A Lys49 phospholipase A(2) homologue from Bothrops asper snake venom induces proliferation, apoptosis and necrosis in a lymphoblastoid cell line

Toxicon. 2005 Apr;45(5):651-60. doi: 10.1016/j.toxicon.2005.01.008.

Abstract

Lys49 phospholipase A(2) homologues are abundant in viperid snake venoms. These proteins have substitutions at the calcium-binding loop and catalytic center which render them enzymatically inactive; however, they display a series of toxic activities, particularly cytotoxicity upon various cell lines in vitro. In this study we explored whether myotoxin II (MT-II), a Lys49 phospholipase A(2) homologue from the venom of the snake Bothrops asper, is capable of inducing various effects in a single cell type, using the lymphoblastoid B cell line CRL-8062 as a model. Cells were incubated with varying concentrations of MT-II for 24 and 48 h, time intervals that are more prolonged than the usual incubation times previously used in the characterization of this toxin. Results indicate that MT-II induces proliferation at low concentrations (0.5-5.0 microg/mL). Apoptosis was predominant at higher toxin levels (5-25 microg/mL), whereas necrosis, associated with overt plasma membrane disruption, occurred at concentrations > or =25 microg/mL, and was the predominant effect at higher MT-II concentrations (50 microg/mL). It is concluded that a single phospholipase A(2) homologue can induce markedly different effects on a single cell line, depending on the concentration used, an observation that may have implications for the action of this type of venom component in vivo.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Apoptosis / drug effects*
  • Bothrops*
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Crotalid Venoms / enzymology*
  • Crotalid Venoms / toxicity
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Group II Phospholipases A2
  • In Situ Nick-End Labeling
  • L-Lactate Dehydrogenase
  • Microscopy, Electron, Transmission
  • Necrosis / chemically induced
  • Neurotoxins / toxicity*
  • Phospholipases A / toxicity*
  • Reptilian Proteins
  • Time Factors

Substances

  • Crotalid Venoms
  • Neurotoxins
  • Reptilian Proteins
  • L-Lactate Dehydrogenase
  • Phospholipases A
  • Group II Phospholipases A2
  • myotoxin II, Bothrops asper