Cardiotoxins

A second group of myotoxic toxins, found almost exclusively in the venoms of cobras, are the cytotoxins (often called cobratoxins, cytolysins, cardiotoxins, or direct lytic factors). These, rather than phospholipases, are almost certainly the primary cause of muscle damage following bites by cobras. Their mechanism of action is not properly known, but it is certainly the case that their action is potentiated by the presence of phospholipases in the venom, even if the phospholipases concerned are not, themselves, myotoxic. The cytotoxins of cobra venom possess no hydrolytic activity of any kind. 

The similarity of the primary structure of different sea snake venoms has already been discussed. Postsynaptic neurotoxins from Elapidae venom have been extensively studied. Elapidae include well-known snakes such as cobra, krait, mambas, coral snakes, and all Australian snakes. Like sea snake toxins, Elapidae toxins can also be grouped into short-chain (Type I) and long-chain (Type II) toxins. Moreover, two types of neurotoxins are also similar to cardiotoxins, especially in the positions of disulfide bonds. However, amino acid sequences between cardiotoxins and sea snake and Elapidae neurotoxins are quite different. In comparing the sequence of sea snake and Elapidae neurotoxins, there is a considerable conservation in amino acid sequence, but the difference is greater than among the various sea snake toxins. 

Cardiotoxin from Naja naja atra Venom C16-A024... 

Since predators of snakes (and humans) have to deal with snake venoms as defenses, they are included here, even though they serve in predation. Snake venoms are primarily enzymes (proteins), especially of the phospholipase A2 type, which breaks down cell membrane phospholipids hydrolytically. Other snake venoms such as cobrotoxin contain peptides with 60-70 amino acid residues. Pharmacologically, they have neurotoxic, cytotoxic, anticoagulant, and other effects. The neurotoxins, in turn, can have pre- or postsynaptic effects. Snake venoms with both neurotoxic and hemolytic effects on the heart are known as cardiotoxins. Cytotoxins attach to the cells of blood vessels and cause hemorrhage. Snake venom factors may stimulate or inhibit blood clotting. Finally, platelet-active factors can contribute to hemorrhage. 

Dendrobatidae Phyllobates aurotaenia Cardiotoxin Neuro toxin Batrachotoxin Homobatrachotoxin... 

In vitro studies elsewhere have shown the presence of a substance in the bark which antagonizes the cardiotoxin present in cobra venom (20). This fraction did not contain alkaloids, however. 

In short, the risks for HF are hypertension, atherosclerotic disease, diabetes mellitus, obesity, metabolic syndrome, use of cardiotoxins and a positive family history of cardiomyopathy. 

Two recent publications provide new and provocative input to this dialogue. One of these involved a series of appearances of a reddish substance on the East Coast called Chinese Love Stone, Black Stone, Rock Hard or Stud 100, being sold as aphrodisiacs. They were to be moistened and rubbed on the genitals, but as might be expected, quite a few were eaten and eventually smoked. They contained steroidal toxins, and were possibly related to some frog origins, but they were claimed to be bufotenine and indeed contained bufotenine in addition to several cardiotoxins as well as 5-MeO-DMT. 

Various types of proteins have been purified using hydrophobic interaction chromatography including alkaline phophatase, estrogen receptors, isolectins, strepavidin, calmodulin, epoxide hydrolase, proteoglycans, hemoglobins, and snake venom toxins (46). In the case of cobra venom toxins, the order of elution of the six cardiotoxins supports the hypothesis that the mechanism of action is related to hydrophobic interactions with the phospholipids in the membrane. 

Rodgers et al. (1984) demonstrated that PbTx-2 was also a powerful cardiotoxin. These toxicological studies highhght the need for the implementation of a regnlar and reliable monitoring program in regions affected by BTX. 

The effect of toxins such as melittin (from the honey-bee venom), myotoxin a, and cardiotoxin (from the snake venom) was investigated by vibrational spectroscopy (Pezolet et al., 1982 Faucon et ah, 1983 Liddle and Tu, 1985 Lafleur et ah, 1987). Monitoring the Raman intensity ratio I(1060)/I(1080) indicated that the lipid/melittin assemblies in DPPC are characterized by a high conformational order, little intermolecular chain-chain interaction, and a low cooperativity of the gel-like liquid crystalline phase transition. The effect of ricin, a toxic lectin, on DPPC and DPPC-cerebroside mixtures was studied by Raman and IR spectroscopy. It was suggested that ricin mainly interacts with the interfacial domains of the bilayers (Picquart et ah, 1989). 

Dodecyl phosphocholine micelles in solution are useful and well characterized as a model membrane system for solution NMR studies. To access the membrane-induced conformation and orientation of cardiotoxins, the interaction of the p-type cardiotoxin II from Naja oxiana snake venom with perdeuterated dodecyl phosphocholine was studied by H NMR spectroscopy and diffusion measurements.247 2D NMR is an efficient tool and has been widely used to study the interaction of dodecyl phosphocholine with peptides and protein.248-250 2D... 

Ab array Cardiotoxin cytokine Mouse skeletal muscle DNA array/proteomics T of osteopontin, C10/CCL6 with muscle injury... 

Hirata A, Masuda S, Tamura T, Kai K, Ojima K, Fukase A, Motoyoshi K, Kamakura K, Miyagoe-Suzuki Y, Takeda S. Expression profiling of cytokines and related genes in regenerating skeletal muscle after cardiotoxin injection A role for osteopontin. Am J Pathol 2003 163(1) 203—15. 

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