Barylyak R. Peculiarities of the functioning of Ca2+-dependent regulatory systems of blood lymphocytes of women with ovarian cancer

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0821U102045

Applicant for

Specialization

  • 222 - Медицина

25-06-2021

Specialized Academic Board

ДФ 35.600.018

Danylo Halytsky Lviv National Medical University

Essay

The objects – regulatory mechanisms of peripheral blood lymphocytes functioning in women with ovarian cancer when the participation of Ca2+-activated, Mg2+-dependent ATP-hydrolase, arginase-NO-synthase and glutathione antioxidant systems; the purpose – to clarify the peculiarities of the main Ca2+-dependent regulatory systems functioning of lymphocytes in the blood of women with ovarian cancer, namely Ca2+-activated, Mg2+-dependent ATP-hydrolase, arginase-NO-synthase and glutathione antioxidant system; methods – biochemical (arginase activities, constitutive and inducible isoforms of NO synthase, Ca2+, Mg2+-ATPase of the plasma membrane and endoplasmic reticulum, glutathione peroxidase, glutathione reductase and glutathione transferase determination), laboratory diagnostics and statistical analysis; results – It was found that the development of ovarian cancer is accompanied by an increase in lipid peroxidation and a decrease in the activities of glutathione peroxidase and glutathione reductase in lymphocytes. Decreased enzymatic activities of Ca2+, Mg2+-ATP-dependent transport systems of the plasma membrane and endoplasmic reticulum of blood lymphocytes of patients with ovarian cancer were revealed, which probably leads to overload of cells by Ca2+. For the first time, the mechanisms of dysfunction of the studied ATPase systems of blood lymphocytes of patients with ovarian cancer have been established, which are in reducing of the enzymes revolutions number and decrease their affinity for the substrate. It was found that during the development of ovary malignant transformation there is an increase in arginase activity in the lymphocytes of the blood, due to an increase in the number of enzyme revolutions. Simultaneously, a decrease in cNOS activity and a multiple increase in iNOS activity occurs. Kinetic analysis showed that the increase in iNOS activity occurs due to an increase in the number of enzyme revolutions and an increase in its affinity for the substrate. Thus, under the conditions of oncopathology development, the ratio of NO-synthase and arginase metabolism of L-arginine is disturbed, which is accompanied by hyperproduction of nitric oxide; introduced – into the scientific and educational process of health care institutions and Danylo Halytsky Lviv National Medical University; branch – medicine.

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