Raventoxins are

neurotoxin Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and matur ...

s from the venom of the spider '' Macrothele raveni''.

Sources

Raventoxins are toxins from the venom of the spider ''Macrothele raveni''. This is a hairy spider, a member of the genus '' Macrothele'', that can be found in the hilly areas of Ningming County, Guangxi Province in China.

Chemistry

Six different types of raventoxin have been described, named raventoxin-I to VI.Zeng, Xiong-zhi, Liang, Song-ping Purification and Preliminary Toxic Research of Raventoxin-II, a Neurotoxic Peptide from the Venom of the Spider Macrothele raveni . Life Science Research. 2001 september; 5(3): 217-220.Zeng Xiong-zhi, Liang Song-ping. Purification and Preliminary Active Characterization of Raventoxin-V, a Novel Insecticidal Toxin Isolated from the Spider Macrothele Rraveni. Journal of Huaihua University. 2007-04Zhang Peng fei, Chen Ping, Xiao Shun yong, Liang Song ping.Purification, Characterization of Raventoxin-VI from the Venom of the Spider Macrothele raveni Life Science Research;2003-02 Raventoxin-I consists of 43 amino acid residues. It has a

molecular mass The molecular mass (''m'') is the mass of a given molecule: it is measured in daltons (Da or u). Different molecules of the same compound may have different molecular masses because they contain different isotopes of an element. The related quant ...

of 4840.11 Da. The toxin is partially homologous to δ-AcTx-Hv1a and δ-AcTx-Ar1, two toxins derived from '' Hadronyche versuta'' and '' Atrax robustus'', respectively. Raventoxin-II has a molecular weight of 3021.56 Da. Raventoxin-III is a basic polypeptide, consisting of 29 amino acid residues. It has a molecular mass of 3286.58 Da. Raventoxin-V has a molecular weight of 3133.48 Da. Raventoxin-VI consists of 51 amino acid residues, and has a molecular weight of 5371.6 Da.

Target and mode of action

All described raventoxins have shown to exert a neurotoxic effect. At low concentration, raventoxin-I enhances muscle contraction, suggesting a direct action of the toxin on muscle, whereas at higher concentration it blocks neuromuscular transmission. No toxins have shown to act similarly. The primary structure of raventoxin-III is identical to that of Magi 5 (β-hexatoxin-Mg1a), a toxin found in the venom of the spider ''Macrothele gigas''. Magi 5 binds at site 4 of the alpha subunit of the mammalian voltage-gated sodium channel Nav1.2 (SCN2A). Binding of Magi 5 to the sodium channels shifts both activation and inactivation to more hyperpolarized voltages and slows the recovery from inactivation. Combined, these effects may lead to increased inactivation of the sodium channels at rest, leading to inhibition and blockage of neuromuscular transmission. The blockage is most probably reversible. Magi-5 competes with the scorpion beta-toxin Css IV for binding to the sodium channel at neurotoxin receptor site 4. One other known property of Magi-5 is its binding to site 3 of the insect sodium channel, observed in lepidopteran larvae, which raises the possibility of homology between the molecular structures of the binding site 3 (in insects) and 4 (in mammals). Raventoxin-VI blocks neuromuscular transmission in a rat phrenic nerve preparation. Intracerebroventricular injection of the toxin leads to paralysis in rat.

Toxicity

Raventoxin-I and raventoxin-III have both shown excitation, spastic paralysis, gasping, a fast heartbeat and

exophthalmos Exophthalmos (also called exophthalmus, exophthalmia, proptosis, or exorbitism) is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral (as is often seen in Graves' disease) or unilateral (as is often seen in ...

in mice. Only raventoxin-I also shows an increase in salivation. Both toxins can cause death in mice, when sufficiently administered. The

LD50 In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a toxin, radiation, or pathogen. The value of LD50 for a substance is the ...

of raventoxin-I is 0.772 mg/kg when intra-abdominally injected in mice. Raventoxin-I and raventoxin-III are not toxic for cockroaches., but administration of Magi-5 (raventoxin-III) in lepidopteran larvae results in temporary paralysis of the insects. Raventoxin-II and raventoxin-V also have insecticidal effects.

Therapeutic use

The effect of administering the whole venom of the Macrothele raveni spider has been studied in several diseases, especially in carcinomata. In HeLa cells, it showed

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dig ...

, direct

lysis Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular bio ...

and apoptosis. The antitumor effect of the venom is also shown in a human breast carcinoma cell line, MCF-7, where cytotoxic changes, apoptosis and necrosis where caused by the venom. After administration of the venom in affected mice, the tumor size significantly decreased compared to the tumor size in control mice.

References

{{reflist Ion channel toxins Neurotoxins Protein toxins Spider toxins