Abstract
Hydrogen sulfide (H2S) is the first inorganic compound identified as both a substrate for mitochondrial oxidative phosphorylation and a transmitter in mammalian cells. H2S seems to mediate effects that are correlated with those of nitric oxide (NO) by a reciprocal regulation. Moreover, H2S is consumed by mitochondrial oxidation mediated by sulfide-quinone reductase-like protein (SQRDL)—the vertebrate homolog of sulfide-quinone oxidoreductase (SQR). There is evidence that SQR plays an essential role in regulating H2S levels in fission yeast. To start understanding the role of SQRDL in the mammalian metabolism of H2S, we examine rat tissues. Our results show that SQRDL protein is present in all tissues tested, albeit restricted to specific mitochondrial populations at the cellular level. We demonstrate a developmental regulation of Sqrdl transcription in the kidney, where SQRDL protein is detectable in glomerular podocytes and in tubular cells of the renal medulla. We also show that Sqrdl transcription in T cells is responsive to external H2S. Taken together, our results suggest that Sqrdl transcription is adaptively regulated, probably to meet the need of H2S oxidation. Thus far, SQRDL has only been studied in a limited set of tissues. The present report demonstrates the presence and specific localization of SQRDL in various mammalian tissues.
Similar content being viewed by others
References
Abe K, Kimura H (1996) The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci 16:1066–1071
Ackermann M, Kubitza M, Maier K, Brawanski A, Hauska G, Pina AL (2011) The vertebrate homolog of sulfide-quinone reductase is expressed in mitochondria of neuronal tissues. Neuroscience 199:1–12
Anbar AD, Knoll AH (2002) Proterozoic ocean chemistry and evolution: a bioinorganic bridge? Science 297:1137–1142
Arieli B, Shahak Y, Taglicht D, Hauska G, Padan E (1994) Purification and characterization of sulfide-quinone reductase, a novel enzyme driving anoxygenic photosynthesis in Oscillatoria limnetica. J Biol Chem 269:5705–5711
Awata S, Nakayama K, Suzuki I, Kodama H (1989) Effect of cysteine on the inactivation of cystathionine gamma-lyase by D, L-propargylglycine. Acta Med Okayama 43:329–335
Beauchamp RO Jr, Bus JS, Popp JA, Boreiko CJ, Andjelkovich DA (1984) A critical review of the literature on hydrogen sulfide toxicity. Crit Rev Toxicol 13:25–97
Bjorndahl L, Kvist U (2011) A model for the importance of zinc in the dynamics of human sperm chromatin stabilization after ejaculation in relation to sperm DNA vulnerability. Syst Biol Reprod Med 57:86–92
Blades MC, Manzo A, Ingegnoli F, Taylor PR, Panayi GS, Irjala H, Jalkanen S, Haskard DO, Perretti M, Pitzalis C (2002) Stromal cellÂderived factor 1 (CXCL12) induces human cell migration into human lymph nodes transplanted into SCID mice. J Immunol 168:4308–4317
Boehning D, Snyder SH (2003) Novel neural modulators. Annu Rev Neurosci 26:105–131
Brown WR, Barclay AN, Sunderland CA, Williams AF (1981) Identification of a glycophorin-like molecule at the cell surface of rat thymocytes. Nature 289:456–460
Bustin SA, Benes V, Nolan T, Pfaffl MW (2005) Quantitative real-time RT-PCR–a perspective. J Mol Endocrinol 34:597–601
Chen Q, Xu S, Huang S, Zhang A, Feng Q, Guo X, Guo M, Chen R, Yang T (2009) Suppression subtractive hybridization analysis of gene expression during late kidney development identifies the developmentally regulated gene rPEA3. Nephron Exp Nephrol 111:e103–e115
Cohen E, Pphir I, Shaul YB (1999) Induced differentiation in HT29, a human colon adenocarcinoma cell line. J Cell Sci 112:2657–2666
d’Emmanuele di Villa Bianca R, Sorrentino R, Maffia P, Mirone V, Imbimbo C, Fusco F, De Palma R, Ignarro LJ, Cirino G (2009) Hydrogen sulfide as a mediator of human corpus cavernosum smooth-muscle relaxation. Proc Natl Acad Sci U S A 106:4513–4518
Eberhardt W, Pfeilschifter J (2007) Nitric oxide and vascular remodeling: spotlight on the kidney. Kidney Int Suppl 106:S9–S16
Elinav E, Strowig T, Kau AL, Henaco-Mejia J, Thaiss CA, Booth CJ, Peaper DR, Bertin J, Eisenbarth SC, Gordon JI, Flavell RA (2011) NLRP6 inflammasome is a regulator of colonic microbial ecology and risk for colitis. Cell 145(5):745–757
Enciso M, Johnston SD, Gosalvez J (2011) Differential resistance of mammalian sperm chromatin to oxidative stress as assessed by a two-tailed comet assay. Reprod Fertil Dev 23:633–637
Florin T, Neale G, Gibson GR, Christl SU, Cummings JH (1991) Metabolism of dietary sulphate: absorption and excretion in humans. Gut 32:766–773
Furne J, Springfield J, Koenig T, DeMaster E, Levitt MD (2001) Oxidation of hydrogen sulfide and methanethiol to thiosulfate by rat tissues: a specialized function of the colonic mucosa. Biochem Pharmacol 62:255–259
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–R1485
Gastpar R, Gehrmann M, Bausero MA, Asea A, Gross C, Schroeder JA, Multhoff G (2005) Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res 65(12):5238–5247
Geng B, Cui Y, Zhao J, Yu F, Zhu Y, Xu G, Zhang Z, Tang C, Du J (2007) Hydrogen sulfide downregulates the aortic L-arginine/nitric oxide pathway in rats. Am J Physiol Regul Integr Comp Physiol 293:R1608–R1618
Gibson GR, Cummings JH, Macfarlane GT (1988) Competition for hydrogen between sulphate-reducing bacteria and methanogenic bacteria from the human large intestine. J Appl Bacteriol 65:241–247
Goubern M, Andriamihaja M, Nubel T, Blachier F, Bouillaud F (2007) Sulfide, the first inorganic substrate for human cells. FASEB J 21:1699–1706
Griesbeck C, Schutz M, Schodl T, Bathe S, Nausch L, Mederer N, Vielreicher M, Hauska G (2002) Mechanism of sulfide-quinone reductase investigated using site-directed mutagenesis and sulfur analysis. Biochemistry 41:11552–11565
Hähnel V, Schwarzfischer L, Fenton MJ, Rehli M (2002) Transcriptional regulation of the human Toll-like receptor 2 gene in monocytes and macrophages. J Immunol 168:5629–5637
Hu LF, Lu M, Hon Wang PT, Bian JS (2011) Hydrogen sulfide: neurophysiology and neuropathology. Antioxid Redox Signal 15:405–419
Ilan N, Mohsenin A, Cheung L, Madri JA (2001) PECAM-1 shedding during apoptosis generates a membrane-anchored truncated molecule with unique signaling characteristics. FASEB J 15(2):362–372
Jones M, Cordell JL, Beyers AD, Tse AG, Mason DY (1993) Detection of T and B cells in many animal species using cross-reactive anti-peptide antibodies. J Immunol 150:5429–5435
Julian D, Statile JL, Wohlgemuth SE, Arp AJ (2002) Enzymatic hydrogen sulfide production in marine invertebrate tissues. Comp Biochem Physiol A 133:105–115
Kamoun P (2004) Endogenous production of hydrogen sulfide in mammals. Amino Acids 26:243–254
Kamoun P, Belardinelli MC, Chabli A, Lallouchi K, Chadefaux-Vekemans B (2003) Endogenous hydrogen sulfide overproduction in Down syndrome. Am J Med Genet A 116A:310–311
Kloesch B, Liszt M, Krehan D, Broell J, Kiener H, Steiner G (2011) High concentrations of hydrogen sulfide elevate the expression of a series of pro-inflammatory genes in fibroblast-like synoviocytes derived from rheumatoid and osteoarthritis pateients. Immunol Lett 141:197–203
Kranzer K, Eckhardt A, Aigner M, Knoll G, Deml L, Speth C, Lehn N, Rehli M, Schneider-Brachert W (2004) Induction of maturation and cytokine release of human dendritic cells by Helicobacter pylori. Infect Immun 72(8):4416–4423
Kranzer K, Söllner L, Aigner M, Lehn N, Deml L, Rehli M, Schneider-Brachert W (2005) Impact of Helicobacter pylori virulence factors and compounds on activation and maturation of human dendritic cells. Infect Immun 73(7):4180–4189
Kumarasamy S, Gopalakrishnan K, Abdul-Majeed S, Partow-Navid R, Farms P, Joe B (2013) Construction of two novel reciprocal conplastic rat strains and characterization of cardiac mitochondria. Am J Physiol Heart Circ Physiol 304:H22–H32
Lagoutte E, Mimoun S, Andriamihaja M, Chaumontet C, Blachier F, Bouillaud F (2010) Oxidation of hydrogen sulfide remains a priority in mammalian cells and causes reverse electron transfer in colonocytes. Biochim Biophys Acta 1797:1500–1511
Larionov A, Krause A, Miller W (2005) A standard curve based method for relative real time PCR data processing. BMC Bioinforma 6:62
Li L, Bhatia M, Zhu YZ, Zhu YC, Ramnath RD, Wang ZJ, Anuar FB, Whiteman M, Salto-Tellez M, Moore PK (2005) Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse. FASEB J 19:1196–1198
Liang J, Jiang D, Griffith J, Yu S, Fan J, Zhao X, Bucala R, Noble PW (2007) CD44 is a negative regulator of acute pulmonary inflammation and lipopolysaccharide-TLR signaling in mouse macrophages. J Immunol 178:2469–2475
Linden DR, Furne J, Stoltz GJ, Abdel-Rehim MS, Levitt MD, Szurszewski JH (2012) Sulfide quinone reductase contributes to hydrogen sulfide metabolism in murine peripheral tissues but not in the central nervous system. Br J Pharmacol 165:2178–2190
Mandal P, Hamilton T (2007) Signaling in lipopolysaccharide-induced stabilization of formyl peptide receptor 1 mRNA in mouse peritoneal macrophages. J Immunol 178:2542–2548
Mandal P, Novotny M, Hamilton TA (2005) Lipopolysaccharide induces formyl peptide receptor 1 gene expression in macrophages and neutrophils via transcriptional and posttranscriptional mechanisms. J Immunol 175:6085–6091
Menezo YJ, Hazout A, Panteix G, Robert F, Rollet J, Cohen-Bacrie P, Chapuis F, Clement P, Benkhalifa M (2007) Antioxidants to reduce sperm DNA fragmentation: an unexpected adverse effect. Reprod Biomed Online 14:418–421
Millero FJ (1986) The thermodynamics and kinetics of the hydrogen sulfide system in natural waters. Mar Chem 18:121–147
Morse JW, Millero FJ, Cornwell JC, Rickard D (1987) The chemistry of the hydrogen sulfide and iron sulfide systems in natural waters. Earth Sci Rev 24:1–42
Mundel P, Gilbert P, Kriz W (1991) Podocytes in glomerulus of rat kidney express a characteristic 44 kD proteon. J Hitsochem Cytochem 39:1047–1056
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
Nicholls P (1975) The effect of sulphide on cytochrome aa3. Isosteric and allosteric shifts of the reduced alpha-peak. Biochim Biophys Acta 396:24–35
Nicolls MR, Aversa GG, Pearce NW, Spinelli A, Berger MF, Gurley KE, Hall BM (1993) Induction of long-term specific tolerance to allografts in rats by therapy with anti-CD3-like monoclonal antibody. Transplantation 55:459–468
Olson KR, Whitfield NL, Bearden SE, St Leger J, Nilson E, Gao Y, Madden JA (2010) Hypoxic pulmonary vasodilation: a paradigm shift with a hydrogen sulfide mechanism. Am J Physiol Regul Integr Comp Physiol 298:R51–R60
Ouml, Lkel S, Grieshaber M (1997) Sulphide oxidation and oxidative phosphorylation in the mitochondria of the lugworm. J Exp Biol 200:83–92
Palm F, Nordquist L (2011) Renal oxidative stress, oxygenation, and hypertension. Am J Physiol Regul Integr Comp Physiol 301:R1229–R1241
Palm F, Teerlink T, Hansell P (2009) Nitric oxide and kidney oxygenation. Curr Opin Nephrol Hypertens 18:68–73
Parrino V, Kraus DW, Doeller JE (2000) ATP production from the oxidation of sulfide in gill mitochondria of the ribbed mussel Geukensia demissa. J Exp Biol 203:2209–2218
Pham T-H, Langmann S, Schwarzfischer L, El Chartouni C, Lichtinger M, Klug M, Krause SW, Rehli M (2007) CCAAT Enhancer-binding protein β regulates constitutive gene expression during late stages of monocyte to macrophage differentiation. J Biol Chem 282(30):21924–21933
Qu K, Lee SW, Bian JS, Low CM, Wong PT (2008) Hydrogen sulfide: neurochemistry and neurobiology. Neurochem Int 52:155–165
Renner K, Kofler R, Gnaiger E (2002) Mitochondrial function in glucocorticoid triggered T-ALL cells with transgenic bcl-2 expression. Mol Biol Rep 29:97–101
Rhee JW, Lee KW, Kim D, Lee Y, Jeon OH, Kwon HJ, Kim DS (2007) NF-kappaB-dependent regulation of matrix metalloproteinase-9 gene expression by lipopolysaccharide in a macrophage cell line RAW 264.7. J Biochem Mol Biol 40:88–94
Robinson AP, White TM, Mason DW (1986) Macrophage heterogeneity in the rat as delineated by two monoclonal antibodies MRC OX-41 and MRC OX-42, the latter recognizing complement receptor type 3. Immunology 57(2):239–247
Rodriguez-Barbero A, Dorado F, Velasco S, Pandiella A, Banas B, Lopez-Novoa JM (2006) TGF beta1 induces COX-2 expression and PGE2 synthesis through MAPK and PI3K pathways in human mesangial cells. Kidney Int 70:901–909
Roediger WE, Moore J, Babidge W (1997) Colonic sulfide in pathogenesis and treatment of ulcerative colitis. Dig Dis Sci 42:1571–1579
Rutledge RG, Cote C (2003) Mathematics of quantitative kinetic PCR and the application of standard curves. Nucleic Acids Res 31:e93
Ryan MJ, Johnson G, Kirk J, Fuerstenberg SM, Zager RA, Torok-Storb B (1994) Hk-2: an immortalized proximal tubule epithelial cell line from normal adult human kidney. Kidney Int 45:48–57
Saleem MA, O’Hare MJ, Reiser J, Coward RJ, Inward CD, Farren T, Xing CY, Ni L, Mathieson PW, Mundel P (2002) A conditionally immortalized human podocyte cell line demonstrating nephrin and podocin expression. J Am Soc Nephrol 13:630–638
Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A 74:5463–5467
Schutz M, Shahak Y, Padan E, Hauska G (1997) Sulfide-quinone reductase from Rhodobacter capsulatus. Purification, cloning, and expression. J Biol Chem 272:9890–9894
Schutz M, Maldener I, Griesbeck C, Hauska G (1999) Sulfide-quinone reductase from Rhodobacter capsulatus: requirement for growth, periplasmic localization, and extension of gene sequence analysis. J Bacteriol 181:6516–6523
Shahak Y, Hauska G (2008) Sulfide oxidation from cyanobacteria to humans: sulfide-quinone oxidoreductase (SQR). In: Hell R, Dahl C, Knaff DB, Leustek T (eds) Advances in photosynthesis and respiration, vol 27. Springer, Dordrecht, pp 319–335
Shen Y, Buick R, Canfield DE (2001) Isotopic evidence for microbial sulphate reduction in the early Archaean era. Nature 410:77–81
Solis M, Romieu-Mourez R, Goubau D, Grandvaux N, Mesplede T, Julkunen I, Nardin A, Salcedo M, Hiscott J (2007) Involvement of TBK1 and IKKepsilon in lipopolysaccharide-induced activation of the interferon response in primary human macrophages. Eur J Immunol 37:528–539
Srilatha B, Adaikan PG, Moore PK (2006) Possible role for the novel gasotransmitter hydrogen sulphide in erectile dysfunction–a pilot study. Eur J Pharmacol 535:280–282
Srilatha B, Adaikan PG, Li L, Moore PK (2007) Hydrogen sulphide: a novel endogenous gasotransmitter facilitates erectile function. J Sex Med 4:1304–1311
Srilatha B, Hu L, Adaikan GP, Moore PK (2009) Initial characterization of hydrogen sulfide effects in female sexual function. J Sex Med 6:1875–1884
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
Strasser-Wozak EMC, Hattmannstorfer R, Hala M, Hartmann BL, Fiegl M, Geley S, Kofler R (1995) Splice site mutation in the glucocorticoid receptor gene causes resistance to glucocorticoid-induced apoptosis in a human acute leukemic cell line. Cancer Res 55:348–353
Tassiulas I, Park-Min KH, Hu Y, Kellerman L, Mevorach D, Ivashkiv LB (2007) Apoptotic cells inhibit LPS-induced cytokine and chemokine production and IFN responses in macrophages. Hum Immunol 68:156–164
Theissen U, Martin W (2008) Sulfide : quinone oxidoreductase (SQR) from the lugworm Arenicola marina shows cyanide- and thioredoxin-dependent activity. FEBS J 275:1131–1139
Theissen U, Hoffmeister M, Grieshaber M, Martin W (2003) Single eubacterial origin of eukaryotic sulfide:quinone oxidoreductase, a mitochondrial enzyme conserved from the early evolution of eukaryotes during anoxic and sulfidic times. Mol Biol Evol 20:1564–1574
Vande Weghe JG, Ow DW (1999) A fission yeast gene for mitochondrial sulfide oxidation. J Biol Chem 274:13250–13257
Vande Weghe JG, Ow DW (2001) Accumulation of metal-binding peptides in fission yeast requires hmt2+. Mol Microbiol 42:29–36
Wang R (2002) Two’s company, three’s a crowd: can H2S be the third endogenous gaseous transmitter? FASEB J 16:1792–1798
Wen Y-D, Wang H, Kho S-H, Rinkiko S, Sheng X, Shen H-M, Zhu Y-Z (2013) Hydrogen sulfide protects HUVECs against hydrogen peroxide induced mitochondrial dysfunction and oxidative stress. PLoS ONE 8(2):1–10
Yong R, Searcy DG (2001) Sulfide oxidation coupled to ATP synthesis in chicken liver mitochondria. Comp Biochem Physiol B 129:129–137
Acknowledgments
We thank Prof. Dr. Alexander Brawanski for his support during the development of this work. We also thank Prof. Dr. Ralph Witzgall, for helpful comments and experimental support. Further thanks go to B. Banas, M. Rehli and K. Renner for providing material and expertise and to C.-L. Schengrund for reviewing this manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ackermann, M., Kubitza, M., Hauska, G. et al. The vertebrate homologue of sulfide-quinone reductase in mammalian mitochondria. Cell Tissue Res 358, 779–792 (2014). https://doi.org/10.1007/s00441-014-1983-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00441-014-1983-9