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.
- 3-Mercaptopyruvate sulfurtransferase knockout mice
- Hydrogen sulfide
ASJC Scopus subject areas
- Clinical Biochemistry
- Cancer Research