Synthesis, Expression and Purification of a Type of Chlorotoxin-like Peptide from the Scorpion, Buthus martensii Karsch, and its Acute Toxicity Analysis

Fu, Yuejun; Yin, Litian; Wang, Wei; Chai, Baofeng; Liang, Aihua

doi:10.1007/s10529-005-2514-2

Cited by 23 publications

(13 citation statements)

References 19 publications

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“…These short-chain toxins are composed of 30 to 40 amino acid residues and are mainly cross-linked by two or four disulfide bridges that are mostly active on K + or Cl -and Ca 2+ channels (7)(8)(9). In such groups we can find a short toxin with four disulfide bonds called chlorotoxin, a chloride-channel blocking toxin extracted from the scorpion Leiurus quinquestriatus (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Comparison of two purified toxic fractions from Mesobuthus eupeus scorpion venom

Shirmardi¹,

Shamsaei²,

Ghanei³

et al. 2010

J. Venom. Anim. Toxins incl. Trop. Dis

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Abstract:Iranian scorpions belong mainly to the Buthidae and Scorpionidae families, distributed into 16 genera and 25 species. In Iran, similar to other parts of the world, there are a few known species of scorpions responsible for severe envenoming; amongst which Mesobuthus eupeus is the most common. Its venom contains several toxin fractions that may affect the ion channel. In the present study purification, labeling and biological evaluation of M. eupeus venom are described. For separation, soluble venom was loaded on a chromatography column packed with Sephadex G-50 gel. Subsequently, the fractions were collected according to UV absorption at a wavelength of 280 nm. Toxic fraction (F3) was loaded on an anionic ion exchanger resin and then on a cationic resin. Finally, toxic subfractions F3.1.6 and F3.1.9 were labeled with 99m Tc and injected into normal mice to distinguish excretion pathway. The venom toxic fraction was successfully obtained in its purified form. Radiolabeling of toxic fractions was performed at high specific activity with radiochemical purity of more than 97 and 95% respectively for F3.1.6 and F3.1.9. Biodistribution studies in normal mice with two toxic fractions usually show rapid clearance of the compounds from blood and tissue except for kidneys. Since tissue distribution studies are very important for clinical purpose, the present findings suggest that 99m Tc labeling of venom is a useful tool for in vivo studies and comprises an excellent approach to monitoring the process of biodistribution and kinetics of toxins.

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Section: Introductionmentioning

confidence: 99%

Comparison of two purified toxic fractions from Mesobuthus eupeus scorpion venom

Shirmardi¹,

Shamsaei²,

Ghanei³

et al. 2010

J. Venom. Anim. Toxins incl. Trop. Dis

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“…Accumulated data have demonstrated that scorpion neurotoxins can specifically interact with Na + , K + , Ca 2+ and Cl -channels, which changes the ion permeability of excitable cells (Possani et al 2000;Fu et al 2005). The scorpion toxins are powerful tools for testing the pharmacological, physiological and even structural characteristics of ion channels and their associated ionic currents (Rodriguez de la Vega et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Functional analysis of the α-neurotoxin, BmαTX14, derived from the Chinese scorpion, Buthus martensii Karsch

et al. 2006

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The gene encoding the BmalphaTX14 (alpha-neurotoxin TX14) protein, derived from the cDNA library of the Chinese scorpion Buthus martensii Karsch, was expressed in Pichia pastoris. The recombinant protein was purified by metal chelate affinity chromatography and gel filtration chromatography. Using patch-clamp technique, electrophysiological activity of rBmalphaTX14 was identified. In the neurons isolated from mice trigeminal root ganglion, the Na+ current amplitude was reduced by 80% under whole cell patch-clamp recording. There were no apparent modifications to the gating mechanism in the presence of rBmalphaTX14. Although BmalphaTX14 shared a high amino acid sequence similarity with other typical alpha-toxins, it has different effects on neurons. Further electrophysiological analysis suggested that rBmalphaTX14 selectively blocked Na+ channels and is a member of a new group of scorpion toxins.

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“…An LD 50 value of 4.3 mg/kg was determined in mice upon i.v. injection of CTX analog [127]. Voltage-dependent CLC which are up regulated in glioblastoma tumors, are blocked by CTX [128].…”

Section: Toxins and Their Target Of Actionmentioning

confidence: 99%

The Molecular Basis of Toxins’ Interactions with Intracellular Signaling via Discrete Portals

Lahiani

Yavin

Lazarovici

2017

Toxins

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An understanding of the molecular mechanisms by which microbial, plant or animal-secreted toxins exert their action provides the most important element for assessment of human health risks and opens new insights into therapies addressing a plethora of pathologies, ranging from neurological disorders to cancer, using toxinomimetic agents. Recently, molecular and cellular biology dissecting tools have provided a wealth of information on the action of these diverse toxins, yet, an integrated framework to explain their selective toxicity is still lacking. In this review, specific examples of different toxins are emphasized to illustrate the fundamental mechanisms of toxicity at different biochemical, molecular and cellular- levels with particular consideration for the nervous system. The target of primary action has been highlighted and operationally classified into 13 sub-categories. Selected examples of toxins were assigned to each target category, denominated as portal, and the modulation of the different portal’s signaling was featured. The first portal encompasses the plasma membrane lipid domains, which give rise to pores when challenged for example with pardaxin, a fish toxin, or is subject to degradation when enzymes of lipid metabolism such as phospholipases A2 (PLA2) or phospholipase C (PLC) act upon it. Several major portals consist of ion channels, pumps, transporters and ligand gated ionotropic receptors which many toxins act on, disturbing the intracellular ion homeostasis. Another group of portals consists of G-protein-coupled and tyrosine kinase receptors that, upon interaction with discrete toxins, alter second messengers towards pathological levels. Lastly, subcellular organelles such as mitochondria, nucleus, protein- and RNA-synthesis machineries, cytoskeletal networks and exocytic vesicles are also portals targeted and deregulated by other diverse group of toxins. A fundamental concept can be drawn from these seemingly different toxins with respect to the site of action and the secondary messengers and signaling cascades they trigger in the host. While the interaction with the initial portal is largely determined by the chemical nature of the toxin, once inside the cell, several ubiquitous second messengers and protein kinases/ phosphatases pathways are impaired, to attain toxicity. Therefore, toxins represent one of the most promising natural molecules for developing novel therapeutics that selectively target the major cellular portals involved in human physiology and diseases.

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Synthesis, Expression and Purification of a Type of Chlorotoxin-like Peptide from the Scorpion, Buthus martensii Karsch, and its Acute Toxicity Analysis

Cited by 23 publications

References 19 publications

Comparison of two purified toxic fractions from Mesobuthus eupeus scorpion venom

Comparison of two purified toxic fractions from Mesobuthus eupeus scorpion venom

Functional analysis of the α-neurotoxin, BmαTX14, derived from the Chinese scorpion, Buthus martensii Karsch

The Molecular Basis of Toxins’ Interactions with Intracellular Signaling via Discrete Portals

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