Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2008; 54(3): 28-35

Search for ways to correctthymic dysfunction in rats with experimental diabetes mellitus

Yu.M. Kolesnik, A.M. Kamyshny, A.V. Abramov.

    Zaporozhye Medical State University



Abstract

We investigated the influence of multiple introductions of NO precursor L-arginine and NOS non-selective blocker N-nitro- L-arginine (NNLA) on thymic morpho-functional status in Wistar male rats with experimental diabetes mellitus (EDM). To reveal insulin-expressing, proliferating, Treg-cells, iNOS+- cells and Bcl-2+-cells, the immunohistochemical methods of direct and indirect immunofluorescence with monoclonal anti- bodies to insulin, PCNA, CD-25 antigen. Bcl-2 and iNOS of rat were used. It was established that NNLA administration to rats with EDM has more pronounced effect in comparison with L-arginine administration, demonstrating an increase in the number of Treg-cells, insulin-expressing and proliferating thymocytes and a decrease in the density of iNOS+- and Bcl- 2+-cells population.

Full text: (PDF, in Ukrainian)

References

  1. Абрамов А.В., Колесник Ю.М., Любомирська В.А., Камишний О.М. Алгоритм автоматичного аналізу лімфоїдної популяції тимуса // Вісн. морфології. –2002. – №2. – С. 261–262.
  2. Барышников А.Ю., Шишкин Ю.В. Иммунологи- ческие проблемы апоптоза. і – М.: Эдиториал УРСС, 2002. – 320 с.
  3. Колесник Ю.М, Камышный А.М., Абрамов А.В. Эффекты NO в иммунной системе: NO и тимус // Запорож. мед. журн. – 2006. – №2. – С.5–11.
  4. Фрейдлин И.С. Регуляторные Т-клетки: происхож- дение и функция // Мед. иммунология. – 2005. – 7, № 4. – С. 347–354.
  5. Ярилин А.А., Донецкова А.Д. Регуляторные Fохр3+ Т-клетки и их роль при аллергии // Рос. аллергол. журн. – 2005. – № 2. – С. 22–26.
  6. Bogdan C. The function of nitric oxide in the immune system // Handbook of Exp. Pharmacol. – 2000. – 3. –Р. 443–492.
  7. Brookes P. Mitochondrial nitric oxide synthase // Mi-tochondrion. – 2004 – 3. – P. 187–204.
  8. Brune B., Gotz C., Mebmer U. et al. Superoxide for- mation and macrophage resistance to nitric oxide medi-ated apoptosis // J. Biol. Сhem. – 1997 – 272. –P. 7253–7258.
  9. 9. Brune B., von Knethen A., Sandau K. Nitric oxide and its role in apoptosis // Eur. J. Pharmacol. – 1998 – 351. – P. 261–272.
  10. 10. Chatenoud L., Bluestone J. CD3-specific antibodies: a portal to the treatment of autoimmunity // Nat. Rev. Immunol. – 2007. – 8. – P.622–632.
  11. Derbinski J., Gabler J., Kyewski B. Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels // J.Exp. Med. – 2005. – 202. – P.33–45.
  12. Elfering S., Sarkela T., Giulivi C. Biochemistry of mi- tochondrial nitric oxide synthase // J. Biol. Chem. – 2002. – 277. – P. 38079–38086.
  13. Flodstrom M., Tyrberg B., Eizirik D., Sandier S. Redu- ced sensitivity of inducible nitric oxide synthase-defi- cient mice to multiple low-dose streptozotocin-induceddiabetes // Diabetes – 1999. – 48. – P. 706–713.
  14. Geenen V., Brilot F., Louis C. et аl. Importance of a thymus dysfunction in the pathophysiology of type 1 diabetes // Rev. Med. Liege. – 2005. – 60. – №5–6. –P.291–296.
  15. Giulivi C. Characterization and function of mitochon-drial nitric-oxide synthase. // Free Radical Biol. Med. – 2003. – 34. – P. 397–408.
  16. Green D., Reed J. Mitochondria and apoptosis // Sci-ence. – 1998. – 281. – P.1309–1312.
  17. Haluzfk M., Nedveldkovi J. The role of nitric oxide in the development of streptozotocin-induced diabetes mellitus: experimental and clinical implications // Physiol. Res. – 2000. – 49. – P. 37–42.
  18. Kojima H., Fujimiya M., Matsumura K. et al. Extrapancreatic insulin-producing cells in multiple organs in diabetes // Proc. Natl. Acad. Sci. USA.– 2004.–101.– P. 2458–2463.
  19. 19. Kroemer G. The proto-oncogene Bcl-2 and its role in regulating apoptosis // Nat. Med. – 1997. – 3. – P.614– 620.
  20. 20. Lindley S., Dayan C. Defective supressor function in CD4+CD25+T-cells from patients with type 1 diabe- Пошук шляхів корекції дисфункції тимуса
  21. ISSN 0201-8489 Фізіол. журн., 2008, Т. 54, № 3 35tes // Diabetes. – 2005. – 54. – P. 92–99.
  22. Luo X., Yang H., Kim I. et al. Systemic transforming grouth factor-beta 1 gene therapy induces Foxp3+ regulatory cells, restores self-tolerance, and facilitates regeneration of beta сell function in overtly diabeticnonobese diabetic mice // Transplantation. – 2005. –79. – P. 1091–1096.
  23. Mebmer U., Brune B. Nitric oxide-induced apoptosis: p53-dependent and p53-independent signaling path- ways // J. Biochem. – 1996. – 319. – P 299–305.
  24. Mebmer U., Reed J., Brune B. Bcl-2 protects mac- rophages from nitric oxide-induced apoptosis // J. Biol. Chem. – 1996. – 271. – P. 20192–20197.
  25. Opferman J., Korsmeyer S. Apoptosis in the develop- ment and maintenance of the immune system // Nat. Immunol. – 2003. – 4. – P.410–415.
  26. Piccirillo C., Tritt M., Sgouroudis E. et al. Control of type I autoimmune diabetes by naturally occurring CD4+CD25+ regulatory Т lymphocytes in neonatalNOD mice // Ann. N. Y.Acad. Sci. – 2005. – 1051. –P. 72–87.
  27. Pop S., Wong C., Culton D. et al. Single cell analysis shows decreasing FoxP3 and TGF beta 1 coexpressing CD4+CD25+ regulatory Т cells during autoimmune diabetes // J. Exp. Med. – 2005. – 201. – P. 1333–1346.
  28. Rietz C., Screpanti V., Brenden N. Overexpression of bcl-2 in T cells affects insulitis in the nonobese dia- betic mouse // Scand. J. Immunol. – 2003. – 57. – №4. –P.342–349.
  29. Sakaguchi S. Naturally arising CD4+ regulatory Т cells for immunologic self-tolerance and negative control of immune responses // Annu. Rev. Immunol. – 2004. –22. – P. 531–562.
  30. 29. Sarkela T., Berthiaume J., Elfering S. et al. The modu- lation of oxygen radical production by endogenous ni- tric oxide in mitochondria // J. Biol. Chem. – 2001. –276. – P. 6945–6949.
  31. 30. Tejedo J., Bernabe J., Ramirez R., Sobrino F. NO in- duces a cGMP-independent release of cytochrome c from mitochondria which precedes caspase 3 activa- tion in insulin producing RINm5F cells // FEBS Lett. –1999. – 459. – P. 238–243.
  32. Thebault K., Debois D., Vallon-Geoffroy K. et al. Ac- celeration of type 1 diabetes mellitus in proinsulin 2-deficient NOD mice // J. Clin. Invest.– 2003.– 111.–P. 851–857.
  33. Throsby M., Homo-Delarche F., Chevenne D., Goya R., Dardenne M., Pleau J. Pancreatic hormone expres-sion in the murine thymus: localization in dendritic cells and macrophages // Endocrinology. – 1998. – 139.–P. 2399–2406.
  34. Trucco M., Giannoukakis N. Immunoregulatory den- dritic cells to prevent and reverse new-onset type 1 diabetes mellitus // Exp. Opin. Biol. Therap. – 2007. –7. – P.951–963.
  35. Williams O., Norton T., Halligey M. The action of Bax and Bcl-2 on T cell selection // J. Exp. Med. – 1998. – 188. – P.1125–1133.
  36. Yoshioka Y., Yamamuro A., Maeda S. Nitric oxide at a low concentration protects murine macrophage RAW264 cells against nitric oxide-induced death via cGMP signaling pathway // Brit. J. Pharmacol. – 2003. –139. – P. 28–34.
  37. Zhang N., Hartig H., Draper D., He Y. The role of apoptosis in the development and function of T lymphocytes // Cell Res. – 2005. – 10. – P.749 – 769
© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.