Studies on the mechanism of action of myoloxins isolated from Bothrops snake venoms
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| Autores: | , |
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| Fecha de Publicación: | 1996 |
| תיאור: | Myotoxins isolated from Bothrops snake venoms are predominantly group II basic phospholipases A₂, including catalytically inactive Lys-49 variants, and represent quantitatively significant components in several Bothrops species. Intramuscular injection of these toxins induces a rapid and severe degenerative process in skeletal muscle, likely initiated at the plasma membrane level, ultimately resulting in selective myonecrosis. Although this in vivo specificity contrasts with their broad cytolytic effects on diverse cultured cell types, muscle damage, cytolysis, and liposome disruption occur even under conditions where phospholipase activity is inhibited, suggesting that enzymatic activity is not essential but may potentiate toxicity. Current evidence supports a mechanistic model in which myotoxins bind to biological membranes through a region distinct from the catalytic site, involving basic and hydrophobic residues near the C-terminus that mediate electrostatic interactions and membrane penetration. Additional acylation may further enhance membrane-disruptive effects. These early membrane alterations lead to destabilization and loss of ion-selective permeability—particularly to calcium—triggering the cascade of pathological changes characteristic of Bothrops myotoxic envenoming. |
| País: | Kérwá |
| מוסד: | Universidad de Costa Rica |
| Repositorio: | Kérwá |
| שפה: | Inglés |
| OAI Identifier: | oai:kerwa.ucr.ac.cr:10669/105007 |
| גישה מקוונת: | https://hdl.handle.net/10669/105007 https://doi.org/10.1016/0041-0101(96)80873-7 |
| מילת מפתח: | Bothrops myotoxins phospholipases A₂ Lys-49 variants membrane disruption skeletal muscle necrosis cytolysis toxin–membrane interaction calcium permeability venom-induced myopathy |