A novel pathway for the production of hydrogen sulfide from D-cysteine in mammalian cells

Abstract

In eukaryotes, hydrogen sulphide acts as a signalling molecule and cytoprotectant. Hydrogen sulphide is known to be produced from L-cysteine by cystathionine b-synthase, cystathionine g-lyase and 3-mercaptopyruvate sulfurtransferase coupled with cysteine aminotransferase. Here we report an additional biosynthetic pathway for the production of hydrogen sulphide from D-cysteine involving 3-mercaptopyruvate sulfurtransferase and D-amino acid oxidase. Unlike the L-cysteine pathway, this D-cysteine-dependent pathway operates predominantly in the cerebellum and the kidney. Our study reveals that administration of D-cysteine protects primary cultures of cerebellar neurons from oxidative stress induced by hydrogen peroxide and attenuates ischaemia-reperfusion injury in the kidney more than L-cysteine. This study presents a novel pathway of hydrogen sulphide production and provides a new therapeutic approach to deliver hydrogen sulphide to specific tissues.

Polysulfide exerts a protective effect against cytotoxicity caused by t‐buthylhydroperoxide through Nrf2 signaling in neuroblastoma cells

“…Intracellular levels of bound sulfur were measured using a previously described method [21]. Briefly, N2A cells treated with Na 2 S 4 were washed with ice-cold phosphate-buffered saline (PBS) and resuspended in lysis buffer [10 mM potassium phosphate buffer (pH 7.4), 0.5% Triton X-100, protease inhibitor cocktail complete (EDTA free, Roche Applied Science, Darmstadt, Germany), 10 mM hydroxylamine, and 10 mM benzoic acid].…”

FRET ratiometric probes reveal the chiral-sensitive cysteine-dependent H2S production and regulation in living cells

“…Kimura has proposed a D-Cys-dependent H 2 S biogenesis as a possible new pathway for H 2 S production in living mammalian cells 12 . Our newly developed FRET-based ratiometric probes have been tested to visualize this new H 2 S biogenesis in situ in living cells.…”

“…Recently, they further reported a novel possible pathway for the production of H 2 S from D-cysteine in mammalian cells 12 . As new biogenesis and biological functions of H 2 S continue to emerge [12][13][14][15] , new biocompatible tools to selectively visualize cellular H 2 S in real-time at its site of release are urgently needed 11 .Fluorescent probes could be used for H 2 S detection in a non-invasive manner in living systems [13][14][15][16][17] . The probebased tools have been successfully used to image endogenous H 2 S production from thiol substrates including LCys and glutathione (GSH) 13 or by vascular endothelial growth factor stimulation 17 .…”

“…Recently, they further reported a novel possible pathway for the production of H 2 S from D-cysteine in mammalian cells 12 . As new biogenesis and biological functions of H 2 S continue to emerge [12][13][14][15] , new biocompatible tools to selectively visualize cellular H 2 S in real-time at its site of release are urgently needed 11 .…”

H2S in the Vasculature: Controversy of Mechanisms in Physiology, Pathology and Beyond

“…3-MST, along with cysteine aminotransferase (CAT) or D-amino acid oxidase (DAO), produces H 2 S from cysteine and α-ketoglutarate in the mitochondria [11,12]. 3-MST/CAT is localized in thoracic aorta ECs and produces H 2 S [13]; however, a vascular effect of 3-MST/CATderived H 2 S is unknown.…”