Raventoxin

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Raventoxins are neurotoxins from the venom of the spider Macrothele raveni .

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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. [1]

Chemistry

Six different types of raventoxin have been described, named raventoxin-I to VI. [1] [2] [3] [4] Raventoxin-I consists of 43 amino acid residues. It has a molecular mass 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. [1] Raventoxin-II has a molecular weight of 3021.56 Da. [2] 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. [1] Raventoxin-VI consists of 51 amino acid residues, and has a molecular weight of 5371.6 Da. [4]

Target and mode of action

All described raventoxins have shown to exert a neurotoxic effect. [1] [2] [3] [4] 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. [1]

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. [5] 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. [5] 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. [1] Magi-5 competes with the scorpion beta-toxin Css IV for binding to the sodium channel at neurotoxin receptor site 4. [5] 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). [6]

Raventoxin-VI blocks neuromuscular transmission in a rat phrenic nerve preparation. Intracerebroventricular injection of the toxin leads to paralysis in rat. [4]

Toxicity

Raventoxin-I and raventoxin-III have both shown excitation, spastic paralysis, gasping, a fast heartbeat and exophthalmos in mice. Only raventoxin-I also shows an increase in salivation. Both toxins can cause death in mice, when sufficiently administered. The LD50 of raventoxin-I is 0.772 mg/kg when intra-abdominally injected in mice. [1] Raventoxin-I and raventoxin-III are not toxic for cockroaches., [1] but administration of Magi-5 (raventoxin-III) in lepidopteran larvae results in temporary paralysis of the insects. [6] Raventoxin-II and raventoxin-V also have insecticidal effects. [2] [3]

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, direct lysis and apoptosis. [7] 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. [8]

Related Research Articles

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α-Bungarotoxin Chemical compound

α-Bungarotoxin is one of the bungarotoxins, components of the venom of the elapid Taiwanese banded krait snake. It is a type of α-neurotoxin, a neurotoxic protein that is known to bind competitively and in a relatively irreversible manner to the nicotinic acetylcholine receptor found at the neuromuscular junction, causing paralysis, respiratory failure, and death in the victim. It has also been shown to play an antagonistic role in the binding of the α7 nicotinic acetylcholine receptor in the brain, and as such has numerous applications in neuroscience research.

<span class="mw-page-title-main">Calciseptine</span> Neurotoxin

Calciseptine (CaS) is a natural neurotoxin isolated from the black mamba Dendroaspis p. polylepis venom. This toxin consists of 60 amino acids with four disulfide bonds. Calciseptine specifically blocks L-type calcium channels, but not other voltage-dependent Ca2+ channels such as N-type and T-type channels.

<span class="mw-page-title-main">Agatoxin</span> Class of toxins

Agatoxins are a class of chemically diverse polyamine and peptide toxins which are isolated from the venom of various spiders. Their mechanism of action includes blockade of glutamate-gated ion channels, voltage-gated sodium channels, or voltage-dependent calcium channels. Agatoxin is named after the funnel web spider which produces a venom containing several agatoxins. There are different agatoxins. The ω-agatoxins are approximately 100 amino acids in length and are antagonists of voltage-sensitive calcium channels and also block the release of neurotransmitters. For instance, the ω-agatoxin 1A is a selective blocker and will block L-type calcium channels whereas the ω-agatoxin 4B will inhibit voltage sensitive P-type calcium channels. The μ-agatoxins only act on insect voltage-gated sodium channels.

Stromatoxin is a spider toxin that blocks certain delayed-rectifier and A-type voltage-gated potassium channels.

<span class="mw-page-title-main">Spider toxin</span> Family of toxins produced by spiders

Spider toxins are a family of proteins produced by spiders which function as neurotoxins. The mechanism of many spider toxins is through blockage of calcium channels.

Pompilidotoxins (PMTXs) are toxic substances that can only be found in the venom of several solitary wasps. This kind of wasp uses their venom to offensively capture prey and is relatively harmless to humans. This is in stark contrast to social insects that defend themselves and their colonies with their venom.

Birtoxin is a neurotoxin from the venom of the South African Spitting scorpion. By changing sodium channel activation, the toxin promotes spontaneous and repetitive firing much like pyrethroid insecticides do

Bestoxin is a neurotoxin from the venom of the South African spitting scorpion Parabuthus transvaalicus. Most likely, it targets sodium channel function, thus promoting spontaneous and repetitive neuronal firing. Following injection into mice, it causes non-lethal writhing behaviour.

Ikitoxin is a neurotoxin from the venom of the South African Spitting scorpion that targets voltage-sensitive sodium channels. It causes unprovoked jumps in mice following intracerebroventricular injections.

Hainantoxins (HNTX) are neurotoxins from the venom of the Chinese bird spider Haplopelma hainanum. Hainantoxins specifically inhibit tetrodotoxin-sensitive Voltage-gated sodium channels, thereby causing blockage of neuromuscular transmission and paralysis. Currently, 13 different hainantoxins are known, but only HNTX-I, -II, -III, -IV and -V have been investigated in detail.

Huwentoxins (HWTX) are a group of neurotoxic peptides found in the venom of the Chinese bird spider Haplopelma schmidti. The species was formerly known as Haplopelma huwenum, Ornithoctonus huwena and Selenocosmia huwena. While structural similarity can be found among several of these toxins, HWTX as a group possess high functional diversity.

Covalitoxin-II is a peptide toxin that is produced by the spider Coremiocnemis validus. It can induce excitatory, non-lethal behavioral symptoms like quivering and jerking in crickets.

Oxotoxins, or oxytoxins, are a group of neurotoxins present in the venom of lynx spiders belonging to the genus Oxyopes, hence the name oxytoxin. They are disulfide-rich peptides. Only two types are so far reported from two different species, the larger oxytoxin 1 (OxyTx1) from Oxyopes kitabensis, and the smaller oxytoxin 2 (OxyTx2) from Oxyopes lineatus. OxyTx1, the first known oxytoxin, was discovered in 2002. It was found to enhance the lethal efficacy of the spider venom by acting together with oxyopinins. It is composed of 69 amino acid residue, which are cross-linked by five disulfide bridges. It is a large peptide having a molecular mass of 8059.2 Da; but shows the size of 9,109.4 Da due to the presence of disulfide bridges. It is a potent insecticide, but non-toxic to mice up to 1 μg/20-g mouse. It acts synergistically with oxyopinins of the same venom to increase the insecticidal effect.

BotIT2 is a neurotoxin from the scorpion Buthus occitanus tunetanus, which modifies activation and slows down the deactivation of voltage gated sodium channels.

ATX-II, also known as neurotoxin 2, Av2, Anemonia viridis toxin 2 or δ-AITX-Avd1c, is a neurotoxin derived from the venom of the sea anemone Anemonia sulcata. ATX-II slows down the inactivation of different voltage-gated sodium channels, including Nav1.1 and Nav1.2, thus prolonging action potentials.

<span class="mw-page-title-main">GiTx1</span>

GiTx1 (β/κ-theraphotoxin-Gi1a) is a peptide toxin present in the venom of Grammostola iheringi. It reduces both inward and outward currents by blocking voltage-gated sodium and potassium channels, respectively.

Protoxin-I, also known as ProTx-I, or Beta/omega-theraphotoxin-Tp1a, is a 35-amino-acid peptide neurotoxin extracted from the venom of the tarantula Thrixopelma pruriens. Protoxin-I belongs to the inhibitory cystine knot (ICK) family of peptide toxins, which have been known to potently inhibit voltage-gated ion channels. Protoxin-I selectively blocks low voltage threshold T-type calcium channels, voltage gated sodium channels and the nociceptor cation channel TRPA1. Due to its unique ability to bind to TRPA1, Protoxin-I has been implicated as a valuable pharmacological reagent with potential applications in clinical contexts with regards to pain and inflammation

<span class="mw-page-title-main">Notexin</span>

Notexin is a toxin produced by the tiger snake (Notechis scutatus). It is a myotoxic and presynaptic, neurotoxic phospholipase A2 (PLA2s). These are enzymes that hydrolyze the bond between a fatty acid tail and glycerol in fatty acids on the 2-position.

References

  1. 1 2 3 4 5 6 7 8 9 Zeng XZ (2003). "Purification and characterization of raventoxin-I and raventoxin-III, two neurotoxic peptides from the venom of the spider Macrothele raveni". Toxicon. 41 (6): 651–6. Bibcode:2003Txcn...41..651Z. doi:10.1016/s0041-0101(02)00361-6. PMID   12727269.
  2. 1 2 3 4 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.
  3. 1 2 3 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. 2007-04
  4. 1 2 3 4 Zhang Peng fei, Chen Ping, Xiao Shun yong, Liang Song ping.Purification, Characterization of Raventoxin-VI from the Venom of the Spider Macrothele raveni[J];Life Science Research;2003-02
  5. 1 2 3 Corzo G, Sabo JK, Bosmans F, Billen B, Villegas E, Tytgat J, Norton RS (2007). "Solution Structure and Alanine Scan of a Spider Toxin That Affects the Activation of Mammalian Voltage-gated Sodium Channels. (2007)". J. Biol. Chem. 282 (7): 4643–4652. doi: 10.1074/jbc.m605403200 . PMID   17148449.
  6. 1 2 Corzo G, Gilles N, Satake H, Villegas E, Nakajima T, Haupt J (Jul 2003). "Distinct primary structures of the major peptide toxins from the venom of the spider Macrothele gigas that bind to sites 3 and 4 in the sodium channel". FEBS Lett. 547 (1–3): 43–50. doi:10.1016/s0014-5793(03)00666-5. PMID   12860384. S2CID   22079371.
  7. ↑ Gao L, Shan BE, Chen J, Liu JH, Song DX, Zhu BC (Mar 2005). "Effects of spider Macrothele raven venom on cell proliferation and cytotoxicity in HeLa cells". Acta Pharmacol. Sin. 26 (3): 369–76. doi: 10.1111/j.1745-7254.2005.00052.x . PMID   15715936.
  8. ↑ Gao L, Yu S, Wu Y, Shan B (Jul 2007). "Effect of spider venom on cell apoptosis and necrosis rates in MCF-7 cells". DNA Cell Biol. 26 (7): 485–9. doi:10.1089/dna.2007.0579. PMID   17630852.
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