RELATIONSHIP BETWEEN THE CELLULAR PRION LEVEL AND ATPASES ACTIVITIES IN THE LIVER AND KIDNEYS OF DIFFERENT AGE WISTAR LINE RATS
M. Kushkevych, N. Kuzmina, V. Vlizlo
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Institute of Animal Biology of NAAS,
38 Vasyl Stus str., Lviv 79034, Ukraine
Transmissible spongioform encephalopathies (TSE) are the central nervous system diseases, the pathological agent of which is the infectious prion (PrPSc). Its precursor is the cellular prion (PrPC), which is localized on the cell membrane and performs many important metabolic functions. However, in unknown conditions it can convert the conformation in the pathological form and cause neurodegeneration. Given that the sporadic cases are registered especially in middle age people, the PrPC age dynamics study is relevant. The PrPC involvement in the regulation of Ca2+-channels and calcium homeostasis is described. In conditions of its conversion into the pathological form the PrPC is not able to perform its function. It causes a violation of different methabolic pathways.
Age dynamics of the cellular prion molecular isoforms quantitative content is detected. Studies were carried out in the laboratory animals’ liver and kidneys by Western blot analysis. PrPC level reduction by 41–57 % in old animals compared to mature animals is demonstrated. Nа+/K+- and Са2+-АТPases activity in different ages rats’ prion replicating tissues is determined. A sharp ion transporters activity decreasing (by 48–86 %) in thirty months animals’ liver and kidneys is showing. Based on the kinetic analysis results of the ATP hydrolysis by studied enzymes the kinetic parameters (initial reaction velocity, maximum amount of reaction product, Michaelis constant and maximum velocity of enzymatic reaction) significant decrease is established. In the thirty months animals’ liver and kidneys the Ca2+-ATPases remain its activity under high calcium ions concentration in the medium. It should be noted that the ions concentration value optimum for the Na+/K+-ATPase is shifting towards the Na+ level increase which is consistent with a increasing of these ions by 4–10 % in the tissues as a whole. Using the correlation analysis method a strong direct correlation between the cellular prion level and studied ion transporters activities is demonstrated (r=0.754–0.889).
Keywords: RATS, LIVER, KIDNEYS, AGE CHANGES, CELLULAR PRION, WESTERN BLOTTING, Nа+/K+- AND Са2+-АТPases
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