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Animal toxins: From molecules to physiology perspectives

TAO Jie, JI Yong-Hua

Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, China； Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China

Abstract

As is known to all, venomous animals are really a threat to people’s life a few decades ago. However, with the emergence of novel scientific discoveries, concepts and technologies, the consideration of these animals moved from devil into treasure of modern medicines. More and more individual toxins secreted and purified from diverse venomous species have been characterized in structural and functional aspects, which also play critical roles in understanding the physiological contribution of targets such as ion channels or receptors as probes. Such “probe tool” has been looked upon the way to achieving novel drugs.
The special issue gathered 8 articles on the current partial state of natural toxin research with novel perspective and biotechnology addresses physiological function, significance in therapeutical probing of natural toxins, localizes the receptor sites of the animal toxins that target ion channels, and summarizes the evolution of relative toxins.
The insecticidal potential of neurotoxins is always a hot topic in toxicological and agricultural fields. The anti-insect toxins are considered as one of the novel insecticides. BmK IT was the second excitatory anti- insect β-toxin discovered in the world. Not only does it have own toxicity, but also it could promote the insecticidal effects of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) which induced apoptosis of insect cells. The contents above were introduced in the article “AcMNPV-mediated expression of BmK IT promotes the apoptosis of Sf9 cells and replication of AcMNPV” [1] in detail.
Nothing is more amazing than the secret of the origin of neurotoxins. So far, there are at least three conserved protein folds shared by ion channel-targeted neurotoxins and antimicrobial defensins. Based on data, neurotoxins were speculated originating from related ancient antimicrobial defensins, which provides an ideal system with a conserved structural scaffold during evolution. The review “Origin of neurotoxins from defensins” [2] describes the novel concept in origin of neurotoxins, focusing on the three conserved protein scaffolds.
In general, neurotoxins acting on ion channels are perceived as new drugs for treating channelopathies. Therefore, it is essential for discovering new toxins as well as summarizing the mechanism of the interaction between the channels and toxins. Am IT, a novel toxin purified from the venom of scorpion Androctonus mauretanicus, exhibited dual activity. It not only reveals an anti-insect compound property, paralyzes insect larvae by binding to Na+ channels, but also exerts toxic activity in mice, which was described in “Characterization of Am IT, an anti-insect β-toxin isolated from the venom of scorpion Androctonus mauretanicus” [3].
Voltage-gated potassium channels (Kv4.1, Kv4.2 and Kv4.3) members of the KCND/Kv4 (Shal) channel family mediate the native and fast inactivating IA current. This current is specifically blocked by short scorpion toxins that belong to the α-KTx15 subfamily. The review “Shal-type (Kv4.x) potassium channel pore blockers from scorpion venoms” [4] summarizes the chemical and pharmacological knowledge of α-KTx15 toxins.
Different from most voltage-gated potassium channels, SK channels are only inhibited by a small quantity of scorpion toxins. For the first time, the interaction model of short chain toxins with SK channel has been illuminated in the paper entitled “Unique interactions between scorpion toxins and small conductance Ca2+-activated potassium channels” [5].
As one kind of membrane proteins, whether the toxin sensitivity of ion channels is regulated by lipid bilayer still remains unclear. In the article “Lipid bilayer modification alters the gating properties and pharmacological sensitivity of voltage-gated sodium channel” [6], the modification of lipid composition on the toxin sensitivity of voltage-gated sodium channels to BmK I and BmK AS, two sodium channel-specific modulators, was detailedly described, which might open a novel mechanism on the interaction between toxin and its specific target.
In addition to being considered as the clinical pilot drugs, toxins could also be used to construct animal models for clinical diseases, such as seizures and pain. BmK I induces a lot of pain responses, including spontaneous reflexes, paroxysmal pain, thermal hypersensitivity, and especially bilateral (mirror-image) mechanical hypersensitivity. In the paper “The molecular regulatory effects of 5-HT3AR on BmK I-induced pain nociception in rats” [7], the pathogenesis pathway of bilateral (mirror-image) mechanical hypersensitivity, BmK I-induced pain, was revealed for the first time.
Because of the rich biodiversity, Brazilian animal venoms have been widely investigated. A great number of biotechnological articles as well as patent applications of drug discovery based on these compounds are reported, including the field of anticancer or antimicrobial drugs, anti-venoms and vaccines, hypotensive compositions, antinociceptive and anti-inflammatory compositions. In the review “Venoms, toxins and derivatives from the Brazilian fauna: valuable sources for drug discovery” [8], the most studied venomous animal species in Brazil and recent patent applications are well described.
With the in-depth research in these fields, we could look forward to many surprising, exciting and useful discoveries from animal toxins research for next coming years.

Received: 　　Accepted:

Corresponding author: 陶杰,吉永华　　E-mail: yhji@staff.shu.edu.cn, jietao_putuo@foxmail.com

Citing This Article：

TAO Jie, JI Yong-Hua. Animal toxins: From molecules to physiology perspectives. Acta Physiol Sin 2015; 67 (3): 237-238 (in Chinese with English abstract).