Eastern coral snake Micrurus fulvius venom toxicity in mice is mainly determined by neurotoxic phospholipases A(2)
Por:
Vergara, I, Pedraza-Escalona, M, Paniagua, D, Restano-Cassulini, R, Zamudio, F, Batista, CVF, Possani, LD, Alagon, A
Publicada:
13 jun 2014
Resumen:
Here we show for the first time that the venom from an elapid (Micrurus
fulvius) contains three finger toxin (3FTxs) peptides with low toxicity
but high content of lethal phospholipases A(2) (PLA(2)). The intravenous
venom LD50 in mice was 0.3 mu g/g. Fractionation on a C-18 column
yielded 22 fractions; in terms of abundance, 58.3% of them were
components of 13-14 kDa and 24.9% were molecules of 6-7 kDa. Two
fractions with PLA(2) activity represented 33.4% of the whole venom and
were the most lethal fractions. Fractions with low molecular mass (<7000
Da) partially and reversibly blocked the nicotinic acetylcholine
receptor (nAChR), with the exception of one that blocked it completely.
The fraction that blocked 100% contained two protein species whose
dose-response was determined; the IC(50)s were 13 +/- 1 and 9.5 +/- 0.3
nM. Despite the apparent effect on nAChR none of the low molecular mass
fractions were lethal in mice, at concentrations of 1 mu g/g. From
2D-PAGE and LC-MS/MS, we identified fourteen species of PLA(2), four
protein species of C-type lectin, three zinc metalloproteinases, one
phosphodiesterase and one 3FTx. The N-terminal amino acid sequence of
fractions with biological interest was obtained.
Biological significance
In contrast with coral snake venoms from South America, M. fulvius has
minor amounts of low molecular mass components, but high content of
PLA(2), which is responsible for the venom lethality of this species.
The results reported here contribute to better understanding of
envenomation development and to improve antivenom design and production.
These findings break from the paradigm that neurotoxicity caused by
Micrurus venoms is mainly attributable to 3FTx neurotoxins and encourage
future studies on Micrurus evolution and venom specialization.
This article is part of a Special Issue entitled Non-model organisms.
(C) 2014 Elsevier B.V. All rights reserved.
Filiaciones:
Vergara, I:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca 62210, Morelos, Mexico
Pedraza-Escalona, M:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca 62210, Morelos, Mexico
Paniagua, D:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca 62210, Morelos, Mexico
Restano-Cassulini, R:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca 62210, Morelos, Mexico
Zamudio, F:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca 62210, Morelos, Mexico
Batista, CVF:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca 62210, Morelos, Mexico
Possani, LD:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca 62210, Morelos, Mexico
Alagon, A:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca 62210, Morelos, Mexico
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