SMDB

	PMID	Title & Author	Abstract	Year
0	30657595	Signalling by hydrogen sulfide and polysulfides via protein S-sulfuration.Hideo Kimura	Hydrogen sulfide (H2 S) is a signalling molecule that regulates neuronal transmission, vascular tone, cytoprotection, inflammatory responses, angiogenesis, and oxygen sensing. Some of these functions have recently been ascribed to its oxidized form polysulfides (H2 Sn ), which can be produced by 3-mercaptopyruvate sulfurtransferase (MPST), also known as a H2 S-producing enzyme. H2 Sn activate ion channels, tumour suppressors, transcription factors, and protein kinases. H2 Sn S-sulfurate (S-sulfhydrate) cysteine residues of these target proteins to modify their activity by inducing conformational changes through the formation of a disulfide bridge between the two cysteine residues involved. The chemical interaction between H2 S and NO also generates H2 Sn , which may be a chemical entity that exerts the synergistic effect of H2 S and NO. MPST also produces redox regulators cysteine persulfide (CysSSH), GSH persulfide (GSSH), and persulfurated proteins. In addition to MPST, haemoproteins such as haemoglobin, myoglobin, neuroglobin, and catalase as well as SOD can produce H2 Sn , and sulfide quinone oxidoreductase and cysteinyl tRNA synthetase can make GSSH and CysSSH. This review focuses on the recent progress in the study of the production and physiological roles of these persulfurated and polysulfurated molecules. LINKED ARTICLES: This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc.	2020
1	26519030	MPST but not CSE is the primary regulator of hydrogen sulfide production and function in the coronary artery.Maggie M Kuo , Dae Hee Kim , Sandeep Jandu , Yehudit Bergman , Siqi Tan , Huilei Wang , Deepesh R Pandey , Theodore P Abraham , Artin A Shoukas , Dan E Berkowitz , Lakshmi Santhanam	Hydrogen sulfide (H2S) has emerged as an important gasotransmitter in the vasculature. In this study, we tested the hypothesis that H2S contributes to coronary vasoregulation and evaluated the physiological relevance of two sources of H2S, namely, cystathionine-γ-lyase (CSE) and 3-mercaptypyruvate sulfertransferase (MPST). MPST was detected in human coronary artery endothelial cells as well as rat and mouse coronary artery; CSE was not detected in the coronary vasculature. Rat coronary artery homogenates produced H2S through the MPST pathway but not the CSE pathway in vitro. In vivo coronary vasorelaxation response was similar in CSE knockout mice, wild-type mice (WT), and WT mice treated with the CSE inhibitor propargylglycine, suggesting that CSE-produced H2S does not have a significant role in coronary vasoregulation in vivo. Ex vivo, the MPST substrate 3-mercaptopyruvate (3-MP) and H2S donor sodium hydrosulfide (NaHS) elicited similar coronary vasoreactivity responses. Pyruvate did not have any effects on vasoreactivity. The vasoactive effect of H2S appeared to be nitric oxide (NO) dependent: H2S induced coronary vasoconstriction in the presence of NO and vasorelaxation in its absence. Maximal endothelial-dependent relaxation was intact after 3-MP and NaHS induced an increase in preconstriction tone, suggesting that endothelial NO synthase activity was not significantly inhibited. In vitro, H2S reacted with NO, which may, in part explain the vasoconstrictive effects of 3-MP and NaHS. Taken together, these data show that MPST rather than CSE generates H2S in coronary artery, mediating its effects through direct modulation of NO. This has important implications for H2S-based therapy in healthy and diseased coronary arteries.	2016
2	32012740	Increased Urinary 3-Mercaptolactate Excretion and Enhanced Passive Systemic Anaphylaxis in Mice Lacking Mercaptopyruvate Sulfurtransferase, a Model of Mercaptolactate-Cysteine Disulfiduria.Noriyuki Akahoshi , Tatsuro Minakawa , Masashi Miyashita , Uran Sugiyama , Chihiro Saito , Rintaro Takemoto , Akihiro Honda , Waka Kamichatani , Shotaro Kamata , Yasumi Anan , Isao Ishii	Mercaptopyruvate sulfurtransferase (Mpst) and its homolog thiosulfate sulfurtransferase (Tst = rhodanese) detoxify cyanide to thiocyanate. Mpst is attracting attention as one of the four endogenous hydrogen sulfide (H2S)/reactive sulfur species (RSS)-producing enzymes, along with cystathionine β-synthase (Cbs), cystathionine γ-lyase (Cth), and cysteinyl-tRNA synthetase 2 (Cars2). MPST deficiency was found in 1960s among rare hereditary mercaptolactate-cysteine disulfiduria patients. Mpst-knockout (KO) mice with enhanced liver Tst expression were recently generated as its model; however, the physiological roles/significances of Mpst remain largely unknown. Here we generated three independent germ lines of Mpst-KO mice by CRISPR/Cas9 technology, all of which maintained normal hepatic Tst expression/activity. Mpst/Cth-double knockout (DKO) mice were generated via crossbreeding with our previously generated Cth-KO mice. Mpst-KO mice were born at the expected frequency and developed normally like Cth-KO mice, but displayed increased urinary 3-mercaptolactate excretion and enhanced passive systemic anaphylactic responses when compared to wild-type or Cth-KO mice. Mpst/Cth-DKO mice were also born at the expected frequency and developed normally, but excreted slightly more 3-mercaptolactate in urine compared to Mpst-KO or Cth-KO mice. Our Mpst-KO, Cth-KO, and Mpst/Cth-DKO mice, unlike semi-lethal Cbs-KO mice and lethal Cars2-KO mice, are useful tools for analyzing the unknown physiological roles of endogenous H2S/RSS production.	2020
3	28877979	Fatty acids promote fatty liver disease via the dysregulation of 3-mercaptopyruvate sulfurtransferase/hydrogen sulfide pathway.Meng Li , Chengfu Xu , Junping Shi , Jiexia Ding , Xingyong Wan , Dahua Chen , Jianguo Gao , Chunxiao Li , Jie Zhang , Yiming Lin , Zhenhua Tu , Xiaoni Kong , Youming Li , Chaohui Yu	Objective: Accumulation of free fatty acids (FFAs) in hepatocytes induces lipotoxicity, leading to non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the underlying mechanisms by which FFA contributes to the pathogenesis of NAFLD via the regulation of 3-mercaptopyruvate sulfurtransferase (MPST), a key enzyme that regulates endogenous hydrogen sulfide (H2S) biosynthesis.Design: Hepatic MPST expression was evaluated in mice and patients with NAFLD. A variety of molecular approaches were used to study the effects of MPST regulation on hepatic steatosis in vivo and in vitro.Results: In vitro treatment of hepatocytes with FFAs upregulated MPST expression, which was partially dependent on NF-κB/p65. Hepatic MPST expression was markedly increased in high fat diet (HFD)-fed mice and patients with NAFLD. Partial knockdown of MPST via adenovirus delivery of MPST short hairpin RNA or heterozygous deletion of the Mpst gene significantly ameliorated hepatic steatosis in HFD-fed mice. Consistently, inhibition of MPST also reduced FFA-induced fat accumulation in L02 cells. Intriguingly, inhibition of MPST significantly enhanced rather than decreased H2S production, whereas MPST overexpression markedly inhibited H2S production. Co-immunoprecipitation experiments showed that MPST directly interacted with and negatively regulated cystathionine γ-lyase (CSE), a major source of H2S production in the liver. Mechanistically, MPST promoted steatosis via inhibition of CSE/H2S and subsequent upregulation of the sterol regulatory element-binding protein 1c pathway, C-Jun N-terminal kinase phosphorylation and hepatic oxidative stress.Conclusions: FFAs upregulate hepatic expression of MPST and subsequently inhibit the CSE/H2S pathway, leading to NAFLD. MPST may be a potential therapeutic target for NAFLD.	2018

Mikami Y , Shibuya N , Kimura Y , et al. Thioredoxin and dihydrolipoic acid are required for 3-mercaptopyruvate sulfurtransferase to produce hydrogen sulfide[J]. Biochemical Journal, 2011, 439(3):479-485.

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