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A Novel Antithrombotic Protease from Marine Worm Sipunculus Nudus.

Abstract
Sipunculus nudus, an old marine species, has great potential for use as functional seafood due to its various bioactivities. Its potential antithrombotic activity pushed us to isolate the bio-active components bio-guided by tracking fibrinolytic activity. As a result, a novel protease named as SK (the kinase obtained from S. nudus) was obtained, which possessed a molecular weight of 28,003.67 Da and 15 N-terminal amino acid sequences of PFPVPDPFVWDTSFQ. SK exerted inhibitory effects on thrombus formation through improving the coagulation system with dose-effect relationship within a certain range. Furthermore, in most cases SK got obviously better effect than that of urokinase. With the help of untargeted mass spectrometry-based metabolomics profiling, arachidonic acid, sphingolipid, and nicotinate and nicotinamide mechanism pathways were found to be important pathways. They revealed that the effect mechanism of SK on common carotid arterial thrombosis induced by FeCl₃ was achieved by inhibiting vessel contraction, platelet aggregation, adhesion, and release, correcting endothelial cell dysfunction and retarding process of thrombus formation. This study demonstrated SK was a promising thrombolytic agent on the basis of its comprehensive activities on thrombosis, and it should get further exploitation and utilization.
AuthorsYa-Hui Ge, Yan-Yan Chen, Gui-Sheng Zhou, Xin Liu, Yu-Ping Tang, Rui Liu, Pei Liu, Na Li, Jie Yang, Jing Wang, Shi-Jun Yue, Huiping Zhou, Jin-Ao Duan
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 19 Issue 10 (Oct 04 2018) ISSN: 1422-0067 [Electronic] Switzerland
PMID30287737 (Publication Type: Journal Article)
Chemical References
  • Fibrinolytic Agents
  • Helminth Proteins
  • Peptide Hydrolases
Topics
  • Animals
  • Carotid Artery Thrombosis (drug therapy)
  • Fibrinolytic Agents (chemistry, metabolism, therapeutic use)
  • Helminth Proteins (chemistry, metabolism, therapeutic use)
  • Male
  • Nematoda (enzymology)
  • Peptide Hydrolases (chemistry, metabolism, therapeutic use)
  • Rats
  • Rats, Sprague-Dawley

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