E.I. Chazov National Medical Research Centre of Cardiology
Moscow, Moscow, Russian Federation
Moscow, Moscow, Russian Federation
Moscow, Moscow, Russian Federation
Moscow, Moscow, Russian Federation
Lomonosov Moscow State University
Moscow, Moscow, Russian Federation
It is known that the modification of biomolecules under conditions of oxidative and carbonyl stress is associated with the generation of free radicals. Active carbonyl compounds, for example, methylglyoxal react with amino groups of proteins and amino acids to form Schiff bases, including dialkylimines. During these reactions of non-enzymatic glycation, free radical intermediates are also formed. At the same time, it is known that nitric oxide (NO) interacts with the advanced glycation end-products. Our study reveals that donors of nitric oxide (PAPA/NONO, S-nitrosothiols) stimulate the production of organic free radicals in the reaction of non-enzymatic glycation of amino acids under methylglyoxal. In contrast, NO metabolites such as glutathione-containing dinitrosyl iron complexes and nitroxyl (HNO) reduce the level of these radicals. It is suggested that the effect of nitric oxide and S-nitrosothiols is associated with the formation of redox-active compounds, which in turn are mediators of free radical production. On the other hand, HNO and dinitrosyl iron complexes act as antioxidants and antiglycating agents. We believe that the dual action of NO and its derivatives plays a critical role in modifying biomolecules during diabetic mellitus.
non-enzymatic glycation, methylglyoxal, free radicals, nitric oxide, S-nitrosothiols, EPR spectroscopy
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