cobrotoxin and Hemolysis

Cardiotoxins, neurotoxins and phospholipase A2 (PLA2) are three major classes of toxic components present in the Taiwan cobra, Naja naja atra of the Elapidae family. Cardiotoxins (or called cytotoxins), a group of major polypeptides of around 60 amino-acid residues present abundantly in the elapid family of snakes, comprise about 45-55% of the crude venom of Taiwan cobra. In contrast to another prominent group of structurally similar neurotoxins with well-established acetylcholine receptors and modes of action, cardiotoxins showed no defined cellular targets and very diverse pharmacological functions. A systematic structure/function comparison of these toxins was made by their relative inhibitory effects on protein kinase C (PKC) isolated from mouse brains. Lethality and hemolysis of various cardiotoxin isoforms were also compared in order to shed some insight on the biological targets and mechanisms of these surface-active amphiphilic polypeptides. A structure comparison of these cardiotoxins based on computer model-building revealed that some defined and subtle differences can be detected upon the superposition of these three-dimensional polypeptide chains, which may reflect the intrinsic differences in the hydrophobic peptide segments present on the surface loops of toxin molecules. The differences seem to correlate with different inhibitory activities exhibited by cardiotoxins in contrast to the lack of activity by cobrotoxin and PLA2 on PKC.

Topics: Animals; Cell Membrane; Cobra Neurotoxin Proteins; Cytotoxins; Erythrocytes; Guinea Pigs; Hemolysis; Lethal Dose 50; Mice; Models, Chemical; Phospholipases A; Phospholipases A2; Protein Conformation; Protein Kinase C; Snake Venoms

Snake venoms contain multimolecular forms of phospholipase A2 which are diverse with respect to their pharmacological properties. A neurotoxic PLA2 from Naja naja naja venom has been purified in two steps. (1) The whole venom was fractionated on CM-Sephadex C-25 column; 4.6% of the total PLA2 activity recovered was found in the NN-V fraction. (2) The NN-Vb-PLA2 fraction was purified to homogeneity by gel filtration of fraction NN-V on Sephadex G-50. It is a basic protein with a mol. wt between 10,500 and 11,000, and is more toxic than other basic PLA2s purified from Naja naja naja venom. The LD50 of NN-Vb-PLA2 is 0.27 mg/kg body wt. It induced neurotoxic symptoms in experimental mice and is devoid of myotoxic, anticoagulant and edema-inducing activities.

Topics: Animals; Chromatography, Gel; Chromatography, Ion Exchange; Cobra Neurotoxin Proteins; Elapid Venoms; Hemolysis; Humans; In Vitro Techniques; Lethal Dose 50; Mice; Molecular Weight; Phospholipases A; Phospholipases A2; Spectrometry, Fluorescence

Topics: Animals; Cobra Neurotoxin Proteins; Elapid Venoms; Hemolysis; Humans; Pancreas; Phospholipases; Phospholipases A; Swine