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Hydrogen Sulfide and its Therapeutic Applications pp 181–202Cite as

Hydrogen Sulfide-Mediated Cellular Signaling and Cytoprotection

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Abstract

Hydrogen sulfide (H2S) is a signaling molecule in the nervous and vascular systems. It also protects various organs from oxidative stress or ischemia-reperfusion injury. H2S is produced from L-cysteine by cystathionine β-synthase (CBS), cystathionine γ–lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase (CAT). We recently found that H2S is also produced from D-cysteine by 3MST along with D-amino acid oxidase (DAO). This pathway is mainly localized to in the cerebellum and the kidney, producing H2S more efficiently than the pathways that utilize L-cysteine as a substrate. The administration of D-cysteine to mice ameliorates renal ischemia-reperfusion injury more effectively than that of L-cysteine, promising a therapeutic application of D-cysteine to renal diseases. We recently found that H2S-derived polysulfides exist in the brain and induce Ca2+ influx by activating transient receptor potential ankyrin-1 (TRPA1) channels approximately 300 times more efficiently than H2S in astrocytes, which surround neuronal synapses and modulate their activity. Polysulfides are possible H2S-derived signaling molecules. This review focuses on the production of H2S from D-cysteine and polysulfides as possible signaling molecules derived from H2S.

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Abbreviations

3MP:

3-Mercaptopyruvate

3MST:

3-Mercaptopyruvate sulfurtransferase

Ca2+ :

Calcium ion

CAT:

Cysteine aminotransferase

CBS:

Cystathionine β–synthase

cGMP:

Cyclic guanosine monophosphate

CHO:

Chinese hamster ovary

CO:

Carbon monoxide

CO2 :

Carbon dioxide

CSE:

Cystathionine γ–lyase

DAO:

D-amino acid oxidase

DHLA:

Dihydrolipoic acid

DTT:

Dithiothreitol

EDHF:

Endothelium-derived hyperpolarizing factor

GAPDH:

Glyceraldehydes-3-phosphate dehydrogenase

Gd3+ :

Gadolinium ion

GFAP:

Glial fibrillary acidic protein

H2O2 :

Hydrogen peroxide

H2S:

Hydrogen sulfide

HEK:

Human embryonic kidney

HPLC:

High pressure liquid chromatography

HSNO:

Thionitrous acid

I2CA:

Indol-2-carboxylate

K+ :

Potassium ion

KATP channel:

ATP-dependent K+ Channel

La3+ :

Lanthanum

LTP:

Long-term potentiation

NAC:

N-acetylcysteine

NAD:

Nicotinamide adenine dinucleotide

NaHS:

Sodium hydrosulfide

NF:

Nuclear factor

NMDA:

N-methyl-D-aspartate

NO:

Nitric oxide

Nrf2 :

Nuclear factor-E2-related factor

O2 :

Oxygen

PLP:

Pyridoxal 5’-phosphate

ROS:

Reactive oxygen species

SAM:

S-adenocyl-L-methionine

siRNA:

Small interfering ribonucleic acid

STAT-3:

Signal transducers and activators of transcription 3

TRPA1:

transient receptor potential ankyrin-1

V-H+ ATPase:

Vacuolar-type H+ adenosine trisphosphatase

γ-GCS:

γ-glutamyl-cysteine synthase

References

  • Abe K, Kimura H (1996) The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci 16:1066–1071

    PubMed  CAS  Google Scholar 

  • Aizenman E, Lipton DA, Loring RH (1989) Selective modulation of NMDA responses by reduction and oxidation. Neuron 2:1257–1263

    Article  PubMed  CAS  Google Scholar 

  • Akagi R (1982) Purification and characterization of cysteine aminotransferase from rat liver cytosol. Acta Med Okayama 36:187–197

    PubMed  CAS  Google Scholar 

  • Bos EM, Leuvenink HGD, Snijder PM, Koosterhuis NJ, Hillebrands J-L, Leemans JC, Florquin S, Goor H (2009) Hydrogen sulfide-induced hypometabolism prevents renal ischemia/reperfusion injury. J Am Soc Nephrol 20:1901–1905

    Article  PubMed  CAS  Google Scholar 

  • Braunstein AE, Goryachenkowa EV, Tolosa EA, Willhardt IH, Yefremova LL (1971) Specificity and some other properties of liver serine sulphhydrase: evidence for its identity with cystathionineβ-synthase. Biochim Biophys Acta 242:247–260

    Article  PubMed  CAS  Google Scholar 

  • Cahoy JD, Emery B, KaushalA FLC, Zamanian JL, Christopherson KS, Xing Y, Lubischer JL, Krieg PA, Krupenko SA, Thompson WJ, Barres BA (2008) A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J Neurosci 28:264–278

    Article  PubMed  CAS  Google Scholar 

  • Calvert JW, Jha S, Gundewar S, Elrod JW, Ramachandran A, Pattillo CB, Kevil CG, Lefer DJ (2009) Hydrogen sulfide mediates cardioprotection through Nrf2 signaling. Circ Res 105:365–374

    Article  PubMed  CAS  Google Scholar 

  • Cavallini D, Mondovi B, De Marco C, Scioscia-Santoro A (1962) The mechanism of desulphhydration of cysteine. Enzymologia 24:253–266

    PubMed  CAS  Google Scholar 

  • Chen X, Jhee KH, Kruger WD (2004) Production of the neuromodulator H2S by cystathionine beta-synthase via the condensation of cysteine and homocystein. J Biol Chem 279:52082–52086

    Article  PubMed  CAS  Google Scholar 

  • Chiku T, Padovani D, Zhu W, Singh S, Vitvitsky V, Banerjee R (2009) H2S biogenesis by human cystathionine γ–lyase leads to the novel sulfur metabolites lanthionine and homolanthionine and is responsive to the grade of hyperhomocysteinemia. J Biol Chem 284:11601–11612

    Article  PubMed  CAS  Google Scholar 

  • Cook SP, Galve-Roperh I, Martinez del Pozo A, Rodriguez-Crespo I (2002) Direct calcium binding results in activation of brain serine racemase. J Biol Chem 277:27782–27792

    Article  PubMed  CAS  Google Scholar 

  • Cooper AJL (1983) Biochemistry of sulfur-containing amino acids. Annu Rev Biochem 52:187–222

    Article  PubMed  CAS  Google Scholar 

  • Dani JW, Chernjavsky A, Smith SJ (1992) Neuronal activity triggers calcium waves in hippocampal astrocyte networks. Neuron 8:429–440

    Article  PubMed  CAS  Google Scholar 

  • Denton RM (2009) Regulation of mitochondrial dehydrogenases by calcium ions. Biochim Biophys Acta 1787:1309–1316

    Article  PubMed  CAS  Google Scholar 

  • Donovan M, Cotter TG (2002) Caspase-independent photoreceptor apoptosis in vivo and differential expression of apoptotic protease activating factor-1 and caspase-3 during retinal development. Cell Death Differ 9:1220–1231

    Article  PubMed  CAS  Google Scholar 

  • Doyle JM, Schinina ME, Bossa F, Doonan S (1990) The amino acid sequence of cytosolic aspartate aminotransferase from human liver. Biochem J 270:651–657

    PubMed  CAS  Google Scholar 

  • Elrod JW, Calvert JW, Morrison J, Doeller JE, Kraus DW, Tao L, Jiao X, Scalia R, Kiss L, Szabo C (2007) Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function. Proc Natl Acad Sci U S A 104:15560–15565

    Article  PubMed  CAS  Google Scholar 

  • Enokido Y, Suzuki E, Iwasawa K, Namekata K, Okazawa H, Kimura H (2005) Cysstathionine beta-synthase, a key enzyme for homocysteine metabolism, is preferentially expressed in the radial glia/astrocyte lineage of developing mouse CNS. FASEB J 19:1854–1856

    PubMed  CAS  Google Scholar 

  • Fellin T, Pascual O, Gobbo S, Pozzan T, Haydon PG, Carmignoto G (2004) Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron 43:729–743

    Article  PubMed  CAS  Google Scholar 

  • Filipovic MR, Miljkovic JL, Nauser T, Royzen M, Klos K, Shubina T, Koppenol WH, Lippard SJ, Ivanovic-Burmazovic I (2012) Chemical characterization of the smallest S-nitrosothiol, HSNO; cellular cross-talk of H2S and S-nitrosothiols. J Am Chem Soc 134:12016–12027

    Article  PubMed  CAS  Google Scholar 

  • Friedman M (2010) Origin, microbiology, nutrition and pharmacology of D-amino acids. Chem Biodivers 7:1491–1530

    Article  PubMed  CAS  Google Scholar 

  • Furne J, Saeed A, Levitt MD (2008) Whole tissue hydrogen sulfide concentrations are orders of magnitude lower than presently accepted values. Am J Physiol Regul Integr Comp Physiol 295:R1479–R1498

    Article  PubMed  CAS  Google Scholar 

  • Goodwin LR, Francom D, Dieken FP, Taylor JD, Warenycia MW, Reiffenstein RJ, Dowling G (1989) Determination of sulfide in brain tissue by gas dialysis/ion chromatography: postmortem studies and two case reports. J Anal Toxicol 13:105–109

    Article  PubMed  CAS  Google Scholar 

  • Gould SJ, Keller GA, Subramani S (1988) Identification of peroxisomal targeting signals located at the carboxy terminus of four peroxisomal proteins. J Cell Biol 107:897–905

    Article  PubMed  CAS  Google Scholar 

  • Griffith OW (1999) Biologic and pharmacologic regulation of mammalian glutathione synthesis. Free Radic Biol Med 27:922–935

    Article  PubMed  CAS  Google Scholar 

  • Hosoki R, Matsuki N, Kimura H (1997) The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. Biochem Biophys Res Commun 237:527–531

    Article  PubMed  CAS  Google Scholar 

  • Ichinohe A, Kanaumi T, Takashima S, Enokido Y, Naai Y, Kimura H (2005) Cystathionine beta-synthase is enriched in the brains of Down’s patients. Biochem Biophys Res Commun 338:1547–1550

    Article  PubMed  CAS  Google Scholar 

  • Ishigami M, Hiraki K, Umemura K, Ogasawara Y, Ishii K, Kimura H (2009) A source of hydrogen sulfide and a mechanism of its release in the brain. Antioxid Redox Signal 11:205–214

    Article  PubMed  CAS  Google Scholar 

  • Ishii I, Akahoshi N, Yu X-N, Kobayashi Y, Namekata K, Komaki G, Kimura H (2004) Murine cystathionine γ-lyase: complete cDNA and genomic sequences, promoter activity, tissue distribution and developmental expression. Biochem J 381:113–123

    Article  PubMed  CAS  Google Scholar 

  • Jouhou H, Yamamoto K, Homma A, Hara M, Kaneko A, Yamada M (2007) Depolarization of isolated horizontal cells of fish acidifies their immediate surrounding by activating V-ATPase. J Physiol 585:401–412

    Article  PubMed  CAS  Google Scholar 

  • Kato A, Ogura M, Suda M (1966) Control mechanism in the rat liver enzyme system converting L-methionine to L-cystine. 3. Noncompetitive inhibition of cystathionine synthetase-serine dehydratase by elemental sulfur and competitive inhibition of cystathionine-homoserine dehydratase by L-cysteine and L-cystine. J Biochem 59:40–48

    PubMed  CAS  Google Scholar 

  • Kawamura N, Tabata H, Sun-Wada GH, Wada Y (2010) Optic nerve compression and retinal degeneration in Tcirg 1 mutant mice lacking the vacuolar type H+-ATP ase a3 subunit. PLoS One 5:e12086

    Article  PubMed  Google Scholar 

  • Kimura H (2010) Hydrogen sulfide: from brain to gut. Antioxid Redox Signal 12:1111–1123

    Article  PubMed  CAS  Google Scholar 

  • Kimura Y, Kimura H (2004) Hydrogen sulfide protects neurons from oxidative stress. FASEB J 18:1165–1167

    PubMed  CAS  Google Scholar 

  • Kimura Y, Dargusch R, Schubert D, Kimura H (2006) Hydrogen sulfide protects HT22 neuronal cells from oxidative stress. Antioxid Redox Signal 8:661–670

    Article  PubMed  CAS  Google Scholar 

  • Kimura Y, Goto Y-I, Kimura H (2010) Hydrogen sulfide increases glutathione production and suppresses oxidative stress in mitochondria. Antioxid Redox Signal 12:1–13

    Article  PubMed  CAS  Google Scholar 

  • Kimura H, Shibuya N, Kimura Y (2012) Hydrogen sulfide is a signaling molecule and a cytoprotectant. Antioxid Redox Signal 17:45–57

    Article  PubMed  CAS  Google Scholar 

  • Kimura Y, Mikami Y, Osumi K, Tsugane M, Oka J-I, Kimura H (2013) Polysulfides are possible H2S-derived signaling molecules in rat brain. FASEB J 27:2451–2457

    Article  PubMed  CAS  Google Scholar 

  • Krishnan N, Fu C, Pappin DJ, Tonks NK (2011) H2S-induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response. Sci Signal 4:ra86

    Article  PubMed  Google Scholar 

  • Krizaj D, Copenhagen DR (2002) Calcium regulation in photoreceptors. Front Biosci 7:d2023–d2044

    Article  PubMed  CAS  Google Scholar 

  • Kwak WJ, Kwon GS, Jin I, Kuriyama H, Sohn HY (2003) Involvement of oxidative stress in the regulation of H2S production during ultradian metabolic oscillation of Saccharomyces cerevisiae. FEMS Microbiol Lett 219:99–104

    Article  PubMed  CAS  Google Scholar 

  • Levitt MD, Abdel-Rehim MS, Furne J (2011) Free and acid-labile hydrogen sulfide concentrations in mouse tissues: anomalously high free hydrogen sulfide in aortic tissue. Antioxid Redox Signal 15:373–378

    Article  PubMed  CAS  Google Scholar 

  • Liardon R, Ledermann S (1986) Racemization kinetics of free and protein-bound amino acids under moderate alkaline treatment. J Agric Food Chem 34:557–565

    Article  CAS  Google Scholar 

  • Meister A, Fraser PE, Tice SV (1954) Enzymatic desulfuration of β-mercaptopyruvate to pyruvate. J Biol Chem 206:561–575

    PubMed  CAS  Google Scholar 

  • Mikami Y, Shibuya N, Kimura Y, Nagahara N, Ogasawara Y, Kimura H (2011a) Thioredoxin and dihydrolipoic acid are required for 3-mercaptopyruvate sulfurtransferase to produce hydrogen sulfide. Biochem J 439:479–485

    Article  PubMed  CAS  Google Scholar 

  • Mikami Y, Shibuya N, Kimura Y, Nagahara N, Yamada M, Kimura H (2011b) Hydrogen sulfide protects the retina from light-induced degeneration by the modulation of Ca2+ influx. J Biol Chem 286:39379–39386

    Article  PubMed  CAS  Google Scholar 

  • Mikami Y, Shibuya N, Ogasawara Y, Kimura H (2013) Hydrogen sulfide is produced by cystathionine γ–lyase at the steady-state low intracellular Ca2+ concentrations. Biochem Biophys Res Commun 431:131–135

    Article  PubMed  CAS  Google Scholar 

  • Misra CH (1989) Is a certain amount of cysteine prerequisite to produce brain damage in neonatal rats? Neurochem Res 14:253–257

    Article  PubMed  CAS  Google Scholar 

  • Modis K, Coletta C, Erdelyi K, Papapetropoulos A, Szabo C (2013) Intramitochondrial hydrogen sulfide production by 3-mercaptopyruvate sulfurtransferase maintains mitochondrial electron flow and supports cellular bioenergetics. FASEB J 27:601–611

    Article  PubMed  CAS  Google Scholar 

  • Morikawa T, Kajimura M, Nakamura T, Hishiki T, Nakanishi T, Yukutake Y, Nagahata Y, Ishikawa M, Hattori K, Takenouchi T, Takahashi T, Ishii I, Matsubara K, Kabe Y, Uchiyama S, Nagata E, Gadalla MM, Snyder SH, Suematsu M (2012) Hypoxic regulation of the cerebral microcirculation is mediated by a carbon monoxide-sensitive hydrogen sulfide pathway. Proc Natl Acad Sci U S A 109:1293–1298

    Article  PubMed  CAS  Google Scholar 

  • Murphy TH, Miyamoto M, Sastre A, Schnaar RL, Coyle JT (1989) Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. Neuron 2:1547–1558

    Article  PubMed  CAS  Google Scholar 

  • Mustafa AK, Gadalla MM, Sen N, Kim S, Mu W, Gazi SK, Barrow RK, Yang G, Wang R, Snyder SH (2009) H2S signals through protein S-sulfhydration. Sci Signal 2:ra72

    Article  PubMed  Google Scholar 

  • Mustafa AK, Sikka G, Gazi SK, Steppan J, Jung SM, Bhunia AK, Barodka VM, Gazi FK, Barrow RK, Wang R, Amzel LM, Berkowitz DE, Snyder SH (2011) Hydrogen fulfide as endothelium-derived hyperpolarizing factor sulfhydrates potassium channels. Circ Res 109:1259–1268

    Article  PubMed  CAS  Google Scholar 

  • Nagahara N, Nishino T (1996) Role of amino acid residues in the active site of rat liver mercaptopyruvate sulfurtransferase. cDNA cloning, overexpression, and site-directed mutagenesis. J Biol Chem 271:27395–27401

    Article  PubMed  CAS  Google Scholar 

  • Nagai Y, Tsugane M, Oka J, Kimura H (2004) Hydrogen sulfide induces calcium waves in astrocytes. FASEB J 18:557–559

    PubMed  CAS  Google Scholar 

  • Nagai Y, Tsugane M, Oka J, Kimura H (2006) Polysulfides induce calcium waves in rat hippocampal astrocytes. J Pharmacol Sci 100(Suppl I):200, ISSN 1347–8613

    Google Scholar 

  • Nagy P, Winterbourn CC (2010) Rapid reaction of hydrogen sulfide with the neutrophil oxidant hypochlorous acid to generate polysulfides. Chem Res Toxicol 23:1541–1543

    Article  PubMed  CAS  Google Scholar 

  • Nielsen RW, Tachibana C, Hansen NE, Winther JR (2011) Trisulfides in proteins. Antioxid Redox Signal 15:67–75

    Article  PubMed  CAS  Google Scholar 

  • Ogasawara Y, Isoda S, Tanabe S (1994) Tissue and subcellular distribution of bound and acid-labile sulfur, and the enzymic capacity for sulfide production in the rat. Biol Pharm Bull 17:1535–1542

    Article  PubMed  CAS  Google Scholar 

  • Ogawa H, Takahashi K, Miura S, Imagawa T, Saito S, Tominaga M, Ohta T (2012) H2S functions as a nociceptive messenger through transient receptor potential ankyrin 1 (TRPA1) activation. Neuroscience 218:335–343

    Article  PubMed  CAS  Google Scholar 

  • Olney JW, Zorumski C, Price MT, Labruyere J (1990) L-cysteine, a bicarbonate-sensitive endogenous excitotoxin. Science 248:596–599

    Article  PubMed  CAS  Google Scholar 

  • Oosumi K, Tsugane M, Ishimami M, Nagai Y, Iwai T, Oka J, Kimura H (2010) Polysulfide activates TRP channels and increases intracellular Ca2+ in astrocytes. Bull Japanese Soc Neurochem 49:517, ISSN: 0037–3796

    Google Scholar 

  • Paul BD, Snyder SH (2012) H2S signalling through protein sulfhydration and beyond. Nat Rev Mol Cell Biol 13:499–507

    Article  PubMed  CAS  Google Scholar 

  • Predmore BL, Lefer DJ (2010) Development of hydrogen sulfide-based therapeutics for cardiovascular disease. J Cardiovasc Transl Res 3:487–498

    Article  PubMed  Google Scholar 

  • Razzak M (2012) Transplantation: hydrogen sulphide reduces warm renal ischaemic injury. Nat Rev Urol 9:670

    Article  PubMed  Google Scholar 

  • Richie JP Jr, Lang CA (1987) The determination of glutathione, cyst(e)ine, and other thiols and disulfides in biological samples using high-performance liquid chromatography with dual electrochemical detection. Anal Biochem 163:9–15

    Article  PubMed  CAS  Google Scholar 

  • Riemenschneider A, Wegele R, Schmidt A, Papenbrock J (2005) Isolation and characterization of a D-cysteine desulfhydrase protein from Arabidopsis thaliana. FEBS J 272:1291–1304

    Article  PubMed  CAS  Google Scholar 

  • Savage JC, Gould DH (1990) Determination of sulfide in brain tissue and rumen fluid by ion-interaction reversed-phase high-performance liquid chromatography. J Chromatogr 526:540–545

    PubMed  CAS  Google Scholar 

  • Schumann U, Subramani S (2008) Special delivery from mitochondria to peroxisomes. Trends Cell Biol 18:253–256

    Article  PubMed  CAS  Google Scholar 

  • Sen N, Paul BD, Gadalla MM, Mustafa AK, Sen T, Xu R, Kim S, Snyder SH (2012) Hydrogen sulfide-linked sulfhydration of NF-κB mediates its antiapoptotic actions. Mol Cell 45:13–24

    Article  PubMed  CAS  Google Scholar 

  • Shan X, Dunbrack RLJ, Christopher SA, Kruger WD (2001) Mutation in the regulatory domain of cystathionine β–synthase can functionally suppress patient-derived mutations in cis. Human Mol Genet 10:635–643

    Article  CAS  Google Scholar 

  • Shatalin K, Shatalina E, Mironov A, Nudler E (2011) H2S: a universal defense against antibiotics in bacteria. Science 334:986–990

    Article  PubMed  CAS  Google Scholar 

  • Shibuya N, Mikami Y, Kimura Y, Nagahara N, Kimura H (2009a) Vascular endothelium expresses 3-mercaptopyruvate sulfurtransferase and produces hydrogen sulfide. J Biochem 146:623–626

    Article  PubMed  CAS  Google Scholar 

  • Shibuya N, Tanaka M, Yoshida M, Ogasawara Y, Togawa T, Ishii K, Kimura H (2009b) 3-Mercaptopyruvate sulfurtransferease produces hydrogen sulfide and bound sulfane sulfur in the brain. Antioxid Redox Signal 11:703–714

    Article  PubMed  CAS  Google Scholar 

  • Shibuya N, Koike S, Tanaka M, Ishigami-Yuasa M, Kimura Y, Ogasawara Y, Fukui K, Nagahara N, Kimura H (2013) A novel pathway for the production of hydrogen sulfide from D-cysteine in mammalian cells. Nat Commun 2371

    Google Scholar 

  • Shigetomi E, Tong X, Kwan KY, Corey DP, Khakh BS (2012) TRPA1 channels regulate astrocyte resting calcium and inhibitory synapse efficacy through GAT-3. Nat Neurosci 15:70–80

    Article  CAS  Google Scholar 

  • Singh S, Padovani D, Leslie RA, Chiku T, Banerjee R (2009) Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions. J Biol Chem 284:22457–22466

    Article  PubMed  CAS  Google Scholar 

  • Stipanuk MH, Beck PW (1982) Characterization of the enzymic capacity for cysteine desulphhydration in liver and kidney of the rat. Biochem J 206:267–277

    PubMed  CAS  Google Scholar 

  • Streng T, Axelsson HE, Hedlund P, Andersson DA, Jordt SE, Bevan S, Andersson KE, Hogestatt ED, Zygmunt PM (2008) Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder. Eur Urol 53:391–399

    Article  PubMed  CAS  Google Scholar 

  • Suh JH, Shenvi SV, Dixon BM, Liu H, Jaiswal AKI, Liu RM, Hagen TM (2004) Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc Natl Acad Sci U S A 101:3381–3386

    Article  PubMed  CAS  Google Scholar 

  • Taniguchi T, Kimura T (1974) Role of 3-mercaptopyruvate sulfurtransferase in the formation of the iron-sulfur chromophore of adrenal ferredoxin. Biochim Biophys Acta 364:284–295

    Article  PubMed  CAS  Google Scholar 

  • Taoka S, Banerjee R (2001) Characterization of NO binding to human cystathionine beta-synthase: possible implications of the effects of CO and NO binding to the human enzyme. J Inorg Biochem 87:245–251

    Article  PubMed  CAS  Google Scholar 

  • Tateishi N, Higashi T, Naruse A, Nakashima K, Shiozaki H (1977) Rat liver glutathione: possible role as a reservoir of cysteine. J Nutr 107:51–60

    PubMed  CAS  Google Scholar 

  • Teague B, Asiedu S, Moore PK (2002) The smooth muscle relaxant effect of hydrogen sulphide in vitro: evidence for a physiological role to control intestinal contractility. Br J Pharmacol 137:139–145

    Article  PubMed  CAS  Google Scholar 

  • Toohey JI (1989) Sulphane sulphur in biological systems: a possible regulatory role. Biochem J 264:625–632

    PubMed  CAS  Google Scholar 

  • Toohey JI (2011) Sulfur signaling: is the agent sulfide or sulfane? Anal Biochem 413:1–7

    Article  PubMed  CAS  Google Scholar 

  • Tripatara P, Patel NSA, Collino M, Gallicchio M, Kieswich J, Castiglia S, Benetti E, Stewart KN, Brown PAJ, Yaqoob MM, Fantozzi R, Thiemermann C (2008) Generation of endogenous hydrogen sulfide by cystathionine γ–lyase limits renal ischemia/reperfusion injury and dysfunction. Lab Invest 88:1038–1048

    Article  PubMed  CAS  Google Scholar 

  • Tsugane M, Nagai Y, Kimura Y, Oka J-I, Kimura H (2007) Differentiated astrocytes acquire sensitivity to hydrogen sulfide that is diminished by the transformation into reactive astrocytes. Antioxid Redox Signal 9:257–269

    Article  PubMed  CAS  Google Scholar 

  • Ubuka T, Umemura S, Yuasa S, Kinuta M, Watanabe K (1978) Purification and characterization of mitochondrial cysteine aminotransferase from rat liver. Physiol Chem Phys 10:483–500

    PubMed  CAS  Google Scholar 

  • Vandiver MS, Paul BD, Xu R, Karuppagounder S, Rao F, Snowman AM, Ko HS, Lee YII, Dawson VL, Dawson TM, Sen N, Snyder SH (2013) Sulfhydration mediates neuroprotective actions of parkin. Nat Commun 4:1626

    Article  PubMed  Google Scholar 

  • Warenycia MW, Goodwin LR, Benishin CG, Reiffenstein RJ, Grancom DM, Taylor JD, Dieken FP (1989) Acute hydrogen sulfide poisoning. Demonstration of selective uptake of sulfide by the brainstem by measurement of brain sulfide levels. Biochem Pharmacol 38:973–981

    Article  PubMed  CAS  Google Scholar 

  • Wenzel A, Grimm C, Samardzija M, Reme CE (2005) Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration. Prog Retin Eye Res 24:275–306

    Article  PubMed  CAS  Google Scholar 

  • Westrop GD, Georg I, Coombs GH (2009) The mercaptopyruvate sulfurtransferase of Trichomonas vaginalis links cysteine catabolism to the production of thioredoxin persulfide. J Biol Chem 284:33485–33494

    Article  PubMed  CAS  Google Scholar 

  • Whiteman M, Armstrong JS, Chu SH, Jia-Ling S, Wong BS, Hheung NS, Halliwell B, Moore PK (2004) The novel neuromodulator hydrogen sulfide: an endogenous peroxynitrite ‘scavenger’? J Neurochem 90:765–768

    Article  PubMed  CAS  Google Scholar 

  • Whiteman M, Cheung NS, Zhu YZ, Chu SH, Siau JL, Wong BS, Armstrong JS, Moore PK (2005) Hydrogen sulphide: a novel inhibitor of hypochlorous acid-mediated oxidative damage in the brain? Biochem Biophys Res Commun 326:794–798

    Article  PubMed  CAS  Google Scholar 

  • Wintner EA, Deckwerth TL, Langston W, Bengtsson A, Leviten D, Hill P, Insko MA, Dumpit R, VandenEkart E, Toombs CF, Szabo C (2010) A monobromobimane-based assay to measure the pharmacokinetic profile of reactive sulphide species in blood. Br J Pharmacol 160:941–957

    Article  PubMed  CAS  Google Scholar 

  • Yang G, Wu L, Jiang B, Yang W, Qi J, Cao K, Meng Q, Mustafa AK, Mu W, Zhang S, Snyder SH, Wang R (2008) H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine γ-lyase. Science 322:587–590

    Article  PubMed  CAS  Google Scholar 

  • Zhao W, Zhang J, Lu Y, Wang R (2001) The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener. EMBO J 20:6008–6016

    Article  PubMed  CAS  Google Scholar 

  • Zhu JXG, Kalbfleisch M, Yang YX, Bihari R, Lobb I, Davison M, Mok A, Cepinskas G, Lawendy A-R, Sener A. (2012) Detrimental effects of prolonged warm renal ischaemia-reperfusion injury are abrogated by supplemental hydrogen sulphide: an analysis using real-time intravital microscopy and polymerase chain reaction. BJU 110:E1218–E1227

    Google Scholar 

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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. Division of Molecular Pharmacology, National Institute of Neuroscience, Ogawa-Higashi, Kodeira 4-1-1, Tokyo, 187-8502, Japan

    Hideo Kimura

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  1. Hideo Kimura
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Correspondence to Hideo Kimura .

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  1. National Institut of Neuroscience, Tokyo, Japan

    Hideo Kimura

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© 2013 Springer-Verlag Wien

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Kimura, H. (2013). Hydrogen Sulfide-Mediated Cellular Signaling and Cytoprotection. In: Kimura, H. (eds) Hydrogen Sulfide and its Therapeutic Applications. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1550-3_9

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