Cytotoxic activities of [Ser⁴⁹]phospholipase A₂ from the venom of the saw-scaled vipers Echis ocellatus, Echis pyramidum leakeyi, Echis carinatus sochureki, and Echis coloratus.

Abstract

Fractionation by reversed-phase HPLC of venom from four species of saw-scaled viper: Echis ocellatus, Echis pyramidum leakeyi, Echis carinatus sochureki, and Echis coloratus led to identification in each sample of an abundant protein with cytotoxic activity against human non-small cell lung adenocarcinoma A549 cells. The active component in each case was identified by MALDI-TOF mass fingerprinting of tryptic digests as [Ser⁴⁹]phospholipase A₂ ([Ser⁴⁹]PLA₂). An isoform of [Ser⁴⁹]PLA₂ containing the single Ala¹⁸→ Val substitution and a partially characterized [Asp⁴⁹]PLA₂ were also present in the E. coloratus venom. LC₅₀ values against A549 cells for the purified [Ser⁴⁹]PLA₂ proteins from the four species are in the range 2.9-8.5 μM. This range is not significantly different from the range of LC₅₀ values against human umbilical vein endothelial HUVEC cells (2.5-12.2 μM) indicating that the [Ser⁴⁹]PLA₂ proteins show no differential anti-tumor activity. The LC₅₀ value for [Ser⁴⁹]PLA₂ from E. ocellatus against human erythrocytes is >100 μM and the MIC values against Escherichia coli and Staphylococcus aureus are >100 μM. It is suggested that the [Ser⁴⁹]PLA₂ proteins play a major role in producing local tissue necrosis and hemorrhage at the site of envenomation.

• Authors: J Michael Conlon, Samir Attoub, Hama Arafat, Milena Mechkarska, Nicholas R Casewell, Robert A Harrison, Juan J Calvete
• Journal: Toxicon : official journal of the International Society on Toxinology (Toxicon) Vol. 71 Pg. 96-104 (Sep 2013) ISSN: 1879-3150 [Electronic] England
• PMID: 23747272 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Antineoplastic Agents
• Viper Venoms
• Phospholipases A2

Topics

• Amino Acid Sequence
• Animals
• Anti-Bacterial Agents (pharmacology)
• Antineoplastic Agents (pharmacology)
• Chromatography, High Pressure Liquid
• Erythrocytes (drug effects, metabolism)
• Escherichia coli (drug effects, growth & development)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Inhibitory Concentration 50
• Molecular Sequence Data
• Phospholipases A2 (isolation & purification, pharmacology)
• Snake Bites (pathology)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Staphylococcus aureus (drug effects, growth & development)
• Viper Venoms (pharmacology)
• Viperidae (classification)