online ISSN 2415-3176
print ISSN 1609-6371
logoЕкспериментальна та клінічна фізіологія і біохімія
Ж. 2023, 96(2): 60–67
https://doi.org/10.25040/ecpb2023.01-02.060

Клінічна медицина


Na+ ,K+ -ATPase as a target of the antiproliferative effect of mitomycin C in the treatment of urethral stricture

D. R. SHEREMETA, D. Z. VOROBETS
Анотація

Summary. Urethral strictures are mostly associated with catheterization, transurethral surgery, urinary tract infection, and trauma. To treat or prevent the formation of urethral strictures in the postoperative period, the antitumor antibiotic mitomycin C is often used. It belongs to the group of alkylating agents that act by cross-linking complementary DNA chains with absolute specificity, and this is where its main antiproliferative effect is manifested. Despite the use of mitomycin C in medicine for a long time, the mechanism of its action on the regulatory systems of the cell is little known. In this regard, it is relevant to study the effect of this antibiotic on ion transport systems, in particular Na + ,K + -ATPase. The study of the mechanism of action of mitomycin C was carried out on peripheral blood lymphocytes of practically healthy men, since lymphocytes are considered the «metabolic mirror» of the body and promptly respond to all external and internal influences. It was found that under the influence of different concentrations of mitomycin C in the range of 10 -5 ...10 -3 M, the value of Na + ,K + -ATPase activity increases dose-dependently and is the highest at 10 -3 M concentration, that is, it increases by 2.6 times (р<0,01). With an increase in the concentration of ATP in the incubation medium, both in the control and under the action of mitomycin C, a monotonous increase in the activity of Na + ,K + -ATPase was observed, reaching a plateau in the presence of 2.0-2.5 mM ATP. In order to find out the mechanism of changes in the Na + ,K + -ATPase activity of blood lymphocytes under the action of mitomycin C, the main kinetic parameters were determined in Lineweaver-Burke coordinates. It was established that the initial maximum rate of ATP hydrolysis in the Na + ,K + -ATPase reaction in blood lymphocytes under the influence of mitomycin C (10 -5 M) increased by 2.5 times (р<0.001). At the same time, the affinity constant under the action of 10 -5 M mitomycin C was 6.7 times (р<0.05) higher than the control, which indicates a decrease in the affinity of ATPase to ATP. Thus, the growth of Na + ,K + -ATPase activity under the action of mitomycin C, which should lead to an decrease in the concentration of Na + ions in the cytoplasm, occurs due to an increase in the number of revolutions of the enzyme. Significant changes in Na + ,K + -ATPase activity under the action of mitomycin C may indicate the involvement of this enzyme in the signaling cascade that regulates cell proliferation.

Article received:30.05.2023

Ключові слова: urethral stricture, mitomycin C, Na + , K + -ATPase, lymphocytes

Повний текст: PDF (Ukr)

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