Abstract
To study the influence of intraperitoneal injected extracellular ubiquitin on regeneration of leucopoiesis calculation of nuclear cell count in bone marrow (BM) and peripheral blood (PB) smears stained with azure-eosin was performed. In the first, control group of animals inhibition of haematopoiesis achieved by means of 100 mg/kg cyclophosphamide LD50 50–200 mg/kg injection. Bone marrow and peripheral blood samples from the first group of rats had been taken at 24, 48, 72, 96 and 168 h points after injection of cytostatic. Animals of the second, test group were injected by 200 μg/mL ubiquitin 72 h later after cytostatic injection. Our experiments revealed that ubiquitin makes corrections in regeneration of leucopoiesis and leads to normalisation of the process. Ubiquitin regulates stem cell activity, normalizes the release of functional cells into bloodstream, supposedly retains progenitor cells in zones of differentiation and maturation, and restores the nuclear cell ratio in PB and BM. We suppose that obtained results are important for elucidation of new pathways of ubiquitinylation and give us possibilities to find new therapeutics for regeneration of leucopoiesis that is very essential for treatment of radiated bone marrow and chemotherapeutic side effects in cancer patients.
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References
Ciechanover, A., The ubiquitin-proteasome pathway: on protein death and cell life, EMBO J., 1998, vol. 17, no. 24, pp. 7151–7160.
Daino, H., Matsumura, I., Takada, K., Odajima, J., Tanaka, H., Ueda, S., Shibayama, H., Ikeda, H., Hibi, M., Machii, T., Hirano, T., and Kanakura, Y., Induction of apoptosis by extracellular ubiquitin in human haematopoietic cells: possible involvement of STAT3 degradation by proteasome pathway in interleukin 6-dependent hematopoietic cells, Blood, 2000, vol. 95, no. 8, pp. 2577–2585.
Daino, H., Shibayama, H., Machii, T., and Kitani, T., Extracellular ubiquitin regulates the growth of human hematopoietic cells, Biochem. Biophys. Res. Commun., 1996, vol. 223, no. 7, pp. 226–228.
Sujashvili, R., Kukuradze, E., Modebadze, I., and Dekanoidze, D., Effect of extracellular ubiquitin on modeled alcoholic liver histoarchitectonics and proliferative activity of hepatocytes, in EMBO, Molecular Insights for Innovative Therapies, Conference, Heidelberg, Germany, 2011.
Sujashvili, R., Bukuradze, E., Modebadze, I., and Dekanoidze, D., In vivo introduced extracellular ubiquitin regulates intracellular processes, Int. J. Biol. Life Sci., 2012, vol. 61, pp. 326–329.
Sujashvili, R., Bukuradze, E., Modebadze, I., and Dekanoidze, D., Ubiquitin in combination with alcohol stimulates proliferative activity of hepatocytes, Georgian Med. News, 2013, no. 10 (223), pp. 86–90.
Sujashvili, R., Ioramashvili, I., Gvinadze, N., and Aptsiauri, K., Inhibition of proliferative activity of bone marrow cells by extracellular ubiquitin, Proc. Georgian Natl. Acad. Sci., Biomed. Ser., 2014, vol. 40, nos. 5–6, pp. 265–270.
Saini, V., Romero, J., Marchese, A., and Majetschak, M., Ubiquitin receptor binding and signaling in primary human leukocytes, Commun. Integr. Biol., 2010, vol. 3, no. 6, pp. 608–610.
Saini, V., Marchese, A., and Majetschak, M., CXC chemokin receptor 4 is a cell surface receptor for extracellular ubiquitin, J. Biol. Chem., 2010, vol. 285, no. 20, pp. 15566–15576.
Deng, X., Xu, J., He, G., Tao, Y., Yang, T., Peng, X., and Cao, Y., Posttranslational modifications of CXCR4: implication in cancer metastasis, Recept. Clin. Investig., 2014, vol. 1, no. 1, pp. 13–19.
Chernock, R.D., Cherla, R.P., and Ganju, R.K., SHP2 and cbl participate in a-chemokine receptor CXCR4- mediated signaling pathway, Blood, 2001, vol. 97, no. 3, pp. 608–615.
Hegedus, C.M., Gunn, L., Skibola, C.F., Zhang, L., Shiao, R., Fu, S., Dalmasso, E.A., Metayer, C., Dahl, G.V., Buffer, P.A., and Smith, M.T., Proteomic analysis of childhood leukemia, Leukemia, 2005, vol. 19, no. 10, pp. 1713–1718.
Eastmond, D.A., Chemical and radiation leukemogenesis in humans and rodents and the value of rodent models for assessing risks of lymphohematopoietic cancers. U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment, Washington Office, Washington, DC, EPA/600/R-97-090, 1997, pp. 1–134.
Ponchin, G., Beaulieu, A., Humblet, C., Thiry, A., Oda, K., Boniver, J., and Defresne, M.-P., Characterization of spontaneous bone marrow recovery after sublethal total body irradiation: Importance of the osteoblastic/adipocytic balance, PLoS One, 2012, vol. 7, no. 2, pp. 1–13.
Shizuru, J.A., Negrin, R.S., and Weissman, I.L., Hematopoietic stem and progenitor cells: clinical and preclinical regeneration of the hematopoietic system, Annu. Rev. Med., 2005, vol. 56, pp. 509–538.
Hollingsworth, J.W., Inhibition by cytotoxic drugs of bone marrow regeneration after irradiation and marrow transplantation, Cancer Res. (AACR), 1959, vol. 19, pp. 165–169.
Orrenius, S., Nicotera, P., and Zhivotovsky, B., Cell death mechanisms and their implication in toxicology, Toxicol. Sci., 2011, vol. 119, no. 1, pp. 2–19.
Kondo, T., Radiation induced cell death and its mechanisms, Radiat. Emerg. Med., 2013, vol. 2, no. 1, pp. 1–4.
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Sujashvili, R., Ioramashvili, I., Aptsiauri, K. et al. Regulation of leucogenesis by extracellular ubiquitin in rodents after chemically induced inhibition. Cytol. Genet. 50, 334–338 (2016). https://doi.org/10.3103/S0095452716050133
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DOI: https://doi.org/10.3103/S0095452716050133