The recombinant disintegrin, jarastatin, inhibits platelet adhesion and endothelial cell migration.

Barbara Barbosa Succar, Roberta F G Saldanha-Gama, Aline Sol Valle, Luciana Serrão Wermelinger, Christina Barja-Fidalgo, Eleonora Kurtenbach, Russolina Benedeta Zingali

Toxicon : official journal of the International Society on Toxinology 2022 Oct 15

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Integrins are transmembrane heterodimeric glycoproteins, present in most cell types that act as mechanoreceptors, connecting extracellular matrix proteins to the cytoskeleton of the cell, mediating several physiological and pathological processes. The disintegrins are peptides capable of modulating the activity of integrins, such as αIIbβ3, responsible for the platelet aggregation and αvβ3, related to angiogenesis. The aim of this study was to produce the recombinant disintegrin jarastatin (rJast), to evaluate its secondary structure and biological activity. rJast was expressed in the yeast Komagataella phaffii (earlier Pichia pastoris) purified using molecular exclusion chromatography and the internal sequence and molecular mass were confirmed by mass spectrometry. The yield was approximately 40 mg/L of culture. rJast inhibited platelet aggregation induced by 2-4 μM ADP, 10 nM thrombin, and 1 μg/mL collagen (IC50 of 244.8 nM, 166.3 nM and 223.5 nM, respectively). It also blocked the adhesion of platelets to collagen under continuous flow in approximately 60% when used 1 μM. We also evaluated the effect of rJast on HMEC-1 cells. rJast significantly inhibited the adhesion of these cells to vitronectin, as well as cell migration (IC50 1.77 μM) without changing the viability. Conclusions: rJast was successfully expressed with activity in human platelets aggregation identical to the native molecule. Also, rJast inhibits adhesion and migration of endothelial cells. Thus, being relevant for the development of anti-thrombotic and anti-angiogenic drugs. Copyright © 2022 Elsevier Ltd. All rights reserved.

Citation

Barbara Barbosa Succar, Roberta F G Saldanha-Gama, Aline Sol Valle, Luciana Serrão Wermelinger, Christina Barja-Fidalgo, Eleonora Kurtenbach, Russolina Benedeta Zingali. The recombinant disintegrin, jarastatin, inhibits platelet adhesion and endothelial cell migration. Toxicon : official journal of the International Society on Toxinology. 2022 Oct 15;217:87-95