Promucetin, a new C-type lectin-like protein modulates coagulation by activating platelets via GPIb

Abstract Background: Snake venom C-type lectin-like proteins (also known as snaclecs) have anticoagulation and procoagulation effects by targeting platelet or coagulation factor IX/X, suggesting their potential as candidates for new anticoagulant drugs. Therefore, this study aims to evaluate the an...

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Main Authors: Xiao-Qin Yu, Qi-Yun Zhang, Shu-Ting Zhou, Qing-Yu Lu, Qian-Yun Sun
Format: Article
Language:English
Published: SciELO 2025-07-01
Series:Journal of Venomous Animals and Toxins including Tropical Diseases
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Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992025000100311&lng=en&tlng=en
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author Xiao-Qin Yu
Qi-Yun Zhang
Shu-Ting Zhou
Qing-Yu Lu
Qian-Yun Sun
author_facet Xiao-Qin Yu
Qi-Yun Zhang
Shu-Ting Zhou
Qing-Yu Lu
Qian-Yun Sun
author_sort Xiao-Qin Yu
collection DOAJ
description Abstract Background: Snake venom C-type lectin-like proteins (also known as snaclecs) have anticoagulation and procoagulation effects by targeting platelet or coagulation factor IX/X, suggesting their potential as candidates for new anticoagulant drugs. Therefore, this study aims to evaluate the antiplatelet and antithrombotic effects of a new snaclec from Protobothrops mucrosquamatus venom and its potential as an anticoagulant candidate. Methods: Promucetin was purified through sequential column chromatography, and its molecular mass was determined by SDS-PAGE. The α- and β-chains of promucetin were identified using liquid chromatography-mass spectrometry (LC-MS). In vitro analyses of platelet aggregation were performed using turbidimetric methods, thromboelastography, and coagulation activity assays. For in vivo experiments, promucetin was administered to rats at varying concentrations, and platelet changes were monitored. The antithrombotic effects of promucetin were assessed using a FeCl₃-induced rat thrombosis model. Results: Promucetin existed as two multimers with molecular weights of 140.1 kDa and 91.9 kDa under non-reducing conditions. Sequence analysis revealed that its α-chain and β-chain shared 71% and 34% homology, respectively, with TMVA from the same snake venom. In vitro platelet aggregation assays indicated that promucetin activated platelets via glycoprotein Ib. Thromboelastography showed that promucetin inhibited both coagulation factor activity and platelet function, resulting in an anticoagulant effect. Specifically, thrombin time was prolonged, while activated partial thromboplastin time and prothrombin time remained unchanged. In vivo, promucetin administration led to a dose-dependent decrease in platelet count. At doses of 25 and 50 μg/kg, promucetin significantly inhibited thrombosis, with inhibition rates of 40.9% and 74.4%, respectively. For comparison, lysine acetylsalicylate produced an inhibition rate of 36.7%. Conclusion: Promucetin exhibits significant ability to modulate coagulation function and effectively inhibit thrombosis by activating platelet via GPIb and reducing platelet count, which helps us understand its biological function in snake bites, it exhibits the potential to be a candidate for anticoagulant therapy.
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series Journal of Venomous Animals and Toxins including Tropical Diseases
spelling doaj-art-a35aab0cffe741099264fb86f76f60312025-08-20T03:33:11ZengSciELOJournal of Venomous Animals and Toxins including Tropical Diseases1678-91992025-07-013110.1590/1678-9199-jvatitd-2025-0003Promucetin, a new C-type lectin-like protein modulates coagulation by activating platelets via GPIbXiao-Qin Yuhttps://orcid.org/0009-0004-3502-2004Qi-Yun Zhanghttps://orcid.org/0000-0002-7117-7888Shu-Ting Zhouhttps://orcid.org/0009-0003-1714-8474Qing-Yu Luhttps://orcid.org/0009-0001-7820-5570Qian-Yun Sunhttps://orcid.org/0000-0001-9691-2028Abstract Background: Snake venom C-type lectin-like proteins (also known as snaclecs) have anticoagulation and procoagulation effects by targeting platelet or coagulation factor IX/X, suggesting their potential as candidates for new anticoagulant drugs. Therefore, this study aims to evaluate the antiplatelet and antithrombotic effects of a new snaclec from Protobothrops mucrosquamatus venom and its potential as an anticoagulant candidate. Methods: Promucetin was purified through sequential column chromatography, and its molecular mass was determined by SDS-PAGE. The α- and β-chains of promucetin were identified using liquid chromatography-mass spectrometry (LC-MS). In vitro analyses of platelet aggregation were performed using turbidimetric methods, thromboelastography, and coagulation activity assays. For in vivo experiments, promucetin was administered to rats at varying concentrations, and platelet changes were monitored. The antithrombotic effects of promucetin were assessed using a FeCl₃-induced rat thrombosis model. Results: Promucetin existed as two multimers with molecular weights of 140.1 kDa and 91.9 kDa under non-reducing conditions. Sequence analysis revealed that its α-chain and β-chain shared 71% and 34% homology, respectively, with TMVA from the same snake venom. In vitro platelet aggregation assays indicated that promucetin activated platelets via glycoprotein Ib. Thromboelastography showed that promucetin inhibited both coagulation factor activity and platelet function, resulting in an anticoagulant effect. Specifically, thrombin time was prolonged, while activated partial thromboplastin time and prothrombin time remained unchanged. In vivo, promucetin administration led to a dose-dependent decrease in platelet count. At doses of 25 and 50 μg/kg, promucetin significantly inhibited thrombosis, with inhibition rates of 40.9% and 74.4%, respectively. For comparison, lysine acetylsalicylate produced an inhibition rate of 36.7%. Conclusion: Promucetin exhibits significant ability to modulate coagulation function and effectively inhibit thrombosis by activating platelet via GPIb and reducing platelet count, which helps us understand its biological function in snake bites, it exhibits the potential to be a candidate for anticoagulant therapy.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992025000100311&lng=en&tlng=enC-type lectin-like proteinsPlatelet aggregationCoagulation functionThrombusSnake venom
spellingShingle Xiao-Qin Yu
Qi-Yun Zhang
Shu-Ting Zhou
Qing-Yu Lu
Qian-Yun Sun
Promucetin, a new C-type lectin-like protein modulates coagulation by activating platelets via GPIb
Journal of Venomous Animals and Toxins including Tropical Diseases
C-type lectin-like proteins
Platelet aggregation
Coagulation function
Thrombus
Snake venom
title Promucetin, a new C-type lectin-like protein modulates coagulation by activating platelets via GPIb
title_full Promucetin, a new C-type lectin-like protein modulates coagulation by activating platelets via GPIb
title_fullStr Promucetin, a new C-type lectin-like protein modulates coagulation by activating platelets via GPIb
title_full_unstemmed Promucetin, a new C-type lectin-like protein modulates coagulation by activating platelets via GPIb
title_short Promucetin, a new C-type lectin-like protein modulates coagulation by activating platelets via GPIb
title_sort promucetin a new c type lectin like protein modulates coagulation by activating platelets via gpib
topic C-type lectin-like proteins
Platelet aggregation
Coagulation function
Thrombus
Snake venom
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992025000100311&lng=en&tlng=en
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AT shutingzhou promucetinanewctypelectinlikeproteinmodulatescoagulationbyactivatingplateletsviagpib
AT qingyulu promucetinanewctypelectinlikeproteinmodulatescoagulationbyactivatingplateletsviagpib
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