Hydrogen sulfide: Neurochemistry and neurobiology

doi:10.1016/j.neuint.2007.05.016

Neurochemistry International

Volume 52, Issues 1–2, January 2008, Pages 155-165

https://doi.org/10.1016/j.neuint.2007.05.016 Get rights and content

Abstract

Current evidence suggests that hydrogen sulfide (H₂S) plays an important role in brain functions, probably acting as a neuromodulator as well as an intracellular messenger. In the mammalian CNS, H₂S is formed from the amino acid cysteine by the action of cystathionine β-synthase (CBS) with serine (Ser) as the by-product. As CBS is a calcium and calmodulin dependent enzyme, the biosynthesis of H₂S should be acutely controlled by the intracellular concentration of calcium. In addition, it is also regulated by S-adenosylmethionine which acts as an allosteric activator of CBS. H₂S, as a sulfhydryl compound, has similar reducing properties as glutathione. In neurons, H₂S stimulates the production of cAMP probably by direct activation of adenylyl cyclase and thus activate cAMP-dependent processes. In astrocytes, H₂S increases intracellular calcium to an extent capable of inducing and propagating a “calcium wave”, which is a form of calcium signaling among these cells. Possible physiological functions of H₂S include potentiating long-term potentials through activation of the NMDA receptors, regulating the redox status, maintaining the excitatory/inhibitory balance in neurotransmission, and inhibiting oxidative damage through scavenging free radicals and reactive species. H₂S is also involved in CNS pathologies such as stroke and Alzheimer's disease. In stroke, H₂S appears to act as a mediator of ischemic injuries and thus inhibition of its production has been suggested to be a potential treatment approach in stroke therapy.

Introduction

Hydrogen sulfide (H₂S) is a poisonous gas used as a chemical reagent. It is a broad-spectrum toxicant as it affects most organ systems in the body. The early symptoms of H₂S exposure include sore throat, dizziness, nausea, and respiratory effects attributed to airway irritation. Acute exposure to H₂S exhibits a very steep dose–response relationship with an LD₅₀ of 15 mg/kg (rats), especially for CNS and respiratory depression, which is the major cause of death in acute H₂S poisoning (Warenycia et al., 1989). The primary cause of death in H₂S poisoning has been attributed to respiratory paralysis (Beauchamp et al., 1984). In addition, pulmonary edema has consistently been reported as the single most notable lesion in autopsies of individuals killed by H₂S poisoning (Burnett et al., 1977). At present, although the mechanism of action for these toxic effects is not clear, it is widely believed that H₂S targets mitochondria at low micromolar concentrations via reversible inhibition of cytochrome c oxidase (Reiffenstein et al., 1992).

It had long been assumed that H₂S exists in animal tissues at very low concentrations because of its toxicity, although it could be produced endogenously. However, more recent studies have shown that H₂S is present in mammalian tissues at levels far higher than first expected, up to 50–160 μmol/L (Goodwin et al., 1989, Warenycia et al., 1989) as measured in rat, human and bovine brain tissues. Abe and Kimura (1996) have shown that sodium hydrosulfide (NaHS, an H₂S donor) at concentrations (10–130 μM) similar to the physiological concentrations of H₂S selectively enhances N-methyl d-aspartate (NMDA) receptor-mediated responses and facilitates the induction of hippocampal long-term potentiation (LTP). This review presents an overview of the current evidence that H₂S plays an important role in brain functions, probably acting as a neuromodulator and/or as an intracellular messenger (Moore et al., 2003).

Section snippets

Physical properties of H₂S

H₂S is the sulfur analog of water with a molecular weight of 34.08. But unlike water, it has weak intermolecular forces and thus exists in the gaseous form at room temperature and pressure. H₂S is a colorless gas characterized by its offensive odor described as the smell of rotten eggs. It can be oxidized by a variety of agents to form sulfur dioxide and sulfuric acid. In the mammalian body, at a physiological pH of 7.4, approximately one-third of H₂S exists as the un-dissociated form and

Biochemical pathways related to the production of H₂S

In mammalian tissues, two pyridoxal-5′-phosphate (PLP)-dependent enzymes – cystathionine-β-synthase (CBS, EC 4.2.1.22) and cystathionine-γ-lyase (γ-cystathionase CSE, EC 4.4.1.1) – are responsible for most of the biosynthesis of H₂S from l-cysteine (Cys). As shown in Fig. 1, H₂S is released from the desulfuration of Cys (Stipanuk and Beck, 1982). Firstly, Cys may be hydrolyzed by CBS to produce H₂S with l-serine (Ser) as the by-product or hydrolyzed by CSE to produce H₂S, pyruvate and ammonia

Biosynthesis of H₂S in the brain via CBS

The primary translational product of both the human and the rat CBS gene is a precursor protein with a molecular weight of 63 kDa (Skovby et al., 1984) that forms tetramers or higher oligomers. Proteolysis of the precursor protein yields the active enzyme of CBS (amino acid residues 40–413) (Skovby et al., 1984, Kraus and Rosenberg, 1983). CBS activities are highly regulated (Miles and Kraus, 2004) and tissue-specific (Quere et al., 1999). It is localized in the cytoplasm and compartmentalized

Precursors of H₂S

Met is an essential amino acid in mammals and thus generally considered as the source of all sulfur-containing amino acids. Cys, on the other hand, is non-essential and can be synthesized from Met via Hcy (the transsulfuration pathway). The mammalian liver regulates its free Cys pool tightly even when dietary source of sulfur-containing amino acid varies from sub- to over-requirement (Lee et al., 2004). This is achieved by regulating the synthesis of glutathione, which acts as a reservoir of

Metabolic fate of H₂S

The metabolism of sulfur amino acid has been reviewed by Stipanuk (2004). Briefly, the sulfur of Met is transferred to serine to form Cys through the transsulfuration pathway. The end products of Cys catabolism are sulfate (77–92% of total sulfur excreted in the urine), ester sulfate (7–9%), and taurine (2–6%). The main metabolic pathway of H₂S is a series of oxidation yielding thiosulfate (S₂O₃²⁻), sulfite (SO₃²⁻) and sulfate (SO₄²⁻) (Beauchamp et al., 1984). The reported amount of thiosulfate

Neurons

Much progress has been made in the past decade in elucidating the roles of H₂S at physiological and pathological conditions at the cellular level. H₂S, at physiological levels, was first shown to selectively stimulate NMDA receptor-mediated currents. This stimulation facilitates the induction of hippocampal LTP, but only in the presence of a weak titanic stimulation. H₂S alone does not induce LTP thus suggesting that H₂S mainly facilitates LTP in active synapses (Abe and Kimura, 1996, Kimura,

Ischemic stroke

A stroke occurs when an artery in the brain is blocked leading to a loss of blood supply to the affected tissues. A lack of oxygen and glucose causes the level of the energy molecule ATP to plummet, ATPase fail and intracellular Na⁺ and Ca²⁺ increase. Membrane depolarization occurs and Glu is released leading to activation of its excitatory receptors and thus more membrane depolarization. Glu transport also fails for a lack of energy supply and extracellular Glu levels soar. All these events

Concluding remarks

Sufficient evidence has accumulated in support of H₂S acting as a signaling molecule in the mammalian CNS. This field is still in its infancy and much will be learnt in the near future about the central roles play by H₂S in health and disease as interest on this molecule grows among neuroscientists. One area that is of particular interest concerns the crosstalk between H₂S and NO in the CNS. It is obvious that the two systems have much in common. For instance, it is well established that NMDA

Acknowledgements

P.T.H. Wong receives a grant from the Biomedical Research Council of Singapore (BMRC 01/1/21/19/169).

References (129)

T. Abel et al.
Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory
Cell
(1997)
M.E. Anderson et al.
Intracellular delivery of cysteine
Methods Enzymol.
(1987)
S.M. Birnbaum et al.
Quantitative nutritional studies with water-soluble, chemically defined diets. III. Individual amino acids as sources of non-essential nitrogen
Arch. Biochem. Biophys.
(1957)
S. Bleich et al.
Homocysteine as a neurotoxin in chronic alcoholism
Prog. Neuropsychopharmacol. Biol. Psychiatry
(2004)
K. Braet et al.
Calcium signal communication in the central nervous system
Biol. Cell
(2004)
J.E. Brenman et al.
Interactions of nitric oxide synthase with the postsynaptic density protein PSD-95 and α1-syntrophin mediated by PDZ domains
Cell
(1996)
X. Chen et al.
Production of the neuromodulator H₂S by cystathionine beta-synthase via the condensation of cysteine and homocysteine
J. Biol. Chem.
(2004)
D.E. Cole et al.
Urinary thiosulfate determined by suppressed ion chromatography with conductimetric detection
J Chromatogr. B Biomed. Appl.
(1995)
J.W. Dani et al.
Neuronal activity triggers calcium waves in hippocampal astrocyte networks
Neuron
(1992)
L. El-Khairy et al.
Lifestyle and cardiovascular disease risk factors as determinants of total cysteine in plasma: the Hordaland Homocysteine study
Am. J. Clin. Nutr.
(1999)

K. Farber et al.

Physiology of microglial cells

Brain Res. Brain Res. Rev.

(2005)

J.D. Finkelstein et al.

Activation of cystathionine synthase by adenosylmethionine and adenosylmethionine

Biochem. Biophys. Res. Commun.

(1975)

B. Geng et al.

Endogenous hydrogen sulfide regulation of myocardial injury induced by isoproterenol

Biochem. Biophys. Res. Commun.

(2004)

D.V. Guebel et al.

Dynamics of sulfur amino acids in mammalian brain: assessment of the astrocytic-neuronal cysteine interaction by a mathematical hybrid model

Biochim. Biophys. Acta

(2004)

Y. Han et al.

Modulating effect of hydrogen sulfide on gamma-aminobutyric acid B receptor in recurrent febrile seizures in rats

Neurosci. Res.

(2005)

M.T. Heafield et al.

Plasma cysteine and sulphate levels in patients with motor neurone, Parkinson's and Alzheimer's disease

Neurosci. Lett.

(1990)

J.H. Horowitz et al.

Evidence for impairment of transsulfuration pathway in cirrhosis

Gastroenterology

(1981)

R. Hosoki et al.

The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide

Biochem. Biophys. Res. Commun.

(1997)

D. Julian et al.

Enzymatic hydrogen sulfide production in marine invertebrate tissues

Comp. Biochem. Physiol. A Mol. Integr. Physiol.

(2002)

J. Kangas et al.

Urinary thiosulphate as an indicator of exposure to hydrogen sulphide vapour

Clin. Chim. Acta

(1987)

H. Kimura

Hydrogen sulfide induces cyclic AMP and modulates the NMDA receptor

Biochem. Biophys. Res. Commun.

(2000)

J. Kraus et al.

Purification and properties of cystathionine beta-synthase from human liver. Evidence for identical subunits

J. Biol. Chem.

(1978)

J.P. Kraus et al.

Cystathionine beta-synthase from human liver: improved purification scheme and additional characterization of the enzyme in crude and pure form

Arch. Biochem. Biophys.

(1983)

V. Kucukatay et al.

Effect of sulfite on cognitive function in normal and sulfite oxidase deficient rats

Neurotoxicol. Teratol.

(2005)

J.I. Lee et al.

Regulation of cysteine dioxygenase and gamma-glutamylcysteine synthetase is associated with hepatic cysteine level

J. Nutr. Biochem.

(2004)

A.S. Leonard et al.

Cyclic AMP-dependent protein kinase and protein kinase C phosphorylate N-methyl-d-aspartate receptors at different sites

J. Biol. Chem.

(1997)

D. Matthias et al.

Homocysteine induced arteriosclerosis-like alterations of the aorta in normotensive and hypertensive rats following application of high doses of methionine

Atherosclerosis

(1996)

E.W. Miles et al.

Cystathionine beta-synthase: structure, function, regulation, and location of homocystinuria-causing mutations

J. Biol. Chem.

(2004)

P.K. Moore et al.

Hydrogen sulfide: from the smell of the past to the mediator of the future?

Trends Pharmacol. Sci.

(2003)

A.H. Moore et al.

Neuroinflammation and anti-inflammatory therapy for Alzheimer's disease

Adv. Drug Deliv. Rev.

(2002)

M.C. Morale et al.

Estrogen, neuroinflammation and neuroprotection in Parkinson's disease: glia dictates resistance versus vulnerability to neurodegeneration

Neuroscience

(2006)

R.R. Myers et al.

The role of neuroinflammation in neuropathic pain: mechanisms and therapeutic targets

Drug Discov. Today

(2006)

Y. Ozkan et al.

Plasma total homocysteine and cysteine levels as cardiovascular risk factors in coronary heart disease

Int. J. Cardiol.

(2002)

M. Puka-Sundvall et al.

Neurotoxicity of cysteine: interaction with glutamate

Brain Res.

(1995)

I. Quere et al.

Spatial and temporal expression of the cystathionine beta-synthase gene during early human development

Biochem. Biophys. Res. Commun.

(1999)

S.P. Raps et al.

Glutathione is present in high concentrations in cultured astrocytes but not in cultured neurons.

Brain Res.

(1989)

M.E. Rice

Ascorbate regulation and its neuroprotective role in the brain

Trends Neurosci.

(2000)

E.D. Roberson et al.

Transient activation of cyclic AMP-dependent protein kinase during hippocampal long-term potentiation

J. Biol. Chem.

(1996)

R. Abbate et al.

Emerging risk factors for ischemic stroke

Neurol. Sci.

(2003)

K. Abe et al.

The possible role of hydrogen sulfide as an endogenous neuromodulator

J. Neurosci.

(1996)

J. Allsop et al.

Methionine adenosyltransferase, cystathionine beta-synthase and cystathionine gamma-lyase activity of rat liver subcellular particles, human blood cells and mixed white cells from rat bone marrow

Clin. Sci. Mol. Med.

(1975)

S. Awata et al.

Changes in cystathionine gamma-lyase in various regions of rat brain during development

Biochem. Mol. Biol. Int.

(1995)

H. Bayir et al.

Assessment of antioxidant reserves and oxidative stress in cerebrospinal fluid after severe traumatic brain injury in infants and children

Pediatr. Res.

(2002)

R.O. Beauchamp et al.

A critical review of the literature on hydrogen sulfide toxicity

Crit. Rev. Toxicol.

(1984)

K. Beyer et al.

Cystathionine beta synthase as a risk factor for Alzheimer disease

Curr. Alzheimer Res.

(2004)

D.S. Bredt et al.

Cloned and expressed nitric oxide synthetase structurally resembles cytochrom P-450 reductase

Nature

(1991)

F.C. Brown et al.

Cystathionine synthase from rat liver: partial purification and properties

Can. J. Biochem.

(1971)

G.K. Brown et al.

Sulfite oxidase deficiency: clinical, neuroradiologic, and biochemical features in two new patients

Neurology

(1989)

W.W. Burnett et al.

Hydrogen sulfide poisoning: review of 5 years’ experience

Can. Med. Assoc. J.

(1977)

D. Cavallini et al.

The mechanism of desulphhydration of cysteine

Enzymologia

(1962)

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ReviewHydrogen sulfide: Neurochemistry and neurobiology

Abstract

Introduction

Section snippets

Physical properties of H2S

Biochemical pathways related to the production of H2S

Biosynthesis of H2S in the brain via CBS

Precursors of H2S

Metabolic fate of H2S

Neurons

Ischemic stroke

Concluding remarks

Acknowledgements

Cell

Methods Enzymol.

Arch. Biochem. Biophys.

Prog. Neuropsychopharmacol. Biol. Psychiatry

Biol. Cell

Cell

J. Biol. Chem.

J Chromatogr. B Biomed. Appl.

Neuron

Am. J. Clin. Nutr.

Brain Res. Brain Res. Rev.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Biochim. Biophys. Acta

Neurosci. Res.

Neurosci. Lett.

Gastroenterology

Biochem. Biophys. Res. Commun.

Comp. Biochem. Physiol. A Mol. Integr. Physiol.

Clin. Chim. Acta

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Arch. Biochem. Biophys.

Neurotoxicol. Teratol.

J. Nutr. Biochem.

J. Biol. Chem.

Atherosclerosis

J. Biol. Chem.

Trends Pharmacol. Sci.

Adv. Drug Deliv. Rev.

Neuroscience

Drug Discov. Today

Int. J. Cardiol.

Brain Res.

Biochem. Biophys. Res. Commun.

Brain Res.

Trends Neurosci.

J. Biol. Chem.

Emerging risk factors for ischemic stroke

Neurol. Sci.

The possible role of hydrogen sulfide as an endogenous neuromodulator

J. Neurosci.

Methionine adenosyltransferase, cystathionine beta-synthase and cystathionine gamma-lyase activity of rat liver subcellular particles, human blood cells and mixed white cells from rat bone marrow

Clin. Sci. Mol. Med.

Changes in cystathionine gamma-lyase in various regions of rat brain during development

Biochem. Mol. Biol. Int.

Assessment of antioxidant reserves and oxidative stress in cerebrospinal fluid after severe traumatic brain injury in infants and children

Pediatr. Res.

A critical review of the literature on hydrogen sulfide toxicity

Crit. Rev. Toxicol.

Cystathionine beta synthase as a risk factor for Alzheimer disease

Curr. Alzheimer Res.

Cloned and expressed nitric oxide synthetase structurally resembles cytochrom P-450 reductase

Nature

Cystathionine synthase from rat liver: partial purification and properties

Can. J. Biochem.

Sulfite oxidase deficiency: clinical, neuroradiologic, and biochemical features in two new patients

Neurology

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Can. Med. Assoc. J.

The mechanism of desulphhydration of cysteine

Enzymologia

Review
Hydrogen sulfide: Neurochemistry and neurobiology

Physical properties of H₂S

Biochemical pathways related to the production of H₂S

Biosynthesis of H₂S in the brain via CBS

Precursors of H₂S

Metabolic fate of H₂S