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A Lys49-PLA2 myotoxin of Bothrops asper triggers a rapid death of macrophages that involves autocrine purinergic receptor signaling

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Date
2012-07-05
Author
Tonello, Fiorella
Simonato, M.
Aita, A.
Pizzo, Paola
Fernández Ulate, Julián
Lomonte, Bruno
Gutiérrez, José María
Montecucco, Cesare
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Abstract
Lys49-PLA2 myotoxins, an important component of various viperid snake venoms, are a class of PLA2-homolog proteins deprived of catalytic activity. Similar to enzymatically active PLA2 (Asp49) and to other classes of myotoxins, they cause severe myonecrosis. Moreover, these toxins are used as tools to study skeletal muscle repair and regeneration, a process that can be very limited after snakebites. In this work, the cytotoxic effect of different myotoxins, Bothrops asper Lys49 and Asp49-PLA2, Notechis scutatus notexin and Naja mossambica cardiotoxin, was evaluated on macrophages, cells that have a key role in muscle regeneration. Only the Lys49-myotoxin was found to trigger a rapid asynchronous death of mouse peritoneal macrophages and macrophagic cell lines through a process that involves ATP release, ATP-induced ATP release and that is inhibited by various purinergic receptor antagonists. ATP leakage is induced also at sublytical doses of the Lys49-myotoxin, it involves Ca2þ release from intracellular stores, and is reduced by inhibitors of VSOR and the maxi-anion channel. The toxin-induced cell death is different from that caused by high concentration of ATP and appears to be linked to localized purinergic signaling. Based on present findings, a mechanism of cell death is proposed that can be extended to other cytolytic proteins and peptides.
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http://hdl.handle.net/10669/688
External link to the item
10.1038/cddis.2012.68
http://www.nature.com/cddis/journal/v3/n7/full/cddis201268a.html
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406575/pdf/cddis201268a.pdf
Cell Death and Disease (2012) 3, e343; doi:10.1038/cddis.2012.68
 
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  • Repositorios universitarios

  • Repositorio del SIBDI-UCR
  • Biblioteca Digital del CIICLA
  • Repositorio Documental Rafael Obregón Loría (CIHAC)
  • Biblioteca Digital Carlos Melendez (CIHAC)
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  • Colección de videos de UPA-VAS
  • Sitios recomendados

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  • Scientific Electronic Library Online (SciELO)
  • Directory of Open Access Journals (DOAJ)
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Repositorio Institucional de la Universidad de Costa Rica. Algunos derechos reservados. Este repositorio funciona con DSpace.
Universidad de Costa Rica