Reductive Nitrosylation of Hemoglobin and Myoglobin and Its Antioxidant Action

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Angeli’s salt is regarded as a nitroxyl donor, so it can counteract hemolysis-driven adverse effects such as the vasoconstrictive effects of free hemoglobin in blood plasma. However, the molecular mechanisms of interaction of nitroxyl with various heme proteins are not fully understood. Oxoferryl forms of hemoproteins emerged under oxidative stress are known to be strong pro-oxidants. This study has been carried out to investigate reductive nitrosylation of metand oxoferryl forms of hemoglobin and myoglobin upon interaction with nitroxyl. Experiments were performed in vitro using electron paramagnetic resonance spectroscopy for detection of nitrosyl forms. The results obtained indicate the antioxidant effect of Angeli’s salt in model systems of hemoglobin or myoglobin oxidation with hydrogen peroxide. Moreover, the addition of hydrogen peroxide to methemoglobin and metmyoglobin led to the appearance of an EPR signal of free radicals with g = 2.005, associated with the protein part of hemoproteins. Thus, nitroxyl acts both as a reducing agent and a nitrosylating agent, thereby preventing the formation of oxoferryl forms of hemoproteides. The therapeutic properties of Angeli’s salt may be largely related to the antioxidant effect it has on blood components.

About the authors

K. B Shumaev

A.H. Bach Institute of Biochemistry, Federal Research Center “Fundamentals of Biotechnology”, Russian Academy of Sciences; National Medical Research Centre of Cardiology named after academician E.I. Chazov, Ministry of Health of the Russian Federation

Email: tomorov@mail.ru
Moscow, Russia; Moscow, Russia

D. I Grachev

Yerevan State University

Yerevan, Armenia

О. V Kosmachevskaya

A.H. Bach Institute of Biochemistry, Federal Research Center “Fundamentals of Biotechnology”, Russian Academy of Sciences

Moscow, Russia

A. F Topunov

A.H. Bach Institute of Biochemistry, Federal Research Center “Fundamentals of Biotechnology”, Russian Academy of Sciences

Moscow, Russia

E. K Ruuge

National Medical Research Centre of Cardiology named after academician E.I. Chazov, Ministry of Health of the Russian Federation

Moscow, Russia

References

  1. Lopez B. E., Shinyashiki M., Han T. H., and Fukuto J. M. Antioxidant actions of nitroxyl (HNO). Free Radic. Biol. Med., 42 (4), 482–491 (2007). doi: 10.1016/j.freeradbiomed.2006.11.015
  2. Li J. C., Velagic A., Qin C. X., Li M., Leo C. H., Kemp-Harper B. K., Ritchie R. H., and Woodman O. L. Diabetes attenuates the contribution of endogenous nitric oxide but not nitroxyl to endothelium dependent relaxation of rat carotid. Arteries Front. Pharmacol., 11, 585740 (2021). DOI: 10.3389/ fphar.2020.585740
  3. Kosmachevskaya O. V., Nasybullina E. I., Pugachenko I. S., Novikova N. N., and Topunov A. F. Antiglycation and Antioxidant Effect of Nitroxyl towards Hemoglobin. Antioxidants, 11 (10), (2022). doi: 10.3390/antiox11102007
  4. Michalski R., Smulik-Izydorczyk R., Pięta J., Rola M., Artelska A., Pierzchała K., Zielonka J., Kalyanaraman B., and Sikora A. B. The Chemistry of HNO: Mechanisms and Reaction Kinetics. Front. Chem., 10, Article 930657 (2022). doi: 10.3389/fchem.2022.930657
  5. Baron C. P. and Andersen H. J. Myoglobin-induced lipid oxidation. A review. Agric. Food Chem., 50 (14), 3887 (2002). doi: 10.1021/jf011394w
  6. Reeder B. J., Svistunenko D. A., Sharpe M. A., and Wilson M. T. Characteristics and mechanism of formation of peroxide-induced heme to protein cross-linking in myoglobin. Biochemistry, 41 (1), 367–375 (2002). doi: 10.1021/bi011335b
  7. Reeder B. J., Svistunenko D. A., Cooper C. E., and Wilson M. T. The radical and redox chemistry of myoglobin and hemoglobin: from in vitro studies to human pathology. Antioxid. Redox Signal., 6 (6), 954-966 (2004). doi: 10.1089/ars.2004.6.954
  8. Wilson M. T. and Reeder B. J. The peroxidatic activities of Myoglobin and Hemoglobin, their pathological consequences and possible medical interventions. Mol. Aspects Med., 84, 101045 (2022). doi: 10.1016/j.mam.2021.101045
  9. Potor L., Bányai E., Becs G., Soares M. P., Balla G., Balla J., and Jeney V. Atherogenesis May Involve the Prooxidant and Proinflammatory Effects of Ferryl Hemoglobin. Oxid. Med. Cell. Longev., 2013, Article ID 676425 (2013). doi: 10.1155/2013/676_25
  10. Solomon S. B., Bellavia L., Sweeney D., Piknova B., Perlegas A., Helms C. C., Ferreyra G. A., King S. B., Raat N. J. H., Kern S. J., Sun J., McPhail L. C., Schechter A. N., Natanson C., Gladwin M. T., and KimShapiro D. B. Angeli’s Salt Counteracts the Vasoactive Effects of Elevated Plasma Hemoglobin. Free Radic. Biol. Med., 53 (12), 2229-2239 (2012). doi: 10.1016/j.freeradbiomed.2012.10.548
  11. Gorbunov N. V., Yalowich J. C., Gaddam A., Thampatty P., Ritov V. B., Kisin E. R., Elsayed N. M., and Kagan V. E. Nitric oxide prevents oxidative damage produced by tert-butyl hydroperoxide in erythroleukemia cells via nitrosylation of heme and non-heme iron. Electron paramagnetic resonance evidence. J. Biol. Chem., 272 (19), 12328–12341 (1997). DOI: 10.1074/ jbc.272.19.12328
  12. Шумаев К. Б, Петрова Н. Э., Заббарова И. В., Ванин А. Ф., Топунов А. Ф., Ланкин В. З. и Рууге Э. К. Взаимодействие оксоферрилмиоглобина и динитрозильных комплексов железа. Биохимия, 69 (5), 699705 (2004). doi: 10.1023/b:biry. 0000029856.67884.c5
  13. Шумаев К. Б., Космачевская О. В., Грачев Д. И., Тимошин А. А., Топунов А. Ф., Ланкин В. З. и Рууге Э. К. Возможный механизм антиоксидантного действия динитрозильных комплексов железа. Биомедицинская химия, 67 (2), 162–168 (2021). doi: 10.18097/PBMC20216702162
  14. Herold S. and K. Rehmann F.-J. Kinetic and mechanistic studies of the reactions of nitrogen monoxide and nitrite with ferryl myoglobin. J. Biol. Inorg. Chem., 6 (5), 543–555 (2001). doi: 10.1007/s007750100231
  15. Herold S. and K. Rehmann F.-J. Kinetics of the reactions of nitrogen monoxide and nitrite with ferryl hemoglobin. Free Radic. Biol. Med., 34 (5), 531–545 (2003). doi: 10.1016/S0891-5849(02)01355-2
  16. Ramirez D. C., Chen Y.-R., and Mason R. P. Immunochemical detection of hemoglobin-derived radicals formed by reaction with hydrogen peroxide: involvement of a protein-tyrosyl radical. Free Radic. Biol. Med. 34 (7), 830–839 (2003). doi: 10.1016/S0891-5849(02)01437-5
  17. Østdal H., Skibsted L. H, and Andersen H. J. Formation of long-lived protein radicals in the reaction between H2O2-activated metmyoglobin and other proteins. Free Radic. Biol. Med. 23 (5), 754–761 (1997). doi: 10.1016/s0891-5849(97)00023-3
  18. Baron C. P., Mǿller J. K. S., Skibsted L. H., and Andersen H. J. Nitrosylmyoglobin as antioxidant – kinetics and proposed mechanism for reduction of hydroperoxides. Free Radic.Res., 41 (8), 892–902 (2007). doi: 10.1080/10715760701416475
  19. Romero N., Radi R., Linares E., Augusto O., Detweiler C. D., Mason R. P., and Denicola A. Reaction of human hemoglobin with peroxynitrite: isomerization to nitrate and secondary formation of protein radicals. J. Biol. Chem., 278 (45), 44049–44057 (2003). doi: 10.1074/jbc.M305895200
  20. Herold S. and Shivashankar K. Metmyoglobin and methemoglobin catalyze the isomerization of peroxynitrite to nitrate. Biochemistry, 42 (47), 14036-14046 (2003). doi: 10.1021/bi0350349
  21. Su J. and Groves J. T. Mechanisms of Peroxynitrite Interactions with Heme Proteins. Inorg. Chem., 49 (14), 6317–6329 (2010). doi: 10.1021/ic902157z
  22. Shumaev K. B., Gubkin A. A., Serezhenkov V. A., Lobysheva I. I., Kosmachevskaya O. V., Ruuge E. K., Lankin V. Z., Topunov A. F., and Vanin A. F. Interaction of reactive oxygen and nitrogen species with albuminand methemoglobin-bound dinitrosyl iron complexes. Nitric Oxide, 18 (1), 37–46 (2008). doi: 10.1023/b:biry.0000029856.67884.c5
  23. Kosmachevskaya O. V., Nasybullina E. I., Shumaev K. B., Novikova N. N., and Topunov A. F. Protective effect of dinitrosyl iron complexes bound with hemoglobin on oxidative modification by peroxynitrite. Int. J. Mol. Sci., 22 (24), 13649 (2021). doi: 10.3390/ijms222413649
  24. Грачев Д. И., Шумаев К. Б., Космачевская О. В., Топунов А. Ф. и Рууге Э. К. Нитрозильные комплексы гемоглобина в различных модельных системах. Биофизика, 66 (6), 1056-1064 (2021). doi: 10.31857/S0006302921060028

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Russian Academy of Sciences