Neutralization of the cytolytic and myotoxic activities of phospholipases A2 from Bothrops asper snake venom by glycosaminoglycans of the heparin/heparan sulfate family.

作者: Bruno Lomonte , Andrej Tarkowski , Ulf Bagge , Lars Å. Hanson

DOI: 10.1016/0006-2952(94)90525-8

关键词: Phospholipase A2AntithrombinVenomSnake venomHeparinBiochemistryHeparan sulfatePhospholipase ABiologyMyotoxin

摘要: Basic phospholipases A2 from the venom of Bothrops asper exhibit skeletal muscle damaging activity in vivo, and cytolytic to a variety cell types culture. Glycosaminoglycans heparin/heparan sulfate family were found be potent blockers action vitro, and, as well, able neutralize purified myotoxins crude vivo. However, neutralizing effect heparins was more vitro than The myotoxin II (a lysine-49 phospholipase isoform) its inhibition by heparin characterized. did not depend on anticoagulant activity, since both standard with low affinity for antithrombin (LA-heparin) had similar efficiency. Heparan molecular mass (5 kDa) also neutralized II. In contrast, different heparin-derived disaccharides unable block cytolysis, implying requirement longer carbohydrate chain structure interaction protein. By chromatography gel diffusion, it demonstrated that form complex all isoforms basic myotoxins, held at least part electrostatic interactions. III, related aspartate-49 isoform same venom, unaffected heparins, despite fact myotoxic inhibited, indicating dissociation two actions.

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