Identification of H2S3 and H2S produced by 3-mercaptopyruvate sulfurtransferase in the brain.
Identification of H2S3 and H2S produced by 3-mercaptopyruvate sulfurtransferase in the brain.
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DOI：
10.1038/srep14774
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发表时间：
2015-10-06
影响因子：
4.6
通讯作者：
Kimura H
中科院分区：
文献类型：
--
作者：
Kimura Y;Toyofuku Y;Koike S;Shibuya N;Nagahara N;Lefer D;Ogasawara Y;Kimura H
多硫化氢（H2Sn）具有比硫化氢（H2S）更多的硫烷硫原子，其具有各种生理作用。我们最近在大脑中发现了H2Sn。H2Sn诱导了一些以前归因于H2S的反应，但其效力比H2S大得多。然而，H_2Sn中硫原子的数目及其产生酶是未知的。在这里，我们检测到H2 S3和H2S，这是从3-巯基丙酮酸（3 MP）通过3-巯基丙酮酸硫转移酶（3 MST），在大脑中产生的。高效液相色谱荧光检测（LC-FL）和串联质谱（LC-MS/MS）分析表明，H2 S3和H2S是由野生型小鼠脑细胞中的3 MP产生的，而不是3 MST敲除（3 MST-KO）小鼠。纯化的重组3 MST和表达3 MST的COS细胞的裂解物从3 MP产生H2 S3，而表达缺陷型3 MST突变体的那些则不产生。H_2S_3定位于细胞的胞浆中。H2 S3也是由H2S通过3 MST和罗丹酸盐生产的。H2 S2被鉴定为次要的H2Sn，并且3 MP不影响H2 S5水平。本研究为H2 S3和H2S的生理学提供了新的见解，以及这些分子参与的疾病的新治疗靶点。
Hydrogen polysulfides (H2Sn) have a higher number of sulfane sulfur atoms than hydrogen sulfide (H2S), which has various physiological roles. We recently found H2Sn in the brain. H2Sn induced some responses previously attributed to H2S but with much greater potency than H2S. However, the number of sulfur atoms in H2Sn and its producing enzyme were unknown. Here, we detected H2S3 and H2S, which were produced from 3-mercaptopyruvate (3 MP) by 3-mercaptopyruvate sulfurtransferase (3MST), in the brain. High performance liquid chromatography with fluorescence detection (LC-FL) and tandem mass spectrometry (LC-MS/MS) analyses showed that H2S3 and H2S were produced from 3 MP in the brain cells of wild-type mice but not 3MST knockout (3MST-KO) mice. Purified recombinant 3MST and lysates of COS cells expressing 3MST produced H2S3 from 3 MP, while those expressing defective 3MST mutants did not. H2S3 was localized in the cytosol of cells. H2S3 was also produced from H2S by 3MST and rhodanese. H2S2 was identified as a minor H2Sn, and 3 MP did not affect the H2S5 level. The present study provides new insights into the physiology of H2S3 and H2S, as well as novel therapeutic targets for diseases in which these molecules are involved.