Neurotoxic, myotoxic and cytolytic activities of the new basic PLA 2 isoforms BmjeTX-I and BmjeTX-II isolated from the Bothrops marajoensis (marajó lancehead) snake venom

L. A. Ponce-Soto, D. Martins-De-souza, S. Marangoni

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The BmjeTX-I and BmjeTX-II isoforms of PLA2 were purified from Bothrops marajoensis venom by ion-exchange chromatography and reverse phase HPLC. Both isoforms showed a molecular mass of 13808.89 Da (BmjeTX-I) and 13863.97 Da (BmjeTX-II) determined by based on the determined primary structures and SDS-PAGE and confirmed experimentally by MALDI-TOF mass spectrometry. Multiple alignment of BmjeTX-I and BmjeTX-II isoforms of PLA2 show high degree of homology with basic PLA2 myotoxins from other Bothrops venoms. Ex vivo, both isoforms caused a blockade of the neuromuscular transmission in young chick biventer cer-vicis preparations in a similar way to other Bothrops species. In chick preparations, contractures to exogenous acetylcholine (55 and 110 μM) or KCl (13.4 mM) were unaltered after complete blockade for the both isoforms BmjeTX-I and BmjeTX-II of PLA2. These results, which strongly suggested a presynaptic mechanism of action for these toxins. In mice, both isoforms induced myonecrosis and a systemic interleukin-6 response upon intramuscular injection. Both isoforms BmjeTX-I and BmjeTX-II of PLA2 also induced moderate marked paw edema, evidencing the local increase in vascular permeability. Since both isoforms of PLA2 exert a strong proinflammatory effect, the enzymatic hydrolysis of phospholipids might be relevant for this phenomenon and produced cytotoxicity in murine skeletal muscle C2C12 myoblasts and myotubes.

Original languageEnglish
Pages (from-to)103-113
Number of pages11
JournalProtein Journal
Volume29
Issue number2
DOIs
StatePublished - Feb 2010
Externally publishedYes

Keywords

  • Bothrops marajoensis
  • C2C12
  • Cytotoxitic
  • Isoforms
  • Myotoxin
  • Neurotoxin
  • Phospholipase a
  • Snake venom

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