LCTX-F2, a Novel Potentiator of Coagulation Factors From the Spider Venom of Lycosa singoriensis.

Pengpeng Li,Er Meng,Qiong Liao,Ren Lai,Mingqiang Rong,James Mwangi,Zhongzhe Zhang

doi:10.3389/fphar.2020.00896

Abstract

Spider venoms contain many functional proteins/peptides such as proteinases, serine/cysteine proteinase inhibitors, insecticidal toxins, and ion channel toxins. However, to date, no peptide toxin with procoagulant activities has been identified from spider venom. In this study, a novel toxin LCTX-F2 with coagulation-promoting activity was identified and characterized in the venom of the spider Lycosa singoriensis (L. singoriensis). LCTX-F2 significantly shortened activated partial thromboplastin time (APTT), clotting time, and plasma recalcification time. This toxin directly interacted with several coagulation factors such as FXIIa, kallikrein, thrombin, and FXa and increased their protease activities. In liver bleeding and tail bleeding mouse models, LCTX-F2 significantly decreased the number of blood cells and bleeding time in a dose-dependent manner. At the same dosage, LCTX-F2 exhibited a more significant procoagulant effect than epsilon aminocaproic acid (EACA). Moreover, LCTX-F2 showed no cytotoxic or hemolytic activity against either normal cells or red blood cells. Our results suggested that LCTX-F2 is a potentiator of coagulation factors with the potential for use in the development of procoagulant drugs.

Highlights

Excessive blood loss is a leading cause of the high mortality rate associated with surgical operations (Willner et al, 2016)
A BLAST search indicated that LCTX-F2 belonged to the toxin 35 superfamily of spider toxins (Figure 1B), and the distribution of eight cysteines was the same as that observed in homologous toxins (LCTX-Ls1a, LCTX-Ls1d, and prothrombin time (PT)-2)
LCTX-F2 was first induced by isopropyl b-D-thiogalactoside (IPTG, 1 mM) and purified from soluble E. coli lysates

Summary

Introduction

Excessive blood loss is a leading cause of the high mortality rate associated with surgical operations (Willner et al, 2016). Reducing blood loss and managing hemostasis are vital during surgery and hemorrhagic shock (Zakaria et al, 2005). Tranexamic acid (TXA), epsilon aminocaproic acid (EACA) (Alkjaersig et al, 1959), aprotinin, and recombinant activated factor VII (rFVIIa) are the most commonly used procoagulant drugs. A Novel Potentiator LCTX-F2 and EACA, competitively inhibit the conversion of plasminogen to plasmin. Aprotinin is used to reduce bleeding during complex heart and liver surgery, and its main function is to slow down fibrinolysis so as to allow the breakdown of blood clots (Willner et al, 2016)

Methods

Results

Conclusion