Mercaptopyruvate acts as endogenous vasodilator independently of 3-mercaptopyruvate sulfurtransferase activity

Emma Mitidieri, Teresa Tramontano, Danila Gurgone, Valentina Citi, Vincenzo Calderone, Vincenzo Brancaleone, Antonia Katsouda, Noriyuki Nagahara, Andreas Papapetropoulos, Giuseppe Cirino, Roberta d'Emmanuele di Villa Bianca, Raffaella Sorrentino

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Hydrogen sulfide (H2S) is produced by the action of cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE) or 3-mercaptopyruvate sulfurtransferase (3-MST). 3-MST converts 3-mercaptopyruvate (MPT) to H2S and pyruvate. H2S is recognized as an endogenous gaseous mediator with multiple regulatory roles in mammalian cells and organisms. In the present study we demonstrate that MPT, the endogenous substrate of 3-MST, acts also as endogenous H2S donor. Colorimetric, amperometric and fluorescence based assays demonstrated that MPT releases H2S in vitro in an enzyme-independent manner. A functional study was performed on aortic rings harvested from C57BL/6 (WT) or 3-MST-knockout (3-MST−/−) mice with and without endothelium. MPT relaxed mouse aortic rings in endothelium-independent manner and at the same extent in both WT and 3-MST−/− mice. N5-(1-Iminoethyl)-L-ornithine dihydrochloride (L-NIO, an inhibitor of endothelial nitric oxide synthase) as well as 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor) did not affect MPT relaxant action. Conversely, hemoglobin (as H2S scavenger), as well as glybenclamide (an ATP-dependent potassium channel blocker) markedly reduced MPT-induced relaxation. The functional data clearly confirmed a non enzymatic vascular effect of MPT. In conclusion, MPT acts also as an endogenous H2S donor and not only as 3-MST substrate. MPT could, thus, be further investigated as a means to increase H2S in conditions where H2S bioavailability is reduced such as hypertension, coronary artery disease, diabetes or urogenital tract disease.

Original languageEnglish (US)
Pages (from-to)53-59
Number of pages7
JournalNitric Oxide - Biology and Chemistry
Volume75
DOIs
StatePublished - May 1 2018

Keywords

  • 3-Mercaptopyruvate sulfurtransferase knockout mice
  • Aorta
  • Hydrogen sulfide
  • Mercaptopyruvate
  • Vasorelaxation

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cancer Research

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