Kosmachevskaya Olga V, Nasybullina Elvira I, Pugachenko Igor S, Novikova Natalia N, Topunov Alexey F
Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, 119071 Moscow, Russia.
National Research Center "Kurchatov Institute", 123182 Moscow, Russia.
Antioxidants (Basel). 2022 Oct 11;11(10):2007. doi: 10.3390/antiox11102007.
Donors of nitroxyl and nitroxyl anion (HNO/NO) are considered to be promising pharmacological treatments with a wide range of applications. Remarkable chemical properties allow nitroxyl to function as a classic antioxidant. We assume that HNO/NO can level down the non-enzymatic glycation of biomolecules. Since erythrocyte hemoglobin (Hb) is highly susceptible to non-enzymatic glycation, we studied the effect of a nitroxyl donor, Angeli's salt, on Hb modification with methylglyoxal (MG) and organic peroxide--butyl hydroperoxide (-BOOH). Nitroxyl dose-dependently decreased the amount of protein carbonyls and advanced glycation end products (AGEs) that were formed in the case of Hb incubation with MG. Likewise, nitroxyl effectively protected Hb against oxidative modification with -BOOH. It slowed down the destruction of heme, formation of carbonyl derivatives and inter-subunit cross-linking. The protective effect of nitroxyl on Hb in this system is primarily associated with nitrosylation of oxidized Hb and reduction of its ferryl form, which lowers the yield of free radical products. We suppose that the dual (antioxidant and antiglycation) effect of nitroxyl makes its application possible as part of an additional treatment strategy for oxidative and carbonyl stress-associated diseases.
硝酰及硝酰阴离子（HNO/NO）供体被认为是具有广泛应用前景的药物治疗手段。显著的化学性质使硝酰能够发挥经典抗氧化剂的作用。我们假设HNO/NO可以降低生物分子的非酶糖基化水平。由于红细胞血红蛋白（Hb）极易发生非酶糖基化，我们研究了硝酰供体安吉利盐对甲基乙二醛（MG）和有机过氧化物——叔丁基过氧化氢（-BOOH）修饰Hb的影响。硝酰剂量依赖性地降低了Hb与MG孵育时形成的蛋白质羰基和晚期糖基化终产物（AGEs）的量。同样，硝酰有效地保护Hb免受-BOOH的氧化修饰。它减缓了血红素的破坏、羰基衍生物的形成以及亚基间交联。在该体系中，硝酰对Hb的保护作用主要与氧化型Hb的亚硝基化及其高铁形式的还原有关，这降低了自由基产物的产量。我们推测，硝酰的双重（抗氧化和抗糖基化）作用使其有可能作为氧化应激和羰基应激相关疾病附加治疗策略的一部分加以应用。
