Savchuk O. Protein-protein interactions in regulating mechanisms of haemostasis under pathological states

Українська версія

Thesis for the degree of Doctor of Science (DSc)

State registration number

0510U000918

Applicant for

Specialization

  • 03.00.04 - Біохімія

27-12-2010

Specialized Academic Board

Д 26.001.24

Taras Shevchenko National University of Kyiv

Essay

The present study is dedicated to the investigation of protein-protein interactions under development of haemostatic system pathological states. The appearance of novel protein-protein interactions which are not distinctive for native state of blood clotting system and fibrinolytic system was shown. Results of the present work demonstrate the necessity of comprehensive approach for haemostatic system state analysis under norm and pathologies. Presented data are essential for understanding of dynamic features course of protein-protein interactions between different haemostatic system branches under pathological states. Results of the work allow developing a strategy for the search of new diagnostics and directed correction methods of haemostatic system pathologies. For the first the evidences of E-fragment of fibrinogen/fibrin and prothrombin complex formation were obtained using in vitro and in vivo model systems. It was established that streptokinase caused significant tissue-type plasminogen activator release from endothelial cells to blood flow. It was proved that streptokinase influence endothelium not only through plasmin formation but also without its participation. Technical approaches presented in the dissertation allow isolation of high-purity proteins, polyclonal antibodies and haemostatic system effectors. The ability to obtain present instruments of protein-protein interactions features course investigation allow thorough study of blood clotting system and fibrinolytic system functioning mechanisms, which is essential not only as a theoretical matter but also for practical application on medical practice. Keywords: protein-protein interactions, haemostatic system, haemostatic cascade pathologies, streptokinase.

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