Destabilase complexes ‐ natural liposome produced by medicinal leeches Hirudo medicinalis

Abstract

Electrophoretic analysis of destabilase preparation demonstrates the presence of protein combinations with MW 12.3, 25 and 50 kD. Fraction (MW 12.3 D) is a monomer of destabilase aggregation having properties of micellar proteins and represents a stable lipid-protein complex, where the role of lipid component is played by the stable analogue of prostacyclin (MW 391 D). The synthesis of a low molecular fraction of destabilase is fulfilled with bacteria--symbiont of leeches Aeromonas hydrophila. When the destabilase (MW 12.3 kD) contacts with blood a process of complexe formation is triggered with hirudin and blood plasma kallikrein inhibitor, forming a stable 'destabilase complex' (DC; MW 25 kD), possessing also a high aggregation capacity. Polymer forms of the destabilase complex form a liposome changing its spatial orientation depending on the nature of the solvent. Such structural organization provides a high stability of DC components and a rapid penetration through cellular membranes (transmembrane transfer) and it also provides prophylactic antithrombotic action in the case of peroral application to animals, due to the blockade of vascular platelets (inhibition of platelet aggregation by prostacyclin analogue) and plasmic (inhibition of thrombin activity and blood plasma kallikrein) links of the hemostasis process. Destabilase fraction with MW 50 kD is a dimer of the destabilase complex. As a result of DC destruction (liposome), hirudin, prostacycline analogue and blood plasma kallikrein inhibitor are released.

Generation of recombinant destabilase-lysozyme from medicinal leeches in three different expression systems

“…Both approaches have sufficient disadvantages. The destabilase isolated from the salivary gland secretions is contaminated with other substances, such as prostaglandins, hirudin, and kallikrein inhibitors [11]. It is not known whether separation of the different forms of destabilase occurs.…”

“…The first is the purification of the protein from salivary gland secretions [11]. The second is the refolding of the recombinant polypeptide that accumulates in E. coli inclusion bodies [9].…”

“…Destabilase was isolated from the natural salivary gland secretions of medicinal leeches in the form of the destabilase complex and not as a pure enzyme. This complex contains destabilase, prostaglandin, hirudin and kallikrein inhibitors [11]. Thus, it has previously been impossible to compare the enzyme activities of the recombinant and natural proteins.…”

The scientific value of the medicinal leech therapy

“…Destabilaz: Stabilize fibrinin çözülmesine neden olur. Kan pıhtılarını eritebilen lizozim bir enzimdir (15).…”

COVID-19: The Importance of the Renaissance of Hirudotherapy to Overcome the Pandemic in Russia and in the World

“…This fact indicates a pronounced effect of the virus on the connective tissue of the vascular endothelium. But even in this case, leechtherapy is shown as a method of regeneration of connective tissue of blood vessels [26,27].…”