In vivo Introduced Extracellular Ubiquitin Regulates Intracellular Processes

Authors: Rusudan Sujashvili, Ekaterine Bakuradze, Irina Modebadze, Davit Dekanoidze

Abstract:

Extracellular ubiquitin in vivo effect on regenerative liver cells and liver histoarchitectonics has been studied. Experiments were performed on mature female white rats. Partial hepatectomy was made using the modified method of Higgins and Anderson. Standard histopathological assessment of liver tissue was used. Proliferative activity of hepatocytes was analyzed by colchicine mitotic index and immunohistochemical staining on ki67. We have found that regardless of number of injections and dose of extracellular ubiquitin liver histology has not been changed, so at tissue level no effect was observed. In vivo double injection of ubiquitin significantly decreases the mitotic activity at 32 hour point after partial hepatectomy. Thus, we can conclude that in vivo injected extracellular ubiquitin inhibits proliferative activity of hepatocytes in partially hepatectomyzed rats.

Keywords: Liver, regeneration, proliferation, ubiquitin.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1062326

References:

[1] Ciechanover A, Schwartz AL The ubiquitin system: pathogenesis of human diseases and drug targeting Biochim Biophys Acta. 2004, 1695(1-3):3-17;
[2] Nalepa G., Rolfe M., Harper W. Drug discovery in the ubiquituinproteasome system. Nature Reviews Drug Discovery 2006; 5: 596-613;
[3] Wang Y, Guan S, Acharya P, Koop DR, Liu Y, Liao M, Burlingame AL, Correia MA. Ubiquitin-dependent proteasomal degradation of human liver cytochrome P450 2E1: identification of sites targeted for phosphorylation and ubiquitination. J Biol Chem. 2011 Mar 18;286(11):9443-56;
[4] Daino H, Shibayama H, Machi T, Kitani T. Extracellular ubiquitin regulates the growth of human hematopoietic cells. Biochem Biophys Res Commun. 1996;223:226;
[5] LI W, LIANG X, KELLENDONK C, POLI V, TAUB R. STAT3 CONTRIBUTES TO THE MITOGENIC RESPONSE OF HEPATOCYTES DURING LIVER REGENERATION. J BIOL CHEM. 2002; 277(32):28411-7;
[6] Xua Y., Fenga D., Wangb Y., Luob Q., Xua L. STAT3 mediates Protection from Liver Inflammation after Partial Hepatectomy, Cell Physiology and Biochemistry, 2009, 23:379-386;
[7] Douglas L. Schmucker and Henry Sanchez Liver Regeneration and Aging: A Current Perspective Current Gerontology and Geriatrics Research Volume 2011, Article ID 526379;
[8] Dzidziguri D.V., Chelidze P.V., Zarandia M.A., Cherkezia E.O., Tumanishvili G.D. The transcriptional and ultrastructure of various nucleolar types isolated from normal and partially hepatectomized rat hepatocites.// J.Epith.Cell Biol., 1994, V.3, p.240-246;
[9] Daino H., Matsumura I., Takada K., Odajima J., Tanaka H., Ueda Sh., Shibayama H., Ikeda H., Hibi M., Machii T., Hirano T. Kanakura Y. Induction of apoptosis by extracellular ubiquitin in human hematopoietic cells: possible involvement of STAT3 degradation by proteasome pathway in interleukin 6-dependent hematopoietic cells Blood, 2000, 95: 2577-2585;
[10] Lodish H; Berk A; Zipursky S.L; Matsudaira P; Baltimore D; Darnell J.E. Molecular Cell Biology.// W. H. Freeman and Company., New York, 2000. -1200ps;
[11] Shibayama H, Machi T, Tokumine Y, et al. Establishment of a new cell line from a patient with hairy cell leukemiaÔÇöJapanese variant. Leuk Lymphoma. 1997, 25:373;
[12] Pancre V, Pierce RJ, Fournier F, et al. Effect of ubiquitin on platelet functions: possible identity with platelet activity suppressive lymphokine (PASL). Eur J Immunol. 1991; 21:2735-2741;
[13] Nakamura M, Xavier RM, Tanigawa Y. Ubiquitinlike moiety of the monoclonal nonspecific suppressor factor beta is responsible for its activity. J Immunol. 1996, 156:532-538.