Vanin Anatoly F
Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow, Russia.
Nitric Oxide. 2016 Apr 1;54:15-29. doi: 10.1016/j.niox.2016.01.006. Epub 2016 Jan 26.
The material presented herein is an overview of the results obtained by our research team during the many years' study of biological activities and occurrence of dinitrosyl iron complexes (DNIC) with thiol-containing ligands in human and animal organisms. With regard to their dose dependence and vast diversity of biological activities, DNIC are similar to the system of endogenous NO, one of the most universal regulators of biological processes. The role of biologically active components in DNIC is played by their iron-dinitrosyl fragments, [Fe(NO)2], endowed with the ability to generate neutral NO molecules and nitrosonium ions (NO(+)). Their release is effected by heme-and thiol-containing proteins, which fulfill the function of biological targets and acceptors of NO and NO(+). Beneficial regulatory effects of DNIC on physiological and metabolic processes are numerous and diverse and include, among other things, lowering of arterial pressure and accelerated healing of skin wounds. In the course of fast decomposition of their Fe(NO)2 fragments (e.g., in the presence of iron chelators), DNIC produce adverse (cytotoxic) effects, which can best be exemplified by their ability to suppress the development of experimental endometriosis in animals. In animal tissues, DNIC with thiol-containing ligands are predominantly represented by the binuclear form, which, contrary to mononuclear DNIC detectable by the 2.03 signal, is EPR-silent. The ample body of evidence on biological activities and occurrence of DNIC gained so far clearly demonstrates that in human and animal organisms DNIC with thiol-containing ligands represent a "working form" of the system of endogenous NO responsible for its accumulation and stabilization in animal tissues as well as its further transfer to its biological targets.
本文介绍的内容是我们的研究团队在多年研究含硫醇配体的二亚硝基铁配合物(DNIC)在人和动物机体中的生物活性及存在情况时所取得的成果概述。就其剂量依赖性和生物活性的广泛多样性而言,DNIC与内源性NO系统相似,内源性NO是生物过程最普遍的调节因子之一。DNIC中生物活性成分的作用由其铁 - 二亚硝基片段[Fe(NO)₂]发挥,该片段具有生成中性NO分子和亚硝基离子(NO⁺)的能力。它们的释放受含血红素和硫醇的蛋白质影响,这些蛋白质履行生物靶点以及NO和NO⁺受体的功能。DNIC对生理和代谢过程具有多种有益的调节作用,包括降低动脉血压以及加速皮肤伤口愈合等。在其Fe(NO)₂片段快速分解过程中(例如在铁螯合剂存在的情况下),DNIC会产生不良(细胞毒性)作用,其抑制动物实验性子宫内膜异位症发展的能力就是最好的例证。在动物组织中,含硫醇配体的DNIC主要以双核形式存在,与可通过2.03信号检测到的单核DNIC不同,它在电子顺磁共振(EPR)中无信号。目前已获得的关于DNIC生物活性及存在情况的大量证据清楚地表明,在人和动物机体中,含硫醇配体的DNIC代表内源性NO系统的一种“活性形式”,负责其在动物组织中的积累和稳定以及向其生物靶点的进一步传递。