Reductive Nitrosylation of Hemoglobin and Myoglobin and Its Antioxidant Action

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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

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