Advanced Research on Animal Venoms in China

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Animal Venoms".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 27576

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Guest Editor
Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
Interests: venomous animals; environmental adaptation; animal toxins; peptides; structure-function; proteomics; drug discovery; thrombus; inflammation; ion channels
Special Issues, Collections and Topics in MDPI journals
Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
Interests: animal toxins; structure-function; natural medicines; drug discovery; platelets; thrombus
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Animals such as snakes, scorpions, spiders, wasps, centipedes, cone snails and toads have evolved to produce venoms in order to adapt to specific ecological environments, as well as for defense or predation. Animal toxins possess rich diversity, high activity and high specificity, which are main reasons why venomous animals have been used in traditional Chinese medicines for thousands of years. These toxins are able to affect the normal functioning of the human body through various physiological and biochemical mechanisms. Animal toxins have become powerful probes to analyze the structure–function of ion channels and receptors. They are also good tools for exploring physiological and pathological mechanisms. In addition, animal toxins are valuable resources for the discovery of innovative drugs.

Recently, Chinese researchers have made many exciting discoveries pertaining to animal toxins. The purpose of this issue is to provide the latest research on the discovery of animal toxins, the mechanism underlining their actions, mining of drug leads from toxins, and the diagnosis and treatment of bites or stings by venomous animals in China. In order to enhance our understanding of these important issues, we encourage experts in the field of animal toxins to contribute research papers and comments on various aspects of animal toxins to this Special Issue.

Prof. Dr. Ren Lai
Dr. Qiumin Lu
Guest Editors

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Keywords

  • venom
  • toxin
  • receptor
  • ion channel
  • snake bites

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Published Papers (12 papers)

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Editorial

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3 pages, 202 KiB  
Editorial
Advanced Research on Animal Venoms in China
by Ren Lai and Qiumin Lu
Toxins 2023, 15(4), 272; https://doi.org/10.3390/toxins15040272 - 6 Apr 2023
Cited by 1 | Viewed by 1393
Abstract
For millennia, scientists, researchers, and the general public have been intrigued by animal venoms due to their potent effects and paradoxical ability to both harm and heal [...] Full article
(This article belongs to the Special Issue Advanced Research on Animal Venoms in China)

Research

Jump to: Editorial

19 pages, 2700 KiB  
Article
A Pore Forming Toxin-like Protein Derived from Chinese Red Belly Toad Bombina maxima Triggers the Pyroptosis of Hippomal Neural Cells and Impairs the Cognitive Ability of Mice
by Qingqing Ye, Qiquan Wang, Wenhui Lee, Yang Xiang, Jixue Yuan, Yun Zhang and Xiaolong Guo
Toxins 2023, 15(3), 191; https://doi.org/10.3390/toxins15030191 - 3 Mar 2023
Cited by 3 | Viewed by 1780
Abstract
Toxin-like proteins and peptides of skin secretions from amphibians play important physiological and pathological roles in amphibians. βγ-CAT is a Chinese red-belly toad-derived pore-forming toxin-like protein complex that consists of aerolysin domain, crystalline domain, and trefoil factor domain and induces various toxic effects [...] Read more.
Toxin-like proteins and peptides of skin secretions from amphibians play important physiological and pathological roles in amphibians. βγ-CAT is a Chinese red-belly toad-derived pore-forming toxin-like protein complex that consists of aerolysin domain, crystalline domain, and trefoil factor domain and induces various toxic effects via its membrane perforation process, including membrane binding, oligomerization, and endocytosis. Here, we observed the death of mouse hippocampal neuronal cells induced by βγ-CAT at a concentration of 5 nM. Subsequent studies showed that the death of hippocampal neuronal cells was accompanied by the activation of Gasdermin E and caspase-1, suggesting that βγ-CAT induces the pyroptosis of hippocampal neuronal cells. Further molecular mechanism studies revealed that the pyroptosis induced by βγ-CAT is dependent on the oligomerization and endocytosis of βγ-CAT. It is well known that the damage of hippocampal neuronal cells leads to the cognitive attenuation of animals. The impaired cognitive ability of mice was observed after intraperitoneal injection with 10 μg/kg βγ-CAT in a water maze assay. Taken together, these findings reveal a previously unknown toxicological function of a vertebrate-derived pore-forming toxin-like protein in the nerve system, which triggers the pyroptosis of hippocampal neuronal cells, ultimately leading to hippocampal cognitive attenuation. Full article
(This article belongs to the Special Issue Advanced Research on Animal Venoms in China)
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10 pages, 2487 KiB  
Article
The Bi-Functional Paxilline Enriched in Skin Secretion of Tree Frogs (Hyla japonica) Targets the KCNK18 and BKCa Channels
by Chuanling Yin, Fanpeng Zeng, Puyi Huang, Zhengqi Shi, Qianyi Yang, Zhenduo Pei, Xin Wang, Longhui Chai, Shipei Zhang, Shilong Yang, Wenqi Dong, Xiancui Lu and Yunfei Wang
Toxins 2023, 15(1), 70; https://doi.org/10.3390/toxins15010070 - 12 Jan 2023
Cited by 1 | Viewed by 2116
Abstract
The skin secretion of tree frogs contains a vast array of bioactive chemicals for repelling predators, but their structural and functional diversity is not fully understood. Paxilline (PAX), a compound synthesized by Penicillium paxilli, has been known as a specific antagonist of large [...] Read more.
The skin secretion of tree frogs contains a vast array of bioactive chemicals for repelling predators, but their structural and functional diversity is not fully understood. Paxilline (PAX), a compound synthesized by Penicillium paxilli, has been known as a specific antagonist of large conductance Ca2+-activated K+ Channels (BKCa). Here, we report the presence of PAX in the secretions of tree frogs (Hyla japonica) and that this compound has a novel function of inhibiting the potassium channel subfamily K member 18 (KCNK18) channels of their predators. The PAX-induced KCNK18 inhibition is sufficient to evoke Ca2+ influx in charybdotoxin-insensitive DRG neurons of rats. By forming π-π stacking interactions, four phenylalanines located in the central pore of KCNK18 stabilize PAX to block the ion permeation. For PAX-mediated toxicity, our results from animal assays suggest that the inhibition of KCNK18 likely acts synergistically with that of BKCa to elicit tingling and buzzing sensations in predators or competitors. These results not only show the molecular mechanism of PAX-KCNK18 interaction, but also provide insights into the defensive effects of the enriched PAX. Full article
(This article belongs to the Special Issue Advanced Research on Animal Venoms in China)
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15 pages, 1634 KiB  
Article
In Vitro Efficacy of Antivenom and Varespladib in Neutralising Chinese Russell’s Viper (Daboia siamensis) Venom Toxicity
by Mimi Lay, Qing Liang, Geoffrey K. Isbister and Wayne C. Hodgson
Toxins 2023, 15(1), 62; https://doi.org/10.3390/toxins15010062 - 11 Jan 2023
Cited by 9 | Viewed by 2515
Abstract
The venom of the Russell’s viper (Daboia siamensis) contains neurotoxic and myotoxic phospholipase A2 toxins which can cause irreversible damage to motor nerve terminals. Due to the time delay between envenoming and antivenom administration, antivenoms may have limited efficacy against [...] Read more.
The venom of the Russell’s viper (Daboia siamensis) contains neurotoxic and myotoxic phospholipase A2 toxins which can cause irreversible damage to motor nerve terminals. Due to the time delay between envenoming and antivenom administration, antivenoms may have limited efficacy against some of these venom components. Hence, there is a need for adjunct treatments to circumvent these limitations. In this study, we examined the efficacy of Chinese D. siamensis antivenom alone, and in combination with a PLA2 inhibitor, Varespladib, in reversing the in vitro neuromuscular blockade in the chick biventer cervicis nerve-muscle preparation. Pre-synaptic neurotoxicity and myotoxicity were not reversed by the addition of Chinese D. siamensis antivenom 30 or 60 min after venom (10 µg/mL). The prior addition of Varespladib prevented the neurotoxic and myotoxic activity of venom (10 µg/mL) and was also able to prevent further reductions in neuromuscular block and muscle twitches when added 60 min after venom. The addition of the combination of Varespladib and antivenom 60 min after venom failed to produce further improvements than Varespladib alone. This demonstrates that the window of time in which antivenom remains effective is relatively short compared to Varespladib and small-molecule inhibitors may be effective in abrogating some activities of Chinese D. siamensis venom. Full article
(This article belongs to the Special Issue Advanced Research on Animal Venoms in China)
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18 pages, 6596 KiB  
Article
Exploring the Pivotal Components Influencing the Side Effects Induced by an Analgesic-Antitumor Peptide from Scorpion Venom on Human Voltage-Gated Sodium Channels 1.4 and 1.5 through Computational Simulation
by Fan Zhao, Liangyi Fang, Qi Wang, Qi Ye, Yanan He, Weizhuo Xu and Yongbo Song
Toxins 2023, 15(1), 33; https://doi.org/10.3390/toxins15010033 - 31 Dec 2022
Cited by 2 | Viewed by 1819
Abstract
Voltage-gated sodium channels (VGSCs, or Nav) are important determinants of action potential generation and propagation. Efforts are underway to develop medicines targeting different channel subtypes for the treatment of related channelopathies. However, a high degree of conservation across its nine subtypes [...] Read more.
Voltage-gated sodium channels (VGSCs, or Nav) are important determinants of action potential generation and propagation. Efforts are underway to develop medicines targeting different channel subtypes for the treatment of related channelopathies. However, a high degree of conservation across its nine subtypes could lead to the off-target adverse effects on skeletal and cardiac muscles due to acting on primary skeletal muscle sodium channel Nav1.4 and cardiac muscle sodium channel Nav1.5, respectively. For a long evolutionary process, some peptide toxins from venoms have been found to be highly potent yet selective on ion channel subtypes and, therefore, hold the promising potential to be developed into therapeutic agents. In this research, all-atom molecular dynamic methods were used to elucidate the selective mechanisms of an analgesic-antitumor β-scorpion toxin (AGAP) with human Nav1.4 and Nav1.5 in order to unravel the primary reason for the production of its adverse reactions on the skeletal and cardiac muscles. Our results suggest that the rational distribution of residues with ring structures near position 38 and positive residues in the C-terminal on AGAP are critical factors to ensure its analgesic efficacy. Moreover, the substitution for residues with benzene is beneficial to reduce its side effects. Full article
(This article belongs to the Special Issue Advanced Research on Animal Venoms in China)
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9 pages, 1329 KiB  
Article
A Novel Peptide from Polypedates megacephalus Promotes Wound Healing in Mice
by Siqi Fu, Canwei Du, Qijian Zhang, Jiayu Liu, Xushuang Zhang and Meichun Deng
Toxins 2022, 14(11), 753; https://doi.org/10.3390/toxins14110753 - 2 Nov 2022
Cited by 6 | Viewed by 1913
Abstract
Amphibian skin contains wound-healing peptides, antimicrobial peptides, and insulin-releasing peptides, which give their skin a strong regeneration ability to adapt to a complex and harsh living environment. In the current research, a novel wound-healing promoting peptide, PM-7, was identified from the skin secretions [...] Read more.
Amphibian skin contains wound-healing peptides, antimicrobial peptides, and insulin-releasing peptides, which give their skin a strong regeneration ability to adapt to a complex and harsh living environment. In the current research, a novel wound-healing promoting peptide, PM-7, was identified from the skin secretions of Polypedates megacephalus, which has an amino acid sequence of FLNWRRILFLKVVR and shares no structural similarity with any peptides described before. It displays the activity of promoting wound healing in mice. Moreover, PM-7 exhibits the function of enhancing proliferation and migration in HUVEC and HSF cells by affecting the MAPK signaling pathway. Considering its favorable traits as a novel peptide that significantly promotes wound healing, PM-7 can be a potential candidate in the development of novel wound-repairing drugs. Full article
(This article belongs to the Special Issue Advanced Research on Animal Venoms in China)
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19 pages, 5647 KiB  
Article
Smp24, a Scorpion-Venom Peptide, Exhibits Potent Antitumor Effects against Hepatoma HepG2 Cells via Multi-Mechanisms In Vivo and In Vitro
by Tienthanh Nguyen, Ruiyin Guo, Jinwei Chai, Jiena Wu, Junfang Liu, Xin Chen, Mohamed A. Abdel-Rahman, Hu Xia and Xueqing Xu
Toxins 2022, 14(10), 717; https://doi.org/10.3390/toxins14100717 - 21 Oct 2022
Cited by 16 | Viewed by 2404
Abstract
Scorpion-venom-derived peptides have become a promising anticancer agent due to their cytotoxicity against tumor cells via multiple mechanisms. The suppressive effect of the cationic antimicrobial peptide Smp24, which is derived from the venom of Scorpio Maurus palmatus, on the proliferation of the [...] Read more.
Scorpion-venom-derived peptides have become a promising anticancer agent due to their cytotoxicity against tumor cells via multiple mechanisms. The suppressive effect of the cationic antimicrobial peptide Smp24, which is derived from the venom of Scorpio Maurus palmatus, on the proliferation of the hepatoma cell line HepG2 has been reported earlier. However, its mode of action against HepG2 hepatoma cells remains unclear. In the current research, Smp24 was discovered to suppress the viability of HepG2 cells while having a minor effect on normal LO2 cells. Moreover, endocytosis and pore formation were demonstrated to be involved in the uptake of Smp24 into HepG2 cells, which subsequently interacted with the mitochondrial membrane and caused the decrease in its potential, cytoskeleton reorganization, ROS accumulation, mitochondrial dysfunction, and alteration of apoptosis- and autophagy-related signaling pathways. The protecting activity of Smp24 in the HepG2 xenograft mice model was also demonstrated. Therefore, our data suggest that the antitumor effect of Smp24 is closely related to the induction of cell apoptosis, cycle arrest, and autophagy via cell membrane disruption and mitochondrial dysfunction, suggesting a potential alternative in hepatocellular carcinoma treatment. Full article
(This article belongs to the Special Issue Advanced Research on Animal Venoms in China)
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23 pages, 6542 KiB  
Article
Transcriptome Sequencing and Comparison of Venom Glands Revealed Intraspecific Differentiation and Expression Characteristics of Toxin and Defensin Genes in Mesobuthus martensii Populations
by Zhiyong Di, Sha Qiao, Xiaoshuang Liu, Shuqing Xiao, Cheng Lei, Yonghao Li, Shaobin Li and Feng Zhang
Toxins 2022, 14(9), 630; https://doi.org/10.3390/toxins14090630 - 11 Sep 2022
Cited by 2 | Viewed by 1993
Abstract
Mesobuthus martensii, a famous and important Traditional Chinese Medicine has a long medical history and unique functions. It is the first scorpion species whose whole genome was sequenced worldwide. In addition, it is the most widespread and infamous poisonous animal in northern [...] Read more.
Mesobuthus martensii, a famous and important Traditional Chinese Medicine has a long medical history and unique functions. It is the first scorpion species whose whole genome was sequenced worldwide. In addition, it is the most widespread and infamous poisonous animal in northern China with complex habitats. It possesses several kinds of toxins that can regulate different ion channels and serve as crucial natural drug resources. Extensive and in-depth studies have been performed on the structures and functions of toxins of M. martensii. In this research, we compared the morphology of M. martensii populations from different localities and calculated the COI genetic distance to determine intraspecific variations. Transcriptome sequencing by RNA-sequencing of the venom glands of M. martensii from ten localities and M. eupeus from one locality was analyzed. The results revealed intraspecific variation in the expression of sodium channel toxin genes, potassium channel toxin genes, calcium channel toxin genes, chloride channel toxin genes, and defensin genes that could be related to the habitats in which these populations are distributed, except the genetic relationships. However, it is not the same in different toxin families. M. martensii and M. eupeus exhibit sexual dimorphism under the expression of toxin genes, which also vary in different toxin families. The following order was recorded in the difference of expression of sodium channel toxin genes: interspecific difference; differences among different populations of the same species; differences between sexes in the same population, whereas the order in the difference of expression of potassium channel toxin genes was interspecific difference; differences between both sexes of same populations; differences among the same sex in different populations of the same species. In addition, there existed fewer expressed genes of calcium channel toxins, chloride channel toxins, and defensins (no more than four members in each family), and their expression differences were not distinct. Interestingly, the expression of two calcium channel toxin genes showed a preference for males and certain populations. We found a difference in the expression of sodium channel toxin genes, potassium channel toxin genes, and chloride channel toxin genes between M. martensii and M. eupeus. In most cases, the expression of one member of the toxin gene clusters distributed in series on the genome were close in different populations and genders, and the members of most clusters expressed in same population and gender tended to be the different. Twenty-one toxin genes were found with the MS/MS identification evidence of M. martensii venom. Since scorpions were not subjected to electrical stimulation or other special treatments before conducting the transcriptome extraction experiment, the results suggested the presence of intraspecific variation and sexual dimorphism of toxin components which revealed the expression characteristics of toxin and defensin genes in M. martensii. We believe this study will promote further in-depth research and use of scorpions and their toxin resources, which in turn will be helpful in standardizing the identification and medical applications of Quanxie in traditional Chinese medicine. Full article
(This article belongs to the Special Issue Advanced Research on Animal Venoms in China)
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33 pages, 5486 KiB  
Article
Venom Variation of Neonate and Adult Chinese Cobras in Captivity Concerning Their Foraging Strategies
by Xuekui Nie, Qianzi Chen, Chen Wang, Wangxiang Huang, Ren Lai, Qiumin Lu, Qiyi He and Xiaodong Yu
Toxins 2022, 14(9), 598; https://doi.org/10.3390/toxins14090598 - 29 Aug 2022
Cited by 3 | Viewed by 2385
Abstract
The venom and transcriptome profile of the captive Chinese cobra (Naja atra) is not characterized  until now. Here, LC-MS/MS and illumine technology were used to unveil the venom and trascriptome of neonates and adults N. atra specimens. In captive Chinese cobra, [...] Read more.
The venom and transcriptome profile of the captive Chinese cobra (Naja atra) is not characterized  until now. Here, LC-MS/MS and illumine technology were used to unveil the venom and trascriptome of neonates and adults N. atra specimens. In captive Chinese cobra, 98 co-existing transcripts for venom-related proteins was contained. A total of 127 proteins belong to 21 protein families were found in the profile of venom. The main components of snake venom were three finger toxins (3-FTx), snake venom metalloproteinase (SVMP), cysteine-rich secretory protein (CRISP), cobra venom factor (CVF), and phosphodiesterase (PDE). During the ontogenesis of captive Chinese cobra, the rearrangement of snake venom composition occurred and with obscure gender difference. CVF, 3-FTx, PDE, phospholipase A2 (PLA2) in adults were more abundant than neonates, while SVMP and CRISP in the neonates was richer than the adults. Ontogenetic changes in the proteome of Chinese cobra venom reveals different strategies for handling prey. The levels of different types of toxin families were dramatically altered in the wild and captive specimens. Therefore, we speculate that the captive process could reshape the snake venom composition vigorously. The clear comprehension of the composition of Chinese cobra venom facilitates the understanding of the mechanism of snakebite intoxication and guides the preparation and administration of traditional antivenom and next-generation drugs for snakebite.  Full article
(This article belongs to the Special Issue Advanced Research on Animal Venoms in China)
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13 pages, 2645 KiB  
Article
The Strong Anti-Tumor Effect of Smp24 in Lung Adenocarcinoma A549 Cells Depends on Its Induction of Mitochondrial Dysfunctions and ROS Accumulation
by Ruiyin Guo, Xuewen Chen, Tienthanh Nguyen, Jinwei Chai, Yahua Gao, Jiena Wu, Jinqiao Li, Mohamed A. Abdel-Rahman, Xin Chen and Xueqing Xu
Toxins 2022, 14(9), 590; https://doi.org/10.3390/toxins14090590 - 27 Aug 2022
Cited by 13 | Viewed by 2112
Abstract
Non-small cell lung cancer (NSCLC) is the leading cause of death in lung cancer due to its aggressiveness and rapid migration. The potent antitumor effect of Smp24, an antimicrobial peptide derived from Egyptian scorpion Scorpio maurus palmatus via damaging the membrane and cytoskeleton [...] Read more.
Non-small cell lung cancer (NSCLC) is the leading cause of death in lung cancer due to its aggressiveness and rapid migration. The potent antitumor effect of Smp24, an antimicrobial peptide derived from Egyptian scorpion Scorpio maurus palmatus via damaging the membrane and cytoskeleton have been reported earlier. However, its effects on mitochondrial functions and ROS accumulation in human lung cancer cells remain unknown. In the current study, we discovered that Smp24 can interact with the cell membrane and be internalized into A549 cells via endocytosis, followed by targeting mitochondria and affect mitochondrial function, which significantly causes ROS overproduction, altering mitochondrial membrane potential and the expression of cell cycle distribution-related proteins, mitochondrial apoptotic pathway, MAPK, as well as PI3K/Akt/mTOR/FAK signaling pathways. In summary, the antitumor effect of Smp24 against A549 cells is related to the induction of apoptosis, autophagy plus cell cycle arrest via mitochondrial dysfunction, and ROS accumulation. Accordingly, our findings shed light on the anticancer mechanism of Smp24, which may contribute to its further development as a potential agent in the treatment of lung cancer cells. Full article
(This article belongs to the Special Issue Advanced Research on Animal Venoms in China)
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14 pages, 2216 KiB  
Article
A Long-Read Genome Assembly of a Native Mite in China Pyemotes zhonghuajia Yu, Zhang & He (Prostigmata: Pyemotidae) Reveals Gene Expansion in Toxin-Related Gene Families
by Yan-Fei Song, Li-Chen Yu, Mao-Fa Yang, Shuai Ye, Bin Yan, Li-Tao Li, Chen Wu and Jian-Feng Liu
Toxins 2022, 14(8), 571; https://doi.org/10.3390/toxins14080571 - 21 Aug 2022
Cited by 4 | Viewed by 2263
Abstract
Pyemotes zhonghuajia Yu, Zhang & He (Prostigmata: Pyemotidae), discovered in China, has been demonstrated as a high-efficient natural enemy in controlling many agricultural and forestry pests. This mite injects toxins into the host (eggs, larvae, pupae, and adults), resulting in its paralyzation and [...] Read more.
Pyemotes zhonghuajia Yu, Zhang & He (Prostigmata: Pyemotidae), discovered in China, has been demonstrated as a high-efficient natural enemy in controlling many agricultural and forestry pests. This mite injects toxins into the host (eggs, larvae, pupae, and adults), resulting in its paralyzation and then gets nourishment for reproductive development. These toxins have been approved to be mammal-safe, which have the potential to be used as biocontrol pesticides. Toxin proteins have been identified from many insects, especially those from the orders Scorpions and Araneae, some of which are now widely used as efficient biocontrol pesticides. However, toxin proteins in mites are not yet understood. In this study, we assembled the genome of P. zhonghuajia using PacBio technology and then identified toxin-related genes that are likely to be responsible for the paralytic process of P. zhonghuajia. The genome assembly has a size of 71.943 Mb, including 20 contigs with a N50 length of 21.248 Mb and a BUSCO completeness ratio of 90.6% (n = 1367). These contigs were subsequently assigned to three chromosomes. There were 11,183 protein coding genes annotated, which were assessed with 91.2% BUSCO completeness (n = 1066). Neurotoxin and dermonecrotic toxin gene families were significantly expanded within the genus of Pyemotes and they also formed several gene clusters on the chromosomes. Most of the genes from these two families and all of the three agatoxin genes were shown with higher expression in the one-day-old mites compared to the seven-day-pregnant mites, supporting that the one-day-old mites cause paralyzation and even death of the host. The identification of these toxin proteins may provide insights into how to improve the parasitism efficiency of this mite, and the purification of these proteins may be used to develop new biological pesticides. Full article
(This article belongs to the Special Issue Advanced Research on Animal Venoms in China)
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16 pages, 3981 KiB  
Article
Scorpion Peptide Smp24 Exhibits a Potent Antitumor Effect on Human Lung Cancer Cells by Damaging the Membrane and Cytoskeleton In Vivo and In Vitro
by Ruiyin Guo, Junfang Liu, Jinwei Chai, Yahua Gao, Mohamed A. Abdel-Rahman and Xueqing Xu
Toxins 2022, 14(7), 438; https://doi.org/10.3390/toxins14070438 - 28 Jun 2022
Cited by 19 | Viewed by 2664
Abstract
Smp24, a cationic antimicrobial peptide identified from the venom gland of the Egyptian scorpion Scorpio maurus palmatus, shows variable cytotoxicity on various tumor (KG1a, CCRF-CEM and HepG2) and non-tumor (CD34+, HRECs, HACAT) cell lines. However, the effects of Smp24 and [...] Read more.
Smp24, a cationic antimicrobial peptide identified from the venom gland of the Egyptian scorpion Scorpio maurus palmatus, shows variable cytotoxicity on various tumor (KG1a, CCRF-CEM and HepG2) and non-tumor (CD34+, HRECs, HACAT) cell lines. However, the effects of Smp24 and its mode of action on lung cancer cell lines remain unknown. Herein, the effect of Smp24 on the viability, membrane disruption, cytoskeleton, migration and invasion, and MMP-2/-9 and TIMP-1/-2 expression of human lung cancer cells have been evaluated. In addition, its in vivo antitumor role and acute toxicity were also assessed. In our study, Smp24 was found to suppress the growth of A549, H3122, PC-9, and H460 with IC50 values from about 4.06 to 7.07 µM and show low toxicity to normal cells (MRC-5) with 14.68 µM of IC50. Furthermore, Smp24 could induce necrosis of A549 cells via destroying the integrity of the cell membrane and mitochondrial and nuclear membranes. Additionally, Smp24 suppressed cell motility by damaging the cytoskeleton and altering MMP-2/-9 and TIMP-1/-2 expression. Finally, Smp24 showed effective anticancer protection in a A549 xenograft mice model and low acute toxicity. Overall, these findings indicate that Smp24 significantly exerts an antitumor effect due to its induction of membrane defects and cytoskeleton disruption. Accordingly, our findings will open an avenue for developing scorpion venom peptides into chemotherapeutic agents targeting lung cancer cells. Full article
(This article belongs to the Special Issue Advanced Research on Animal Venoms in China)
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