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Physiological and Pathophysiological Functions of Hydrogen Sulfide

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Gasotransmitters: Physiology and Pathophysiology

Abstract

Since being identified in mammalian brain, hydrogen sulfide (H2S), a well-known toxic gas with a smell of rotten eggs, was predicted to have physiological functions. Three H2S-producing enzymes have since been identified and their physiological regulation has been intensively studied. The effects of H2S on neuromodulation, smooth muscle relaxation, inflammation, and angiogenesis indicate that it functions as a signaling molecule. It also protects the nervous system and the cardiovascular system from oxidative insults, suggesting a cytoprotective role for the molecule. In contrast to these physiological functions, pathophysiological roles for H2S have also been demonstrated. Patients with ethylmalonic encephalopathy have mutations in mitochondrial dioxygenase, causing high levels of H2S to be produced, with consequent damage to the brain and skeletal muscle. Levels of cystathionine β-synthase (CBS), an H2S-producing enzyme, are 3 times higher in patients with Down’s syndrome compared to normal individuals. In this article, in addition to the basic properties of H2S, physiological and pathophysiological aspects of this important molecule are reviewed.

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Abbreviations

Ag2S:

Silver sulfide

cAMP:

Cyclic adenosine monophosphate

CAT:

Cysteine aminotransferase

CBS:

Cystathionine β-synthase

CFTR:

Cystic fibrosis transmembrane conductance regulator

CO:

Carbon monoxide

CSE:

Cystathionine γ-lyase

DHLA:

Dihydrolipoic acid

DS:

Down’s syndrome

DTT:

Dithiothreitol

EDHF:

Endothelium-derived hyperpolarizing factor

EDRF:

Endothelium-derived relaxing factor

EGF:

Epidermal growth factor

ER:

Endoplasmic reticulum

Gd3+ :

Gadolinium

GMP:

Guanosine monophosphate

GqPCR:

Gq-protein-coupled receptor

HCl:

Hydrochloric acid

H2O:

Water

HO-2:

Hemeoxygenase-2

HOCl:

Hypochlorous acid

H2S:

Hydrogen sulfide

H2S2O3 :

Thiosulfate

K+ :

Potassium

KATP :

ATP-dependent K+ channel

La3+ :

Lanthanoid

L-DOPA:

Levodopa

MDRF:

Muscle-derived relaxing factor

3MP:

3-Mercaptopyruvate

3MST:

3-Mercaptopyruvate sulfurtransferase

NADH:

Nicotinamide adenine dinucleotide

NADPH:

Nicotinamide adenine dinucleotide phosphate

NF:

Nuclear factor

NMDA:

N-methyl-D-aspartate

NO:

Nitric oxide

NOS:

Nitrix oxide synthase

NSAID:

Non-steroidal anti-inflammatory drugs

ONOO− :

Peroxynitrite

O2 :

Oxygen

O2 − :

Superoxide

PTP:

Protein tyrosine phosphatase

PERK:

Protein kinase-like ER kinase

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

SQR:

Sulfide-quinone oxidoreductase

TGF:

Transforming growth factor

TNF-α:

Tumor necrosis factor-α

TRP:

Transient receptor potential

TUNEL:

Terminal dUTP nick-end labeling

UPR:

Unfolded protein response

V–H+ :

ATPase

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Acknowledgements

This work was supported by a grant from National Institute of Neuroscience and KAKENHI (23659089) from Grant-in-Aid for Challenging Exploratory Research to H.K.

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Authors and Affiliations

  1. National Institute of Neuroscience, Kodaira, Tokyo, Japan

    Hideo Kimura

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  1. Hideo Kimura
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Correspondence to Hideo Kimura .

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  1. , Department of Cell Biology, University of Salzburg, Heilbrunnerstr. 34, Salzburg, 5020, Austria

    Anton Hermann

  2. , Department of Human and Animal Physiolog, Kazan Federal University, ul. Kremlevskaya 18, Kazan, 420008, Russia

    Guzel F. Sitdikova

  3. , Department of Cell Biology, University of Salzburg, Hellbrunnerstr. 34, Salzburg, 5020, Austria

    Thomas M. Weiger

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Kimura, H. (2012). Physiological and Pathophysiological Functions of Hydrogen Sulfide. In: Hermann, A., Sitdikova, G., Weiger, T. (eds) Gasotransmitters: Physiology and Pathophysiology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30338-8_3

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