Division of Cardiovascular Medicine, Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, Ohio, USA.
Antioxid Redox Signal. 2020 Jun 1;32(16):1172-1187. doi: 10.1089/ars.2019.7881. Epub 2020 Jan 28.
Cytoglobin (Cygb) was discovered as a new addition to the globin superfamily and subsequently identified to have potent nitric oxide (NO) dioxygenase function. Cygb plays a critical role in the oxygen-dependent regulation of NO levels and vascular tone. In recent years, the mechanism of the Cygb-mediated NO dioxygenation has been studied in isolated protein, smooth muscle cell, isolated blood vessel, and animal model systems. Studies in mice have demonstrated that Cygb plays a critical role in regulating blood pressure and vascular tone. This review summarizes advances in the knowledge of NO dioxygenation/metabolism regulated by Cygb. Advances in measurement of NO diffusion dynamics across blood vessels and kinetic modeling of Cygb-mediated NO dioxygenation are summarized. The oxygen-dependent regulation of NO degradation by Cygb is also reviewed along with how Cygb paradoxically generates NO from nitrite under anaerobic conditions. The important role of Cygb in the regulation of vascular function and disease is reviewed. Cygb is a more potent NO dioxygenase (NOD) than previously known globins with structural differences in heme coordination and environment, conferring it with a higher rate of reduction and more rapid process of NO dioxygenation with unique oxygen dependence. Various cellular reducing systems regenerate the catalytic oxyferrous Cygb species, supporting a high rate of NO dioxygenation. There remains a critical need to further characterize the factors and processes that modulate Cygb-mediated NOD function, and to develop pharmacological or other approaches to modulate Cygb function and expression.
细胞红蛋白（Cygb）作为球蛋白超家族的新成员被发现，随后被确定具有强烈的一氧化氮（NO）双氧酶功能。Cygb 在依赖氧的 NO 水平和血管张力调节中发挥关键作用。近年来，Cygb 介导的 NO 双氧化作用机制已在分离蛋白、平滑肌细胞、分离血管和动物模型系统中进行了研究。在小鼠中的研究表明，Cygb 在调节血压和血管张力方面起着关键作用。本综述总结了 Cygb 调节的 NO 双氧化/代谢知识的进展。总结了 NO 在血管中扩散动力学的测量进展和 Cygb 介导的 NO 双氧化的动力学模型。还综述了 Cygb 对依赖氧的 NO 降解的调节，以及 Cygb 在厌氧条件下如何从亚硝酸盐产生 NO 的悖论。还综述了 Cygb 在血管功能和疾病调节中的重要作用。Cygb 是一种比以前已知的球蛋白更强效的 NO 双氧酶（NOD），其血红素配位和环境的结构差异赋予其更高的还原率和更快的 NO 双氧化过程，并具有独特的氧依赖性。各种细胞还原系统再生催化的氧亚铁 Cygb 物种，支持高的 NO 双氧化率。进一步表征调节 Cygb 介导的 NOD 功能的因素和过程，并开发药理学或其他方法来调节 Cygb 功能和表达仍然是至关重要的。
