Presynaptic effects of snake venom toxins which have phospholipase A2 activity (β-bungarotoxin, taipoxin, crotoxin)

Su, M.J.; Chang, C.C.

doi:10.1016/0041-0101(84)90003-5

Cited by 67 publications

(34 citation statements)

References 20 publications

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“…In the mid 1980s, Su and Chang [11] studied the effect of b-BuTx on the nerve terminal and summarized the series of events during neurotoxicity as: (1) initial weak reduction in the spontaneous acetylcholine release, (2) subsequent enhancement of the release of acetylcholine and (3) a final decrease in the release of acetylcholine leading to complete failure of neurotransmission. Subsequently, several studies were done to understand the effect of b-BuTx in the nerve terminals.…”

Section: Introductionmentioning

confidence: 99%

Protein complexes in snake venom

Doley

Kini

2009

Cell. Mol. Life Sci.

200

125

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Snake venom contains mixture of bioactive proteins and polypeptides. Most of these proteins and polypeptides exist as monomers, but some of them form complexes in the venom. These complexes exhibit much higher levels of pharmacological activity compared to individual components and play an important role in pathophysiological effects during envenomation. They are formed through covalent and/or non-covalent interactions. The subunits of the complexes are either identical (homodimers) or dissimilar (heterodimers; in some cases subunits belong to different families of proteins). The formation of complexes, at times, eliminates the non-specific binding and enhances the binding to the target molecule. On several occasions, it also leads to recognition of new targets as protein-protein interaction in complexes exposes the critical amino acid residues buried in the monomers. Here, we describe the structure and function of various protein complexes of snake venoms and their role in snake venom toxicity.

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Section: Introductionmentioning

confidence: 99%

Protein complexes in snake venom

Doley

Kini

2009

Cell. Mol. Life Sci.

200

125

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“…In general, it is accepted that both Ca 2+ -dependent phospholipid hydrolysis2223 and binding to membrane acceptors may participate in the presynaptic neurotoxicity induced by CTX242526. However, some studies have shown that the catalytic activity alone does not explain the neurotoxicity of CTX, indicating that other regions of CB must be involved in neurotoxicity, such as Tyr2227 and the C-terminal region28.…”

mentioning

confidence: 99%

Biophysical studies suggest a new structural arrangement of crotoxin and provide insights into its toxic mechanism

Fernandes

Pazin²,

Dreyer

et al. 2017

Sci Rep

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Crotoxin (CTX) is the main neurotoxin found in Crotalus durissus rattlesnake venoms being composed by a nontoxic and non-enzymatic component (CA) and a toxic phospholipase A2 (CB). Previous crystallographic structures of CTX and CB provided relevant insights: (i) CTX structure showed a 1:1 molecular ratio between CA and CB, presenting three tryptophan residues in the CA/CB interface and one exposed to solvent; (ii) CB structure displayed a tetrameric conformation. This study aims to provide further information on the CTX mechanism of action by several biophysical methods. Our data show that isolated CB can in fact form tetramers in solution; however, these tetramers can be dissociated by CA titration. Furthermore, CTX exhibits a strong reduction in fluorescence intensity and lifetime compared with isolated CA and CB, suggesting that all tryptophan residues in CTX may be hidden by the CA/CB interface. By companying spectroscopy fluorescence and SAXS data, we obtained a new structural model for the CTX heterodimer in which all tryptophans are located in the interface, and the N-terminal region of CB is largely exposed to the solvent. Based on this model, we propose a toxic mechanism of action for CTX, involving the interaction of N-terminal region of CB with the target before CA dissociation.

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“…The mechanism of action of taipoxin has been studied mainly at the NMJ, where it causes depletion of transmitter and SVs from motor nerve terminals (Su and Chang, 1984;Cull-Candy et al, 1976;Harris et al, 2000). NMJ are not well suited for biochemical and molecular investigations; recently, however, taipoxin was shown to be active on cultured neurons isolated from various regions of the central nervous system, where it induces release of neurotransmitter with the formation of bulges along the axon (Rigoni et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Tpx induces blockade of neurotransmitter release, which eventually results in the death of the poisoned animal by respiratory failure. However, under certain experimental conditions, the development of neurotransmission failure at NMJs is preceded by a phase of facilitation of release, raising the possibility that blockade occurs because of depletion of the store of SVs (Su and Chang, 1984). Indeed, electron microscopic pictures taken at late stages of intoxication show the presence of swollen and enlarged axon terminals virtually devoid of SVs (Cull-Candy et al, 1976;Harris et al, 2000).…”

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confidence: 99%

Taipoxin Induces Synaptic Vesicle Exocytosis and Disrupts the Interaction of Synaptophysin I with VAMP2

et al. 2005

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The application of the snake neurotoxin taipoxin to hippocampal neurons in culture induced Ca 2ϩ -dependent synaptic vesicle (SV) exocytosis, with swelling of nerve terminals and redistribution of SV proteins to the axolemma. Using digital imaging videomicroscopy to measure fluorescence resonance energy transfer in live neurons, we also found that taipoxin modulates the machinery for neurosecretion by causing dissociation of the SV proteins synaptobrevin 2 and synaptophysin I at a stage preceding taipoxin-induced facilitation of SV fusion. These early effects of the toxin are followed by severe impairment of SV exo-endocytosis, which might underlie the prevention of neurotransmitter release reported after intoxication by taipoxin.

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Presynaptic effects of snake venom toxins which have phospholipase A2 activity (β-bungarotoxin, taipoxin, crotoxin)

Cited by 67 publications

References 20 publications

Protein complexes in snake venom

Protein complexes in snake venom

Biophysical studies suggest a new structural arrangement of crotoxin and provide insights into its toxic mechanism

Taipoxin Induces Synaptic Vesicle Exocytosis and Disrupts the Interaction of Synaptophysin I with VAMP2

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