BACKGROUND： Studies have shown that scorpion venom heat-resistant protein （SVHRP） exhibits protective effects on primary cultured hippocampal neurons. OBJECTIVE： To determine the effects of SVHRP on astrocyte acti...BACKGROUND： Studies have shown that scorpion venom heat-resistant protein （SVHRP） exhibits protective effects on primary cultured hippocampal neurons. OBJECTIVE： To determine the effects of SVHRP on astrocyte activity and synaptic density in the hippocampus induced by amyloid β peptide 1-40 （Aβ1-40） neurotoxicity. DESIGN, TIME AND SETTING： The randomized, controlled, animal experiment was performed at the Central Laboratory, the Laboratory of Human Anatomy, and the Laboratory of Physiology, in Dalian Medical University between March 2006 and June 2008. MATERIALS： Aβ1-40 was provided by Biosource, USA; SVHRP was a patented biological product of Dalian Medical University （No. ZL01 1 06166.9）. METHODS： A total of 27 healthy, 2-month-old, male SD rats were randomly assigned to 3 groups： control, Aβ, and SVHRP, with 9 rats in each group. Alzheimer＇s disease was simulated with 10 μg Aβ1-40 bilaterally injected into the hippocampus of the Aβ and SVHRP groups. The control group was injected with 2 μL 0.05% trifluoroacetic acid. One day following model establishment, the SVHRP group received an intraperitoneal injection of 2 μg/100 g SVHRP, while the control group and Aβ group received 0.5 mL/100 g tri-distilled water, once per day, for 10 consecutive days. MAIN OUTCOME MEASURES： At 16 days following model establishment, synaptophysin （p38） expression in CA1-CA4 regions of the rat hippocampus was determined by immunohistochemistry. Glial fibrillary acidic protein （GFAP） expression surrounding the hippocampal Aβ1-40 injected area was also detected. At 11 days following model establishment, escape latency, swimming time, and distance to target quadrant were measured using the Morris water maze. RESULTS： Compared with the control group, the Aβ group exhibited notably reduced p38 expression （P 〈 0.05） and notably increased GFAP expression in the rat hippocampus （P 〈 0.05）. Water maze results demonstrated that escape latency was prolonged （P 〈 0.05）, and swimming time and distance to the target quadrant were shortened in the Aβ group. Compared with the Aβ group, the SVHRP group exhibited notably increased p38 expression （P 〈 0.05） and notably decreased GFAP expression in the rat hippocampus （P 〈 0.05）. Water maze results demonstrated that escape latency was significantly reduced （P 〈 0.05）, and swimming time and distance to the target quadrant were significantly prolonged. CONCLUSION： SVHRP inhibited exogenous Aβ1-40-induced astrocyte activation and synaptic density decline in the rat hippocampus. Place navigation and spatial searching results showed that SVHRP blocked Aβ1-40-induced impaired learning and memory.展开更多
In order to investigate the cardiovascular effects of the scorpion(Buthus martensiKarsch)venom(BmKv),the left ventricle of the rats was catheterized via the right carotidartery.The LVP,LVEDP,+dp/dt max,Vmax,HR and BP ...In order to investigate the cardiovascular effects of the scorpion(Buthus martensiKarsch)venom(BmKv),the left ventricle of the rats was catheterized via the right carotidartery.The LVP,LVEDP,+dp/dt max,Vmax,HR and BP were observed.The results showedthat intravenous injection of the BmKv(60μg/kg),in comparison with the control,elicited obvi-ous hypertension and increase of cardiac contractility,both of which lasted for 1h,while theheart rate had no significant change rand that pretreating the rats with alpha-adrenergic blocker,phentolamine,antagonized the hypertensive effects,but did not antagonize the increase of cardiaccontractility.Pretreatment with beta-adrenergic blocker,propranolol,has no influence on the ef-fects of the venom.It is suggested that the hypertensive effects are due to the activation of al-pha-adrenergic receptor,whereas the increase of cardiac contractility may not be resulted fromthe activation of beta-adrenergic receptor.The BmKv treated with dithiothreitol before injectionhad no cardiovascular effects,indicating that the intact disulfide bridges play a decisive role inthe cardiovascular effects of the BmKv.展开更多
Background: About 50 species of scorpions cause fatal scorpionism worldwide.Most of these are members of the Buthidae family, and include, among others,Mesobuthus eupeus, Androctonus crassicauda, Leiurus abdullahbayra...Background: About 50 species of scorpions cause fatal scorpionism worldwide.Most of these are members of the Buthidae family, and include, among others,Mesobuthus eupeus, Androctonus crassicauda, Leiurus abdullahbayrami, Leiurus quinquestriatus, Tityus pachyurus and Androctonus australis. Because high doses of scorpion venom and antivenom can cause death and hypersensitive reactions, there is a need to develop a formula that can be used to calculate both lethal and effective doses for scorpion venom and antivenom, respectively, thereby obviating the need for laboratory experiments.Methods: In view of this, a literature search was carried out with the aim of modifying the formula(LD_(50)=ED_(50)/3× W_a × 10^(-4))for calculation of the median lethal dose(LD_(50)) of scorpion venom and the ED_(50) of antivenom. The human equivalent dose(HED) formula was assessed for extrapolation of LD_(50) and ED_(50) from animals to human for comparison and relevance with the new formula.Results: The findings showed that the newly developed formula(LD_(50)= ED_(50)^(1/3)×W_a× 10^(-4)) yielded results that are very close to the reported values. Therefore, the newly developed and HED formulas can be used for calculation of LD_(50) and ED_(50) values for scorpion venom and antivenom, respectively.Conclusion: The new formula yielded better results than the HED formula, confirming its predictive validity, precision, and reliability, thereby obviating the need for rigorous experiments and justifying the principles of reduction, refinement, and replacement(3 Rs).展开更多
The Tityus serrulatus scorpion is considered the most dangerous scorpion in Brazil and is responsible for several cases of human envenomation annually. In this study, we performed transcriptome profiling of the T. ser...The Tityus serrulatus scorpion is considered the most dangerous scorpion in Brazil and is responsible for several cases of human envenomation annually. In this study, we performed transcriptome profiling of the T. serrulatus venom gland. In addition to transcripts with housekeeping functions, such as those related to protein synthesis, energy supply and structural processes, transcripts from thirty-five families of venom peptides or proteins were identified. These transcripts included three new complete sequences of toxins and more than a dozen putative venom gland proteins/peptides. The venom gland transcriptome profile was verified by comparison with the previously determined proteomic profile. In conclusion, this transcriptome data provides novel insights into the putative mechanisms underlying the venomous character of T. serrulatus. The collected data of scorpion transcripts and proteins/peptides described herein may be an important resource for identifying candidate targets of molecular therapies and preventative measures.展开更多
The nucleotide sequence deduced from the amino acid sequence of the scorpion insectotoxin AaIT was chemically synthesized and was expressed in Escherichia coli. The authenticity of this in vitro expressed peptide was ...The nucleotide sequence deduced from the amino acid sequence of the scorpion insectotoxin AaIT was chemically synthesized and was expressed in Escherichia coli. The authenticity of this in vitro expressed peptide was confirmed by N-terminal peptide sequencing. Two groups of bioassays, artificial diet incorporation assay and contact insecticidal effect assay, were carried out separately to verify the toxicity of this recombinant toxin. At the end of a 24 h experimental period, more than 60% of the testing diamondback moth (Plutella xylostella) larvae were killed in both groups with LC50 value of 18.4 microM and 0.70 microM respectively. Cytotoxicity assay using cultured Sf9 insect cells and MCF-7 human cells demonstrated that the toxin AaIT had specific toxicity against insect cells but not human cells. Only 0.13 microM recombinant toxin was needed to kill 50% of cultured insect cells while as much as 1.3 microM toxin had absolutely no effect on human cells. Insect cells produced obvious intrusions from their plasma membrane before broken up. We infer that toxin AaIT bind to a putative sodium channel in these insect cells and open the channel persistently, which would result in Na+ influx and finally cause destruction of insect cells.展开更多
Poisonous organisms are represented in many taxa, including kingdom Animalia. During evolution, animals have developed special organs for production and injection of venoms. Animal venoms are complex mixtures, composi...Poisonous organisms are represented in many taxa, including kingdom Animalia. During evolution, animals have developed special organs for production and injection of venoms. Animal venoms are complex mixtures, compositions of which depend on species producing venom. The most known and studied poisonous terrestrial animals are snakes, scorpions and spiders. Among marine animals, these are jellyfishes, anemones and cone snails. The toxic substances in the venom ofthese animals are mainly of protein and peptide origin. Recent studies have indicated that the single venom may contain up to several hundred different components producing diverse physiological effects. Bites or stings by certain poisonous species result in severe envenomations leading in some cases to death. This raises the problem of bite treatment. The most effective treatment so far is the application of antivenoms. To enhance the effectiveness of such treatments, the knowledge of venom composition is needed. On the other hand, venoms contain substances with unique biological properties, which can be used both in basic science and in clinical applications. The best example of toxin application in basic science is α-bungarotoxin the discovery of which made a big impact on the studies of nicotinic acetylcholine receptor. Today compositions of venom from many species have already been examined. Based on these data, one can conclude that venoms contain a large number of individual components belonging to a limited number of structural types. Often minor changes in the amino acid sequence give rise to new biological properties. Change in the living conditions of poisonous animals lead to alterations in the composition of venoms resulting in appearance of new toxins. At the same time introduction of new methods of proteomics and genomics lead to discoveries of new compounds, which may serve as research tools or as templates for the development of novel drugs. The application of these sensitive and comprehensive methods allows studying either of venoms available in tiny amounts or of low abundant components in already known venoms.展开更多
Evolution and natural selection have endowed animal venoms,including scorpion venoms,with a wide range of pharmacological properties.Consequently,scorpions,their venoms,and/or their body parts have been used since tim...Evolution and natural selection have endowed animal venoms,including scorpion venoms,with a wide range of pharmacological properties.Consequently,scorpions,their venoms,and/or their body parts have been used since time immemorial in traditional medicines,especially in Africa and Asia.With respect to their pharmacological potential,bioactive peptides from scorpion venoms have become an important source of scientific research.With the rapid increase in the characterization of various components from scorpion venoms,a large number of peptides are identified with an aim of combating a myriad of emerging global health problems.Moreover,some scorpion venom-derived peptides have been established as potential scaffolds helpful for drug development.In this review,we summarize the promising scorpion venoms-derived peptides as drug candidates.Accordingly,we highlight the data and knowledge needed for continuous characterization and development of additional natural peptides from scorpion venoms,as potential drugs that can treat related diseases.展开更多
基金Supported by: the National Natural Science Foundation of China, No. 30770737
文摘BACKGROUND： Studies have shown that scorpion venom heat-resistant protein （SVHRP） exhibits protective effects on primary cultured hippocampal neurons. OBJECTIVE： To determine the effects of SVHRP on astrocyte activity and synaptic density in the hippocampus induced by amyloid β peptide 1-40 （Aβ1-40） neurotoxicity. DESIGN, TIME AND SETTING： The randomized, controlled, animal experiment was performed at the Central Laboratory, the Laboratory of Human Anatomy, and the Laboratory of Physiology, in Dalian Medical University between March 2006 and June 2008. MATERIALS： Aβ1-40 was provided by Biosource, USA; SVHRP was a patented biological product of Dalian Medical University （No. ZL01 1 06166.9）. METHODS： A total of 27 healthy, 2-month-old, male SD rats were randomly assigned to 3 groups： control, Aβ, and SVHRP, with 9 rats in each group. Alzheimer＇s disease was simulated with 10 μg Aβ1-40 bilaterally injected into the hippocampus of the Aβ and SVHRP groups. The control group was injected with 2 μL 0.05% trifluoroacetic acid. One day following model establishment, the SVHRP group received an intraperitoneal injection of 2 μg/100 g SVHRP, while the control group and Aβ group received 0.5 mL/100 g tri-distilled water, once per day, for 10 consecutive days. MAIN OUTCOME MEASURES： At 16 days following model establishment, synaptophysin （p38） expression in CA1-CA4 regions of the rat hippocampus was determined by immunohistochemistry. Glial fibrillary acidic protein （GFAP） expression surrounding the hippocampal Aβ1-40 injected area was also detected. At 11 days following model establishment, escape latency, swimming time, and distance to target quadrant were measured using the Morris water maze. RESULTS： Compared with the control group, the Aβ group exhibited notably reduced p38 expression （P 〈 0.05） and notably increased GFAP expression in the rat hippocampus （P 〈 0.05）. Water maze results demonstrated that escape latency was prolonged （P 〈 0.05）, and swimming time and distance to the target quadrant were shortened in the Aβ group. Compared with the Aβ group, the SVHRP group exhibited notably increased p38 expression （P 〈 0.05） and notably decreased GFAP expression in the rat hippocampus （P 〈 0.05）. Water maze results demonstrated that escape latency was significantly reduced （P 〈 0.05）, and swimming time and distance to the target quadrant were significantly prolonged. CONCLUSION： SVHRP inhibited exogenous Aβ1-40-induced astrocyte activation and synaptic density decline in the rat hippocampus. Place navigation and spatial searching results showed that SVHRP blocked Aβ1-40-induced impaired learning and memory.
文摘In order to investigate the cardiovascular effects of the scorpion(Buthus martensiKarsch)venom(BmKv),the left ventricle of the rats was catheterized via the right carotidartery.The LVP,LVEDP,+dp/dt max,Vmax,HR and BP were observed.The results showedthat intravenous injection of the BmKv(60μg/kg),in comparison with the control,elicited obvi-ous hypertension and increase of cardiac contractility,both of which lasted for 1h,while theheart rate had no significant change rand that pretreating the rats with alpha-adrenergic blocker,phentolamine,antagonized the hypertensive effects,but did not antagonize the increase of cardiaccontractility.Pretreatment with beta-adrenergic blocker,propranolol,has no influence on the ef-fects of the venom.It is suggested that the hypertensive effects are due to the activation of al-pha-adrenergic receptor,whereas the increase of cardiac contractility may not be resulted fromthe activation of beta-adrenergic receptor.The BmKv treated with dithiothreitol before injectionhad no cardiovascular effects,indicating that the intact disulfide bridges play a decisive role inthe cardiovascular effects of the BmKv.
文摘Background: About 50 species of scorpions cause fatal scorpionism worldwide.Most of these are members of the Buthidae family, and include, among others,Mesobuthus eupeus, Androctonus crassicauda, Leiurus abdullahbayrami, Leiurus quinquestriatus, Tityus pachyurus and Androctonus australis. Because high doses of scorpion venom and antivenom can cause death and hypersensitive reactions, there is a need to develop a formula that can be used to calculate both lethal and effective doses for scorpion venom and antivenom, respectively, thereby obviating the need for laboratory experiments.Methods: In view of this, a literature search was carried out with the aim of modifying the formula(LD_(50)=ED_(50)/3× W_a × 10^(-4))for calculation of the median lethal dose(LD_(50)) of scorpion venom and the ED_(50) of antivenom. The human equivalent dose(HED) formula was assessed for extrapolation of LD_(50) and ED_(50) from animals to human for comparison and relevance with the new formula.Results: The findings showed that the newly developed formula(LD_(50)= ED_(50)^(1/3)×W_a× 10^(-4)) yielded results that are very close to the reported values. Therefore, the newly developed and HED formulas can be used for calculation of LD_(50) and ED_(50) values for scorpion venom and antivenom, respectively.Conclusion: The new formula yielded better results than the HED formula, confirming its predictive validity, precision, and reliability, thereby obviating the need for rigorous experiments and justifying the principles of reduction, refinement, and replacement(3 Rs).
文摘The Tityus serrulatus scorpion is considered the most dangerous scorpion in Brazil and is responsible for several cases of human envenomation annually. In this study, we performed transcriptome profiling of the T. serrulatus venom gland. In addition to transcripts with housekeeping functions, such as those related to protein synthesis, energy supply and structural processes, transcripts from thirty-five families of venom peptides or proteins were identified. These transcripts included three new complete sequences of toxins and more than a dozen putative venom gland proteins/peptides. The venom gland transcriptome profile was verified by comparison with the previously determined proteomic profile. In conclusion, this transcriptome data provides novel insights into the putative mechanisms underlying the venomous character of T. serrulatus. The collected data of scorpion transcripts and proteins/peptides described herein may be an important resource for identifying candidate targets of molecular therapies and preventative measures.
基金This work was supported by a grant from 863High Technology Program,Chinese Ministry of Sci-ence and Technology
文摘The nucleotide sequence deduced from the amino acid sequence of the scorpion insectotoxin AaIT was chemically synthesized and was expressed in Escherichia coli. The authenticity of this in vitro expressed peptide was confirmed by N-terminal peptide sequencing. Two groups of bioassays, artificial diet incorporation assay and contact insecticidal effect assay, were carried out separately to verify the toxicity of this recombinant toxin. At the end of a 24 h experimental period, more than 60% of the testing diamondback moth (Plutella xylostella) larvae were killed in both groups with LC50 value of 18.4 microM and 0.70 microM respectively. Cytotoxicity assay using cultured Sf9 insect cells and MCF-7 human cells demonstrated that the toxin AaIT had specific toxicity against insect cells but not human cells. Only 0.13 microM recombinant toxin was needed to kill 50% of cultured insect cells while as much as 1.3 microM toxin had absolutely no effect on human cells. Insect cells produced obvious intrusions from their plasma membrane before broken up. We infer that toxin AaIT bind to a putative sodium channel in these insect cells and open the channel persistently, which would result in Na+ influx and finally cause destruction of insect cells.
基金Supported by The research funding from Russian Foundation for Basic Research,No.15-04-01843
文摘Poisonous organisms are represented in many taxa, including kingdom Animalia. During evolution, animals have developed special organs for production and injection of venoms. Animal venoms are complex mixtures, compositions of which depend on species producing venom. The most known and studied poisonous terrestrial animals are snakes, scorpions and spiders. Among marine animals, these are jellyfishes, anemones and cone snails. The toxic substances in the venom ofthese animals are mainly of protein and peptide origin. Recent studies have indicated that the single venom may contain up to several hundred different components producing diverse physiological effects. Bites or stings by certain poisonous species result in severe envenomations leading in some cases to death. This raises the problem of bite treatment. The most effective treatment so far is the application of antivenoms. To enhance the effectiveness of such treatments, the knowledge of venom composition is needed. On the other hand, venoms contain substances with unique biological properties, which can be used both in basic science and in clinical applications. The best example of toxin application in basic science is α-bungarotoxin the discovery of which made a big impact on the studies of nicotinic acetylcholine receptor. Today compositions of venom from many species have already been examined. Based on these data, one can conclude that venoms contain a large number of individual components belonging to a limited number of structural types. Often minor changes in the amino acid sequence give rise to new biological properties. Change in the living conditions of poisonous animals lead to alterations in the composition of venoms resulting in appearance of new toxins. At the same time introduction of new methods of proteomics and genomics lead to discoveries of new compounds, which may serve as research tools or as templates for the development of novel drugs. The application of these sensitive and comprehensive methods allows studying either of venoms available in tiny amounts or of low abundant components in already known venoms.
基金This work was supported by the National Natural Science Foundation of China(Nos.31930015,31900332 and 31900375)the Foundation of Chinese Academy of Sciences(No.XDB31000000)+1 种基金the Biological Resources Program,Chinese Academy of Sciences(No.KFJ-BRP-008-003)the KC Wong Education Foundation and Yunnan Province Grant(Nos.2019ZF003,2019YT053,202003AD150008,202001AT070121,202001AW-070015,202001AT070106,2021000097 and 202101AS070057).
文摘Evolution and natural selection have endowed animal venoms,including scorpion venoms,with a wide range of pharmacological properties.Consequently,scorpions,their venoms,and/or their body parts have been used since time immemorial in traditional medicines,especially in Africa and Asia.With respect to their pharmacological potential,bioactive peptides from scorpion venoms have become an important source of scientific research.With the rapid increase in the characterization of various components from scorpion venoms,a large number of peptides are identified with an aim of combating a myriad of emerging global health problems.Moreover,some scorpion venom-derived peptides have been established as potential scaffolds helpful for drug development.In this review,we summarize the promising scorpion venoms-derived peptides as drug candidates.Accordingly,we highlight the data and knowledge needed for continuous characterization and development of additional natural peptides from scorpion venoms,as potential drugs that can treat related diseases.
