title: A Lys49 phospholipase A(2) homologue from Bothrops asper snake venom induces proliferation, apoptosis and necrosis in a lymphoblastoid cell line.
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.
authors.affiliation: Departamento de Microbiología e Inmunología, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Mora
authors.forename: Berta
authors.initials: B
authors.lastname: Valverde
authors.forename: Cecilia
authors.initials: C
authors.lastname: Díaz
authors.forename: Bruno
authors.initials: B
authors.lastname: Lomonte
authors.forename: José María
authors.initials: JM
authors.lastname: Gutiérrez
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D017837:Bothrops; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003435:Crotalid Venoms / Q000201:enzymology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D054501:Group II Phospholipases A2; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase; D046529:Microscopy, Electron, Transmission; D009336:Necrosis / Q000139:chemically induced; D009498:Neurotoxins / Q000633:toxicity*; D010741:Phospholipases A / Q000633:toxicity*; D030162:Reptilian Proteins; D013997:Time Factors
chemical_list: D003435:Crotalid Venoms; D009498:Neurotoxins; D030162:Reptilian Proteins; D007770:L-Lactate Dehydrogenase; D010741:Phospholipases A; D054501:Group II Phospholipases A2; C061056:myotoxin II, Bothrops asper