Myotoxins from snake venoms

Myotoxins from snake venoms

Reports and Abstracts 1399 Myers, R. A., Cruz, L. J., Rivier, J. E. and Olivera, B. M. (1993) Chem. Rev. 93, 1923. Olivera, B. M., Rivier, J. E., Sc...

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Reports and Abstracts

1399

Myers, R. A., Cruz, L. J., Rivier, J. E. and Olivera, B. M. (1993) Chem. Rev. 93, 1923. Olivera, B. M., Rivier, J. E., Scott, J. K., Hillyard, D. R. and Cruz, L. J. (1991) J. biol. Chem. 266, 2067. Shon, K. J., Hasson, A., Spira, M. E., Cruz, L, J., Gray, W. R. and Olivera, B. M. (1994) Biochemistry 33, 11,420. Myotoxins from snake venoms. P. Gopalakrishnakone (Department of Anatomy, National University of Singapore, Kent Ridge, Singapore 0511).

The term 'myotoxin' is used by toxinologists to describe a toxin which causes deleterious effect/s on skeletal muscle as shown by biochemical, pharmacological or morphological evidence. The terms 'myonecrotic' and 'local tissue damage' also need redefining. Whether 'local myotoxic' is synonymous with 'myonecrotic', and 'myonecrosis' is always part of 'local tissue damage' needs some clarification. There are two types of toxins which cause muscle damage: crotoxin, taipoxin, notexin and mojave toxin produce muscle degeneration followed by regeneration when injected locally, whereas PLA 2 from Enhydrina schistosa and PLA2s from Australian elapids of the species Pseudechis produce systemic myotoxicity, characterized by myogtobinuria and generalized muscle damage. Muscle damage could be observed by light and electron microscopic methods. The changes include dilatation of sarcoplasmic reticulum, vacuolation, oedema within 4 hr of injection of toxin, followed by disruption and hypercontraction of the fibres with inflammatory changes by about 6 hr. The inflammatory reaction characterized by infiltration by phagocytic cells was maximally seen between 12 and 24hr. Evidence of regeneration starts by 36 hr and complete regeneration is seen by 7-10 days. The mechanism by which these toxins cause muscle damage is not fully understood. However, the disruption of sarcolemmal membrane, increase in influx of Ca 2+ into sarcoplasm, as well as Ca 2+ activated neutral proteases have a definitive role in this process. The possible mechanism(s) for muscle degeneration as well as structure-function activity of the PLA2 myotoxins in reference to enzymatic activity, neurotoxicity and myotoxicity will also be discussed. Structure-function studies o f sea anemone peptide toxins. G. S. Gendeh, 1 K. Jeyaseelan t and M. C. M. Chung 2 (i Department of Biochemistry, and 2Bioprocessing Technology Centre, National University of Singapore).

Sea anemones (phylum Cnidaria) have been reported to possess a number of interesting toxins. These include the membrane-active cytolysins and neurotoxins that interact with the sodium channel. The other toxins, which are mainly peptide in nature, however, have not been extensively characterized. This communication presents our preliminary results on the purification and identification of some of these peptides. The peptides were isolated from the water extract of a local sea anemone, Heteractis magnifica, using the following sequential steps: Sephadex G-50 gel filtration, cation-exchange chromatography (Mono S, FPLC system), and reverse-phase HPLC. These peptides were then subjected to partial N-terminal amino acid sequencing analyses, and identified through homology searches using various protein sequence databases. Using this approach, we have identified several isoforms of trypsin inhibitors and a potassium channel inhibitor. Morphological changes induced by an acidic phospholipase A 2from the venom of Ophiophagus hannah on cardiac muscle o f mice. M. Z. Huang and P. Gopalakrishnakone (Venom and Toxin Research Group, Department of Anatomy, Faculty of Medicine, National University of Singapore, Singapore).

An acidic phospholipase A: (PLA2) was isolated from the venom of Ophiophagus hannah (king cobra) by CM-Sephadex C-50 ion-exchange column chromatography and gel filtration on Sephadex G-50. The purified PLA: has a mol. wt of 13,000 and isoelectric point 5.7. It has been shown that the PLA2 can cause a cardiotoxic action on rat heart (Huang et al., 1991, 1993). Electron microscopic study confirmed that the PLA2 caused myodegeneration in the myocardium of mice in a dose-related manner. Morphological changes induced by the PLA2 were examined by light and electron microscopy following intravenous injection of the PLA 2 to mice. Light microscopic examination of cardiac muscle failed to show any significant changes. Electron microscopic analysis showed that the PLA 2 appears to disrupt the sarcolemma of cardiac muscle cells. Changes in the cardiac muscle included disorganized myofibrils, dissolution and degeneration of filaments, dilatation of the sarcoplasmic reticuhim and floccular degeneration of mitochondria. Huang, M. Z. et al. (1991) Acta Biochim. Biophys. Sinica 23, 70-77. Huang, M. Z. et al. (1993) Toxicon 31, 627-635. Molecular cloning o f genes encoding toxins in the venom ofNaja naja sputatrix. K. Jeyaseelan, l A. Armugam, 2 L. Earnest,' M. S. L. Yeo, t R. Lachumanan, t N. H. Tan,: P. Gopalakrishnakone 3 and C. H. Tan ~(Departments of ~Biochemistry and 3Anatomy, National University of Singapore, 10 Kent Ridge Crescent, Singapore 051 I; and tDepartment of Biochemistry, University of Malaya, 59100 Kuala Lumpur, Malaysia).

Snakebite is a public health problem in most tropical countries. Cobra envenomation causes significant mortality and morbidity, causing a variety of symptoms, the most important being potentially fatal neurotoxic and