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