Isolation of a Novel Metalloproteinase from Agkistrodon Venom and Its Antithrombotic Activity Analysis
Snake venom contains large amounts of active proteins and peptides. In this study, a novel snake protein, metalloproteinase SP, was successfully isolated from the venom of <i>Agkistrodon </i><i>acutus</i> by multi-gel chromatography. The isolated protein exhibits anti-platele...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2019-08-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/20/17/4088 |
id |
doaj-8e8673cacc0740448217845b281fc7c2 |
---|---|
record_format |
Article |
spelling |
doaj-8e8673cacc0740448217845b281fc7c22020-11-24T22:13:41ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-08-012017408810.3390/ijms20174088ijms20174088Isolation of a Novel Metalloproteinase from Agkistrodon Venom and Its Antithrombotic Activity AnalysisJin Huang0Hui Fan1Xiaojian Yin2Fang Huang3State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, ChinaSnake venom contains large amounts of active proteins and peptides. In this study, a novel snake protein, metalloproteinase SP, was successfully isolated from the venom of <i>Agkistrodon </i><i>acutus</i> by multi-gel chromatography. The isolated protein exhibits anti-platelet aggregation activity. Animal experiments showed that it exhibited defibration, anticoagulation, and antithrombotic effects and contributes to improved blood rheology and antiplatelet aggregation. In vivo experiments demonstrated that it prolonged clotting time, partial thromboplastin time, prothrombin time, thrombin time, fibrinogen time and reduced fibrinogen content of mice. Also, metalloproteinase SP inhibited carrageenan-induced tail thrombosis, ADP-induced acute pulmonary embolism, and ADP, Arachidonic acid (AA), or collagen-induced platelet aggregation. In vitro experiments showed that the protein cleaved the α, β, and γ chains of fibrinogen. Metabolomic analysis upon metalloproteinase SP treatment revealed that 14 metabolites, which are mainly involved in phenylalanine, tyrosine, and tryptophan biosynthesis, responded to metalloproteinase SP treatment. In summary, the isolated snake venom protein inhibits formation of acute pulmonary embolism probably through regulating and restoring perturbed energy, lipid, and amino acid metabolism.https://www.mdpi.com/1422-0067/20/17/4088Agkistrodon venommetalloproteinasefibrinogenantithromboticmetabolomics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jin Huang Hui Fan Xiaojian Yin Fang Huang |
spellingShingle |
Jin Huang Hui Fan Xiaojian Yin Fang Huang Isolation of a Novel Metalloproteinase from Agkistrodon Venom and Its Antithrombotic Activity Analysis International Journal of Molecular Sciences Agkistrodon venom metalloproteinase fibrinogen antithrombotic metabolomics |
author_facet |
Jin Huang Hui Fan Xiaojian Yin Fang Huang |
author_sort |
Jin Huang |
title |
Isolation of a Novel Metalloproteinase from Agkistrodon Venom and Its Antithrombotic Activity Analysis |
title_short |
Isolation of a Novel Metalloproteinase from Agkistrodon Venom and Its Antithrombotic Activity Analysis |
title_full |
Isolation of a Novel Metalloproteinase from Agkistrodon Venom and Its Antithrombotic Activity Analysis |
title_fullStr |
Isolation of a Novel Metalloproteinase from Agkistrodon Venom and Its Antithrombotic Activity Analysis |
title_full_unstemmed |
Isolation of a Novel Metalloproteinase from Agkistrodon Venom and Its Antithrombotic Activity Analysis |
title_sort |
isolation of a novel metalloproteinase from agkistrodon venom and its antithrombotic activity analysis |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-08-01 |
description |
Snake venom contains large amounts of active proteins and peptides. In this study, a novel snake protein, metalloproteinase SP, was successfully isolated from the venom of <i>Agkistrodon </i><i>acutus</i> by multi-gel chromatography. The isolated protein exhibits anti-platelet aggregation activity. Animal experiments showed that it exhibited defibration, anticoagulation, and antithrombotic effects and contributes to improved blood rheology and antiplatelet aggregation. In vivo experiments demonstrated that it prolonged clotting time, partial thromboplastin time, prothrombin time, thrombin time, fibrinogen time and reduced fibrinogen content of mice. Also, metalloproteinase SP inhibited carrageenan-induced tail thrombosis, ADP-induced acute pulmonary embolism, and ADP, Arachidonic acid (AA), or collagen-induced platelet aggregation. In vitro experiments showed that the protein cleaved the α, β, and γ chains of fibrinogen. Metabolomic analysis upon metalloproteinase SP treatment revealed that 14 metabolites, which are mainly involved in phenylalanine, tyrosine, and tryptophan biosynthesis, responded to metalloproteinase SP treatment. In summary, the isolated snake venom protein inhibits formation of acute pulmonary embolism probably through regulating and restoring perturbed energy, lipid, and amino acid metabolism. |
topic |
Agkistrodon venom metalloproteinase fibrinogen antithrombotic metabolomics |
url |
https://www.mdpi.com/1422-0067/20/17/4088 |
work_keys_str_mv |
AT jinhuang isolationofanovelmetalloproteinasefromagkistrodonvenomanditsantithromboticactivityanalysis AT huifan isolationofanovelmetalloproteinasefromagkistrodonvenomanditsantithromboticactivityanalysis AT xiaojianyin isolationofanovelmetalloproteinasefromagkistrodonvenomanditsantithromboticactivityanalysis AT fanghuang isolationofanovelmetalloproteinasefromagkistrodonvenomanditsantithromboticactivityanalysis |
_version_ |
1725800069717819392 |