<div>Hydrogen sulfide signaling in the central nervous system</div><div>-Comparison with nitric oxide-</div><div>Hideo Kimura</div><div>Sanyo Onoda City University</div><div>Corresponding should be addressed to Prof. Hideo Kimura, 1-1-1
Daigaku-Dori, Sanyo-Onoda, Yamaguchi 756-0884, Japan</div><div>Phone: +81-836-39-9128</div><div>E-mail: <i>kimura@rs.socu.ac.jp</i></div><div>Abstract: 148 words</div><div>Text: 5720 words</div><div>Abstract</div><div>Hydrogen sulfide (H<sub>2</sub>S) together with polysulfides
(H<sub>2</sub>S<sub>n</sub>, n&gt;2) are signaling
molecules like nitric oxide (NO) with various physiological roles
including regulation of neuronal transmission, vascular tone,
inflammation, oxygen sensing etc. H<sub>2</sub>S and
H<sub>2</sub>S<sub>n</sub> 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 H<sub>2</sub>S, H<sub>2</sub>S<sub>n</sub> 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
H<sub>2</sub>S and H<sub>2</sub>S<sub>n</sub> with
S-sulfuration compared with those of NO and S-nitrosynation, and discuss
on their roles in physiology and pathophysiology.</div><div>Abbreviations</div><div>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; FADH<sub>2</sub>, 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; H<sub>2</sub>S, hydrogen
sulfide; H<sub>2</sub>S<sub>n</sub>, 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</div>