Role of heat shock proteins 27 and 70, and ubiquitin in oxidative modification of proteins, and the implementation of dexamethasone-induced apoptosis of jurkat tumor cells the conditions of inhibited heat shock proteins 27
- DOI
- 10.5922/ATB-2025-1-2-2
- Pages
- 31-41
Abstract
This study aims to investigate the molecular mechanisms underlying the involvement of heat shock proteins 27 and 70 and ubiquitin in the oxidative modification of proteins, as well as the execution of dexamethasone-induced apoptosis in Jurkat tumor cells under inhibition of heat shock protein 27. It was assessed how 5-(5-ethyl-2-hydroxy-4-methoxyphenyl)-4-(4-methoxyphenyl)isoxazole at a final concentration of 0.1 µM and/or dexamethasone at a final concentration of 10 µM affected cytoplasmic exposure of phosphatidylserine followed by annexin V binding, the number of FasL and TNFα receptors, and the reduction of mitochondrial membrane potential in cells. Their effects were also examined with respect to the levels of OH• radicals, free sulfhydryl groups of cysteine in proteins, protein-bound glutathione, oxidized tryptophan residues, bi-tyrosine cross-links, carbonyl derivatives of proteins, ubiquitin, ubiquitin ligase, NFkB, Apaf-1, and heat shock proteins 27 and 70, as well as caspase-3 activity in Jurkat tumor cells.
The observed changes in the levels of heat shock proteins 27 and 70, ubiquitin, oxidative modifications of amino acid residues, and proteins were associated with the execution of apoptosis in Jurkat tumor cells. When exposed simultaneously to 5-(5-ethyl-2-hydroxy-4-methoxyphenyl)-4-(4-methoxyphenyl)-isoxazole and dexamethasone, Jurkat tumor cells exhibited correlations between the activation of irreversible oxidative modifications and the reduction of reversible oxidative modifications of proteins, associated with the execution of apoptosis involving TNFα and Fas receptors.
The findings indicate that heat shock proteins 27 and 70, together with ubiquitin, participate in both reversible and irreversible oxidative modifications of amino acid residues and proteins, as well as in the execution of dexamethasone-induced apoptosis in Jurkat tumor cells when heat shock protein 27 is inhibited.
Reference
1. Pistritto G., Trisciuoglio D., Ceci C., Garufi A., D’Orazi G. Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY). 2016, 8(4), 603—619, DOI: 10.18632/aging.100934.
2. Kulbay M., Paimboeuf A., Ozdemir D., Bernier J. Review of cancer cell resistance mechanisms to apoptosis and actual targeted therapies. Journal of cellular biochemistry. 2022, 123(11), 1736—1761, DOI: 10.1002/jcb.30173.
3. Hayes J. D., Dinkova-Kostova A. T., Tew K. D. Oxidative Stress in Cancer. Cancer Cell. 2020, 38(2), 167—197, DOI: 10.1016/j.ccell.2020.06.001.
4. Wu J., Liu T., Rios Z., Mei Q., Lin X., Cao S. Heat Shock Proteins and Cancer. Trends in pharmacological sciences. 2017, 38(3), 226—256, DOI: 10.1016/j.tips.2016.11.009.
5. Ahmed K., Zaidi S. F., Mati-Ur-Rehman, Rehman R., Kondo T. Hyperthermia and protein homeostasis: Cytoprotection and cell death. Journal of thermal biology. 2020, 91, 102615, DOI: 10.1016/j.jtherbio.2020.102615.
6. Szyller J., Bil-Lula I. Heat Shock Proteins in Oxidative Stress and Ischemia/Reperfusion Injury and Benefits from Physical Exercises: A Review to the Current Knowledge. Oxidative medicine and cellular longevity. 2021, 2021, 6678457, DOI: 10.1155/2021/6678457.
7. Lang B. J., Prince T. L., Okusha Y., Bunch H., Calderwood S. K. Heat shock proteins in cell signaling and cancer. Biochimica et biophysica acta. Molecular cell research. 2022, 1869(3), 119187, DOI: 10.1016/j.bbamcr.2021.119187.
8. Takakuwa J. E., Nitika, Knighton L. E., Truman A. W. Oligomerization of Hsp70: Current Perspectives on Regulation and Function. Frontiers in molecular biosciences. 2019, 6, 81, DOI: 10.3389/fmolb.2019.00081.
9. Nosareva O. L., Stepovaya E. A., Ryazantseva N. V., Zakirova E. V., Mazunin I. O., Litvinova L. S. et al. Disruption of Expression of mRNA Hsp27 and Ubiquitin as a Mechanism of Escaping from Apotosis of Jurkat Line Tumor Cells. Bulletin of Siberian medicine. 2015, 14(1), 66—72, DOI: 10.20538/1682-0363-2015-1-66-72.
10. Saini J., Sharma P. K. Clinical, Prognostic and Therapeutic Significance of Heat Shock Proteins in Cancer. Current drug targets. 2018, 19(13), 1478—1490, DOI: 10.2174/138945011866617082312124.
11. Boliukh I., Rombel-Bryzek A., Żuk O., Radecka B. The role of heat shock proteins in neoplastic processes and the research on their importance in the diagnosis and treatment of cancer. Contemporary oncology (Poznań, Poland). 2021, 25(2), 73—79, DOI: 10.5114/wo.2021.106006.
12. Nosareva O. L., Stepovaya E. A., Shakhristova E. V., Alekseeva O. N., Kuzmenko D. I., Sadykova A. A. et al. The role of redox status and oxidative modification of proteins in implementing apoptosis in human blood lymphocytes in norm and under experimental oxidative stress. Rossiĭskii fiziologicheskiĭ zhurnal imeni I. M. Sechenova. 2019, 105(3), 327— 338, DOI: 10.1134/S0869813919030063.
13. Dilek O. Current Probes for Imaging Carbonylation in Cellular Systems and Their Relevance to Progression of Diseases. Technology in cancer research & treatment. 2022, 21, 15330338221137303, DOI: 10.1177/15330338221137303.
14. Wang H., Yang L., Liu M., Luo J. Protein post-translational modifications in the regulation of cancer hallmarks. Cancer gene therapy. 2023, 30(4), 529—547, DOI: 10.1038/s41417-022-00464-3.
15. Regimbeau M., Abrey J., Vautrot V., Causse S., Gobbo J., Garrido C. Heat shock proteins and exosomes in cancer theranostics. Seminars in cancer biology. 2022, 86(Pt 1), 46—57, DOI: 10.1016/j.semcancer.2021.07.014.
16. Lampros M., Vlachos N., Voulgaris S., Alexiou G. A. The Role of Hsp27 in Chemotherapy Resistance. Biomedicines. 2022, 10(4), 897, DOI: 10.3390/biomedicines10040897.
17. Kumar S., Stokes J., Singh U. P., Scissum Gunn K., Acharya A., Manne U. et al. Targeting Hsp70: A possible therapy for cancer. Cancer letters. 2016, 374(1), 156—166, DOI: 10.1016/j.canlet.2016.01.056.
18. Swatek K. N., Komander D. Ubiquitin modifications. Cell research. 2016, 26(4), 399— 422, DOI: 10.1038/cr.2016.39.
19. Song L., Luo Z. Q. Post-translational regulation of ubiquitin signaling. The Journal of cell biology. 2019, 218(6), 1776—1786, DOI: 10.1083/jcb.201902074.
20. Dikic I., Schulman B. A. An expanded lexicon for the ubiquitin code. Nature reviews. Molecular cell biology. 2023, 24(4), 273—287, DOI: 10.1038/s41580-022-00543-1.
21. Nosareva O. L., Stepovaya E. A., Ryazantseva N. V., Shakhristova E. V., Orlov D. S., Novitsky V. V. The role of ubiquitin in regulation of apoptosis in Jurkat cells. Bulletin of Siberian medicine. 2018, 17(3), 96—104, DOI: 10.20538/1682-0363-2018-3-96-104.
22. Ryazantseva N. V., Stepovaya E. A., Nosareva O. L., Konovalova E. V., Orlov D. S., Naumova A. I. et al. Role of heat shock protein 27 in regulation of glutathione system and apoptosis of Jurkat tumor cells and blood lymphocytes. Bulletin of experimental biology and medicine. 2014, 158(9), 366—369, DOI: 10.1007/s10517-015-2766-3.
23. Nosareva O. L., Stepovaya E. A., Ryazantseva N. V., Shakhristova E. V., Egorova M. Y., Novitsky V. V. The Role of the Glutathione System in Oxidative Modification of Proteins and Dysregulation of Apoptosis in Jurkat Tumor Cells. Bulletin of experimental biology and medicine. 2017, 164(8), 228—231, DOI: 10.1007/s10517-017-3957- x.
24. Kurop M. K., Huyen C. M., Kelly J. H., Blagg B. S. J. The heat shock response and small molecule regulators. European journal of medicinal chemistry. 2021, 226, 113846, DOI: 10.1016/j.ejmech.2021.113846.
25. Dubinina E. E. Products of oxygen metabolism in the functional activity of cells (life and death, creation and destruction). Physiological, clinical and biochemical aspects. Medical Press: St. Petersburg. 2006, ISBN 5-85474-072-9.