Specific binding of crotoxin to brain synaptosomes and synaptosomal membranes

Degn, Laura L.; Seebart, Corrine; Kaiser, Ivan I.

doi:10.1016/0041-0101(91)90080-b

Cited by 40 publications

(12 citation statements)

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“…at the neuromuscular junction crotoxin and pbungarotoxin potentiate each other's toxicity [16]. Different p-neurotoxins also show very variable efficiency in competing with the binding of crotoxin on nervous membranes [17]. On Torpedo synaptosomes also, agkistrodotoxin, crotoxin and p-bungarotoxin exert different pharmacological effects [5].…”

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confidence: 99%

Snake‐venom phospholipase A₂ neurotoxins

Choumet

Saliou

Fideler

et al. 1993

European Journal of Biochemistry

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The venoms from Crotalinae and Viperinae snakes contain only two kinds of phospholipase Az neurotoxins (p-neurotoxins) : single-chain B-neurotoxins, such as agkistrodotoxin and ammodytoxin-A, and dimeric p-neurotoxins, which, in the case of the best studied ones, crotoxin-like toxins, consist of the non-covalent association of a phospholipase A2 (CB) and a non-enzymatic chaperon (CA). Possible evolutionary relationships of these p-neurotoxins have been investigated by analyzing whether CA could behave as a chaperon toward agkistrodotoxin and ammodytoxin, as it does in the crotoxin complex.CA increased the lethal potency of agkistrodotoxin and modified its pharmacological effect on Torpedo synaptosomes. Sedimentation experiments proved that CA can form an heterocomplex with agkistrodotoxin. Agkistrodotoxin prevented the binding to CA of an anti-CA mAb which recognizes an epitope at the zone of interaction between crotoxin subunits, suggesting the association of CA and agkistrodotoxin implicated the same zone.A 10-fold molar excess of CA over ammodytoxin modified the effect of ammodytoxin on acetylcholine release but did not increase the lethal potency of ammodytoxin. Sedimentation experiments showed CA and ammodytoxin can form an heterocomplex which is less stable than CA . agkistrodotoxin. Ammodytoxin A did not compete with the anti-CA mAb.These observations are in good agreement with the sequence similarities between CB and agkistrodotoxin (80%) and ammodytoxin A (60%).Phospholipases A2 (PLA2s) are ubiquitous enzymes which catalyze the specific hydrolysis of the 2-acyl ester bond of 1,2-diacyl-

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confidence: 99%

Snake‐venom phospholipase A₂ neurotoxins

Choumet

Saliou

Fideler

et al. 1993

European Journal of Biochemistry

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“…These results are to be compared with those performed on guinea pig brain synaptosomal membranes (Degn et al, 1991;Tzeng et al, 1986). These authors also described a single class of sites without cooperativity.…”

Section: Resultsmentioning

confidence: 99%

Model for the interaction of crotoxin, a phospholipase A2 neurotoxin, with presynaptic membranes

Délot

Bon²

1993

Biochemistry

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Crotoxin is a phospholipase A2 neurotoxin that impairs the release of acetylcholine at neuromuscular junctions, primarily at the presynaptic level. It associates a phospholipase A2 subunit, CB, with a chaperon subunit, CA. We have shown elsewhere that the purely cholinergic synaptosomes from the Torpedo electric organ provided a convenient model to study the pharmacology of crotoxin and other related neurotoxins [Délot, E., & Bon, C. (1992) J. Neurochem. 58, 311-319]. In the present experiments, we labeled crotoxin with 125I and demonstrated saturable binding to Torpedo presynaptic membranes. In the range of concentrations that was effective on synaptosomes, crotoxin bound to a single class of sites without cooperativity. The binding was affected by divalent cations, and its kinetics was rather complex. We observed a competition between crotoxin and related neurotoxins, but not CB. Although CA could not bind, it could compete efficiently with crotoxin. We compare our results with those previously obtained by others on guinea pig brain membranes. On Torpedo membranes, as on all models tested, CB was the major species bound to the membrane, while CA remained in solution. However, the mechanism underlying this phenomenon had never been clarified. The major question is the time scale of the events, i.e., does CB bind before or after dissociating from CA? Our results indicate that the predominant pathway involves the formation of a ternary complex between crotoxin's subunits and the acceptor site preceding the release of CA.

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“…Crotoxin is a beta-neurotoxin, acting pre-synaptically on muscular junctions blocking the signal transduction (Degn et al, 1991). Crotoxin is heterodimeric, composed by a nontoxic acidic subunit (crotapotin) acting as a chaperone, delivering the basic PLA 2 subunit to the synaptic cleft, blocking the release of acetylcholine.…”

Section: Crotoxin-like Toxins and Other Plamentioning

confidence: 99%

Proteomic analysis of the rare Uracoan rattlesnake Crotalus vegrandis venom: Evidence of a broad arsenal of toxins

Viala

Hildebrand

Fucase

et al. 2015

Toxicon

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The investigation of venoms has many clinical, pharmacological, ecological and evolutionary outcomes. The Crotalus spp. venom can cause hemorrhage, neurotoxicity, myotoxicity, coagulopathy and hypotension. Although neurotoxicity and hemorrhage usually does not occur for the same species, the rare Venezuelan species Crotalus vegrandis presents both characteristic. Different from the other species it has a restricted ecological niche and geographical distribution. Nevertheless, it has a raising medical importance as this rattlesnake population is increasing. Few works describe its neurotoxic and hemorrhagic features, but other toxins might play an important role in envenomation. We combined proteomic methods to identify for the first time the main components of it venom: 2D SDS-PAGE and gel-filtration chromatography for protein mixture decomplexation; LC-MS(2) of low molecular mass fractions and tryptic peptides; bioinformatic identification of toxin families and specific protein species based on unique peptide analysis and sequence database enriched with species-specific venom gland transcripts; and finally polyclonal anti-crotamine Western-blotting. Our results point to a broad arsenal of toxins in C. vegrandis venom: PIII and PII metalloproteases, crotoxin subunits, other phospholipases, isoforms of serine proteases and lectins, l-amino-acid oxidase, nerve growth factor, as well as other less abundant toxins.

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Specific binding of crotoxin to brain synaptosomes and synaptosomal membranes

Cited by 40 publications

References 29 publications

Snake‐venom phospholipase A₂ neurotoxins

Snake‐venom phospholipase A₂ neurotoxins

Model for the interaction of crotoxin, a phospholipase A2 neurotoxin, with presynaptic membranes

Proteomic analysis of the rare Uracoan rattlesnake Crotalus vegrandis venom: Evidence of a broad arsenal of toxins

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Specific binding of crotoxin to brain synaptosomes and synaptosomal membranes

Cited by 40 publications

References 29 publications

Snake‐venom phospholipase A2 neurotoxins

Snake‐venom phospholipase A2 neurotoxins

Model for the interaction of crotoxin, a phospholipase A2 neurotoxin, with presynaptic membranes

Proteomic analysis of the rare Uracoan rattlesnake Crotalus vegrandis venom: Evidence of a broad arsenal of toxins

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Snake‐venom phospholipase A₂ neurotoxins

Snake‐venom phospholipase A₂ neurotoxins