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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. 2011; 57(6): 3-14


Hydrogen sulfideinhibits ca[sup]2+[/sup]-induced mitochondrial permeability transition pore opening in adult and oldrat heart

N.A. Strutynska, O.M. Semenykhina, S.V. Chorna, G.L.vavilova, V.F. Sagach.

    Ін-т фізіології ім. О.О. Богомольця НАН України,Київ


Abstract

In experiments in vivo and in vitro on the mitochondria iso­lated from adult and old rat hearts, we studied the effects of a donor of hydrogen sulfide (H2S), NaHS, and H2S biosynthesis substrate, L-cysteine, on the sensitivity of the mitochondrial permeability transition pore (mPTP) opening to its natural inductor, Ca2+. We found that NaHS (10-12 to 10-4 mol/l) influ­enced mitochondrial swelling in a concentration-dependent manner. It was also demonstrated that the addition of NaHS (10-12 to 10-8 mol/l) to the calcium-free medium resulted in moderate a swelling of mitochondria from both adult and old rat hearts. At 10-10 mol/l NaHS, the maximal values of the mitochondrial swelling observed in both adult and old hearts were 11 and 15 ,%, respectively. A specific inhibitor of KAT P -channels, 5-hydroxydecanoate (5-HD; 10-4 mol/l) decreased the mitochondrial swelling in the presence of NaHS (10-10 mol/ l), which can be indicative of the contribution of these channels to the calcium-independent conductance of the mitochondrial membranes in the rat hearts. The H2S donor NaHS used in physiological concentrations (10-6, 10-5 and 5 10-5 mol/l) exer­ted the inhibiting effect on the Ca2+-induced mPTP opening in adult hearts (corresponding values of such effect were 31, 76, and 77%, respectively), while in old hearts the protector ef­fect of NaHS was observed only at its concentration of 10-5 mol/l. Therefore, the donor of H2S used in the tested concentrations (10-12 to 10-4 mol/l) exerted ambiguous effect on the mitochondrial swelling: low concentrations of NaHS (10-12 to 10-8 mol/l) increased the mitochondrial swelling, while its physiological concentrations (10-6 to 5 10-5 mol/l) exerted the protective effect on Ca2+-induced mitochondrial swelling in adult and old hearts. Pre-incubation of isolated mitochon­dria with 5-HD (10-4 mol/l) resulted in a decrease in the protec­tive effect evoked by NaHS (10-5 mol/l) on Ca2+-induced mPTP opening, which is indicative of the possible involvement of mitochondrial KAT P -channels in the H2S-dependent inhibition of mPTP formation in both adult and old rat hearts. In experi­ments in vivo, single intraperitoneal injections of both NaHS (10-4 mol/kg) and L-cysteine ((10-3 mol/kg) resulted in a de­crease in the sensitivity of mPTP to its inductor Ca2+ in adult and old rat hearts. The action of L-cysteine, as compared with that of NaHS, was more effective in prevention of Ca2+-in-duced mitochondrial swelling. We observed a rise in Ca2+ concentration by one order of magnitude, which evoked the mitochondrial swelling in adult and old hearts. In experiments in vivo in which we used a specific blocker of cystathionine-g-lyase, propargylglycine (10-4 mol/kg) that is involved in the synthesis of H2S, we observed an increase in the sensitivity of mPTP opening in old hearts because of a decrease in the thresh­old Ca2+ concentration required for mitochondrial swelling by two orders of magnitude. We demonstrate the involvement of endogenous H2S in the control of mPTP formation in adult and old hearts. Our studies are indicative of the involvement of H2S in modulation of changes in the permeability of mitochon-drial membranes, which can be an important regulatory factor in the development of cardiovascular diseases.

Keywords: Ін-т фізіології ім. О.О. Богомольця НАН України, Київ

References

  1. Баскаков М.Б., Гусакова СВ., Желудева А.С., Смаглий Л.В., Ковалев И.В., Вторушина Т.А., Носов Д.С., Еременко К.В., Медведев М.А., Орлов С.Н. Влияние сероводорода на сократительную актив­ность гладкомышечных клеток аорты крысы// Бюл. сибир. медицины. - 2010. - №6. - С. 12-17.
  2. Мойбенко А.А., Досенко В.Е., Пархоменко А.Н. Эндогенные механизмы кардиопротекции как основа патогенетической терапии заболеваний сердца. - К.: Наук. думка, 2008. -С. 206-251.
  3. Сагач В.Ф., Рудик О.В., Вавілова Г.Л., Коцюруба А.В., Ткаченко Ю.П. Мелатонін відновлює ішемічну толерантність та зменшує чутливість відкриттямітохондріальної пори в серці старих щурів // Фізіол. жури. - 2006. - 52, №3. - С 3-14.
  4. Сагач В.Ф., Вавілова Г.Л., Рудик О.В., Струтинська Н.А. Вивільнення неіденти-фікованих речовин мітохондріального походження - показник відкриття мітохондріальної пори серця шурів // Там само. - 2003. - 49, №5. -С 3-12.
  5. Сагач В.Ф., Вавілова Г.Л., Струтинська Н.А., Рудик О.В. Старіння підвищує чутливість до індукторів мітохондріальної пори в серці щурів // Там само. - 2004. - 50, №2. -С 49-63.
  6. Шиманская Т.В., Добровольский Ф.В., Вавилова Г.Л., Струтинская Н.А., Рудык Е.В., Сагач В.Ф. NO-зависимая модуляция чувствительности открытия митохондриальной поры при ишемии/реперфузии изолированного сердца // Рос. физиол. журн. - 2009. -95, №1. -С. 28-37.
  7. Cai W.J., Wang M.J., Moore P.K., Jin H.M., Yao T., Zhu Y.C. The novel proangiogenic effect of hydrogen sulfide is dependent on Akt phosphorylation // Cardiovasc. Res. - 2007. - 76. - P. 29-34.
  8. Chang L., Geng B., Yu F., Zhao J., Jiang H., Du J, Tang C. Hydrogen sulfide inhibits myocardial injury induced by homocysteine in rats // Amino Acids. - 2008. - 34. -P. 573-585.
  9. 9. Elsey D.J., Fowkes R.C., Baxter G.F. Regulation of cardiovascular cell function by hydrogen sulphide (H S) // Cell. Biochem. Funct. - 2010. - 28. - P. 95-106.2
  10. 10. Halestrap A. What is the mitochondrial permeability transition pore?// Molecular and cell. Cardiol. - 2009. -46. - P.821-831.
  11. Javadov S, Karmazyn M, Escobales N. Mitochondrial permeability transition pore opening as a promising therapeutic target in cardiac diseases// Pharmacol. Exp. Ther. -2009. - 330(3) - P. 670-678.
  12. Ji Y, Pang Q.F., Xu G., Wang L., Wang J.K., Zeng YM. Exogenous hydrogen sulfide postconditioning protects isolated rat hearts against ischemia-reperfusion injury // Eur. J. Pharmacol. - 2008. - 587. - P. 1-7.
  13. Kapoor A., Thiemermann C. Hydrogen sulfide, neurogenic inflammation, and cardioprotection: a tale of rotten eggs and vanilloid receptors // Crit. Care Med. -2010. - 38. - P. 728-730.
  14. Kimura H. Hydrogen sulfide: its production, release and functions // Amino Acids. - 2010. - 45. - P. 56-61.
  15. Kubo S., Doe I., Kurokawa Y, Nishikawa H., Kawabata A. Direct inhibition of endothelial nitric oxide syn­thase by hydrogen sulfide: Contribution to dual modula- tion of vascular tension // Toxicology. - 2007. - 232. -P. 138-146.
  16. Lowicka E., Beltowski J. Hydrogen sulfide (H S) - the third gas of interested for pharmacologists // Pharma-col. Rep. - 2007. - 59. - P. 4-24.
  17. Li L., Hsu A., Moore P.K. Actions and interactions of nitric oxide, carbon monoxide and hydrogen sulphide in the cardiovascular system and in inflammation-a tale of three gases// Pharmacol. Ther. - 2009. - 123. -P. 386-400.
  18. Li L., Rose P., Moore P.K. Hydrogen sulphide and cell signalling // Annu. Rev. Pharmacol. Toxicol. - 2011. -51. – P. 169-187.
  19. 19. Mancardi D., Penna C, Merlino A., Del Soldato P, Wink D.A., Pagliaro P. Physiological and pharmaco­logical featurers of the novel gasotransmitter : hydro­gen sulphide // Biochem. Biohys. Acta. - 2009. - 1787. -P. 864-872.
  20. 20. Rui W. Two’s company, three’s a crowd: can H S be the third endogenous gaseous transmitter // FASEB J. -2002. - 16. - P. 1792-1798.
  21. Szabo C. Hydrogen sulphide and its therapeutic poten­tial // Nat. Rev. Drug Discov. - 2007. - 6. - P. 917-935.
  22. Sivarajah A., Collino M., Yasin M., Benetti E., Gallicchio M., Mazzon E, Cuzzocrea S, Fantozzi R, Thiemermann C. Anti-apoptotic and anti-inflammatory effects of hydrogen sulfide in a rat model of regional myocardial I/R // Shock. - 2009. - 31. - P. 267-274.
  23. Stipanuk M.H. Sulfur amino acid metabolism: path­ways for production and removal of homocysteine and cysteine // Annu. Rev. Nutr. - 2004. - 24. - P. 539-577.
  24. Tang G., Wu L., Liang W., Wang R. Direct stimulation of К-АТФ channels by exogenous and endogenous hydrogen sulfide in vascular smooth muscle cells // Mol. Pharmacol. - 2005. - 68. - P. 1757-1764.
  25. Wagner F., Asfar P., Calzia E., Radermacher P., Szaby C. Bench-to-bedside review: Hydrogen sulfide - the third gaseous transmitter: applications for critical care // Critical Care. - 2009. - 13. - P. 213-222.
  26. Whiteman M., Moore P.K. Hydrogen sulfide and the vasculature: a novel vasculoprotective entity and regulator of nitric oxide bioavailability // J. Cell. Mol. Med. - 2009. - 13. - P. 488-507.
  27. Zhu Y.Z., Wang Z.J., Ho P., Loke YY, Zhu Y.C, Huang S.H., Tan C.S., Whiteman M., Lu J., Moore P.K. Hy­drogen sulfide and its possible roles in myocardial is­chemia in experimental rats // Appl. Physiol. - 2007. -102. - P. 261-268.

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