Proteolytic system parameters in the brain of rats with hyperhomocysteinemia

Tatyana Synelnyk; Nataliia Raksha; Oleksandra Kostiuk; Olga Kharchenko; Sofia Rymsha; Viktoria Korol; Anatoliy Korol; Oksana Bernyk; Oleksandr Maievskyi

doi:10.4081/jbr.2024.12232

Authors

Tatyana Synelnyk
synelnykt@gmail.com
Educational and Scientific Center "Institute of Biology and Medicine" of Taras Shevchenko National University of Kyiv, Kyiv, Ukraine. https://orcid.org/0000-0002-7131-0642
Nataliia Raksha Educational and Scientific Center "Institute of Biology and Medicine" of Taras Shevchenko National University of Kyiv, Kyiv, Ukraine.
Oleksandra Kostiuk Educational and Scientific Center "Institute of Biology and Medicine" of Taras Shevchenko National University of Kyiv, Kyiv, Ukraine. https://orcid.org/0000-0002-4509-3701
Olga Kharchenko Educational and Scientific Center "Institute of Biology and Medicine" of Taras Shevchenko National University of Kyiv, Kyiv, Ukraine.
Sofia Rymsha National Pirogov Memorial Medical University, Vinnytsia, Ukraine.
Viktoria Korol National Pirogov Memorial Medical University, Vinnytsia, Ukraine.
Anatoliy Korol National Pirogov Memorial Medical University, Vinnytsia, Ukraine.
Oksana Bernyk Educational and Scientific Center "Institute of Biology and Medicine" of Taras Shevchenko National University of Kyiv, Ukraine.
Oleksandr Maievskyi Educational and Scientific Center "Institute of Biology and Medicine" of Taras Shevchenko National University of Kyiv, Ukraine. https://orcid.org/0000-0002-9128-1033

Hyperhomocysteinemia (HHcy) is now being actively studied as a potential risk factor and/or biomarker for numerous pathological conditions, including brain diseases. This study aimed to analyze the proteolytic processes in the brains of rats with HHcy. Total proteolytic activity, metal-dependent, and serine proteases activities, the content of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases-1, cytokines, serine proteases, total protein and medium and low molecular-weight substances (MLMWS), were evaluated. HHcy was induced by DL-homocysteine thiolactone (HTL) daily intragastric administration (200 mg·kg^–1of body weight) to young and adult albino non-linear male rats for 8 weeks following rat sacrifice and brain harvesting. It was established that HHcy causes an increase in total proteolytic activity and a rise in MLMWS levels in rat brains. Serine protease activity increased to a greater extent compared to metal-dependent one, and bigger changes were observed in young rats. Rise in MMP-9 and -10 levels (in young animals), a decline in MMP-3 and -8 levels, and a decrease in the content of interleukin-1β, interferon-γ, interleukin-4 and tumor necrosis factor-α (the last two in young animals) was also detected. No significant changes were found in serine protease content. Therefore, proteolysis intensification in the brain of rats with HHcy is more likely caused by protease up-regulation through mechanisms stimulated by homocysteine, HTL, and oxidative stress, without involving pro-inflammatory signaling pathways.

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Synelnyk, T., Raksha, N., Kostiuk, O., Kharchenko, O., Rymsha , S., Korol , V., Korol , A., Bernyk , O., & Maievskyi , O. (2024). Proteolytic system parameters in the brain of rats with hyperhomocysteinemia . Journal of Biological Research - Bollettino Della Società Italiana Di Biologia Sperimentale. https://doi.org/10.4081/jbr.2024.12232