Bothrops envenomation is complex and provokes prominent local tissue damage and systemic disturbances,but little is known about their effects on the male reproductive system.After intratesticular injection,the bioacti...Bothrops envenomation is complex and provokes prominent local tissue damage and systemic disturbances,but little is known about their effects on the male reproductive system.After intratesticular injection,the bioactive peptide fraction(Bj-PF)obtained from Bothrops jararaca snake venom changes the structure of different stages of the seminiferous epithelium cycle in adult mice.For the first time,we investigated whether local envenomation of Bj-PF induces toxicological effects on the male reproductive system,particularly on the seminiferous epithelium and Sertoli cells.Male adult mice were treated with 0.24 mg.kg^(-1) by intramuscular(i.m.)injection for 24 h.The testes samples were collected for morphological and morphometric evaluation.The toxicological effects of Bj-PF were also analyzed on mitochondrial metabolism and nitrite(NO2)production in 15P-1 Sertoli cell culture.Bj-PF changed the structure and function of the seminiferous epithelium,particularly the disruption of the epithelium and the presence of degenerated germ cells in the adluminal compartment,but there were no alterations in the basal compartment.Bj-PF increased the thickness of the seminiferous epithelium and decreased the lumen diameter of the tubule.Semiquantitative histological assessment of the degree of tubule degeneration revealed that Bj-PF also increased the number of hypospermatogenic tubules compared to control.Bj-PF reduced NO2 levels in 15P-1 Sertoli cells without changing the mitochondrial metabolism.Overall,the fact that Bj-PF alters the structure and function of the seminiferous epithelium suggests that bioactive peptides found in B.jararaca snake venom can have toxicological effects on the reproductive systems of affected male mice,providing new insight into the biological characteristics of snake venom and therapeutic strategies for envenomation inflammation.展开更多
Many active secretions produced by animals have been employed in the development of new drugs to treat diseases such as hypertension and cancer.Snake venom toxins coutributed significantly to the treatment of many med...Many active secretions produced by animals have been employed in the development of new drugs to treat diseases such as hypertension and cancer.Snake venom toxins coutributed significantly to the treatment of many medical conditions.There are many published studies describing and elucidating the anti-cancer potential of snake venom.Cancer therapy is one of the main areas for the use of protein peptides and enzymes originating from animals of different species.Some of these proteins or peptides and enzymes from snake venom when isolated and evaluated may bind specifically to cancer cell membranes,affecting the migration and proliferation of these cells.Some of substances found in the snake venom present a great potential as anti-tumor agent.In this review,we presented the main results of recent years of research involving the active compounds of snake venom that have anticancer activity.展开更多
Snake venoms are folk medicines used since ages. The components of snake venoms have high specific affinity and actions on cells and cell components. Also snake venoms are largely cytotoxic to tumor cells than normal ...Snake venoms are folk medicines used since ages. The components of snake venoms have high specific affinity and actions on cells and cell components. Also snake venoms are largely cytotoxic to tumor cells than normal cells. In addition to these, they have several therapeutic actions that make them an attractive option in the management of cancer. The advent of modern technologies has greatly helped in extracting and identifying new components of therapeutic interests in short time. The article highlights the importance of snake venoms in the management of cancer, so as to motivate curious researchers to devote their skills in this fascinating area. This in turn may bring hope, smile and relief to several cancer patients in future.展开更多
Snake venom is a complex cocktail including a variety of biological active proteins and proteinaceous components, which have considerable medical and pharmacological importance. N-Glycosylation is widely impli- cated ...Snake venom is a complex cocktail including a variety of biological active proteins and proteinaceous components, which have considerable medical and pharmacological importance. N-Glycosylation is widely impli- cated as a common modification in numerous venom proteins and impacts the in vivo venomic functions. However, systematic survey of N-glycome and N-glycoproteome on snake venoms has not been undertaken. In this study, em- ploying combination of N-glycomics and N-glycoproteomics strategies, we explored the N-glycosylation including both N-glycoproteins and N-glyco-chains in three venoms from Agkistrodon blomhoffii, Naja naja atra Cantor and Vipera russelii siamensis Smith, respectively, which are amongst the most abundant venomous snakes in Asia. As a result, numbers of N-glycoproteins and N-glycans were identified. However, the overlaps of N-glycoproteins and N-glycans of the three venoms were small. Thus, the exploration results of N-glycome and N-glycoproteome indicate that N-glycosylation increases the complexity and variety of the three venoms. Our research provided some new horizons for the comprehensive understanding of venoms variation, which is helpful for the basic venom re- search as well as the management of snake envenomation.展开更多
THE snake venom zinc-metalloproteinases and matrix metalloproteinases (MMP) have the similar active site and biological function. They all belong to the MMP super-family. Some
The haemorrhagin AaH Ⅲ isolated from the snake venom of Agkistrodon acutus is one of the few al-kaline ones in snake venoms. Its crystals belong to space group P212121 with a = 9. 573 4 nm, b = 4. 996 7 nm and c = 4....The haemorrhagin AaH Ⅲ isolated from the snake venom of Agkistrodon acutus is one of the few al-kaline ones in snake venoms. Its crystals belong to space group P212121 with a = 9. 573 4 nm, b = 4. 996 7 nm and c = 4. 728 8 nm. Its crystal structure was determined by the molecular replacement method according to the model of metalloproteinase Adamalysin n from eastern rattlesnake venom. The AaHⅢ structure has been refined by PROLSQ. The final R factor was 0.254 and the RMS deviations of bond lengths and angles were 0. 001 8 nm and 1.5°. The structure comparison suggested that AaHⅢ has a similar structure to other snake venom zinc-metalloproteinases. They all belong to matrix metalloproteinases super-family.展开更多
Bactericidal/permeability-increasing protein(BPI)and LPS-binding protein(LBP)play an important role in host defence.Current evidence shows that BPI/LBP may be widely existed in different cells and tissue types of anim...Bactericidal/permeability-increasing protein(BPI)and LPS-binding protein(LBP)play an important role in host defence.Current evidence shows that BPI/LBP may be widely existed in different cells and tissue types of animals.A full-length cDNA clone encoding a BPI/LBP homologue(dBPI),1757 bp in size,was characterized in venom gland of the hundred-pace snake Deinagkistrodon acutus.Its deduced amino acid sequence of 417 residues had 13.8%-21.5% identity to BPI like 1(BPIL1)and BPI like 3(BPIL3)of other animals.Conserved cysteine residues which are involved in disulfide bond formation between the final strand of the N-terminal beta sheet and the long alpha helix of BPI are identified as Cys146-Cys183 of dBPI.Phylogenetic tree analysis showed that the BPI/LBP homologues formed five large clusters and dBPI was in a large cluster including BPIL1 and BPIL3.dBPI mRNA shows a tissue specific expression in venom gland.This is the first study to identify the cDNA encoding BPI/LBP homologues from reptiles.展开更多
Two cDNAs encoding hemorrhagic snake venom metalloproteinase acutolysin A and non-hemorrhagic metalloproteinase (BR) were cloned into the expression vector pET-22b, respectively, and the corresponding two recombinant ...Two cDNAs encoding hemorrhagic snake venom metalloproteinase acutolysin A and non-hemorrhagic metalloproteinase (BR) were cloned into the expression vector pET-22b, respectively, and the corresponding two recombinant proteins, A-22b and BR-22b, were produced in inclusion bodies in E. coli BL21(DE3). The recombinant proteins were then subjected to solubilization, purification and refolding in vitro. A-22b showed hemorrhagic activity but no detectable proteolytic activities toward fibrinogen and fibronectin. Natural acutolysin A had both hemorrhagic activity and proteolytic activity toward these substrates. BR-22b showed the proteolytic activities toward fibrinogen, but no hemorrhagic activity. In addition, two chimeric genes, C1 and C2, were constructed and cloned into pET-22b, and the corresponding recombinant proteins, C1-22b and C2-22b, were also expressed in inclusion bodies. C1-22b involved N-terminal 110 amino acids of BR and C-terminal 95 amino acids of acutolysin A, while C2-22b contained N-terminal 108 amino acids of acutolysin A and C-terminal 112 amino acids of BR. The biological activities of C2-22b and C1-22b were similar to those of A-22b and BR-22b, respectively. Our results suggested that N-terminal major subdomain of a snake venom metalloproteinase might play a key role in hemorrhagic activity and have an appreciable effect on the selectivity for protein substrates.展开更多
Matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI/MS) is a new, powerful analytical tool for the investigation of large biomolecules. Since its inception in 1986 by Koichi Tanaka and ...Matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI/MS) is a new, powerful analytical tool for the investigation of large biomolecules. Since its inception in 1986 by Koichi Tanaka and Franz Hillenkamp separately, MALDI/MS has been successfully applied to the investigation of展开更多
Haemorrhagins,Which cause local haemorrhage or even death after injection into exper-imental animals,exist widely in many kinds of snake venoms.Almost allthe haemorrhagins reported are zinc-metalloproteinases with hig...Haemorrhagins,Which cause local haemorrhage or even death after injection into exper-imental animals,exist widely in many kinds of snake venoms.Almost allthe haemorrhagins reported are zinc-metalloproteinases with highly conserved amino acid se-quences.Some of them could degrade the proteins in matrices so that they are the im-portant targets for drugs to combat diseases such as arthritis and cancer.Snake venommetalloproteinases can be divided into three classes based on their molecular展开更多
基金supported by the State of São Paulo Research Foundation(FAPESP)the Coordination for the Improvement of Higher Education Personnel(CAPES)(Finance Code 001).
文摘Bothrops envenomation is complex and provokes prominent local tissue damage and systemic disturbances,but little is known about their effects on the male reproductive system.After intratesticular injection,the bioactive peptide fraction(Bj-PF)obtained from Bothrops jararaca snake venom changes the structure of different stages of the seminiferous epithelium cycle in adult mice.For the first time,we investigated whether local envenomation of Bj-PF induces toxicological effects on the male reproductive system,particularly on the seminiferous epithelium and Sertoli cells.Male adult mice were treated with 0.24 mg.kg^(-1) by intramuscular(i.m.)injection for 24 h.The testes samples were collected for morphological and morphometric evaluation.The toxicological effects of Bj-PF were also analyzed on mitochondrial metabolism and nitrite(NO2)production in 15P-1 Sertoli cell culture.Bj-PF changed the structure and function of the seminiferous epithelium,particularly the disruption of the epithelium and the presence of degenerated germ cells in the adluminal compartment,but there were no alterations in the basal compartment.Bj-PF increased the thickness of the seminiferous epithelium and decreased the lumen diameter of the tubule.Semiquantitative histological assessment of the degree of tubule degeneration revealed that Bj-PF also increased the number of hypospermatogenic tubules compared to control.Bj-PF reduced NO2 levels in 15P-1 Sertoli cells without changing the mitochondrial metabolism.Overall,the fact that Bj-PF alters the structure and function of the seminiferous epithelium suggests that bioactive peptides found in B.jararaca snake venom can have toxicological effects on the reproductive systems of affected male mice,providing new insight into the biological characteristics of snake venom and therapeutic strategies for envenomation inflammation.
文摘Many active secretions produced by animals have been employed in the development of new drugs to treat diseases such as hypertension and cancer.Snake venom toxins coutributed significantly to the treatment of many medical conditions.There are many published studies describing and elucidating the anti-cancer potential of snake venom.Cancer therapy is one of the main areas for the use of protein peptides and enzymes originating from animals of different species.Some of these proteins or peptides and enzymes from snake venom when isolated and evaluated may bind specifically to cancer cell membranes,affecting the migration and proliferation of these cells.Some of substances found in the snake venom present a great potential as anti-tumor agent.In this review,we presented the main results of recent years of research involving the active compounds of snake venom that have anticancer activity.
文摘Snake venoms are folk medicines used since ages. The components of snake venoms have high specific affinity and actions on cells and cell components. Also snake venoms are largely cytotoxic to tumor cells than normal cells. In addition to these, they have several therapeutic actions that make them an attractive option in the management of cancer. The advent of modern technologies has greatly helped in extracting and identifying new components of therapeutic interests in short time. The article highlights the importance of snake venoms in the management of cancer, so as to motivate curious researchers to devote their skills in this fascinating area. This in turn may bring hope, smile and relief to several cancer patients in future.
基金Supported by the National Basic Research Program of China（No.2013CB911201）, the National High Technology Research and Development Program of China（No.2012AA020200）, the National Natural Science Foundation of China（No.31100590） and the Shanghai Municipal Natural Science Foundation, China（No. 11ZR1403000）.
文摘Snake venom is a complex cocktail including a variety of biological active proteins and proteinaceous components, which have considerable medical and pharmacological importance. N-Glycosylation is widely impli- cated as a common modification in numerous venom proteins and impacts the in vivo venomic functions. However, systematic survey of N-glycome and N-glycoproteome on snake venoms has not been undertaken. In this study, em- ploying combination of N-glycomics and N-glycoproteomics strategies, we explored the N-glycosylation including both N-glycoproteins and N-glyco-chains in three venoms from Agkistrodon blomhoffii, Naja naja atra Cantor and Vipera russelii siamensis Smith, respectively, which are amongst the most abundant venomous snakes in Asia. As a result, numbers of N-glycoproteins and N-glycans were identified. However, the overlaps of N-glycoproteins and N-glycans of the three venoms were small. Thus, the exploration results of N-glycome and N-glycoproteome indicate that N-glycosylation increases the complexity and variety of the three venoms. Our research provided some new horizons for the comprehensive understanding of venoms variation, which is helpful for the basic venom re- search as well as the management of snake envenomation.
文摘THE snake venom zinc-metalloproteinases and matrix metalloproteinases (MMP) have the similar active site and biological function. They all belong to the MMP super-family. Some
基金Project supported by the Chinese Academy of Sciences, State Key Laboratory of Biomacromolecules and State Education Commission of China.
文摘The haemorrhagin AaH Ⅲ isolated from the snake venom of Agkistrodon acutus is one of the few al-kaline ones in snake venoms. Its crystals belong to space group P212121 with a = 9. 573 4 nm, b = 4. 996 7 nm and c = 4. 728 8 nm. Its crystal structure was determined by the molecular replacement method according to the model of metalloproteinase Adamalysin n from eastern rattlesnake venom. The AaHⅢ structure has been refined by PROLSQ. The final R factor was 0.254 and the RMS deviations of bond lengths and angles were 0. 001 8 nm and 1.5°. The structure comparison suggested that AaHⅢ has a similar structure to other snake venom zinc-metalloproteinases. They all belong to matrix metalloproteinases super-family.
基金funded by a grant from the local government of Zhejiang Province for the Specially Supported Discipline of Zoology
文摘Bactericidal/permeability-increasing protein(BPI)and LPS-binding protein(LBP)play an important role in host defence.Current evidence shows that BPI/LBP may be widely existed in different cells and tissue types of animals.A full-length cDNA clone encoding a BPI/LBP homologue(dBPI),1757 bp in size,was characterized in venom gland of the hundred-pace snake Deinagkistrodon acutus.Its deduced amino acid sequence of 417 residues had 13.8%-21.5% identity to BPI like 1(BPIL1)and BPI like 3(BPIL3)of other animals.Conserved cysteine residues which are involved in disulfide bond formation between the final strand of the N-terminal beta sheet and the long alpha helix of BPI are identified as Cys146-Cys183 of dBPI.Phylogenetic tree analysis showed that the BPI/LBP homologues formed five large clusters and dBPI was in a large cluster including BPIL1 and BPIL3.dBPI mRNA shows a tissue specific expression in venom gland.This is the first study to identify the cDNA encoding BPI/LBP homologues from reptiles.
文摘Two cDNAs encoding hemorrhagic snake venom metalloproteinase acutolysin A and non-hemorrhagic metalloproteinase (BR) were cloned into the expression vector pET-22b, respectively, and the corresponding two recombinant proteins, A-22b and BR-22b, were produced in inclusion bodies in E. coli BL21(DE3). The recombinant proteins were then subjected to solubilization, purification and refolding in vitro. A-22b showed hemorrhagic activity but no detectable proteolytic activities toward fibrinogen and fibronectin. Natural acutolysin A had both hemorrhagic activity and proteolytic activity toward these substrates. BR-22b showed the proteolytic activities toward fibrinogen, but no hemorrhagic activity. In addition, two chimeric genes, C1 and C2, were constructed and cloned into pET-22b, and the corresponding recombinant proteins, C1-22b and C2-22b, were also expressed in inclusion bodies. C1-22b involved N-terminal 110 amino acids of BR and C-terminal 95 amino acids of acutolysin A, while C2-22b contained N-terminal 108 amino acids of acutolysin A and C-terminal 112 amino acids of BR. The biological activities of C2-22b and C1-22b were similar to those of A-22b and BR-22b, respectively. Our results suggested that N-terminal major subdomain of a snake venom metalloproteinase might play a key role in hemorrhagic activity and have an appreciable effect on the selectivity for protein substrates.
文摘Matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI/MS) is a new, powerful analytical tool for the investigation of large biomolecules. Since its inception in 1986 by Koichi Tanaka and Franz Hillenkamp separately, MALDI/MS has been successfully applied to the investigation of
基金Project supported by the State Key Laboratory of Biomacromolecules, Chinese Academy of Science and State Foundation Commission of China.
文摘Haemorrhagins,Which cause local haemorrhage or even death after injection into exper-imental animals,exist widely in many kinds of snake venoms.Almost allthe haemorrhagins reported are zinc-metalloproteinases with highly conserved amino acid se-quences.Some of them could degrade the proteins in matrices so that they are the im-portant targets for drugs to combat diseases such as arthritis and cancer.Snake venommetalloproteinases can be divided into three classes based on their molecular
