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 journalArticle

6 Citations (Scopus)

Abstract

Hydrogen sulfide (H 2 S) 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 H 2 S and pyruvate. H 2 S 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 H 2 S donor. Colorimetric, amperometric and fluorescence based assays demonstrated that MPT releases H 2 S 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 H 2 S 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 H 2 S donor and not only as 3-MST substrate. MPT could, thus, be further investigated as a means to increase H 2 S in conditions where H 2 S 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
Externally publishedYes

Fingerprint

Vasodilator Agents
Cystathionine
3-mercaptopyruvic acid
Endothelium
Hemoglobin H
Gasotransmitters
Potassium Channel Blockers
Hydrogen Sulfide
Lyases
Glyburide
Nitric Oxide Synthase Type III
Guanylate Cyclase
Substrates
Medical problems
Pyruvic Acid
Knockout Mice
Biological Availability
Blood Vessels
Coronary Artery Disease
Assays

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cancer Research

Cite this

Mitidieri, E., Tramontano, T., Gurgone, D., Citi, V., Calderone, V., Brancaleone, V., ... Sorrentino, R. (2018). Mercaptopyruvate acts as endogenous vasodilator independently of 3-mercaptopyruvate sulfurtransferase activity. Nitric Oxide - Biology and Chemistry, 75, 53-59. https://doi.org/10.1016/j.niox.2018.02.003

Mercaptopyruvate acts as endogenous vasodilator independently of 3-mercaptopyruvate sulfurtransferase activity. / Mitidieri, Emma; Tramontano, Teresa; Gurgone, Danila; Citi, Valentina; Calderone, Vincenzo; Brancaleone, Vincenzo; Katsouda, Antonia; Nagahara, Noriyuki; Papapetropoulos, Andreas; Cirino, Giuseppe; d'Emmanuele di Villa Bianca, Roberta; Sorrentino, Raffaella.

In: Nitric Oxide - Biology and Chemistry, Vol. 75, 01.05.2018, p. 53-59.

Research output: Contribution to journalArticle

Mitidieri, E, Tramontano, T, Gurgone, D, Citi, V, Calderone, V, Brancaleone, V, Katsouda, A, Nagahara, N, Papapetropoulos, A, Cirino, G, d'Emmanuele di Villa Bianca, R & Sorrentino, R 2018, 'Mercaptopyruvate acts as endogenous vasodilator independently of 3-mercaptopyruvate sulfurtransferase activity', Nitric Oxide - Biology and Chemistry, vol. 75, pp. 53-59. https://doi.org/10.1016/j.niox.2018.02.003
Mitidieri, Emma ; Tramontano, Teresa ; Gurgone, Danila ; Citi, Valentina ; Calderone, Vincenzo ; Brancaleone, Vincenzo ; Katsouda, Antonia ; Nagahara, Noriyuki ; Papapetropoulos, Andreas ; Cirino, Giuseppe ; d'Emmanuele di Villa Bianca, Roberta ; Sorrentino, Raffaella. / Mercaptopyruvate acts as endogenous vasodilator independently of 3-mercaptopyruvate sulfurtransferase activity. In: Nitric Oxide - Biology and Chemistry. 2018 ; Vol. 75. pp. 53-59.
@article{867029a066a84fcd9f7e11bd898ebaa0,
title = "Mercaptopyruvate acts as endogenous vasodilator independently of 3-mercaptopyruvate sulfurtransferase activity",
abstract = "Hydrogen sulfide (H 2 S) 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 H 2 S and pyruvate. H 2 S 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 H 2 S donor. Colorimetric, amperometric and fluorescence based assays demonstrated that MPT releases H 2 S 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 H 2 S 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 H 2 S donor and not only as 3-MST substrate. MPT could, thus, be further investigated as a means to increase H 2 S in conditions where H 2 S bioavailability is reduced such as hypertension, coronary artery disease, diabetes or urogenital tract disease.",
keywords = "3-Mercaptopyruvate sulfurtransferase knockout mice, Aorta, Hydrogen sulfide, Mercaptopyruvate, Vasorelaxation",
author = "Emma Mitidieri and Teresa Tramontano and Danila Gurgone and Valentina Citi and Vincenzo Calderone and Vincenzo Brancaleone and Antonia Katsouda and Noriyuki Nagahara and Andreas Papapetropoulos and Giuseppe Cirino and {d'Emmanuele di Villa Bianca}, Roberta and Raffaella Sorrentino",
year = "2018",
month = "5",
day = "1",
doi = "10.1016/j.niox.2018.02.003",
language = "English (US)",
volume = "75",
pages = "53--59",
journal = "Nitric Oxide - Biology and Chemistry",
issn = "1089-8603",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Mercaptopyruvate acts as endogenous vasodilator independently of 3-mercaptopyruvate sulfurtransferase activity

AU - Mitidieri, Emma

AU - Tramontano, Teresa

AU - Gurgone, Danila

AU - Citi, Valentina

AU - Calderone, Vincenzo

AU - Brancaleone, Vincenzo

AU - Katsouda, Antonia

AU - Nagahara, Noriyuki

AU - Papapetropoulos, Andreas

AU - Cirino, Giuseppe

AU - d'Emmanuele di Villa Bianca, Roberta

AU - Sorrentino, Raffaella

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Hydrogen sulfide (H 2 S) 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 H 2 S and pyruvate. H 2 S 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 H 2 S donor. Colorimetric, amperometric and fluorescence based assays demonstrated that MPT releases H 2 S 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 H 2 S 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 H 2 S donor and not only as 3-MST substrate. MPT could, thus, be further investigated as a means to increase H 2 S in conditions where H 2 S bioavailability is reduced such as hypertension, coronary artery disease, diabetes or urogenital tract disease.

AB - Hydrogen sulfide (H 2 S) 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 H 2 S and pyruvate. H 2 S 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 H 2 S donor. Colorimetric, amperometric and fluorescence based assays demonstrated that MPT releases H 2 S 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 H 2 S 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 H 2 S donor and not only as 3-MST substrate. MPT could, thus, be further investigated as a means to increase H 2 S in conditions where H 2 S bioavailability is reduced such as hypertension, coronary artery disease, diabetes or urogenital tract disease.

KW - 3-Mercaptopyruvate sulfurtransferase knockout mice

KW - Aorta

KW - Hydrogen sulfide

KW - Mercaptopyruvate

KW - Vasorelaxation

UR - http://www.scopus.com/inward/record.url?scp=85042454785&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042454785&partnerID=8YFLogxK

U2 - 10.1016/j.niox.2018.02.003

DO - 10.1016/j.niox.2018.02.003

M3 - Article

VL - 75

SP - 53

EP - 59

JO - Nitric Oxide - Biology and Chemistry

JF - Nitric Oxide - Biology and Chemistry

SN - 1089-8603

ER -