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Contribution of cysteine aminotransferase and mercaptopyruvate sulfurtransferase to hydrogen sulfide production in peripheral neurons
Author(s) -
Miyamoto Ryo,
Otsuguro Kenichi,
Yamaguchi Soichiro,
Ito Shigeo
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12698
Subject(s) - cystathionine beta synthase , aminooxyacetic acid , sulfurtransferase , dorsal root ganglion , biochemistry , cysteine , biology , hydrogen sulfide , cystathionine gamma lyase , chemistry , microbiology and biotechnology , enzyme , anatomy , dorsum , sulfur , organic chemistry
Hydrogen sulfide (H 2 S) is a gaseous neuromodulator produced from L‐cysteine. H 2 S is generated by three distinct enzymatic pathways mediated by cystathionine γ‐lyase (CSE), cystathionine β‐synthase (CBS), and mercaptopyruvate sulfurtransferase (MPST) coupled with cysteine aminotransferase (CAT). This study investigated the relative contributions of these three pathways to H 2 S production in PC12 cells (rat pheochromocytoma‐derived cells) and the rat dorsal root ganglion. CBS, CAT, and MPST, but not CSE, were expressed in the cells and tissues, and appreciable amounts of H 2 S were produced from L‐cysteine in the presence of α‐ketoglutarate, together with dithiothreitol. The production of H 2 S was inhibited by a CAT inhibitor (aminooxyacetic acid), competitive CAT substrates (L‐aspartate and oxaloacetate), and RNA interference (RNAi) against MPST. Immunocytochemistry revealed a mitochondrial localization of MPST in PC12 cells and dorsal root ganglion neurons, and the amount of H 2 S produced by CAT/MPST at pH 8.0, a physiological mitochondrial matrix pH , was comparable to that produced by CSE and CBS in the liver and the brain, respectively. Furthermore, H 2 S production was markedly increased by alkalization. These results indicate that CAT and MPST are primarily responsible for H 2 S production in peripheral neurons, and that the regulation of mitochondrial metabolism may influence neuronal H 2 S generation.In the peripheral nervous system, hydrogen sulfide (H 2 S) has been implicated in neurogenic pain or hyperalgesia. This study provides evidence that H 2 S is synthesized in peripheral neurons through two mitochondrial enzymes, cysteine aminotransferase (CAT) and mercaptopyruvate sulfurtransferase (MPST). We propose that mitochondrial metabolism plays key roles in the physiology and pathophysiology of the peripheral nervous system via regulation of neuronal H 2 S production.