Phospholipases A2 isolated from Micrurus lemniscatus coral snake venom: Behavioral, electroencephalographic, and neuropathological aspects

Oliveira, D.A.; Harasawa, C.; Seibert, Carla Simone; Casais-e-Silva, Luciana Lyra; Pimenta, Daniel C.; Lebrun, Ivo; Sandoval, Maria Regina Lopes

doi:10.1016/j.brainresbull.2007.10.007

Cited by 22 publications

(20 citation statements)

References 45 publications

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“…Concurrently, Goularte et al [181,206] reported significant neurotoxicity in M. nigrocinctus venom. Oliveira et al [207] reported on the neurotoxic effects (behavioral, EEG and histopathologic) of intrahippocampal injection of four neurotoxic PLA 2 s from M. l. lemniscatus venom. These toxins were convulsive, but not epileptogenic at low doses (2.1 µg/rat).…”

Section: Resultsmentioning

confidence: 99%

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

Aird

Silva

Qiu

et al. 2017

Toxins

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Venom gland transcriptomes and proteomes of six Micrurus taxa (M. corallinus, M. lemniscatus carvalhoi, M. lemniscatus lemniscatus, M. paraensis, M. spixii spixii, and M. surinamensis) were investigated, providing the most comprehensive, quantitative data on Micrurus venom composition to date, and more than tripling the number of Micrurus venom protein sequences previously available. The six venomes differ dramatically. All are dominated by 2–6 toxin classes that account for 91–99% of the toxin transcripts. The M. s. spixii venome is compositionally the simplest. In it, three-finger toxins (3FTxs) and phospholipases A2 (PLA2s) comprise >99% of the toxin transcripts, which include only four additional toxin families at levels ≥0.1%. Micrurus l. lemniscatus venom is the most complex, with at least 17 toxin families. However, in each venome, multiple structural subclasses of 3FTXs and PLA2s are present. These almost certainly differ in pharmacology as well. All venoms also contain phospholipase B and vascular endothelial growth factors. Minor components (0.1–2.0%) are found in all venoms except that of M. s. spixii. Other toxin families are present in all six venoms at trace levels (<0.005%). Minor and trace venom components differ in each venom. Numerous novel toxin chemistries include 3FTxs with previously unknown 8- and 10-cysteine arrangements, resulting in new 3D structures and target specificities. 9-cysteine toxins raise the possibility of covalent, homodimeric 3FTxs or heterodimeric toxins with unknown pharmacologies. Probable muscarinic sequences may be reptile-specific homologs that promote hypotension via vascular mAChRs. The first complete sequences are presented for 3FTxs putatively responsible for liberating glutamate from rat brain synaptosomes. Micrurus C-type lectin-like proteins may have 6–9 cysteine residues and may be monomers, or homo- or heterodimers of unknown pharmacology. Novel KSPIs, 3× longer than any seen previously, appear to have arisen in three species by gene duplication and fusion. Four species have transcripts homologous to the nociceptive toxin, (MitTx) α-subunit, but all six species had homologs to the β-subunit. The first non-neurotoxic, non-catalytic elapid phospholipase A2s are reported. All are probably myonecrotic. Phylogenetic analysis indicates that the six taxa diverged 15–35 million years ago and that they split from their last common ancestor with Old World elapines nearly 55 million years ago. Given their early diversification, many cryptic micrurine taxa are anticipated.

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Section: Resultsmentioning

confidence: 99%

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

Aird

Silva

Qiu

et al. 2017

Toxins

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“…With an Mw of 12,809.40 Da MsPLA 2 -I presented a mass according to that expected for a Micrurus PLA 2 being between 12 and 18 kDa (Murakami and Kudo, 2001;Oliveira et al, 2008;Rey-Súarez et al, 2011). The fragment of 60 amino acids obtained by the sequencing of MsPLA 2 -I when aligned with sequences of PLA 2 s of other Micrurus species presented 80% similarity with the enzyme from M. altirostris (Ciscotto et al, 2011).…”

Section: Discussionmentioning

confidence: 96%

Biological characterization of the Amazon coral Micrurus spixii snake venom: Isolation of a new neurotoxic phospholipase A2

Terra

Moreira-Dill

Simões-Silva

et al. 2015

Toxicon

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The Micrurus genus is the American representative of Elapidae family. Micrurus spixii is endemic of South America and northern states of Brazil. Elapidic venoms contain neurotoxins that promote curare-mimetic neuromuscular blockage. In this study, biochemical and functional characterizations of M. spixii crude venom were performed and a new neurotoxic phospholipase A2 called MsPLA2-I was isolated. M. spixii crude venom caused severe swelling in the legs of tested mice and significant release of creatine kinase (CK) showing its myotoxic activity. Leishmanicidal activity against Leishmania amazonensis (IC50 1.24 μg/mL) was also observed, along with antiplasmodial activity against Plasmodium falciparum, which are unprecedented for Micrurus venoms. MsPLA2-I with a Mr 12,809.4 Da was isolated from the crude venom of M. spixii. The N-terminal sequencing of a fragment of 60 amino acids showed 80% similarity with another PLA2 from Micrurus altirostris. This toxin and the crude venom showed phospholipase activity. In a mouse phrenic nerve-diaphragm preparation, M. spixii venom and MsPLA2-I induced the blockage of both direct and indirect twitches. While the venom presented a pronounced myotoxic activity, MsPLA2-I expressed a summation of neurotoxic activity. The results of this study make M. spixii crude venom promising compounds in the exploration of molecules with microbicidal potential.

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“…Other PLA2s purified from the venom of M. lemniscatus from specimens collected in Bahia, Brazil, displayed potent neurotoxicity when injected directly into the hipoccampus of rats, but not when administered i.v. (Oliveira et al, 2008) and induced cytotoxicity in a primary cell culture of rat hippocampal neurons (de Carvalho et al, 2014). Many venom PLA2s have been shown to induce inflammation characterized by increase of vascular permeability (Zuliani et al, 2005a, Corasolla Carregari et al, 2013, edema formation (Ferreira et al, 2013, Kumar et al, 2015, and recruitment and activation of leukocytes (Zuliani et al, 2005b, Moreira et al, 2011.…”

Section: Discussionmentioning

confidence: 98%

Lemnitoxin, the major component of Micrurus lemniscatus coral snake venom, is a myotoxic and pro-inflammatory phospholipase A2

et al. 2016

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Phospholipases A2 isolated from Micrurus lemniscatus coral snake venom: Behavioral, electroencephalographic, and neuropathological aspects

Cited by 22 publications

References 45 publications

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

Biological characterization of the Amazon coral Micrurus spixii snake venom: Isolation of a new neurotoxic phospholipase A2

Lemnitoxin, the major component of Micrurus lemniscatus coral snake venom, is a myotoxic and pro-inflammatory phospholipase A2

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