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海洋蠕虫中的一种新型抗血栓蛋白酶

A Novel Antithrombotic Protease from Marine Worm .

机构信息

Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.

出版信息

Int J Mol Sci. 2018 Oct 4;19(10):3023. doi: 10.3390/ijms19103023.

DOI:10.3390/ijms19103023
PMID:30287737
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6213608/
Abstract

, 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 ) 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.

摘要

, 一种古老的海洋物种,由于其各种生物活性,具有巨大的用作功能性海鲜的潜力。其潜在的抗血栓活性促使我们通过跟踪纤溶活性进行生物导向分离生物活性成分。结果,获得了一种名为 SK(从 中获得的激酶)的新型蛋白酶,其分子量为 28003.67Da,N 端 15 个氨基酸序列为 PFPVPDPFVWDTSFQ。SK 通过改善凝血系统在一定范围内发挥抑制血栓形成的作用,且呈剂量效应关系。此外,在大多数情况下,SK 的效果明显优于尿激酶。借助基于非靶向质谱的代谢组学分析,发现花生四烯酸、鞘脂、烟酸和烟酰胺途径是重要途径。结果表明,SK 通过抑制血管收缩、血小板聚集、黏附和释放,纠正内皮细胞功能障碍和延缓血栓形成过程,对 FeCl₃诱导的颈总动脉血栓形成发挥作用。本研究表明,基于其对血栓形成的综合作用,SK 是一种有前途的溶栓剂,应进一步开发和利用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2349/6213608/1b433136a71f/ijms-19-03023-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2349/6213608/67ed96c99f12/ijms-19-03023-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2349/6213608/892b6d708354/ijms-19-03023-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2349/6213608/ba6788ca9bf4/ijms-19-03023-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2349/6213608/c405c5c88a0b/ijms-19-03023-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2349/6213608/801c0d60f603/ijms-19-03023-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2349/6213608/1b433136a71f/ijms-19-03023-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2349/6213608/67ed96c99f12/ijms-19-03023-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2349/6213608/892b6d708354/ijms-19-03023-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2349/6213608/ba6788ca9bf4/ijms-19-03023-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2349/6213608/c405c5c88a0b/ijms-19-03023-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2349/6213608/801c0d60f603/ijms-19-03023-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2349/6213608/1b433136a71f/ijms-19-03023-g006.jpg

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