Multiple role of 3‐mercaptopyruvate sulfurtransferase: antioxidative function, H₂S and polysulfide production and possible SO_x production

Abstract

are on the enzyme surface. MPST is found in all tissues, particularly in the kidneys, although the localization of its activity differs in each tissue. In this review, four functions of MPST are reviewed: (i) antioxidative function: Cys 247 is redox-sensitive and serves as a redox-sensing switch. It is oxidized to cysteine sulfenate, which has a low redox potential, upon which the enzyme is inactivated. Then, reduced thioredoxin (Trx) with a reducing system (Trx reductase and NADPH) reduces the sulfenate to restore activity; meanwhile, Cys 154 and Cys 263 form an intermolecular disulfide bond, which serves as another redox-sensing switch. Consequently, Trx specifically cleaves the intermolecular disulfide bond by converting it from the inactive form (dimer) to the active form (monomer). (ii) Hydrogen sulfide and polysulfide production: hydrogen sulfide is produced via reduction of the persulfurated sulfur-acceptor substrate by reduced Trx or Trx with a reducing system; as an alternative process, stable polysulfurated or persulfurated Cys 247 as a reaction intermediate is reduced by Trx with a reducing system to release hydrogen sulfide and polysulfides. (iii) Possible sulfur oxide production: sulfur oxides (SO, SO 2 and SO 3 ) can be produced in the redox cycle of sulfane sulfur formed at the catalytic site Cys 247 (Cys-SO À , Cys-SO 2À and Cys-SO 3À ) as reaction intermediates and released by reduced Trx or Trx with a reducing system. (iv) Possible anxiolytic-like effects: MPST-knockout mice exhibited anxiolytic-like effects.Abbreviations MALDI-TOF-MS, matrix-assisted laser desorption/ionization time-of-flight MS; MPST, 3-mercaptopyruvate sulfurtransferase; NBD-Cl, 4-chloro-7-nitrobenzofurazan; Trx, thioredoxin; TST, thiosulfate sulfuransferase; TUM, tRNA thiouridine modification protein

3‐Mercaptopyruvate sulfurtransferase supports endothelial cell angiogenesis and bioenergetics

“…These findings coupled with results from our previous studies (Coletta et al, 2015) lead us to speculate that the PI3K/ Akt and the PKG/VASP signalling pathways may serve as the basis for VEGF/3-MST crosstalk and that exposure of ECs to VEGF increases 3-MST activity. We hypothesize that the increase in 3-MST activity in reducing intracellular environments such as hypoxia could potentiate the effects of increased VEGF production contributing to the action of the"angiogenic/metabolic switch" (Kimura, 2015;Modis, Asimakopoulou, Coletta, Papapetropoulos, & Szabo, 2013;Nagahara, 2018). The area under the curve for each respiratory parameter was collected from five independent experiments and plotted as a percentage of shNT values after subtracting the non-mitochondrial respiration values.…”

Role of 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation, Migration, and Bioenergetics in Murine Colon Cancer Cells

“…The endogenous gaseous transmitter hydrogen sulfide (H 2 S) has been implicated in multiple regulatory processes in mammalian cells in health and disease. In mammalian cells, there are at least three significant enzymatic sources of H 2 S: Cystathionine-beta-synthase (CBS), cystathionine-gamma-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) [1][2][3][4]. In the last decade, a novel concept emerged in the field of cancer biology, demonstrating that various cancer cells can increase their endogenous H 2 S levels and utilize H 2 S in an autocrine and paracrine manner to promote cell proliferation, cytoprotective signalling, cellular bioenergetics, and angiogenesis.…”

“…Depending on the type of cancer, CBS, CSE and/or 3-MST have been implicated as enzymatic sources of H 2 S [3][4][5][6][7]. From these three enzymes, the function of the 3-MST system in cancer cells is the least understood.…”

Human DND1-RRM2 forms a non-canonical domain swapped dimer

“…(Nagahara, 2011;Wouters et al). Rat mercaptopyruvate sulfurtransferase also shows monomer dimer switch under such redox regulation (Nagahara, 2018). The hinge loop in RRM2 also consist of an exposed Sulphur atom in cysteine residue which when present in oxidizing condition favors this dimerization by forming a disulphide bond.…”