| Title | MARK activation in human blood mononuclear cells in types 1 and 2 diabetes |
| Publication Type | Journal Article |
| Year of Publication | 2020 |
| Authors | Pushkarev, VV, Sokolova, LK, Kovzun, OI, Cherviakova, SA, Vatseba, TS, Pushkarev, VM, Tronko, MD |
| Abbreviated Key Title | Dopov. Nac. akad. nauk Ukr. |
| DOI | 10.15407/dopovidi2020.03.094 |
| Issue | 3 |
| Section | Biochemistry |
| Pagination | 94-99 |
| Date Published | 3/2020 |
| Language | Ukrainian |
| Abstract | The peripheral blood mononuclear cells (PBMC) mainly includes monocytes and lymphocytes involved in the development of diabetes mellitus and other autoimmune diseases. Ret/Ras/Raf/MEK/ERK (mitogen-activated protein kinases, MAPK) is a signaling cascade that controls cellular processes such as proliferation, survival, angiogenesis, cell growth, and motility. The aim of the work was to study the activation in PBMC of the main effector protein kinase of this cascade — ЕRК1/2. Enzyme-linked immunosorbent assay kits were used to determine the amount of phospho-ЕRК1/2. It is shown that activation of ЕRК1/2 in PBMC of patients with type 2 diabetes is not observed, while it increased significantly in pa tients with type 1 diabetes or autoimmune thyroiditis. However, in patients with type 1 diabetes with autoimmune thyroiditis, the activation of ЕRК1/2 in PBMC decreases to a control level, which can be explained by the competition between the two autoimmune processes for common signaling pathways. The role of the MAPK cascade in the pathogenesis of autoimmune diseases is discussed. |
| Keywords | autoimmune thyroiditis, mitogen-activated protein kinases, peripheral blood mononuclear cells, types 1 and 2 diabetes |
1. Subramanian, V. & Ferrante, A. W. Jr. (2009). Obesity, inflammation, and macrophages. Nestle Nutr. Workshop Ser. Paediatr. Program., 63, pp. 151-159. https://doi.org/10.1159/000209979
2. Tronko, N. D., Pushkarev, V. M., Sokolova, L. K., Pushkarev, V. V. & Kovzun, O. I. (2018). Molecular mechanisms of pathogenesis of diabetes and its complications. Kyiv: Isdatelskii Dom Medkniga (in Russian).
3. Buzdugă, C. M., Costea, C. F., Dumitrescu, G. F., Turliuc, M. D., Bogdănici, C. M., Cucu, A., Dumitrescu, N., Indrei, L., Şapte, E. & Apostol, D. G. C. (2017). Cytological, histopathological and immunological aspects of autoimmune thyroiditis: a review Rom. J. Morphol. Embryol. 58, No. 3, pp. 731-738.
4. Iddah, M. A. & Macharia, B. N. (2013). Autoimmune thyroid disorders. ISRN Endocrinol. 2013, 509764. https://doi.org/10.1155/2013/509764
5. Mendoza, M., Er, E. & Blenis, J. (2011). The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation. Trends Biochem. Sci., 36, No. 6, pp. 320-328. https://doi.org/10.1016/j.tibs.2011.03.006
6. Wortzel, I. & Seger, R. (2011). The ERK cascade: distinct functions within various subcellular organelles. Genes Cancer, 2, No. 3, pp. 195-209. https://doi.org/10.1177/1947601911407328
7. Vatseba, T. S., Sokolova, L. K., Pushkarev, V. V., Kovzun, O. I., Guda, B. B., Pushkarev, V. M. & Tronko, M. D. (2019). Activation of the PI3K/Akt/mTOR/p70S6K1 signaling cascade in the mononuclear cells of pe ripheral blood: association with insulin and insulin-like growth factor levels in the blood of patients with cancer and diabetes. Cytol. Genet., 53, No. 6, pp. 489-493.
8. Delves, P. J., Martin, S. J., Burton, D. R. & Roitt, I. M. (2017). Roitt’s essential immunology. 13th ed. Wiley and Sons, Ltd.
9. Arthur, J. S. C. & Ley, S. C. (2013). Mitogen-activated protein kinases in innate immunity. Nat. Rev. Immunol., 13, pp. 679-692. https://doi.org/10.1038/nri3495
10. Pushkarev, V., Guda, B., Pushkarev, V. & Tronko, N. (2018). Oncogene toxicity in thyroid carcinomas and other types of tumors. Cytol. Genet., 521, No. 52, pp. 54-61. https://doi.org/10.3103/S0095452718010103
11. Guda, B. B., Pushkarev, V. V., Kovzun, O. I., Pushkarev, V. M. & Tronko, M. D. (2019). Toxicity of MAPK in thyroid carcinoma. Mechanisms of suppression of signal cascade (review of literature and own data). Spytalna Khirurgiya, 3, pp. 84-96 (in Ukrainian). https://doi.org/10.11603/2414-4533.2019.3.10551
12. Ciliberti, M. G., Albenzio, M., Inghese, C., Santillo, A., Marino, R., Sevi, A. & Caroprese, M. (2017). Peripheral blood mononuclear cell proliferation and cytokine production in sheep as affected by cortisol level and duration of stress. J. Dairy Sci., 100, No. 1, pp. 750-756. https://doi.org/10.3168/jds.2016-11688
13. Zheng, Q., Xu, J., Gao, H., Tao, R., Li, W., Shang, S. & Gu, W. (2015). Receptor expression and responsiveness of human peripheral blood mononuclear cells to a human cytomegalovirus encoded CC chemokine. Braz. J. Infect. Dis., 19, No. 4, pp. 403-409. https://doi.org/10.1016/j.bjid.2015.05.007
14. Zheng, Q., Tao, R., Gao, H., Xu, J., Shang, S. & Zhao, N. (2012). HCMV-encoded UL128 enhances TNF-a and IL-6 expression and promotes PBMC proliferation through the MAPK/ERK pathway in vitro. Viral Immunol., 25, No. 2, pp. 98-105. https://doi.org/10.1089/vim.2011.0064
