Myotoxin II, a snake venom Lys49 phospholipase A2 homolog, induces activation of the ryanodine receptor in artificial bilayers
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| Auteurs: | , , , , , , |
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| Formaat: | artículo original |
| Publicatiedatum: | 2025 |
| Omschrijving: | Envenomation by viperid snakes causes acute muscle tissue injury (myonecrosis). An important group of myotoxic components comprises catalytically-inactive Lys49 phospholipase A2 homologs, which disrupt the integrity of the plasma membrane of skeletal muscle fibers through a mechanism that does not involve phospholipid hydrolysis. However, it remains unknown whether other mechanisms are involved in the cytotoxic action of these myotoxins. In this work, isolated calcium release channels (ryanodine receptor, RyR1) incorporated into an artificial lipid bilayer were used to study the action of the Lys49 phospholipase A2 homolog myotoxin II (Mt-II) from the venom of Bothrops asper. Mt-II induced a dose-dependent activation of the RyR1. The open probability of the channel increased with the dose of the toxin. The maximal conductance of the channel remained unchanged during the toxin treatment. Furthermore, the analysis of the open and closed states showed a slight toxin dependency of the latter. These findings suggest that, in addition to the calcium influx from the extracellular space through the disrupted plasma membrane, Ca2+ release from the internal stores may also occur. However, incubation of C2C12 myotubes in culture with the RyR1 antagonist dantrolene did not reduce the extent of cytotoxicity induced by Mt-II, suggesting that the RyR1-mediated increase in cytosolic Ca2+ does not contribute to the overall myotoxicity of this toxin. |
| Land: | Kérwá |
| Instelling: | Universidad de Costa Rica |
| Repositorio: | Kérwá |
| Taal: | Inglés |
| OAI Identifier: | oai:kerwa.ucr.ac.cr:10669/104084 |
| Online toegang: | https://www.sciencedirect.com/science/article/pii/S0041010125003654 https://hdl.handle.net/10669/104084 https://doi.org/10.1016/j.toxicon.2025.108590 |
| Keyword: | Myotoxin Bothrops asper Ryanodine membrane bilayer Phospholipase A2 Lysine-49 |