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dc.creatorFernández Ulate, Julián
dc.creatorCaccin, Paola
dc.creatorKoster, Grielof
dc.creatorLomonte, Bruno
dc.creatorGutiérrez, José María
dc.creatorMontecucco, Cesare
dc.creatorPostle, Anthony D.
dc.date.accessioned2017-06-12T14:58:52Z
dc.date.available2017-06-12T14:58:52Z
dc.date.issued2013-07-12
dc.identifier.citationhttp://onlinelibrary.wiley.com/doi/10.1111/febs.12386/abstractes_ES
dc.identifier.issn1742-4658
dc.identifier.urihttp://hdl.handle.net/10669/30088
dc.description.abstractBothrops snakes are the major cause of ophidian envenomings in Latin America. Their venom contains myotoxins that cause prominent muscle damage, which may lead to permanent disability. These toxins include myotoxins Mt-I and Mt-II, which share the phospholipase A2 (PLA2) fold, but Mt-II lacks enzymatic activity because the essential active site Asp49 is replaced by Lys. Both myotoxins cause sarcolemma alterations, with Ca2+ entry and loss of ATP and K+ from muscle cells, but the molecular lesions at the basis of their cellular action are not known, particularly the role of phospholipid hydrolysis. Here we tested their PLA2 activity in vivo, and evaluated the hypothesis that Ca2+-activated endogenous PLA2s may be involved in the action of Mt-II. The time course of phospholipid hydrolysis by Mt-I and Mt-II in myotubes in culture and in tibialis anterior mouse muscles was determined. Mt-I rapidly hydrolyzed phosphatidylcholine and phosphatidylethanolamine but not phosphatidylserine, but no phospho-lipids were hydrolyzed in the presence of Mt-II. Whole Bothrops asper venom induced a higher extent of phospholipid hydrolysis than Mt-I alone. These results demonstrate in vivo PLA2 activity of Mt-I for the first time, and indicate that it acts only on the external monolayer of the sarcolemma. They also exclude activation of endogenous PLA2s in the action of Mt-II, implying that plasma membrane disruption by this toxin does not depend on phospholipid hydrolysis. Therefore, both Bothrops myotoxins induce Ca2+ entry and release of ATP and cause myonecrosis, but through different biochemical mechanisms.es_ES
dc.description.sponsorshipUniversità di Padova Progetto Strategico///Italiaes_ES
dc.description.sponsorshipFondazione Cassa di Risparmio di Padova e Rovigo///Italiaes_ES
dc.description.sponsorshipInternational Centre for Genetic Engineering and Biotechnology/[Collaborative Research Programme Program COS-08-03]/ICGEB/Italiaes_ES
dc.language.isoen_USes_ES
dc.sourceThe FEBS Journal; Volumen 280, Número 16. 2013es_ES
dc.subjectFatty acidses_ES
dc.subjectLysophospholipidses_ES
dc.subjectPLA2 activityes_ES
dc.subjectSnake myotoxinses_ES
dc.subjectToxicityes_ES
dc.titleMuscle phospholipid hydrolysis by Bothrops asper Asp49 and Lys49 phospholipase A2 myotoxins – distinct mechanisms of actiones_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.typeArtículo científicoes_ES
dc.identifier.doi10.1111/febs.12386
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)es_ES
dc.identifier.pmid23763831


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