Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan Kansas, USA.
J Biol Chem. 2021 Jan-Jun;296:100336. doi: 10.1016/j.jbc.2021.100336. Epub 2021 Jan 26.
Soluble guanylate cyclase (sGC) is a heme-containing heterodimeric enzyme that generates many molecules of cGMP in response to its ligand nitric oxide (NO); sGC thereby acts as an amplifier in NO-driven biological signaling cascades. Because sGC helps regulate the cardiovascular, neuronal, and gastrointestinal systems through its cGMP production, boosting sGC activity and preventing or reversing sGC inactivation are important therapeutic and pharmacologic goals. Work over the last two decades is uncovering the processes by which sGC matures to become functional, how sGC is inactivated, and how sGC is rescued from damage. A diverse group of small molecules and proteins have been implicated in these processes, including NO itself, reactive oxygen species, cellular heme, cell chaperone Hsp90, and various redox enzymes as well as pharmacologic sGC agonists. This review highlights their participation and provides an update on the processes that enable sGC maturation, drive its inactivation, or assist in its recovery in various settings within the cell, in hopes of reaching a better understanding of how sGC function is regulated in health and disease.
可溶性鸟苷酸环化酶（sGC）是一种含有血红素的异二聚体酶，可响应其配体一氧化氮（NO）生成许多 cGMP 分子；因此，sGC 作为 NO 驱动的生物信号级联反应中的放大器。由于 sGC 通过其 cGMP 的产生帮助调节心血管、神经元和胃肠道系统，因此提高 sGC 的活性和防止或逆转 sGC 的失活是重要的治疗和药理学目标。过去二十年的研究揭示了 sGC 成熟为功能性的过程、sGC 失活的方式以及 sGC 从损伤中恢复的方式。包括 NO 本身、活性氧、细胞血红素、细胞伴侣 Hsp90 和各种氧化还原酶以及药理学 sGC 激动剂在内的多种小分子和蛋白质已被牵连到这些过程中。本综述强调了它们的参与，并提供了有关在细胞内各种环境中促进 sGC 成熟、驱动其失活或协助其恢复的过程的最新信息，以期更好地了解 sGC 功能在健康和疾病中的调节方式。
