Proteolytic system parameters in the brain of rats with hyperhomocysteinemia

Submitted: December 25, 2023
Accepted: March 28, 2024
Published: April 24, 2024
Abstract Views: 85
PDF: 56
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

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–1 of 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.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

López-Otín C, Overall CM. Protease degradomics: a new challenge for proteomics. Nat Rev Mol Cell Biol 2002;3:509–19. DOI: https://doi.org/10.1038/nrm858
Vizovisek M, Ristanovic D, Menghini S, et al. The tumor proteolytic landscape: a challenging frontier in cancer diagnosis and therapy. Int J Mol Sci 2021;22:2514. DOI: https://doi.org/10.3390/ijms22052514
Patel S. A critical review on serine protease: key immune manipulator and pathology mediator. Allergol Immunopathol (Madr) 2017;45:579–91. DOI: https://doi.org/10.1016/j.aller.2016.10.011
Chang M. Matrix metalloproteinase profiling and their roles in disease. RSC advances 2023;13:6304–16. DOI: https://doi.org/10.1039/D2RA07005G
Raksha N, Halenova T, Maievskyi O, et al. Biochemical disorders in the thyroid gland in rats with hyperhomocysteinemia. Biomed Res Ther 2022;9:5065–74. DOI: https://doi.org/10.15419/bmrat.v9i5.740
Jakubowski H. Homocysteine modification in protein structure/function and human disease. Physiol Rev 2019;99:555–604. DOI: https://doi.org/10.1152/physrev.00003.2018
Al Mutairi F. Hyperhomocysteinemia: clinical insights. J Cent Nerv Syst Dis 2020;12:1179573520962230. DOI: https://doi.org/10.1177/1179573520962230
Nevmerzhytska NM, Orzheshkovskyi VV, Dzevulska IV, et al. Mechanisms of toxic effects of homocysteine on the nervous system. Neurophysiology 2019;51:379–87. DOI: https://doi.org/10.1007/s11062-020-09832-x
Xu R, Huang F, Wang Y, et al. Gender- and age-related differences in homocysteine concentration: a cross-sectional study of the general population of China. Sci Rep 2020;10:17401. DOI: https://doi.org/10.1038/s41598-020-74596-7
Wu JT. Circulating homocysteine is an inflammation marker and a risk factor of life-threatening inflammatory diseases. J Biomed Lab Sci 2007;19:107–12.
Moradi Binabaj M, Joshaghani HR, Nejabat M. Role of homocysteine in diseases: a review. mljgoums 2016;10:1–14. DOI: https://doi.org/10.18869/acadpub.mlj.10.5.1
Smith AD, Refsum H. Homocysteine – from disease biomarker to disease prevention. J Intern Med 2021;290:826–54. DOI: https://doi.org/10.1111/joim.13279
Perła-Kaján J, Jakubowski H. Dysregulation of epigenetic mechanisms of gene expression in the pathologies of hyperhomocysteinemia. Int J Mol Sci 2019;20:3140. DOI: https://doi.org/10.3390/ijms20133140
Rehman T, Shabbir MA, Inam-Ur-Raheem M, et al. Cysteine and homocysteine as biomarker of various diseases. Food Sci Nutr 2020;8:4696–4707. DOI: https://doi.org/10.1002/fsn3.1818
Jakubowski H. Protective mechanisms against protein damage in hyperhomocysteinemia: systemic and renal detoxification of homocysteine-thiolactone. Biomed Genet Genomics 2016;1:40–43. DOI: https://doi.org/10.15761/BGG.1000108
Stangl G, Weisse K, Dinger C, et al. Homocysteine thiolactone-induced hyperhomocysteinemia does not alter concentrations of cholesterol and SREBP-2 target gene mRNAS in rats. Exp Biol Med (Maywood) 2007;232:81–7.
Bradford MM. A rаpid and sensitive method for quantities of utilizing the principle of protein binding. Anal Biochem 1976;86:193–200.
Munilla-Moran R, Stark JR. Protein digestion in early turbot larvae, Scophthalmus maximus (L.). Aquaculture (Amsterdam, Netherlands) 1989;8:315–27. DOI: https://doi.org/10.1016/0044-8486(89)90156-7
Crowther JR. The ELISA guidebook. Methods Mol Biol 2000;149:1–413. DOI: https://doi.org/10.1385/1592590497
Koval TV, Ishchuk TV, Grebinyk DM, et al. Matrix metalloproteinase functioning in case of esophagus acid burn. Biomed Res-Tokyo 2018;29:3169–73. DOI: https://doi.org/10.4066/biomedicalresearch.29-18-394
Raetska YB, Chornenka NM, Koval TV, et al. Cytokine profile indicators in rat blood serum in a model of esophagus burn induced by antioxidant chemical preparation. Biomed Res Ther 2017;4:1591–606. DOI: https://doi.org/10.15419/bmrat.v4i9.367
Magdeldin S, Moser A. Affinity chromatography. Principles and applications. In: Magdeldin S, ed. Affinity chromatography [Internet]. Rijeka: Intech Open Science; 2012. pp 3–28. DOI: https://doi.org/10.5772/39087
Palamarchuk M., Bobr A., Mudrak A. et al. Proteolytic homeostasis in the tissue of the spleen and the heart of rats injected with the venom of Vipera berus berus and Vipera berus nikolskii. Curr. Appl. Sci. Technol. 2023;23:1–13. DOI: https://doi.org/10.55003/cast.2023.06.23.015
Raksha N, Vovk T, Halenova T, et al. Influence of Vipera berus berus and Vipera berus nikolskii venom on protein-peptide profile in the liver, kidneys and small intestine of rats. Curr. Top. Pept. Protein Res. 2022;23:63–72.
Borowczyk K, Shih DM, Jakubowski H. Metabolism and neurotoxicity of homocysteine thiolactone in mice: evidence for a protective role of paraoxonase 1. J Alzheimers Dis 2012;30:225–31. DOI: https://doi.org/10.3233/JAD-2012-111940
Rasić-Marković A, Stanojlović O, Hrncić D, et al. The activity of erythrocyte and brain Na+/K+ and Mg2+-ATPases in rats subjected to acute homocysteine and homocysteine thiolactone administration. Mol Cell Biochem 2009;327:39–45. DOI: https://doi.org/10.1007/s11010-009-0040-6
Lehotsky J, Kovalska M, Baranovicova E, et al. Ischemic brain injury in hyperhomocysteinemia. In: Pluta R, ed. Cerebral Ischemia. Brisbane (AU): Exon Publications; 2021:61–72. DOI: https://doi.org/10.36255/exonpublications.cerebralischemia.2021.hyperhomocysteinemia
Zia A, Pourbagher-Shahri AM, Farkhondeh T, Samarghandian S. Molecular and cellular pathways contributing to brain aging. Behav Brain Funct 2021;17:6. DOI: https://doi.org/10.1186/s12993-021-00179-9
Raksha N, Kostyuk O, Synelnyk T, et al. Effect of hyperhomocysteinemia on proteolytic activity in the spleen. Biomed Biotechnol Res J 2023;7:170–75. DOI: https://doi.org/10.4103/bbrj.bbrj_32_23
Raksha N, Maievskyi O, Dzevulska I, et al. Proteolytic activity in the heart of rats with hyperhomocysteinemia. Wiad Lek 2022;75:831–35. DOI: https://doi.org/10.36740/WLek202204115
Hassan EA. The Relation between homocysteine, oxidative stress and atherosclerosis disease. Indian J Public Health Res Dev 2019;10:537–42. DOI: https://doi.org/10.5958/0976-5506.2019.01626.7
Wang L, Niu H, Zhang J. Homocysteine induces mitochondrial dysfunction and oxidative stress in myocardial ischemia/reperfusion injury through stimulating ROS production and the ERK1/2 signaling pathway. Exp Ther Med 2020;20:938–44. DOI: https://doi.org/10.3892/etm.2020.8735
Rai M, Curley M, Coleman Z, Demontis F. Contribution of proteases to the hallmarks of aging and to age-related neurodegeneration. Aging cell 2022;21:e13603. DOI: https://doi.org/10.1111/acel.13603
Chu M, Teng J, Guo L, et al. Mild hyperhomocysteinemia induces blood-brain barrier dysfunction but not neuroinflammation in the cerebral cortex and hippocampus of wild-type mice. Can J Physiol Pharmacol 2021;99:847-56. DOI: https://doi.org/10.1139/cjpp-2020-0507
Li X, Li C, Zhang W, et al. Inflammation and aging: signaling pathways and intervention therapies. Signal Transduct Target Ther 2023;8:239. DOI: https://doi.org/10.1038/s41392-023-01502-8
Rea IM, Gibson DS, McGilligan V., et al. Age and age-related diseases: role of inflammation triggers and cytokines. Front Immunol 2018;9:586. DOI: https://doi.org/10.3389/fimmu.2018.00586
Freitas-Rodríguez S, Folgueras AR, López-Otín C. The role of matrix metalloproteinases in aging: tissue remodeling and beyond. Biochim Biophys Acta Mol Cell Res 2017;1864:2015–2025. DOI: https://doi.org/10.1016/j.bbamcr.2017.05.007

How to Cite

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, 97(1). https://doi.org/10.4081/jbr.2024.12232