Українська Русский 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. 2007; 53(5): 22-28


The nitric oxideand superoxide synthesis in protective action of ecdysterone in mitochondrias of rat.shearts with streptozotocin-induced diabet

Ju.P. Korkach , O.V. Rudyk, A.V.Kotsuruba , O.D. Prysyazhna , V.F. Sagach

    O.O. Bogomoletz Institute of Physiology, NationalAcademy of Sciences of Ukraine, Kyiv;O.V. Palladin Institute of Biochemistry National Academyof Sciences of Ukraine, Kyiv;


Abstract

This study evaluated generation of O2*- and NO in heart mitochondria isolated from 9-week old streptozotocin (STZ). induced diabetic rats and the effect of ecdysterone treatment on these parameters. Mitochondria isolated from 9-weeek old placebo.treated rats were used as control. Several parameters were evaluated: O2*- production, the levels of stable NO metabolites nitrate, nitrite and total nitrosothiols, the level of bilirubine (as marker of CO generation), inducible (iNOS) and constitutive (nNOS) mtNOS, NADH- dependent nitrate reductase (NR) and inducible arginase II (AII) activity .We observed that diabetes was accompanied by a significant decrease in nNOS activity, nitrite, total nitrosothiols and bilirubine content while iNOS, NR and AII activity, as well as O2*- generation was increased in heart mitochondria. Ecdysterone treatment normalized the levels of stable NO metabolites, ability to generate superoxide, iNOS and nNOS activity, but not bilirubine level, NR and AII activity. These results suggest that ecdysterone treatment attenuates diabetes?induced mitochondrial alterations protecting against oxidative and nitrosative stresses. Thus, ecdysterone therapy, besides its well known importance in the maintenance of glycemic control, may help to protect against mitochondrial dysfunction associated to several age-related disorders.

References

  1. Аликулов З.А., Львов Н.П. Кретович В.Л. Нитрат- и нитрит- редуктазная активности молока // Био- химия. – 1980. – 45, №9. – C. 1714–1718.
  2. Костерин С.А., Браткова Н.Ф., Курский М.Д. Роль сарколеммы и митохондрий в обеспечении кальцие- вого контроля расслабления миометрия // Там же. – 1985. – 50, №8. – С.1350–1361.
  3. Коцюруба А.В., Коркач Ю.П., Рудык Е.В. и др. Эффективность экдистерона как ингибитора МРТ в митохондриях сердца старых крыс; кардиопро- текция путем коррекции окислительного (de novo) и восстановительного (salvage) путей синтеза NO в митохондриях: Материалы международ. симпоз. «Активные формы кислорода, азота и хлора в регуляции клеточных функций в норме и патоло- гии» (28–29 сент. 2006 г., Гродно). – Ч.1. – С.157–162.
  4. Кузьменко А.И., Морозова Р.П., Николенко И.А., Донченко Г.В. Изучение антиокислительного эффекта 20-гидроксиэкдизона в модельной системе // Укр.биохим.журн. – 1999. – 71, №3. – С. 35–38.
  5. Синяченко О.В., Звягина Т.В. Оксид азота в терапевтической практике. – Донецк, 2001.– 256 c.
  6. Холодова Ю.Д Фитоэкдистероиды// Биохимия животных и человека. – 1987.- №11. – C.27–41.
  7. Шугалей В.С., Козина А.С. Содержание мочевины и активность аргиназы в органах крыс при акклима- тизации к холоду // Физиол. журн. СССР. –1977. – № 8. – C.1199–1202.
  8. Brodsky S.V., Gao S., Li H., Goligorsky M.S. Hyper- glycemic switch from mitochondrial nitric oxide to su- peroxide production in endothelial cells // Amer. J. Physiol. Heart. Circulat. Physiol. – 2002. – 283, № 5. – Р. 2130–2109.
  9. 9. Chicoine L.G., Paffet M.L., Young T.L., Nelin L.D. Arginase inhibition increases nitric oxide production in bovine pulmonary arterial endothelial cells //Amer. J. Physiol. Luhg. Cell. Mol. Physiol. – 2004. – 287, №1. – P. 60–68.
  10. 10. Costantini P., Belzacq A.S., Vieira H.L. et. al. Oxida- tion of a critical thiol residue of the adenine nucleotide translocator enforces Bcl-2-independent permeability transition pore opening and apoptosis // Oncogene. – 2000. – 19, №2. – Р.307–317.
  11. Сrompton M. Bax, Bid and the permeabilization of the mitochondrial outer membrane in apoptosis // Curr. Opin. Cell. Biol. – 2000. – 12, №4. – Р.414–419.
  12. Gerdel D., Cederbaum A.J. Inhibition of the catalitic activity of alkoholdegydrogenase by NO is associated with S-nitrosylation and the release of zinc // Biochem- istry. – 1996. – 35, № 50. – P.16186–16194.
  13. Green L.L., Wagner D.A., Glogowski J. et al. Analysis of nitrate, nitrite and [15N] nitrate in biological fluids // Anal. Biochem. – 1982. – 126, № 1. – P.131–138.
  14. Gunter T.E., Yule D.I., Gunter K.K. et al. Calcium and mitochondria // FEBS Cell. – 2004. – 567, №1. – Р. 96–102.
  15. Huang Q., Shao L., Jiang H. et. аl. Effect of insulin on oxygen free radicals and oxidative phosphorylation in liver mitochondria of diabetic rats // Acta Pharm. Sin. – 2001. – 22, №5. – Р. 455–458.
  16. Kuthan H., Ullrich U., Estabrook R.W. A guantitative test for superoxide radicals produced in biological sys- tems // Biochem. J. – 1982. – 203, №3. – Р. 551–558.
  17. Loke K.E., Laycock S.K. Mital S. et. al. Nitric oxide modulates mitochondrial respitation in failing human heart // Circulation. – 1999. – 100, № 12. – Р.1291–1297.
  18. Sagach V.F., Vavilova G.L. Rudyk O.V., Strutyns’ka N.A. The Sensitivity of the nitichondrial permesbility transition pore opening in diabetic rat heart // Укр. біохім. журн. – 2005. – 72, №2. – С. 73.
  19. 19. Salter M., Knowles R.G., Moncada S. Widespread tis- sue distribution, species and changes in activity of Ca2+- - dependent and Ca2+ -independent nitric oxide syntases // FEBS Lett. – 1991. – 291, № 1. – P. 145–149.
  20. 20. Schipper H.M. Heme oxygenase-1: transducer of pathological brain iron sequestration under oxidative stress //Ann N Y Acad Sci. – 2004. –1012. – P.84–93.
  21. Srinivasan S, Hatley M.E., Bolick D.T. et. аl. Hyperglycaemia-induced superoxide production de- creases eNOS expression via AP-1 activation in aortic endothelial cells // Diabetologia. – 2004. – 47, №10. – Р.1727–1734.
  22. Xu W.M., Liu L.Z., Charles I.S. Microencapsulated iNOS-expressing cells cause tumor suppression in mice // FASEB J. – 2001. –15. – P.131–148.
  23. Zhang Z., Naughton D., Winyard P.G. Generation of nitric oxide by a nitrite reductase activity of xanthine oxidase: a potential pathway for nitric oxide formation in the absence of nitric oxide synthase activity // Biochem. and Biophys. Res. Commun. – 1998. – 249, №3. – P. 767–772.

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2019.