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Toxins 2018, 10(11), 429; https://doi.org/10.3390/toxins10110429

Isolation and Characterization of Poecistasin, an Anti-Thrombotic Antistasin-Type Serine Protease Inhibitor from Leech Poecilobdella manillensis

1
Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China
2
Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, Yunnan, China
3
College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 20 September 2018 / Revised: 13 October 2018 / Accepted: 24 October 2018 / Published: 26 October 2018
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Abstract

Antistasin, first identified as a potent inhibitor of the blood coagulation factor Xa, is a novel family of serine protease inhibitors. In this study, we purified a novel antistasin-type inhibitor from leech Poecilobdella manillensis called poecistasin. Amino acid sequencing of this 48-amino-acid protein revealed that poecistasin was an antistasin-type inhibitor known to consist of only one domain. Poecistasin inhibited factor XIIa, kallikrein, trypsin, and elastase, but had no inhibitory effect on factor Xa and thrombin. Poecistasin showed anticoagulant activities. It prolonged the activated partial thromboplastin time and inhibited FeCl3-induced carotid artery thrombus formation, implying its potent function in helping Poecilobdella manillensis to take a blood meal from the host by inhibiting coagulation. Poecistasin also suppressed ischemic stroke symptoms in transient middle cerebral artery occlusion mice model. Our results suggest that poecistasin from the leech Poecilobdella manillensis plays a crucial role in blood-sucking and may be an excellent candidate for the development of clinical anti-thrombosis and anti-ischemic stroke medicines. View Full-Text
Keywords: Antistasin-type inhibitor; Poecilobdella manillensis; poecistasin; coagulation; thrombus formation; ischemic stroke Antistasin-type inhibitor; Poecilobdella manillensis; poecistasin; coagulation; thrombus formation; ischemic stroke
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Tang, X.; Chen, M.; Duan, Z.; Mwangi, J.; Li, P.; Lai, R. Isolation and Characterization of Poecistasin, an Anti-Thrombotic Antistasin-Type Serine Protease Inhibitor from Leech Poecilobdella manillensis. Toxins 2018, 10, 429.

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