Hydrogen sulfide signaling in the central nervous system
-Comparison with nitric oxide-
Hideo Kimura
Sanyo Onoda City University
Corresponding should be addressed to Prof. Hideo Kimura, 1-1-1 Daigaku-Dori, Sanyo-Onoda, Yamaguchi 756-0884, Japan
Phone: +81-836-39-9128
E-mail: kimura@rs.socu.ac.jp
Abstract: 148 words
Text: 5720 words
Abstract
Hydrogen sulfide (H2S) together with polysulfides (H2Sn, n>2) are signaling molecules like nitric oxide (NO) with various physiological roles including regulation of neuronal transmission, vascular tone, inflammation, oxygen sensing etc. H2S and H2Sn diffuse to the target proteins to S-sulfurate their cysteine residues to induce the conformational changes to alter the activity. On the other hand, 3-mercaptopyruvate sulfurtransferase transfers sulfur from a substrate 3-mercaptopyruvate to the cysteine residues of acceptor proteins. A similar mechanism has also been identified in S-nitrosylation. S-sulfuration and S-nitrosylation by enzymes proceed only inside the cell, while reactions induced by H2S, H2Sn and NO even extend to the surrounding cells. Disturbance of signaling by these molecules as well as S-sulfuration and S-nitrosylation causes many neuronal diseases. This review focuses on the signaling by H2S and H2Sn with S-sulfuration compared with those of NO and S-nitrosynation, and discuss on their roles in physiology and pathophysiology.
Abbreviations
Aβ1-42, amyloid β-protein; AD, Alzheimer’s disease; ADAM17, disintegrin and metalloproteinase domain-containing protein 17; AGEs, advanced glycation end products; APP, amyloid precursor protein; ATP, adenosine trisphosphate; BACE, β-secretase; CAT, cysteine aminotransferase; CBS, cystathionine β‐synthase; CFTR, cystic fibrosys transmembrane receptor; CSE, cystathionine γ‐lyase; CysSSH, cysteine persulfide; DAO, D‐amino acid oxidase; DS, Down’s syndrome; DTT, dithiothreitol; EDHF, endothelium-derived hyperpolarizing factor; EDRF, endothelium-derived relaxation factor; EE, ethylmalonyl encephalopathy; ETHE1, sulfur dioxygenase; FADH2, flavin adenine dinucleotide; γ-GCS, γ-glutamyl cysteine synthetase; GAPDH, Glyceraldehyde-3-phosphate dehydrogenase; GCL, glutamate cysteine ligase; GSH, glutathione; GSSH, GSH persulfide; HD, Huntington’s disease; H2S, hydrogen sulfide; H2Sn, hydrogen polysulfides; HNO, nitroxyl; HSNO, thionitrous acid; HSSNO, nitrosopersulfide; Keap1, kelch ECH‐associating protein 1; LTP, long-term potentiation; MAPK, mitogen-activated protein kinase; 3MP, 3‐mercaptopyruvate; MPST, 3‐mercaptopyruvate sulfurtransferase; NADH, nicotinamide adenine dinucleotide; NADPH, nicotinamide adenine dinucleotide phosphate; NMDA, N-methyl-D-aspartate; NO, nitric oxide; NOS, NO synthase; Nrf2, nuclear factor erythroid 2‐related factor 2; PD, Parkinson’s disease; PIP2, phospholipid phosphatidylinositol (4,5)‐biphosphate; PK3K, phosphoinositide 3-kinase; PKG1α, protein kinase G1α; PPI, prepulse inhibition; PS, presenilin; PTEN, tumour suppressor phosphatase and tensin homologue; ROS, reactive oxygen species; SOD, super oxide dismutase; SQR, sulfur quinon oxidoreductase; SSNO−, nitrosopersulfide; STAT3, signal transducer and activator of transcription 3; TRPA1, transient receptor potential ankyrin 1