Takano Yoko, Echizen Honami, Hanaoka Kenjiro
Graduate School of Pharmaceutical Sciences, The University of Tokyo , Tokyo, Japan .
Antioxid Redox Signal. 2017 Oct 1;27(10):669-683. doi: 10.1089/ars.2017.7070. Epub 2017 May 18.
Hydrogen sulfide (HS) plays roles in many physiological processes, including relaxation of vascular smooth muscles, mediation of neurotransmission, inhibition of insulin signaling, and regulation of inflammation. Also, hydropersulfide (R-S-SH) and polysulfide (-S-S-S-) have recently been identified as reactive sulfur species (RSS) that regulate the bioactivities of multiple proteins via S-sulfhydration of cysteine residues (protein Cys-SSH) and show cytoprotection. Chemical tools such as fluorescent probes and selective inhibitors are needed to establish in detail the physiological roles of HS and polysulfide. Recent Advances: Although many fluorescent probes for HS are available, fluorescent probes for hydropersulfide and polysulfide have only recently been developed and used to detect these sulfur species in living cells.
In this review, we summarize recent progress in developing chemical tools for the study of HS, hydropersulfide, and polysulfide, covering fluorescent probes based on various design strategies and selective inhibitors of HS- and polysulfide-producing enzymes (cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase), and we summarize their applications in biological studies.
Despite recent progress, the precise biological functions of HS, hydropersulfide, and polysulfide remain to be fully established. Fluorescent probes and selective inhibitors are effective chemical tools to study the physiological roles of these sulfur molecules in living cells and tissues. Therefore, further development of a broad range of practical fluorescent probes and selective inhibitors as tools for studies of RSS biology is currently attracting great interest. Antioxid. Redox Signal. 27, 669-683.
硫化氢（HS）在许多生理过程中发挥作用，包括血管平滑肌舒张、神经传递介导、胰岛素信号抑制以及炎症调节。此外，氢过硫化物（R-S-SH）和多硫化物（-S-S-S-）最近被确定为活性硫物种（RSS），它们通过半胱氨酸残基的S-巯基化（蛋白质Cys-SSH）调节多种蛋白质的生物活性，并具有细胞保护作用。需要荧光探针和选择性抑制剂等化学工具来详细确定HS和多硫化物的生理作用。最新进展：尽管有许多用于HS的荧光探针，但用于氢过硫化物和多硫化物的荧光探针直到最近才被开发出来，并用于检测活细胞中的这些硫物种。
在本综述中，我们总结了用于研究HS、氢过硫化物和多硫化物的化学工具的最新进展，涵盖基于各种设计策略的荧光探针以及HS和多硫化物生成酶（胱硫醚γ-裂合酶、胱硫醚β-合酶和3-巯基丙酮酸硫转移酶）的选择性抑制剂，并总结了它们在生物学研究中的应用。
尽管最近取得了进展，但HS、氢过硫化物和多硫化物的确切生物学功能仍有待充分确定。荧光探针和选择性抑制剂是研究这些硫分子在活细胞和组织中的生理作用的有效化学工具。因此，作为RSS生物学研究工具的广泛实用荧光探针和选择性抑制剂的进一步开发目前引起了极大兴趣。《抗氧化与氧化还原信号》27卷，669 - 683页。
