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

作者：Shibuya, Norihiro; Koike, Shin; Tanaka, Makiko; Ishigami-Yuasa, Mari; Kimura, Yuka; Ogasawara, Yuki; Fukui, Kiyoshi; Nagahara, Noriyuki; Kimura, Hideo^*

来源：Nature Communications, 2013, 4(1): 1366.

DOI：10.1038/ncomms2371

• AMINO-ACID OXIDASE
• CYSTATHIONINE-GAMMA-LYASE
• 3-MERCAPTOPYRUVATE SULFURTRANSFERASE
• SULFANE SULFUR
• D-ASPARTATE
• RAT-KIDNEY
• D-SERINE
• H2S
• BRAIN
• LIVER

In eukaryotes, hydrogen sulphide acts as a signalling molecule and cytoprotectant. Hydrogen sulphide is known to be produced from L-cysteine by cystathionine beta-synthase, cystathionine gamma-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.

• 出版日期2013-1