Kimura Hideo
National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan,
Handb Exp Pharmacol. 2015;230:61-81. doi: 10.1007/978-3-319-18144-8_3.
Hydrogen sulfide (H2S) has been recognized as a signaling molecule as well as a cytoprotective molecule. H2S modulates neurotransmission, regulates vascular tone, protects various tissues and organs, regulates inflammation, induces angiogenesis, and detects cellular oxygen levels. H2S is produced from L-cysteine by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) together with cysteine aminotransferase (CAT). Recently, a novel pathway for the production of H2S from D-cysteine was identified, involving D-amino acid oxidase (DAO) together with 3MST. Sulfuration (also called sulfhydration), which adds sulfur atoms to the cysteine residues of target proteins to modify protein activity, has been extensively studied as a mode of H2S action. Recently, hydrogen polysulfides (H2Sn, where n=3-7; n=2 is termed as persulfide) have been found to sulfurate target proteins in the brain, including transient receptor potential ankyrin 1 (TRPA1) channels, Kelch-like ECH-associating protein 1 (Keap1), and phosphatase and tensin homolog (PTEN), much more potently than H2S. The physiological stimuli that trigger the production of H2S and polysulfides, and the mechanisms maintaining their local levels, remain unknown. Understanding the regulation of H2Sn (including H2S) production, and the specific stimuli that induce their release, will provide new insight into the biology of H2S and will provide novel avenues for therapeutic development in diseases involving H2S-related substances.
硫化氢（H₂S）已被公认为一种信号分子以及细胞保护分子。H₂S调节神经传递、调节血管张力、保护各种组织和器官、调节炎症、诱导血管生成并检测细胞氧水平。H₂S由L-半胱氨酸通过胱硫醚β-合酶（CBS）、胱硫醚γ-裂合酶（CSE）、3-巯基丙酮酸硫转移酶（3MST）以及半胱氨酸转氨酶（CAT）共同产生。最近，发现了一条由D-半胱氨酸产生H₂S的新途径，涉及D-氨基酸氧化酶（DAO）和3MST。硫化作用（也称为硫氢化作用），即将硫原子添加到靶蛋白的半胱氨酸残基上以改变蛋白活性，作为H₂S的一种作用方式已得到广泛研究。最近，已发现多硫化氢（H₂Sn，其中n = 3 - 7；n = 2称为过硫化物）比H₂S更有效地使大脑中的靶蛋白硫化，包括瞬时受体电位锚蛋白1（TRPA1）通道、 Kelch样ECH相关蛋白1（Keap1）和磷酸酶及张力蛋白同源物（PTEN）。触发H₂S和多硫化物产生的生理刺激以及维持其局部水平的机制仍然未知。了解H₂Sn（包括H₂S）产生的调节以及诱导其释放的特定刺激，将为H₂S生物学提供新的见解，并为涉及H₂S相关物质的疾病治疗开发提供新途径。
