depressant activity of the venoms of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V), and the neutralization of neurotoxicity by a monospecific antivenom. On chick biventer cervicis nerve-muscle preparation, all venoms abolished the indirect twitches, with NK-T venom being the most potent (shortest t90, time to 90% twitch inhibition), followed by NK-V and NK-M...
July 2016: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
H K Das, D Das, R Doley, P P Sahu
Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve...
2016: Scientific Reports
Naadiya Carrim, Jane F Arthur, Justin R Hamilton, Elizabeth E Gardiner, Robert K Andrews, Niamh Moran, Michael C Berndt, Pat Metharom
BACKGROUND: Platelets are essential for maintaining haemostasis and play a key role in the pathogenesis of cardiovascular disease. Upon ligation of platelet receptors through subendothelial matrix proteins, intracellular reactive oxygen species (ROS) are generated, further amplifying the platelet activation response. Thrombin, a potent platelet activator, can signal through GPIbα and protease-activated receptor (PAR) 1 and PAR4 on human platelets, and recently has been implicated in the generation of ROS...
December 2015: Redox Biology
Chandrasekhar Chanda, Angshuman Sarkar, Dibakar Chakrabarty
A metalloproteinase anticoagulant toxin of molecular weight 66 kDa has been purified from the venom of Indian monocled cobra (Naja kaouthia). This toxin named as NKV 66 cleaved fibrinogen in a dose and time dependent manner. The digestion process was specific to Aα chain and cleaved fibrinogen to peptide fragments. NKV 66 completely liquefied the fibrin clots developed in vitro in 18 h. Plasma recalcification time and thrombin time were significantly prolonged following treatment of plasma with NKV 66. NKV 66 significantly inhibited ADP and collagen induced platelet aggregation in a dose dependent manner...
January 15, 2016: Archives of Biochemistry and Biophysics
Choo Hock Tan, Kae Yi Tan, Shin Yee Fung, Nget Hong Tan
BACKGROUND: The king cobra (Ophiophagus hannah) is widely distributed throughout many parts of Asia. This study aims to investigate the complexity of Malaysian Ophiophagus hannah (MOh) venom for a better understanding of king cobra venom variation and its envenoming pathophysiology. The venom gland transcriptome was investigated using the Illumina HiSeq™ platform, while the venom proteome was profiled by 1D-SDS-PAGE-nano-ESI-LCMS/MS. RESULTS: Transcriptomic results reveal high redundancy of toxin transcripts (3357...
2015: BMC Genomics
Diganta Das, Maitreyee Sharma, Hemanga Kumar Das, Partha Pratim Sahu, Robin Doley
Snake venom three finger toxins (3FTxs) are a non-enzymatic family of venom proteins abundantly found in elapids. We have purified a 7579.5 ± 0.591 Da 3FTx named as Nk-3FTx from the venom of Naja kaouthia of North East India origin. The primary structure was determined by a combination of N-terminal sequencing and electrospray ionization liquid chromatography-mass spectrometry/mass spectrometry. Biochemical and biological characterization reveal that it is nontoxic to human cell lines and exhibit mild anticoagulant activity when tested on citrated human plasma...
February 2016: Journal of Biochemical and Molecular Toxicology
Ekaterina N Lyukmanova, Zakhar O Shenkarev, Mikhail A Shulepko, Alexander S Paramonov, Anton O Chugunov, Helena Janickova, Eva Dolejsi, Vladimir Dolezal, Yuri N Utkin, Victor I Tsetlin, Alexander S Arseniev, Roman G Efremov, Dmitry A Dolgikh, Mikhail P Kirpichnikov
Weak toxin from Naja kaouthia (WTX) belongs to the group of nonconventional "three-finger" snake neurotoxins. It irreversibly inhibits nicotinic acetylcholine receptors and allosterically interacts with muscarinic acetylcholine receptors (mAChRs). Using site-directed mutagenesis, NMR spectroscopy, and computer modeling, we investigated the recombinant mutant WTX analogue (rWTX) which, compared with the native toxin, has an additional N-terminal methionine residue. In comparison with the wild-type toxin, rWTX demonstrated an altered pharmacological profile, decreased binding of orthosteric antagonist N-methylscopolamine to human M1- and M2-mAChRs, and increased antagonist binding to M3-mAChR...
September 25, 2015: Journal of Biological Chemistry
Tanmoy Bhowmik, Partha Pratim Saha, Anjan Dasgupta, Antony Gomes
Limited efficacy of current first-line treatment for leukemia calls attention for further development of efficient strategies. Recently, much attention has been given to nanoparticle-based drug delivery systems loaded with dual drugs to improve current disease therapies by overcoming toxicity. In the present study, we document to explore an approach to conjugate gold nanoparticles (GNPs) with protein toxin (NKCT1), a protein toxin from the Indian cobra (Naja kaouthia) venom, and to establish its antileukemic activity...
2013: Cancer Nanotechnology
Choo Hock Tan, Kae Yi Tan, Sin Ee Lim, Nget Hong Tan
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...
August 3, 2015: Journal of Proteomics
Jatuporn Phaopongthai, Jureeporn Noiphrom, Supat Phaopongthai, Narumol Pakmanee, Jirapast Sichaem
This study evaluates the in vitro anti-snake venom potential of Peristrophe bivalvis (PB) extracts against Naja kaouthia (NK) and Trimeresurus albolabris (TA) venoms, including inhibition of cytotoxic effects and enzymatic activities, and the binding-precipitation of extracts and venom proteins analysis. In addition, the antioxidant, cytotoxic and in vivo acute oral toxic activities of PB extracts are also reported. The in vitro cytotoxic and enzymatic analysis reveals that the ethanol extracts of stems and leaves of PB showed good anti-snake venom activity against NK and TA venoms...
2016: Natural Product Research
Andreas H Laustsen, José María Gutiérrez, Brian Lohse, Arne R Rasmussen, Julián Fernández, Christina Milbo, Bruno Lomonte
The venom proteome of the monocled cobra, Naja kaouthia, from Thailand, was characterized by RP-HPLC, SDS-PAGE, and MALDI-TOF-TOF analyses, yielding 38 different proteins that were either identified or assigned to families. Estimation of relative protein abundances revealed that venom is dominated by three-finger toxins (77.5%; including 24.3% cytotoxins and 53.2% neurotoxins) and phospholipases A2 (13.5%). It also contains lower proportions of components belonging to nerve growth factor, ohanin/vespryn, cysteine-rich secretory protein, C-type lectin/lectin-like, nucleotidase, phosphodiesterase, metalloproteinase, l-amino acid oxidase, cobra venom factor, and cytidyltransferase protein families...
June 1, 2015: Toxicon: Official Journal of the International Society on Toxinology
Kae Yi Tan, Choo Hock Tan, Shin Yee Fung, Nget Hong Tan
UNLABELLED: Previous studies showed that venoms of the monocled cobra, Naja kaouthia from Thailand and Malaysia are substantially different in their median lethal doses. The intraspecific venom variations of N. kaouthia, however, have not been fully elucidated. Here we investigated the venom proteomes of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V) through reverse-phase HPLC, SDS-PAGE and tandem mass spectrometry. The venom proteins comprise 13 toxin families, with three-finger toxins being the most abundant (63-77%) and the most varied (11-18 isoforms) among the three populations...
April 29, 2015: Journal of Proteomics
Catherine A Vulfius, Igor E Kasheverov, Vladislav G Starkov, Alexey V Osipov, Tatyana V Andreeva, Sergey Yu Filkin, Elena V Gorbacheva, Maxim E Astashev, Victor I Tsetlin, Yuri N Utkin
Phospholipases A2 represent the most abundant family of snake venom proteins. They manifest an array of biological activities, which is constantly expanding. We have recently shown that a protein bitanarin, isolated from the venom of the puff adder Bitis arietans and possessing high phospholipolytic activity, interacts with different types of nicotinic acetylcholine receptors and with the acetylcholine-binding protein. To check if this property is characteristic to all venom phospholipases A2, we have studied the capability of these enzymes from other snakes to block the responses of Lymnaea stagnalis neurons to acetylcholine or cytisine and to inhibit α-bungarotoxin binding to nicotinic acetylcholine receptors and acetylcholine-binding proteins...
2014: PloS One
Shan Gong, Qian Liang, Qi Zhu, Dayong Ding, Qizhang Yin, Jin Tao, Xinghong Jiang
In this study we report that cobratoxin (CbTX), a long-chain postsynaptic α-neurotoxin isolated from the Thailand cobra, Naja naja kaouthia, has antinociceptive effect in rats with neuropathic pain. The neuropathic pain model was established in rats with partial sciatic nerve ligature (PSNL) method. The pain response was examined behaviorally with mechanical paw withdrawal and thermal paw withdrawal method. Different doses (0.56, 1.12 and 4.50 μg/kg) of CbTX were injected intrathecally. Injection of CbTX resulted in a significant dose-dependent antinociception as evidenced by increased mechanical withdrawal threshold and thermal withdrawal latency...
January 2015: Toxicon: Official Journal of the International Society on Toxinology
Partha Pratim Saha, Tanmoy Bhowmik, Anjan Kumar Dasgupta, Antony Gomes
Nanoscience and Nanotechnology have found their way in the fields of pharmacology and medicine. The conjugation of drug to nanoparticles combines the properties of both. In this study, gold nanoparticle (GNP) was conjugated with NKCT1, a cytotoxic protein toxin from Indian cobra venom for evaluation of anti-arthritic activity and toxicity in experimental animal models. GNP conjugated NKCT1 (GNP-NKCT1) synthesized by NaBH4 reduction method was stable at room temperature (25 +/- 2 degrees C), pH 7.2. Hydrodynamic size of GNP-NKCT1 was 68-122 nm...
August 2014: Indian Journal of Experimental Biology
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