Isolation and characterization of elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom

Bungarus fasciatus is one of three species of krait found in Malaysia. Envenoming by B. fasciatus results in neurotoxicity due to the presence of presynaptic and postsynaptic neurotoxins. Antivenom, either monovalent or polyvalent, is the treatment of choice in systemically envenomed patients. In th...

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Main Authors: Rusmili, M.R.A., Yee, T.T., Mustafa, Mohd Rais, Othman, L., Hodgson, W.C.
Format: Article
Language:English
Published: Elsevier 2014
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Online Access:http://eprints.um.edu.my/9830/1/Isolation_and_characterization_of_alpha.pdf
http://eprints.um.edu.my/9830/
https://doi.org/10.1016/j.bcp.2014.01.004
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spelling my.um.eprints.98302019-08-08T08:27:12Z http://eprints.um.edu.my/9830/ Isolation and characterization of elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom Rusmili, M.R.A. Yee, T.T. Mustafa, Mohd Rais Othman, L. Hodgson, W.C. R Medicine Bungarus fasciatus is one of three species of krait found in Malaysia. Envenoming by B. fasciatus results in neurotoxicity due to the presence of presynaptic and postsynaptic neurotoxins. Antivenom, either monovalent or polyvalent, is the treatment of choice in systemically envenomed patients. In this study, we have isolated a postsynaptic neurotoxin which we named α-elapitoxin-Bf1b. This toxin has an approximate molecular weight of 6.9 kDa, with LCMS/MS data showing that it is highly homologous with Neurotoxin 3FTx-RI, a toxin identified in the Bungarus fasciatus venom gland transcriptome. α-Elapitoxin-Bf1b also shared similarity with short-chain neurotoxins from Laticauda colubrina and Pseudechis australis. α-Elapitoxin-Bf1b produced concentration- and time-dependent neurotoxicity in the indirectly-stimulated chick biventer cervicis muscle preparation, an effect partially reversible by repetitive washing of the preparation. The pA2 value for α-elapitoxin-Bf1b of 9.17 ± 0.64, determined by examining the effects of the toxin on cumulative carbacol concentration-response curves, indicated that the toxin is more potent than tubocurarine and α-bungarotoxin. Pre-incubation of Bungarus fasciatus monovalent and neuro polyvalent antivenom failed to prevent the neurotoxic effects of α-elapitoxin-Bf1b in the chick biventer cervicis muscle preparation. In conclusion, the isolation of a postsynaptic neurotoxin that cannot be neutralized by either monovalent and polyvalent antivenoms may indicate the presence of isoforms of postsynaptic neurotoxins in Malaysian B. fasciatus venom. Elsevier 2014 Article PeerReviewed application/pdf en http://eprints.um.edu.my/9830/1/Isolation_and_characterization_of_alpha.pdf Rusmili, M.R.A. and Yee, T.T. and Mustafa, Mohd Rais and Othman, L. and Hodgson, W.C. (2014) Isolation and characterization of elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom. Biochemical Pharmacology, 88 (2). pp. 229-236. ISSN 0006-2952 https://doi.org/10.1016/j.bcp.2014.01.004 doi:10.1016/j.bcp.2014.01.004
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
language English
topic R Medicine
spellingShingle R Medicine
Rusmili, M.R.A.
Yee, T.T.
Mustafa, Mohd Rais
Othman, L.
Hodgson, W.C.
Isolation and characterization of elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom
description Bungarus fasciatus is one of three species of krait found in Malaysia. Envenoming by B. fasciatus results in neurotoxicity due to the presence of presynaptic and postsynaptic neurotoxins. Antivenom, either monovalent or polyvalent, is the treatment of choice in systemically envenomed patients. In this study, we have isolated a postsynaptic neurotoxin which we named α-elapitoxin-Bf1b. This toxin has an approximate molecular weight of 6.9 kDa, with LCMS/MS data showing that it is highly homologous with Neurotoxin 3FTx-RI, a toxin identified in the Bungarus fasciatus venom gland transcriptome. α-Elapitoxin-Bf1b also shared similarity with short-chain neurotoxins from Laticauda colubrina and Pseudechis australis. α-Elapitoxin-Bf1b produced concentration- and time-dependent neurotoxicity in the indirectly-stimulated chick biventer cervicis muscle preparation, an effect partially reversible by repetitive washing of the preparation. The pA2 value for α-elapitoxin-Bf1b of 9.17 ± 0.64, determined by examining the effects of the toxin on cumulative carbacol concentration-response curves, indicated that the toxin is more potent than tubocurarine and α-bungarotoxin. Pre-incubation of Bungarus fasciatus monovalent and neuro polyvalent antivenom failed to prevent the neurotoxic effects of α-elapitoxin-Bf1b in the chick biventer cervicis muscle preparation. In conclusion, the isolation of a postsynaptic neurotoxin that cannot be neutralized by either monovalent and polyvalent antivenoms may indicate the presence of isoforms of postsynaptic neurotoxins in Malaysian B. fasciatus venom.
format Article
author Rusmili, M.R.A.
Yee, T.T.
Mustafa, Mohd Rais
Othman, L.
Hodgson, W.C.
author_facet Rusmili, M.R.A.
Yee, T.T.
Mustafa, Mohd Rais
Othman, L.
Hodgson, W.C.
author_sort Rusmili, M.R.A.
title Isolation and characterization of elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom
title_short Isolation and characterization of elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom
title_full Isolation and characterization of elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom
title_fullStr Isolation and characterization of elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom
title_full_unstemmed Isolation and characterization of elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom
title_sort isolation and characterization of elapitoxin-bf1b, a postsynaptic neurotoxin from malaysian bungarus fasciatus venom
publisher Elsevier
publishDate 2014
url http://eprints.um.edu.my/9830/1/Isolation_and_characterization_of_alpha.pdf
http://eprints.um.edu.my/9830/
https://doi.org/10.1016/j.bcp.2014.01.004
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