Isolation and characterization of α-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:	Ahmad Rusmili, Muhamad Rusdi, Ting, Yee Tee, Mustafa, Mohd Rais, Othman, Iekhsan, Hodgson, Wayne C.
Format:	Article
Language:	English
Published:	Elsevier Ltd. 2014
Subjects:	RM Therapeutics. Pharmacology
Online Access:	http://irep.iium.edu.my/37197/ http://irep.iium.edu.my/37197/ http://irep.iium.edu.my/37197/ http://irep.iium.edu.my/37197/1/1-s2.0-S0006295214000288-main.pdf

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spelling	iium-371972014-07-08T04:13:58Z http://irep.iium.edu.my/37197/ Isolation and characterization of α-elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom Ahmad Rusmili, Muhamad Rusdi Ting, Yee Tee Mustafa, Mohd Rais Othman, Iekhsan Hodgson, Wayne C. RM Therapeutics. Pharmacology 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 Ltd. 2014 Article PeerReviewed application/pdf en http://irep.iium.edu.my/37197/1/1-s2.0-S0006295214000288-main.pdf Ahmad Rusmili, Muhamad Rusdi and Ting, Yee Tee and Mustafa, Mohd Rais and Othman, Iekhsan and Hodgson, Wayne C. (2014) Isolation and characterization of α-elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom. Biochemical Pharmacology, 88 (2). pp. 229-236. ISSN 0006-2952 http://www.sciencedirect.com/science/article/pii/S0006295214000288 10.1016/j.bcp.2014.01.004
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	RM Therapeutics. Pharmacology
spellingShingle	RM Therapeutics. Pharmacology Ahmad Rusmili, Muhamad Rusdi Ting, Yee Tee Mustafa, Mohd Rais Othman, Iekhsan Hodgson, Wayne C. Isolation and characterization of α-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	Ahmad Rusmili, Muhamad Rusdi Ting, Yee Tee Mustafa, Mohd Rais Othman, Iekhsan Hodgson, Wayne C.
author_facet	Ahmad Rusmili, Muhamad Rusdi Ting, Yee Tee Mustafa, Mohd Rais Othman, Iekhsan Hodgson, Wayne C.
author_sort	Ahmad Rusmili, Muhamad Rusdi
title	Isolation and characterization of α-elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom
title_short	Isolation and characterization of α-elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom
title_full	Isolation and characterization of α-elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom
title_fullStr	Isolation and characterization of α-elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom
title_full_unstemmed	Isolation and characterization of α-elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom
title_sort	isolation and characterization of α-elapitoxin-bf1b, a postsynaptic neurotoxin from malaysian bungarus fasciatus venom
publisher	Elsevier Ltd.
publishDate	2014
url	http://irep.iium.edu.my/37197/ http://irep.iium.edu.my/37197/ http://irep.iium.edu.my/37197/ http://irep.iium.edu.my/37197/1/1-s2.0-S0006295214000288-main.pdf
first_indexed	2023-09-18T20:53:21Z
last_indexed	2023-09-18T20:53:21Z
_version_	1777410141322215424

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

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