Kinetic properties of glutathione-S-transferase in prostate gland biopsies of patients with benign prostatic hyperplasia and chronic prostatitis

  • M. E. Kushynska Danylo Halytsky Lviv National Medical University
  • O. K. Onufrovych Danylo Halytsky Lviv National Medical University
  • D. Z. Vorobets Danylo Halytsky Lviv National Medical University
  • A. S. Besedina Danylo Halytsky Lviv National Medical University
  • G. V. Galyk Danylo Halytsky Lviv National Medical University
  • O. I. Pershyn Danylo Halytsky Lviv National Medical University
  • R. V. Fafula Danylo Halytsky Lviv National Medical University
  • Z. D. Vorobets Danylo Halytsky Lviv National Medical University
DOI: https://doi.org/10.15421/0225164
Keywords: prostatic hyperplasia, chronic prostatitis, glutathione-S-transferase, oxidative stress, malondialdehyde.

Abstract

The molecular and stromal mechanisms associated with the pathogenesis of prostate hyperplasia as a metabolic disorder are not yet fully understood, but it is believed that the etiology of hyperplasia is influenced by a number of factors, including aging, hormonal changes, metabolic syndrome, dietary factors, inflammation, oxidative stress, and, more recently, suppression of apo p tosis in prostate tissue. A number of studies emphasize the disruption of pro/antioxidant status in the development of prostate hyperplasia. The aim of the research is to study the activity and kinetic characteristics of glutathione-S-transferase (GsT) in pro s tate biopsies from patients with benign hyperplasia and hyperplasia with chronic prostatitis. The prostate tissue (biopsies) from two groups of patients were used. Group 1 consisted of patients with benign prostatic hyperplasia (n = 14); group 2 consisted of patients with benign prostatic hyperplasia and chronic prostatitis (n = 14). It was shown that GsT activity in the soluble fraction of prostate biopsies from patients with benign hyperplasia with chronic prostatitis was 1.60 times higher than in patients without chronic prostatitis. It was found that the kinetics of the GsT reaction is consistent with the patterns of a zero-order reaction in the range of 0–3 min: in this time interval, the dependence graph of the product formation on the incubation period was practically linear. It was shown that the value of V 0 in patients with prostatic hyperplasia with chronic prostatitis wa s almost twice as high as that in patients without chronic prostatitis. Over the entire range of GSH concentrations, enzyme activity in samples from patients with inflammation was higher than in patients without chronic prostatitis. Similar changes were also observed with an increase in the concentration of 1-chloro-2,4-dinitrobenzene in the incubation medium at a constant GSH concentrations. Calculation of the kinetic parameters of GsT activity shows that the maximum reaction rate of accumulation of the optically active dinitrobenzene conjugate, determined by GSH, was 1.44 times higher in patients with chronic prostatitis compared to the first group. The affinity constant for GSH in this group of patients was 2.28 times higher compared to patients without chronic prostatitis. When interpre t ing the obtained kinetic parameters determined by GSH, it is shown that GsT activity in patients with benign prostatic hyperplasia without chronic prostatitis is reduced both due to a decrease in the enzyme reaction rate (V max decreases) and due to a increase in the enzyme's affinity for GSH (KGSH decreases).

References

Alnasser, S. M. (2024). The role of glutathione S-transferases in human disease pathogenesis and their current inhibitors. Genes and Diseases, 12(4), 101482.

Bathige, S. D., Umasuthan, N., Saranya Revathy, K., Lee, Y., Kim, S., Cho, M. Y., Park, M. A., Whang, I., & Lee, J. (2014). A mu class glutathione S-transferase from Manila clam Ruditapes philippinarum (RpGSTμ): Cloning, mRNA expression, and conjugation assays. Comparative Biochemistry and Physiology C: Toxicology and Pharmacology, 162, 85–95.

Bostwick, D. G., Meiers, I., & Shanks, J. H. (2007). Glutathione S-transferase: Differential expression of alpha, mu, and pi isoenzymes in benign prostate, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma. Human Pathology, 38(9), 1394–1401.

Butterfield, D. A., Bader Lange, M. L., & Sultana, R. (2010). Involvements of the lipid peroxidation product HNE in the pathogenesis and progression of Alzheimer’s disease. Biochimica et Biophysica Acta, 1801, 924–929.

Chatterjee, A., & Gupta, S. (2018). The multifaceted role of glutathione S-transferases in cancer. Cancer Letters, 433, 33–42.

Chughtai, B., Lee, R., Te, A., & Kaplan, S. (2011). Role of inflammation in benign prostatic hyperplasia. Reviews in Urology, 13(3), 147–150.

Dann, A. T., Kenyon, A. P., Seed, P. T., Poston, L., Shennan, A. H., & Tribe, R. M. (2004). Glutathione S-transferase and liver function in intrahepatic cholestasis of pregnancy and pruritus gravidarum. Hepatology, 40(6), 1406–1414.

Ercan, M., Alp, H. H., Kocaturk, H., Bakan, N., & Gul, M. (2019). Oxidative stress before and after surgery in benign prostatic hyperplasia patients. Andrologia, 51, e13326.

Fafula, R. V., Paranyak, N. M., Besedina, A. S., Vorobets, D. Z., Iefremova, U. P., Onufrovych, O. K., & Vorobets, Z. D. (2019). Biological significance of glutathione S-transferases in human sperm cells. Journal of Human Reproductive Sciences, 12(1), 24–28.

Grimsrud, P. A., Picklo, M. J., Griffin, T. J., & Bernlohr, D. A. (2007). Carbonylation of adipose proteins in obesity and insulin resistance: Identification of adipocyte fatty acid-binding protein as a cellular target of 4-hydroxynonenal. Molecular and Cellular Proteomics, 6, 624–637.

Habig, H. W., Pabst, M. J., & Jacoby, W. B. (1974). Glutathione S-transferases. Journal of Biological Chemistry, 249, 7130–7139.

Kim, E. H., Larson, J. A., & Andriole, G. L. (2016). Management of benign prostatic hyperplasia. Annual Review of Medicine, 67, 137–151.

Konwar, R., Manchanda, P. K., Chaudhary, P., Nayak, V. L., Singh, V., & Bid, H. K. (2010). Glutathione S-transferase gene variants and risk of benign prostate hyperplasia in a North Indian population. Asian Pacific Journal of Cancer Prevention, 11(2), 365–370.

Kosterin, S. O., & Karakhim, S. O. (2020). Biochemical kinetics. Naukova Dumka, Kyiv.

Lv, N., Huang, C., Huang, H., Dong, Z., Chen, X., Lu, C., & Zhang, Y. (2023). Overexpression of glutathione S-transferases in human diseases: Drug targets and therapeutic implications. Antioxidants, 12(11), 1970.

Mayer, R. J., & Ofial, A. R. (2019). Nucleophilicity of glutathione: A link to Michael acceptor reactivities. Angewandte Chemie International Edition, 58(49), 17704–17708.

Mazari, A. M. A., Zhang, L., Ye, Z.-W., Zhang, J., Tew, K. D., & Townsend, D. M. (2023). The multifaceted role of gluta-thione S-transferases in health and disease. Biomolecules, 13(4), 688.

Naber, K. G., & Weidner, W. (2000). Chronic prostatitis – an infectious disease? Journal of Antimicrobial Chemotherapy, 46(2), 157–161.

Piaggi, S., Raggi, C., Corti, A., Pitzalis, E., Mascherpa, M. C., Saviozzi, M., Pompella, A., & Casini, A. F. (2010). Glutathione transferase omega 1-1 (GSTO1-1) plays an anti-apoptotic role in cell resistance to cisplatin toxicity. Carcinogenesis, 31(5), 804–811.

Roehrborn, C. G. (2008). BPH progression: Concept and key learning from MTOPS, ALTESS, COMBAT, and ALF-ONE. BJU International, 101(S3), 17–21.

Roehrborn, C., & McConnell, J. (2002). Etiology, pathophysiology, epidemiology and natural history of benign prostatic hyperplasia. In: Walsh, P. et al. (Eds.). Campbell’s Urology. 8th ed. Saunders, Philadelphia. Pp. 1297–1336.

Samiec, P. S., Dahm, L. J., & Jones, D. P. (2000). Glutathione S-transferase in mucus of rat small intestine. Toxicological Sciences, 54(1), 52–59.

Singh, R. R., & Reindl, K. M. (2021). Glutathione S-transferases in cancer. Antioxidants, 10, 701.

Strange, R. C., Spiteri, M. A., Ramachandran, S., & Fryer, A. A. (2001). Glutathione-S-transferase family of enzymes. Mutation Research, 482(1–2), 21–36.

Sugar, L. M. (2006). Inflammation and prostate cancer. Canadian Journal of Urology, 13(S1), 46–47.

Vorobets, M. Z., Fafula, R. V., Besedina, A. S., Onufrovych, O. K., & Vorobets, D. Z. (2018). Glutathione S-transferase as a marker of oxidative stress in human ejaculated spermatozoa from patients with pathospermia. Regulatory Mechanisms in Biosystems, 9(2), 287–292.

Wang, Z., Liang, S., Lian, X., Liu, L., Zhao, S., Xuan, Q., Guo, L., Liu, H., Yang, Y., Dong, T., Cao, J., & Liu, S. (2015). Identification of proteins responsible for adriamycin resistance in breast cancer cells using proteomics analysis. Scientific Reports, 5, 9301.

Zabaiou, N., Mabed, D., Lobaccaro, J. M., & Lahouel, M. (2016). Oxidative stress in benign prostate hyperplasia. Andrologia, 48(1), 69–73.

Zhou, C., Huang, Y., & Przedborski, S. (2008). Oxidative stress in Parkinson’s disease: A mechanism of pathogenic and therapeutic significance. Annals of the New York Academy of Sciences, 1147, 93–104.

Zimniak, P. (2008). Detoxification reactions: Relevance to aging. Ageing Research Reviews, 7(4), 281–300.

Published
2025-11-14
How to Cite
Kushynska, M. E., Onufrovych, O. K., Vorobets, D. Z., Besedina, A. S., Galyk, G. V., Pershyn, O. I., Fafula, R. V., & Vorobets, Z. D. (2025). Kinetic properties of glutathione-S-transferase in prostate gland biopsies of patients with benign prostatic hyperplasia and chronic prostatitis. Regulatory Mechanisms in Biosystems, 16(4), e25164. https://doi.org/10.15421/0225164
Issue
Vol 16 No 4 (2025): Regulatory Mechanisms in Biosystems
Section
Статті

Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons «Attribution» 4.0 License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

Most read articles by the same author(s)