Abstract
Carbon monoxide (CO), hydrogen sulfide (H2S), and nitric oxide (NO) constitute endogenous gaseous molecules produced by specific enzymes. These gases are chemically simple, but exert multiple effects and act through shared molecular targets to control both physiology and pathophysiology in the cardiovascular system (CVS). The gases act via direct and/or indirect interactions with each other in proteins such as heme-containing enzymes, the mitochondrial respiratory complex, and ion channels, among others. Studies of the major impacts of CO, H2S, and NO on the CVS have revealed their involvement in controlling blood pressure and in reducing cardiac reperfusion injuries, although their functional roles are not limited to these conditions. In this review, the basic aspects of CO, H2S, and NO, including their production and effects on enzymes, mitochondrial respiration and biogenesis, and ion channels are briefly addressed to provide insight into their biology with respect to the CVS. Finally, potential therapeutic applications of CO, H2S, and NO with the CVS are addressed, based on the use of exogenous donors and different types of delivery systems.
Keywords
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Abe K, Kimura H (1996) The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci 16:1066–1071
Acin-Perez R, Fernandez-Silva P, Peleato ML, Perez-Martos A, Enriquez JA (2008) Respiratory active mitochondrial supercomplexes. Mol Cell 32:529–539
Akbarali HI, Kang M (2015) Postranslational modification of ion channels in colonic inflammation. Curr Neuropharmacol 13:234–238
Akrouh A, Halcomb SE, Nichols CG, Sala-Rabanal M (2009) Molecular biology of K(ATP) channels and implications for health and disease. IUBMB Life 61:971–978
Alexander SP, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Catterall WA, Spedding M, Peters JA, Harmar AJ (2013) The concise guide to pharmacology 2013/14: ion channels. Br J Pharmacol 170:1607–1651
Algalarrondo V, Nattel S (2016) Potassium channel remodeling in heart disease. Card Electrophysiol Clin 8:337–347
Allen BW, Stamler JS, Piantadosi CA (2009) Hemoglobin, nitric oxide and molecular mechanisms of hypoxic vasodilation. Trends Mol Med 15:452–460
Al-Magableh MR, Kemp-Harper BK, Hart JL (2015) Hydrogen sulfide treatment reduces blood pressure and oxidative stress in angiotensin II-induced hypertensive mice. Hypertens Res 38:13–20
Almeida AS, Figueiredo-Pereira C, Vieira HL (2015) Carbon monoxide and mitochondria-modulation of cell metabolism, redox response and cell death. Front Physiol 6:33
Alonso-Carbajo L, Kecskes M, Jacobs G, Pironet A, Syam N, Talavera K, Vennekens R (2017) Muscling in on TRP channels in vascular smooth muscle cells and cardiomyocytes. Cell Calcium 66:48–61
Amin AS, Tan HL, Wilde AA (2010) Cardiac ion channels in health and disease. Heart Rhythm 7:117–126
Anand P, Stamler JS (2012) Enzymatic mechanisms regulating protein S-nitrosylation: implications in health and disease. J Mol Med (Berl) 90:233–244
Andersen ME, Clewell HJ 3rd, Mahle DA, Gearhart JM (1994) Gas uptake studies of deuterium isotope effects on dichloromethane metabolism in female B6C3F1 mice in vivo. Toxicol Appl Pharmacol 128:158–165
Andreadou I, Iliodromitis EK, Rassaf T, Schulz R, Papapetropoulos A, Ferdinandy P (2015) The role of gasotransmitters NO, H2S and CO in myocardial ischaemia/reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning. Br J Pharmacol 172:1587–1606
Andrei SR, Sinharoy P, Bratz IN, Damron DS (2016) TRPA1 is functionally co-expressed with TRPV1 in cardiac muscle: co-localization at z-discs, costameres and intercalated discs. Channels 10:395–409
Ash-Bernal R, Wise R, Wright SM (2004) Acquired methemoglobinemia: a retrospective series of 138 cases at 2 teaching hospitals. Medicine 83:265–273
Asimakopoulou A, Panopoulos P, Chasapis CT, Coletta C, Zhou Z, Cirino G, Giannis A, Szabo C, Spyroulias GA, Papapetropoulos A (2013) Selectivity of commonly used pharmacological inhibitors for cystathionine β synthase (CBS) and cystathionine γ lyase (CSE). Br J Pharmacol 169:922–932
Avanzato D, Merlino A, Porrera S, Wang R, Munaron L, Mancardi D (2014) Role of calcium channels in the protective effect of hydrogen sulfide in rat cardiomyoblasts. Cell Physiol Biochem 33:1205–1214
Babot M, Birch A, Labarbuta P, Galkin A (2014) Characterisation of the active/de-active transition of mitochondrial complex I. Biochim Biophys Acta 1837:1083–1092
Bai CX, Namekata I, Kurokawa J, Tanaka H, Shigenobu K, Furukawa T (2005) Role of nitric oxide in Ca2+ sensitivity of the slowly activating delayed rectifier K+ current in cardiac myocytes. Circ Res 96:64–72
Balakumar P, Kathuria S, Taneja G, Kalra S, Mahadevan N (2012) Is targeting eNOS a key mechanistic insight of cardiovascular defensive potentials of statins? J Mol Cell Cardiol 52:83–92
Barouch LA, Harrison RW, Skaf MW, Rosas GO, Cappola TP, Kobeissi ZA, Hobai IA, Lemmon CA, Burnett AL, O'Rourke B, Rodriguez ER, Huang PL, Lima JA, Berkowitz DE, Hare JM (2002) Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature 416:337–339
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
Basudhar D, Ridnour LA, Cheng R, Kesarwala AH, Heinecke J, Wink DA (2016) Biological signaling by small inorganic molecules. Coord Chem Rev 306:708–723
Bathoorn E, Slebos DJ, Postma DS, Koeter GH, van Oosterhout AJ, van der Toorn M, Boezen HM, Kerstjens HA (2007) Anti-inflammatory effects of inhaled carbon monoxide in patients with COPD: a pilot study. Eur Respir J 30:1131–1137
Belikova NA, Vladimirov YA, Osipov AN, Kapralov AA, Tyurin VA, Potapovich MV, Basova LV, Peterson J, Kurnikov IV, Kagan VE (2006) Peroxidase activity and structural transitions of cytochrome c bound to cardiolipin-containing membranes. Biochemistry 45:4998–5009
Beltowski J (2015) Hydrogen sulfide in pharmacology and medicine – an update. Pharmacol Rep 67:647–658
Beltowski J, Jamroz-Wisniewska A (2014) Hydrogen sulfide and endothelium-dependent vasorelaxation. Molecules 19:21183–21199
Bendall JK, Douglas G, McNeill E, Channon KM, Crabtree MJ (2014) Tetrahydrobiopterin in cardiovascular health and disease. Antioxid Redox Signal 20:3040–3077
Benoit G, Cooney A, Giguere V, Ingraham H, Lazar M, Muscat G, Perlmann T, Renaud JP, Schwabe J, Sladek F, Tsai MJ, Laudet V (2006) International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol Rev 58:798–836
Bianco CL, Toscano JP, Bartberger MD, Fukuto JM (2017) The chemical biology of HNO signaling. Arch Biochem Biophys 617:129–136
Bilban M, Haschemi A, Wegiel B, Chin BY, Wagner O, Otterbein LE (2008) Heme oxygenase and carbon monoxide initiate homeostatic signaling. J Mol Med (Berl) 86:267–279
Blackstone E, Morrison M, Roth MB (2005) H2S induces a suspended animation-like state in mice. Science 308:518
Boczkowski J, Poderoso JJ, Motterlini R (2006) CO–metal interaction: vital signaling from a lethal gas. Trends Biochem Sci 31:614–621
Bolotina VM, Najibi S, Palacino JJ, Pagano PJ, Cohen RA (1994) Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle. Nature 368:850–853
Bouillaud F, Blachier F (2011) Mitochondria and sulfide: a very old story of poisoning, feeding, and signaling? Antioxid Redox Signal 15:379–391
Boycott HE, Dallas ML, Elies J, Pettinger L, Boyle JP, Scragg JL, Gamper N, Peers C (2013) Carbon monoxide inhibition of Cav3.2 T-type Ca2+ channels reveals tonic modulation by thioredoxin. FASEB J 27:3395–3407
Brahimi-Horn MC, Pouyssegur J (2007) Oxygen, a source of life and stress. FEBS Lett 581:3582–3591
Bredt DS (2003) Nitric oxide signaling specificity – the heart of the problem. J Cell Sci 116:9–15
Brookes PS (2005) Mitochondrial H(+) leak and ROS generation: an odd couple. Free Radic Biol Med 38:12–23
Burger DE, Lu X, Lei M, Xiang FL, Hammoud L, Jiang M, Wang H, Jones DL, Sims SM, Feng Q (2009) Neuronal nitric oxide synthase protects against myocardial infarction-induced ventricular arrhythmia and mortality in mice. Circulation 120:1345–1354
Burwell LS, Brookes PS (2008) Mitochondria as a target for the cardioprotective effects of nitric oxide in ischemia-reperfusion injury. Antioxid Redox Signal 10:579–599
Burwell LS, Nadtochiy SM, Tompkins AJ, Young S, Brookes PS (2006) Direct evidence for S-nitrosation of mitochondrial complex I. Biochem J 394:627–634
Burwell LS, Nadtochiy SM, Brookes PS (2009) Cardioprotection by metabolic shut-down and gradual wake-up. J Mol Cell Cardiol 46:804–810
Buys E, Sips P (2014) New insights into the role of soluble guanylate cyclase in blood pressure regulation. Curr Opin Nephrol Hypertens 23:135–142
Cacanyiova S, Berenyiova A, Kristek F (2016a) The role of hydrogen sulphide in blood pressure regulation. Physiol Res 65:S273–s289
Cacanyiova S, Berenyiova A, Kristek F, Drobna M, Ondrias K, Grman M (2016b) The adaptive role of nitric oxide and hydrogen sulphide in vasoactive responses of thoracic aorta is triggered already in young spontaneously hypertensive rats. J Physiol Pharmacol 67:501–512
Calvert JW, Lefer DJ (2010) Clinical translation of nitrite therapy for cardiovascular diseases. Nitric Oxide 22:91–97
Campbell DL, Stamler JS, Strauss HC (1996) Redox modulation of L-type calcium channels in ferret ventricular myocytes. Dual mechanism regulation by nitric oxide and S-nitrosothiols. J Gen Physiol 108:277–293
Campuzano O, Beltran-Alvarez P, Iglesias A, Scornik F, Perez G, Brugada R (2010) Genetics and cardiac channelopathies. Genet Med 12:260–267
Carpenter AW, Schoenfisch MH (2012) Nitric oxide release part II. Therapeutic applications. Chem Soc Rev 41:3742–3752
Carter RN, Morton NM (2016) Cysteine and hydrogen sulphide in the regulation of metabolism: insights from genetics and pharmacology. J Pathol 238:321–332
Cary SP, Winger JA, Marletta MA (2005) Tonic and acute nitric oxide signaling through soluble guanylate cyclase is mediated by nonheme nitric oxide, ATP, and GTP. Proc Natl Acad Sci U S A 102:13064–13069
Cassina A, Radi R (1996) Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch Biochem Biophys 328:309–316
Cattaruzza M, Hecker M (2008) Protein carbonylation and decarboylation: a new twist to the complex response of vascular cells to oxidative stress. Circ Res 102:273–274
Catterall WA (2000) Structure and regulation of voltage-gated Ca2+ channels. Annu Rev Cell Dev Biol 16:521–555
Cebova M, Kosutova M, Pechanova O (2016) Cardiovascular effects of gasotransmitter donors. Physiol Res 65:S291–s307
Chatzianastasiou A, Bibli SI, Andreadou I, Efentakis P, Kaludercic N, Wood ME, Whiteman M, Di Lisa F, Daiber A, Manolopoulos VG, Szabo C, Papapetropoulos A (2016) Cardioprotection by H2S donors: nitric oxide-dependent and independent mechanisms. J Pharmacol Exp Ther 358:431–440
Chaudhary KR, El-Sikhry H, Seubert JM (2011) Mitochondria and the aging heart. J Geriatr Cardiol 8:159–167
Chen Q, Camara AK, Stowe DF, Hoppel CL, Lesnefsky EJ (2007) Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion. Am J Physiol Cell Physiol 292:C137–C147
Chen YY, Chu HM, Pan KT, Teng CH, Wang DL, Wang AH, Khoo KH, Meng TC (2008) Cysteine S-nitrosylation protects protein-tyrosine phosphatase 1B against oxidation-induced permanent inactivation. J Biol Chem 283:35265–35272
Chen J, Gao J, Sun W, Li L, Wang Y, Bai S, Li X, Wang R, Wu L, Li H, Xu C (2016) Involvement of exogenous H2S in recovery of cardioprotection from ischemic post-conditioning via increase of autophagy in the aged hearts. Int J Cardiol 220:681–692
Chevalier M, Gilbert G, Roux E, Lory P, Marthan R, Savineau JP, Quignard JF (2014) T-type calcium channels are involved in hypoxic pulmonary hypertension. Cardiovasc Res 103:597–606
Clark JE, Naughton P, Shurey S, Green CJ, Johnson TR, Mann BE, Foresti R, Motterlini R (2003) Cardioprotective actions by a water-soluble carbon monoxide-releasing molecule. Circ Res 93:e2–e8
Clayton DA (1991) Replication and transcription of vertebrate mitochondrial DNA. Annu Rev Cell Biol 7:453–478
Coburn RF, Williams WJ, Kahn SB (1966) Endogenous carbon monoxide production in patients with hemolytic anemia. J Clin Invest 45:460–468
Cohen MV, Yang XM, Downey JM (2006) Nitric oxide is a preconditioning mimetic and cardioprotectant and is the basis of many available infarct-sparing strategies. Cardiovasc Res 70:231–239
Coletta C, Papapetropoulos A, Erdelyi K, Olah G, Modis K, Panopoulos P, Asimakopoulou A, Gero D, Sharina I, Martin E, Szabo C (2012a) Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation. Proc Natl Acad Sci U S A 109:9161–9166
Coletta C, Papapetropoulos A, Erdelyi K, Olah G, Módis K, Panopoulos P, Asimakopoulou A, Gerö D, Sharina I, Martin E, Szabo C (2012b) Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation. Proc Natl Acad Sci 109:9161–9166
Cooper CE, Brown GC (2008) The inhibition of mitochondrial cytochrome oxidase by the gases carbon monoxide, nitric oxide, hydrogen cyanide and hydrogen sulfide: chemical mechanism and physiological significance. J Bioenerg Biomembr 40:533–539
Cooper CE, Giulivi C (2007) Nitric oxide regulation of mitochondrial oxygen consumption II: molecular mechanism and tissue physiology. Am J Physiol Cell Physiol 292:C1993–C2003
Cooper GJ, Zhou Y, Bouyer P, Grichtchenko II, Boron WF (2002) Transport of volatile solutes through AQP1. J Physiol 542:17–29
Cordes CM, Bennett RG, Siford GL, Hamel FG (2009) Nitric oxide inhibits insulin-degrading enzyme activity and function through S-nitrosylation. Biochem Pharmacol 77:1064–1073
Cortese-Krott MM, Fernandez BO, Kelm M, Butler AR, Feelisch M (2015) On the chemical biology of the nitrite/sulfide interaction. Nitric Oxide 46:14–24
da Cunha FM, Torelli NQ, Kowaltowski AJ (2015) Mitochondrial retrograde signaling: triggers, pathways, and outcomes. Oxidative Med Cell Longev 2015:482582
Dahm CC, Moore K, Murphy MP (2006) Persistent S-nitrosation of complex I and other mitochondrial membrane proteins by S-nitrosothiols but not nitric oxide or peroxynitrite: implications for the interaction of nitric oxide with mitochondria. J Biol Chem 281:10056–10065
Daiber A, Munzel T (2015) Organic nitrate therapy, nitrate tolerance, and nitrate-induced endothelial dysfunction: emphasis on redox biology and oxidative stress. Antioxid Redox Signal 23:899–942
Dallas ML, Boyle JP, Milligan CJ, Sayer R, Kerrigan TL, McKinstry C, Lu P, Mankouri J, Harris M, Scragg JL, Pearson HA, Peers C (2011) Carbon monoxide protects against oxidant-induced apoptosis via inhibition of Kv2.1. FASEB J 25:1519–1530
Dallas ML, Yang Z, Boyle JP, Boycott HE, Scragg JL, Milligan CJ, Elies J, Duke A, Thireau J, Reboul C, Richard S, Bernus O, Steele DS, Peers C (2012) Carbon monoxide induces cardiac arrhythmia via induction of the late Na+ current. Am J Respir Crit Care Med 186:648–656
Dampney RA (1994) Functional organization of central pathways regulating the cardiovascular system. Physiol Rev 74:323–364
Derbyshire ER, Marletta MA (2012) Structure and regulation of soluble guanylate cyclase. Annu Rev Biochem 81:533–559
Di Lisa F, Bernardi P (2015) Modulation of mitochondrial permeability transition in ischemia-reperfusion injury of the heart. Advantages and limitations. Curr Med Chem 22:2480–2487
Di Lisa F, Canton M, Menabo R, Kaludercic N, Bernardi P (2007) Mitochondria and cardioprotection. Heart Fail Rev 12:249–260
Diaz F, Moraes CT (2008) Mitochondrial biogenesis and turnover. Cell Calcium 44:24–35
Ding Y, McCoubrey WK Jr, Maines MD (1999) Interaction of heme oxygenase-2 with nitric oxide donors. Is the oxygenase an intracellular “sink” for NO? Eur J Biochem 264:854–861
Dioum EM, Rutter J, Tuckerman JR, Gonzalez G, Gilles-Gonzalez MA, SL MK (2002) NPAS2: a gas-responsive transcription factor. Science 298:2385–2387
Dong DL, Zhang Y, Lin DH, Chen J, Patschan S, Goligorsky MS, Nasjletti A, Yang BF, Wang WH (2007) Carbon monoxide stimulates the Ca2(+)-activated big conductance k channels in cultured human endothelial cells. Hypertension 50:643–651
Dorsey P, Keel C, Klavens M, Hellstrom WJ (2010) Phosphodiesterase type 5 (PDE5) inhibitors for the treatment of erectile dysfunction. Expert Opin Pharmacother 11:1109–1122
Drose S, Stepanova A, Galkin A (2016) Ischemic A/D transition of mitochondrial complex I and its role in ROS generation. Biochim Biophys Acta 1857:946–957
Du J, Yan H, Tang C (2003) Endogenous H2S is involved in the development of spontaneous hypertension. Beijing Da Xue Xue Bao 35:102
Dugbartey GJ (2016) Diabetic nephropathy: a potential savior with “rotten-egg” smell. Pharmacol Rep 69:331–339
Earley S (2012) TRPA1 channels in the vasculature. Br J Pharmacol 167:13–22
Eberhardt M, Dux M, Namer B, Miljkovic J, Cordasic N, Will C, Kichko TI, de la Roche J, Fischer M, Suarez SA, Bikiel D, Dorsch K, Leffler A, Babes A, Lampert A, Lennerz JK, Jacobi J, Marti MA, Doctorovich F, Hogestatt ED, Zygmunt PM, Ivanovic-Burmazovic I, Messlinger K, Reeh P, Filipovic MR (2014) H2S and NO cooperatively regulate vascular tone by activating a neuroendocrine HNO-TRPA1-CGRP signalling pathway. Nat Commun 5:4381
Elies J, Scragg JL, Huang S, Dallas ML, Huang D, MacDougall D, Boyle JP, Gamper N, Peers C (2014) Hydrogen sulfide inhibits Cav3.2 T-type Ca2+ channels. FASEB J 28:5376–5387
Elies J, Scragg JL, Boyle JP, Gamper N, Peers C (2016) Regulation of the T-type Ca(2+) channel Cav3.2 by hydrogen sulfide: emerging controversies concerning the role of H2S in nociception. J Physiol 594:4119–4129
Elrod JW, Calvert JW, Morrison J, Doeller JE, Kraus DW, Tao L, Jiao X, Scalia R, Kiss L, Szabo C, Kimura H, Chow CW, Lefer DJ (2007) Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function. Proc Natl Acad Sci U S A 104:15560–15565
Enokido Y, Suzuki E, Iwasawa K, Namekata K, Okazawa H, Kimura H (2005) Cystathionine 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
Ertuna E, Loot AE, Fleming I, Yetik-Anacak G (2017) The role of eNOS on the compensatory regulation of vascular tonus by H2S in mouse carotid arteries. Nitric Oxide 69:45–50
Ewing JF, Raju VS, Maines MD (1994) Induction of heart heme oxygenase-1 (HSP32) by hyperthermia: possible role in stress-mediated elevation of cyclic 3′:5′-guanosine monophosphate. J Pharmacol Exp Ther 271:408–414
Fang L, Zhao J, Chen Y, Ma T, Xu G, Tang C, Liu X, Geng B (2009) Hydrogen sulfide derived from periadventitial adipose tissue is a vasodilator. J Hypertens 27:2174–2185
Farrugia G, Szurszewski JH (2014) Carbon monoxide, hydrogen sulfide, and nitric oxide as signaling molecules in the gastrointestinal tract. Gastroenterology 147:303–313
Fayad-Kobeissi S, Ratovonantenaina J, Dabire H, Wilson JL, Rodriguez AM, Berdeaux A, Dubois-Rande JL, Mann BE, Motterlini R, Foresti R (2016) Vascular and angiogenic activities of CORM-401, an oxidant-sensitive CO-releasing molecule. Biochem Pharmacol 102:64–77
Feelisch M, Schonafinger K, Noack E (1992) Thiol-mediated generation of nitric oxide accounts for the vasodilator action of furoxans. Biochem Pharmacol 44:1149–1157
Fernandez-Falgueras A, Sarquella-Brugada G, Brugada J, Brugada R, Campuzano O (2017) Cardiac channelopathies and sudden death: recent clinical and genetic advances. Biology 6
Ferreira R (2010) The reduction of infarct size – forty years of research. Rev Port Cardiol 29:1037–1053
Filipovic MR, Eberhardt M, Prokopovic V, Mijuskovic A, Orescanin-Dusic Z, Reeh P, Ivanovic-Burmazovic I (2013) Beyond H2S and NO interplay: hydrogen sulfide and nitroprusside react directly to give nitroxyl (HNO). A new pharmacological source of HNO. J Med Chem 56:1499–1508
Fink B, Bassenge E (1997) Unexpected, tolerance-devoid vasomotor and platelet actions of pentaerythrityl tetranitrate. J Cardiovasc Pharmacol 30:831–836
Finkel MS, Oddis CV, Jacob TD, Watkins SC, Hattler BG, Simmons RL (1992) Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 257:387–389
Finsterer J, Kothari S (2014) Cardiac manifestations of primary mitochondrial disorders. Int J Cardiol 177:754–763
Fowler B (2005) Homocystein – an independent risk factor for cardiovascular and thrombotic diseases. Ther Umsch 62:641–646
Francis SH, Busch JL, Corbin JD, Sibley D (2010) cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacol Rev 62:525–563
Frey N, Katus HA, Olson EN, Hill JA (2004) Hypertrophy of the heart: a new therapeutic target? Circulation 109:1580–1589
Gao L, Cheng C, Sparatore A, Zhang H, Wang C (2015) Hydrogen sulfide inhibits human platelet aggregation in vitro in part by interfering gap junction channels: effects of ACS14, a hydrogen sulfide-releasing aspirin. Heart Lung Circ 24:77–85
Garbers DL, Chrisman TD, Wiegn P, Katafuchi T, Albanesi JP, Bielinski V, Barylko B, Redfield MM, Burnett JC Jr (2006) Membrane guanylyl cyclase receptors: an update. Trends Endocrinol Metab 17:251–258
Ge Y, Moss RL (2012) Nitroxyl, redox switches, cardiac myofilaments, and heart failure: a prequel to novel therapeutics? Circ Res 111:954–956
Geng B, Yang J, Qi Y, Zhao J, Pang Y, Du J, Tang C (2004a) H2S generated by heart in rat and its effects on cardiac function. Biochem Biophys Res Commun 313:362–368
Geng B, Chang L, Pan C, Qi Y, Zhao J, Pang Y, Du J, Tang C (2004b) Endogenous hydrogen sulfide regulation of myocardial injury induced by isoproterenol. Biochem Biophys Res Commun 318:756–763
Ghosh S, Gal J, Marczin N (2010) Carbon monoxide: endogenous mediator, potential diagnostic and therapeutic target. Ann Med 42:1–12
Grabellus F, Schmid C, Levkau B, Breukelmann D, Halloran PF, August C, Takeda N, Takeda A, Wilhelm M, Deng MC, Baba HA (2002) Reduction of hypoxia-inducible heme oxygenase-1 in the myocardium after left ventricular mechanical support. J Pathol 197:230–237
Greiner R, Palinkas Z, Basell K, Becher D, Antelmann H, Nagy P, Dick TP (2013) Polysulfides link H2S to protein thiol oxidation. Antioxid Redox Signal 19:1749–1765
Griscavage JM, Fukuto JM, Komori Y, Ignarro LJ (1994) Nitric oxide inhibits neuronal nitric oxide synthase by interacting with the heme prosthetic group. Role of tetrahydrobiopterin in modulating the inhibitory action of nitric oxide. J Biol Chem 269:21644–21649
Gunasekar PG, Prabhakaran K, Li L, Zhang L, Isom GE, Borowitz JL (2004) Receptor mechanisms mediating cyanide generation in PC12 cells and rat brain. Neurosci Res 49:13–18
Guo JP, Milhoan KA, Tuan RS, Lefer AM (1994) Beneficial effect of SPM-5185, a cysteine-containing nitric oxide donor, in rat carotid artery intimal injury. Circ Res 75:77–84
Hara MR, Snyder SH (2006) Nitric oxide-GAPDH-Siah: a novel cell death cascade. Cell Mol Neurobiol 26:527–538
Hare JM (2003) Nitric oxide and excitation-contraction coupling. J Mol Cell Cardiol 35:719–729
Hare GM, Tsui AK, Crawford JH, Patel RP (2013) Is methemoglobin an inert bystander, biomarker or a mediator of oxidative stress – the example of anemia? Redox Biol 1:65–69
Harteneck C, Plant TD, Schultz G (2000) From worm to man: three subfamilies of TRP channels. Trends Neurosci 23:159–166
Hartsfield CL (2002) Cross talk between carbon monoxide and nitric oxide. Antioxid Redox Signal 4:301–307
Hartsfield CL, Alam J, Cook JL, Choi AM (1997) Regulation of heme oxygenase-1 gene expression in vascular smooth muscle cells by nitric oxide. Am J Phys 273:L980–L988
Hassall CJ, Hoyle CH (1997) Heme oxygenase-2 and nitric oxide synthase in guinea-pig intracardiac neurones. Neuroreport 8:1043–1046
Hayashi S, Omata Y, Sakamoto H, Higashimoto Y, Hara T, Sagara Y, Noguchi M (2004) Characterization of rat heme oxygenase-3 gene. Implication of processed pseudogenes derived from heme oxygenase-2 gene. Gene 336:241–250
Hayashida R, Kondo K, Morita S, Unno K, Shintani S, Shimizu Y, Calvert JW, Shibata R, Murohara T (2017) Diallyl trisulfide augments ischemia-induced angiogenesis via an endothelial nitric oxide synthase-dependent mechanism. Circ J 81:870–878
Heales SJ, Bolanos JP, Stewart VC, Brookes PS, Land JM, Clark JB (1999) Nitric oxide, mitochondria and neurological disease. Biochim Biophys Acta 1410:215–228
Heine CL, Schmidt R, Geckl K, Schrammel A, Gesslbauer B, Schmidt K, Mayer B, Gorren AC (2015) Selective irreversible inhibition of neuronal and inducible nitric-oxide synthase in the combined presence of hydrogen sulfide and nitric oxide. J Biol Chem 290:24932–24944
Heneberg P (2014) Reactive nitrogen species and hydrogen sulfide as regulators of protein tyrosine phosphatase activity. Antioxid Redox Signal 20:2191–2209
Hinkel R, Lange P, Petersen B, Gottlieb E, Ng JK, Finger S, Horstkotte J, Lee S, Thormann M, Knorr M, El-Aouni C, Boekstegers P, Reichart B, Wenzel P, Niemann H, Kupatt C (2015) Heme oxygenase-1 gene therapy provides cardioprotection via control of post-ischemic inflammation: an experimental study in a pre-clinical pig model. J Am Coll Cardiol 66:154–165
Hishiki T, Yamamoto T, Morikawa T, Kubo A, Kajimura M, Suematsu M (2012) Carbon monoxide: impact on remethylation/transsulfuration metabolism and its pathophysiologic implications. J Mol Med (Berl) 90:245–254
Ho JJ, Man HS, Marsden PA (2012) Nitric oxide signaling in hypoxia. J Mol Med (Berl) 90:217–231
Hoffmann LS, Chen HH (2014) cGMP: transition from bench to bedside: a report of the 6th international conference on cGMP generators, effectors and therapeutic implications. Naunyn Schmiedeberg's Arch Pharmacol 387:707–718
Hom J, Sheu SS (2009) Morphological dynamics of mitochondria – a special emphasis on cardiac muscle cells. J Mol Cell Cardiol 46:811–820
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
Hsu MF, Meng TC (2010) Enhancement of insulin responsiveness by nitric oxide-mediated inactivation of protein-tyrosine phosphatases. J Biol Chem 285:7919–7928
Hua W, Chen Q, Gong F, Xie C, Zhou S, Gao L (2013) Cardioprotection of H2S by downregulating iNOS and upregulating HO-1 expression in mice with CVB3-induced myocarditis. Life Sci 93:949–954
Huang P, Chen S, Wang Y, Liu J, Yao Q, Huang Y, Li H, Zhu M, Wang S, Li L, Tang C, Tao Y, Yang G, Du J, Jin H, Down-regulated CBS (2015) H2S pathway is involved in high-salt-induced hypertension in Dahl rats. Nitric Oxide 46:192–203
Humphries ES, Dart C (2015) Neuronal and cardiovascular potassium channels as therapeutic drug targets: promise and pitfalls. J Biomol Screen 20:1055–1073
Iciek M, Kowalczyk-Pachel D, Bilska-Wilkosz A, Kwiecien I, Gorny M, Wlodek L (2015) S-sulfhydration as a cellular redox regulation. Biosci Rep 36. pii: e00304
Iglesias DE, Bombicino SS, Valdez LB, Boveris A (2015) Nitric oxide interacts with mitochondrial complex III producing antimycin-like effects. Free Radic Biol Med 89:602–613
Immenschuh S, Baumgart-Vogt E, Tan M, Iwahara S, Ramadori G, Fahimi HD (2003) Differential cellular and subcellular localization of heme-binding protein 23/peroxiredoxin I and heme oxygenase-1 in rat liver. J Histochem Cytochem 51:1621–1631
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
Ishii I, Akahoshi N, XN Y, Kobayashi Y, Namekata K, Komaki G, Kimura H (2004) Murine cystathionine gamma-lyase: complete cDNA and genomic sequences, promoter activity, tissue distribution and developmental expression. Biochem J 381:113–123
Ishii I, Akahoshi N, Yamada H, Nakano S, Izumi T, Suematsu M (2010) Cystathionine gamma-Lyase-deficient mice require dietary cysteine to protect against acute lethal myopathy and oxidative injury. J Biol Chem 285:26358–26368
Jacobson JR (2009) Statins in endothelial signaling and activation. Antioxid Redox Signal 11:811–821
Jaggar JH, Li A, Parfenova H, Liu J, Umstot ES, Dopico AM, Leffler CW (2005) Heme is a carbon monoxide receptor for large-conductance Ca2+−activated K+ channels. Circ Res 97:805–812
Jain SK, Bull R, Rains JL, Bass PF, Levine SN, Reddy S, McVie R, Bocchini JA (2010) Low levels of hydrogen sulfide in the blood of diabetes patients and streptozotocin-treated rats causes vascular inflammation? Antioxid Redox Signal 12:1333–1337
Jarosz AP, Wei W, Gauld JW, Auld J, Ozcan F, Aslan M, Mutus B (2015) Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is inactivated by S-sulfuration in vitro. Free Radic Biol Med 89:512–521
Jennings ML (2013) Transport of H2S and HS(−) across the human red blood cell membrane: rapid H2S diffusion and AE1-mediated Cl(−)/HS(−) exchange. Am J Physiol Cell Physiol 305:C941–C950
Ji X, Zhou C, Ji K, Aghoghovbia RE, Pan Z, Chittavong V, Ke B, Wang B (2016) Click and release: a chemical strategy toward developing gasotransmitter prodrugs by using an intramolecular Diels-Alder reaction. Angew Chem Int Ed 55:15846–15851
Johnson RA, Lavesa M, DeSeyn K, Scholer MJ, Nasjletti A (1996) Heme oxygenase substrates acutely lower blood pressure in hypertensive rats. Am J Phys 271:H1132–H1138
Jugdutt BI (1994) Use of nitroglycerin for the treatment of acute myocardial infarction. Heart Vessel 9:3–13
Kabil O, Yadav V, Banerjee R (2016) Heme-dependent metabolite switching regulates H2S synthesis in response to endoplasmic reticulum (ER) stress. J Biol Chem 291:16418–16423
Kaczara P, Motterlini R, Rosen GM, Augustynek B, Bednarczyk P, Szewczyk A, Foresti R, Chlopicki S (2015) Carbon monoxide released by CORM-401 uncouples mitochondrial respiration and inhibits glycolysis in endothelial cells: A role for mitoBKCa channels. Biochim Biophys Acta 1847:1297–1309
Kajimura M, Fukuda R, Bateman RM, Yamamoto T, Suematsu M (2010) Interactions of multiple gas-transducing systems: hallmarks and uncertainties of CO, NO, and H2S gas biology. Antioxid Redox Signal 13:157–192
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
Kanai A, Epperly M, Pearce L, Birder L, Zeidel M, Meyers S, Greenberger J, de Groat W, Apodaca G, Peterson J (2004) Differing roles of mitochondrial nitric oxide synthase in cardiomyocytes and urothelial cells. Am J Physiol Heart Circ Physiol 286:H13–H21
Kaniak-Golik A, Skoneczna A (2015) Mitochondria-nucleus network for genome stability. Free Radic Biol Med 82:73–104
Kashfi K, Olson KR (2013) Biology and therapeutic potential of hydrogen sulfide and hydrogen sulfide-releasing chimeras. Biochem Pharmacol 85:689–703
Kawano T, Zoga V, Kimura M, Liang MY, HE W, Gemes G, McCallum JB, Kwok WM, Hogan QH, Sarantopoulos CD (2009) Nitric oxide activates ATP-sensitive potassium channels in mammalian sensory neurons: action by direct S-nitrosylation. Mol Pain 5:1744–8069
Keef KD, Hume JR, Zhong J (2001) Regulation of cardiac and smooth muscle Ca(2+) channels (Ca(V)1.2a,b) by protein kinases. Am J Physiol Cell Physiol 281:C1743–C1756
Kevil CG, Patel RP (2010) S-nitrosothiol biology and therapeutic potential in metabolic disease. Curr Opin Investig Drugs 11:1127–1134
Kida M, Sugiyama T, Yoshimoto T, Ogawa Y (2013) Hydrogen sulfide increases nitric oxide production with calcium-dependent activation of endothelial nitric oxide synthase in endothelial cells. Eur J Pharm Sci 48:211–215
Kim JB (2014) Channelopathies. Korean J Pediatr 57:1–18
Kim HP, Ryter SW, Choi AM (2006) CO as a cellular signaling molecule. Annu Rev Pharmacol Toxicol 46:411–449
Kimura H (2014) The physiological role of hydrogen sulfide and beyond. Nitric Oxide 41:4–10
Kimura H (2016) Hydrogen polysulfide (H2S n ) signaling along with hydrogen sulfide (H2S) and nitric oxide (NO). J Neural Transm (Vienna) 123:1235–1245
Kina-Tanada M, Sakanashi M, Tanimoto A, Kaname T, Matsuzaki T, Noguchi K, Uchida T, Nakasone J, Kozuka C, Ishida M, Kubota H, Taira Y, Totsuka Y, Kina SI, Sunakawa H, Omura J, Satoh K, Shimokawa H, Yanagihara N, Maeda S, Ohya Y, Matsushita M, Masuzaki H, Arasaki A, Tsutsui M (2017) Long-term dietary nitrite and nitrate deficiency causes the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice. Diabetologia 60(6):1138–1151
Knecht KR, Milam S, Wilkinson DA, Fedinec AL, Leffler CW (2010) Time-dependent action of carbon monoxide on the newborn cerebrovascular circulation. Am J Physiol Heart Circ Physiol 299:H70–H75
Kohlhaas M, Nickel AG, Bergem S, Casadei B, Laufs U, Maack C (2017) Endogenous nitric oxide formation in cardiac myocytes does not control respiration during beta-adrenergic stimulation. J Physiol 595:3781–3798
Kokkinos P (2014) Cardiorespiratory fitness, exercise, and blood pressure. Hypertension 64:1160–1164
Kolluru GK, Prasai PK, Kaskas AM, Letchuman V, Pattillo CB (2016) Oxygen tension, H2S, and NO bioavailability: is there an interaction? J Appl Physiol 120:263–270
Kondo K, Bhushan S, King AL, Prabhu SD, Hamid T, Koenig S, Murohara T, Predmore BL, Gojon G Sr, Gojon G Jr, Wang R, Karusula N, Nicholson CK, Calvert JW, Lefer DJ (2013) H(2)S protects against pressure overload-induced heart failure via upregulation of endothelial nitric oxide synthase. Circulation 127:1116–1127
Koppen M, Langer T (2007) Protein degradation within mitochondria: versatile activities of AAA proteases and other peptidases. Crit Rev Biochem Mol Biol 42:221–242
Kovick RB, Tillisch JH, Berens SC, Bramowitz AD, Shine KI (1976) Vasodilator therapy for chronic left ventricular failure. Circulation 53:322–328
Kozai D, Sakaguchi R, Ohwada T, Mori Y (2015) Deciphering subtype-selective modulations in TRPA1 biosensor channels. Curr Neuropharmacol 13:266–278
Kubo S, Doe I, Kurokawa Y, Nishikawa H, Kawabata A (2007) Direct inhibition of endothelial nitric oxide synthase by hydrogen sulfide: contribution to dual modulation of vascular tension. Toxicology 232:138–146
Kuo IY, Howitt L, Sandow SL, McFarlane A, Hansen PB, Hill CE (2014) Role of T-type channels in vasomotor function: team player or chameleon? Pflugers Arch 466:767–779
Kyle BD, Braun AP (2014) The regulation of BK channel activity by pre- and post-translational modifications. Front Physiol 5:316
Laggner H, Hermann M, Esterbauer H, Muellner MK, Exner M, Gmeiner BM, Kapiotis S (2007) The novel gaseous vasorelaxant hydrogen sulfide inhibits angiotensin-converting enzyme activity of endothelial cells. J Hypertens 25:2100–2104
Lancaster JR Jr (2006) Nitroxidative, nitrosative, and nitrative stress: kinetic predictions of reactive nitrogen species chemistry under biological conditions. Chem Res Toxicol 19:1160–1174
Lancel S, Hassoun SM, Favory R, Decoster B, Motterlini R, Neviere R (2009) Carbon monoxide rescues mice from lethal sepsis by supporting mitochondrial energetic metabolism and activating mitochondrial biogenesis. J Pharmacol Exp Ther 329:641–648
Lang JD Jr, Teng X, Chumley P, Crawford JH, Isbell TS, Chacko BK, Liu Y, Jhala N, Crowe DR, Smith AB, Cross RC, Frenette L, Kelley EE, Wilhite DW, Hall CR, Page GP, Fallon MB, Bynon JS, Eckhoff DE, Patel RP (2007) Inhaled NO accelerates restoration of liver function in adults following orthotopic liver transplantation. J Clin Invest 117:2583–2591
Lee SR, Han J (2017) Mitochondrial metabolic inhibition and cardioprotection. Korean Circ J 47:168–170
Lee BS, Heo J, Kim YM, Shim SM, Pae HO, Kim YM, Chung HT (2006) Carbon monoxide mediates heme oxygenase 1 induction via Nrf2 activation in hepatoma cells. Biochem Biophys Res Commun 343:965–972
Lee SW, Cheng Y, Moore PK, Bian JS (2007) Hydrogen sulphide regulates intracellular pH in vascular smooth muscle cells. Biochem Biophys Res Commun 358:1142–1147
Lee S, Kim N, Noh Y, Xu Z, Ko K, Rhee B, Han J (2016) Mitochondrial DNA, mitochondrial dysfunction, and cardiac manifestations. Front Biosci (Landmark Ed) 21:1410–1426
Lefer AM, Lefer DJ (1993) Pharmacology of the endothelium in ischemia-reperfusion and circulatory shock. Annu Rev Pharmacol Toxicol 33:71–90
Lefer AM, Murohara T (1995) Comparative pharmacology of nitric oxide and nitric oxide generators on cardiac contractility in mammalian species. Int J Cardiol 50:239–242
Leitner LM, Wilson RJ, Yan Z, Godecke A (2017) Reactive oxygen species/nitric oxide mediated inter-organ communication in skeletal muscle wasting diseases. Antioxid Redox Signal 26:700–717
Leon-Paravic CG, Figueroa VA, Guzman DJ, Valderrama CF, Vallejos AA, Fiori MC, Altenberg GA, Reuss L, Retamal MA (2014) Carbon monoxide (CO) is a novel inhibitor of connexin hemichannels. J Biol Chem 289:36150–36157
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
Li S, Yang G (2015) Hydrogen sulfide maintains mitochondrial DNA replication via demethylation of TFAM. Antioxid Redox Signal 23:630–642
Li L, Whiteman M, Guan YY, Neo KL, Cheng Y, Lee SW, Zhao Y, Baskar R, Tan CH, Moore PK (2008) Characterization of a novel, water-soluble hydrogen sulfide-releasing molecule (GYY4137): new insights into the biology of hydrogen sulfide. Circulation 117:2351–2360
Li H, Zhang C, Sun W, Li L, Wu B, Bai S, Li H, Zhong X, Wang R, Wu L, Xu C (2015) Exogenous hydrogen sulfide restores cardioprotection of ischemic post-conditioning via inhibition of mPTP opening in the aging cardiomyocytes. Cell Biosci 5:43
Li X-H, Xue W-L, Wang M-J, Zhou Y, Zhang C-C, Sun C, Zhu L, Liang K, Chen Y, Tao B-B, Tan B, Yu B, Zhu Y-C (2017) H2S regulates endothelial nitric oxide synthase protein stability by promoting microRNA-455-3p expression. Sci Rep 7:44807
Liu Y, Li S, Li Z, Zhang J, Han JS, Zhang Y, Yin ZT, Wang HS (2017) A safety evaluation of profound hypothermia-induced suspended animation for delayed resuscitation at 90 or 120 min. Mil Med Res 4:16
Lloyd D (2006) Hydrogen sulfide: clandestine microbial messenger? Trends Microbiol 14:456–462
Lo Faro ML, Fox B, Whatmore JL, Winyard PG, Whiteman M (2014) Hydrogen sulfide and nitric oxide interactions in inflammation. Nitric Oxide 41:38–47
Long Q, Yang K, Yang Q (2015) Regulation of mitochondrial ATP synthase in cardiac pathophysiology. Am J Cardiovasc Dis 5:19–32
Lowicka E, Beltowski J (2007) Hydrogen sulfide (H2S) – the third gas of interest for pharmacologists. Pharmacol Rep 59:4–24
Lundberg JO, Gladwin MT, Weitzberg E (2015) Strategies to increase nitric oxide signalling in cardiovascular disease. Nat Rev Drug Discov 14:623–641
Magierowski M, Magierowska K, Szmyd J, Surmiak M, Sliwowski Z, Kwiecien S, Brzozowski T (2016) Hydrogen sulfide and carbon monoxide protect gastric mucosa compromised by mild stress against alendronate injury. Dig Dis Sci 61:3176–3189
Maines MD (1988) Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J 2:2557–2568
Malekova L, Krizanova O, Ondrias K (2009) H(2)S and HS(−) donor NaHS inhibits intracellular chloride channels. Gen Physiol Biophys 28:190–194
Mani S, Li H, Untereiner A, Wu L, Yang G, Austin RC, Dickhout JG, Lhotak S, Meng QH, Wang R (2013) Decreased endogenous production of hydrogen sulfide accelerates atherosclerosis. Circulation 127:2523–2534
Marshall HE, Stamler JS (1999) Exhaled nitric oxide (NO), NO synthase activity, and regulation of nuclear factor (NF)-kappaB. Am J Respir Cell Mol Biol 21:296–297
Martelli A, Rapposelli S, Calderone V (2006) NO-releasing hybrids of cardiovascular drugs. Curr Med Chem 13:609–625
Martin E, Berka V, Tsai AL, Murad F (2005) Soluble guanylyl cyclase: the nitric oxide receptor. Methods Enzymol 396:478–492
Martins PN, Reuzel-Selke A, Jurisch A, Atrott K, Pascher A, Pratschke J, Buelow R, Neuhaus P, Volk HD, Tullius SG (2005) Induction of carbon monoxide in the donor reduces graft immunogenicity and chronic graft deterioration. Transplant Proc 37:379–381
Martins PN, Reutzel-Selke A, Jurisch A, Denecke C, Attrot K, Pascher A, Kotsch K, Pratschke J, Neuhaus P, Volk HD, Tullius SG (2006) Induction of carbon monoxide in donor animals prior to organ procurement reduces graft immunogenicity and inhibits chronic allograft dysfunction. Transplantation 82:938–944
Matsumoto T, Takahashi M, Nakae I, Kinoshita M (1995) Vasorelaxing effect of S-nitrosocaptopril on dog coronary arteries: no cross-tolerance with nitroglycerin. J Pharmacol Exp Ther 275:1247–1253
McBride HM, Neuspiel M, Wasiak S (2006) Mitochondria: more than just a powerhouse. Curr Biol 16:R551–R560
McCleskey EW, Fox AP, Feldman D, Tsien RW (1986) Different types of calcium channels. J Exp Biol 124:177–190
McCoubrey WK Jr, Huang TJ, Maines MD (1997) Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3. Eur J Biochem 247:725–732
McMahon TJ, Ahearn GS, Moya MP, Gow AJ, Huang YC, Luchsinger BP, Nudelman R, Yan Y, Krichman AD, Bashore TM, Califf RM, Singel DJ, Piantadosi CA, Tapson VF, Stamler JS (2005) A nitric oxide processing defect of red blood cells created by hypoxia: deficiency of S-nitrosohemoglobin in pulmonary hypertension. Proc Natl Acad Sci U S A 102:14801–14806
Megson IL, Leslie SJ (2009) LA-419, a nitric-oxide donor for the treatment of cardiovascular disorders. Curr Opin Investig Drugs 10:276–285
Meigh L, Greenhalgh SA, Rodgers TL, Cann MJ, Roper DI, Dale N (2013) CO(2)directly modulates connexin 26 by formation of carbamate bridges between subunits. eLife 2:e01213
Mikami Y, Shibuya N, Kimura Y, Nagahara N, Yamada M, Kimura H (2011) Hydrogen sulfide protects the retina from light-induced degeneration by the modulation of Ca2+ influx. J Biol Chem 286:39379–39386
Mikami Y, Shibuya N, Ogasawara Y, Kimura H (2013) Hydrogen sulfide is produced by cystathionine gamma-lyase at the steady-state low intracellular Ca(2+) concentrations. Biochem Biophys Res Commun 431:131–135
Milkiewicz M, Ispanovic E, Doyle JL, Haas TL (2006) Regulators of angiogenesis and strategies for their therapeutic manipulation. Int J Biochem Cell Biol 38:333–357
Mistry RK, Brewer AC (2017) Redox regulation of gasotransmission in the vascular system: a focus on angiogenesis. Free Radic Biol Med 108:500–516
Miyamoto R, Koike S, Takano Y, Shibuya N, Kimura Y, Hanaoka K, Urano Y, Ogasawara Y, Kimura H (2017) Polysulfides (H2Sn) produced from the interaction of hydrogen sulfide (H2S) and nitric oxide (NO) activate TRPA1 channels. Sci Rep 7:45995
Modis K, Panopoulos P, Coletta C, Papapetropoulos A, Szabo C (2013) Hydrogen sulfide-mediated stimulation of mitochondrial electron transport involves inhibition of the mitochondrial phosphodiesterase 2A, elevation of cAMP and activation of protein kinase A. Biochem Pharmacol 86:1311–1319
Modis K, Bos EM, Calzia E, van Goor H, Coletta C, Papapetropoulos A, Hellmich MR, Radermacher P, Bouillaud F, Szabo C (2014) Regulation of mitochondrial bioenergetic function by hydrogen sulfide. Part II. Pathophysiological and therapeutic aspects. Br J Pharmacol 171:2123–2146
Modis K, Ju Y, Ahmad A, Untereiner AA, Altaany Z, Wu L, Szabo C, Wang R (2016) S-sulfhydration of ATP synthase by hydrogen sulfide stimulates mitochondrial bioenergetics. Pharmacol Res 113:116–124
Montgomery MR, Rubin RJ (1971) The effect of carbon monoxide inhalation on in vivo drug metabolism in the rat. J Pharmacol Exp Ther 179:465–473
Morrison ML, Blackwood JE, Lockett SL, Iwata A, Winn RK, Roth MB (2008) Surviving blood loss using hydrogen sulfide. J Trauma 65:183–188
Motterlini R, Foresti R (2017) Biological signaling by carbon monoxide and carbon monoxide-releasing molecules (CO-RMs). Am J Physiol Cell Physiol 11
Motterlini R, Otterbein LE (2010) The therapeutic potential of carbon monoxide. Nat Rev Drug Discov 9:728–743
Motterlini R, Sawle P, Hammad J, Bains S, Alberto R, Foresti R, Green CJ (2005) CORM-A1: a new pharmacologically active carbon monoxide-releasing molecule. FASEB J 19:284–286
Munoz-Sanchez J, Chanez-Cardenas ME (2014) A review on hemeoxygenase-2: focus on cellular protection and oxygen response. Oxidative Med Cell Longev 2014:604981
Munzel T, Feil R, Mulsch A, Lohmann SM, Hofmann F, Walter U (2003) Physiology and pathophysiology of vascular signaling controlled by guanosine 3′,5′-cyclic monophosphate-dependent protein kinase [corrected]. Circulation 108:2172–2183
Musameh MD, Fuller BJ, Mann BE, Green CJ, Motterlini R (2006) Positive inotropic effects of carbon monoxide-releasing molecules (CO-RMs) in the isolated perfused rat heart. Br J Pharmacol 149:1104–1112
Mustafa AK, Gadalla MM, Snyder SH (2009a) Signaling by gasotransmitters. Sci Signal 2:re2
Mustafa AK, Gadalla MM, Sen N, Kim S, Mu W, Gazi SK, Barrow RK, Yang G, Wang R, Snyder SH (2009b) H2S signals through protein S-sulfhydration. Sci Signal 2:ra72
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 sulfide as endothelium-derived hyperpolarizing factor sulfhydrates potassium channels. Circ Res 109:1259
Nagpure BV, Bian JS (2016) Interaction of hydrogen sulfide with nitric oxide in the cardiovascular system. Oxidative Med Cell Longev 2016:6904327
Napoli C, Cirino G, Del Soldato P, Sorrentino R, Sica V, Condorelli M, Pinto A, Ignarro LJ (2001) Effects of nitric oxide-releasing aspirin versus aspirin on restenosis in hypercholesterolemic mice. Proc Natl Acad Sci U S A 98:2860–2864
Ndisang JF, Tabien HE, Wang R (2004) Carbon monoxide and hypertension. J Hypertens 22:1057–1074
Nesci S, Ventrella V, Trombetti F, Pirini M, Pagliarani A (2016) Preferential nitrite inhibition of the mitochondrial F1FO-ATPase activities when activated by Ca(2+) in replacement of the natural cofactor Mg(2+). Biochim Biophys Acta 1860:345–353
Nicholson CK, Lambert JP, Molkentin JD, Sadoshima J, Calvert JW (2013) Thioredoxin 1 is essential for sodium sulfide-mediated cardioprotection in the setting of heart failure. Arterioscler Thromb Vasc Biol 33:744–751
Niemeyer BA, Mery L, Zawar C, Suckow A, Monje F, Pardo LA, Stuhmer W, Flockerzi V, Hoth M (2001) Ion channels in health and disease. 83rd Boehringer Ingelheim Fonds International Titisee Conference. EMBO Rep 2:568–573
Nilius B, Carbone E (2014) Amazing T-type calcium channels: updating functional properties in health and disease. Pflugers Arch 466:623–626
Nilius B, Hess P, Lansman JB, Tsien RW (1985) A novel type of cardiac calcium channel in ventricular cells. Nature 316:443–446
Nishida M, Sawa T, Kitajima N, Ono K, Inoue H, Ihara H, Motohashi H, Yamamoto M, Suematsu M, Kurose H, van der Vliet A, Freeman BA, Shibata T, Uchida K, Kumagai Y, Akaike T (2012) Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration. Nat Chem Biol 8:714–724
Nisoli E, Falcone S, Tonello C, Cozzi V, Palomba L, Fiorani M, Pisconti A, Brunelli S, Cardile A, Francolini M, Cantoni O, Carruba MO, Moncada S, Clementi E (2004) Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals. Proc Natl Acad Sci U S A 101:16507–16512
Niture SK, Khatri R, Jaiswal AK (2014) Regulation of Nrf2-an update. Free Radic Biol Med 66:36–44
Nussbaum C, Klinke A, Adam M, Baldus S, Sperandio M (2013) Myeloperoxidase: a leukocyte-derived protagonist of inflammation and cardiovascular disease. Antioxid Redox Signal 18:692–713
Nystul TG, Roth MB (2004) Carbon monoxide-induced suspended animation protects against hypoxic damage in Caenorhabditis elegans. Proc Natl Acad Sci U S A 101:9133–9136
Ohno K, Okuda K, Uehara T (2015) Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide. Biochem Biophys Res Commun 456:245–249
Okubo K, Takahashi T, Sekiguchi F, Kanaoka D, Matsunami M, Ohkubo T, Yamazaki J, Fukushima N, Yoshida S, Kawabata A (2011) Inhibition of T-type calcium channels and hydrogen sulfide-forming enzyme reverses paclitaxel-evoked neuropathic hyperalgesia in rats. Neuroscience 188:148–156
Okubo K, Matsumura M, Kawaishi Y, Aoki Y, Matsunami M, Okawa Y, Sekiguchi F, Kawabata A (2012) Hydrogen sulfide-induced mechanical hyperalgesia and allodynia require activation of both Cav3.2 and TRPA1 channels in mice. Br J Pharmacol 166:1738–1743
Oliver JJ, Hughes VE, Dear JW, Webb DJ (2010) Clinical potential of combined organic nitrate and phosphodiesterase type 5 inhibitor in treatment-resistant hypertension. Hypertension 56:62–67
Otterbein LE, Foresti R, Motterlini R (2016) Heme oxygenase-1 and carbon monoxide in the heart: the balancing act between danger signaling and pro-survival. Circ Res 118:1940–1959
Owens EO (2010) Endogenous carbon monoxide production in disease. Clin Biochem 43:1183–1188
Ozen M, Zhao H, Lewis DB, Wong RJ, Stevenson DK (2015) Heme oxygenase and the immune system in normal and pathological pregnancies. Front Pharmacol 6:84
Pacher P, Beckman JS, Liaudet L (2007) Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87:315–424
Pagliaro P, Gattullo D, Rastaldo R, Losano G (2001) Involvement of nitric oxide in ischemic preconditioning. Ital Heart J 2:660–668
Palmer RM, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526
Papapetropoulos A, Pyriochou A, Altaany Z, Yang G, Marazioti A, Zhou Z, Jeschke MG, Branski LK, Herndon DN, Wang R, Szabó C (2009) Hydrogen sulfide is an endogenous stimulator of angiogenesis. Proc Natl Acad Sci 106:21972–21977
Papapetropoulos A, Hobbs AJ, Topouzis S (2015a) Extending the translational potential of targeting NO/cGMP-regulated pathways in the CVS. Br J Pharmacol 172:1397–1414
Papapetropoulos A, Foresti R, Ferdinandy P (2015b) Pharmacology of the “gasotransmitters” NO, CO and H2S: translational opportunities. Br J Pharmacol 172:1395–1396
Pardee KI, Xu X, Reinking J, Schuetz A, Dong A, Liu S, Zhang R, Tiefenbach J, Lajoie G, Plotnikov AN, Botchkarev A, Krause HM, Edwards A (2009) The structural basis of gas-responsive transcription by the human nuclear hormone receptor REV-ERBbeta. PLoS Biol 7:e43
Park CM, Nagel RL (1984) Sulfhemoglobinemia. Clinical and molecular aspects. N Engl J Med 310:1579–1584
Patel HH, Insel PA (2009) Lipid rafts and caveolae and their role in compartmentation of redox signaling. Antioxid Redox Signal 11:1357–1372
Paul BD, Snyder SH (2012) H2S signalling through protein sulfhydration and beyond. Nat Rev Mol Cell Biol 13:499–507
Paul BT, Manz DH, Torti FM, Torti SV (2017) Mitochondria and iron: current questions. Expert Rev Hematol 10:65–79
Pearce LL, Kanai AJ, Birder LA, Pitt BR, Peterson J (2002) The catabolic fate of nitric oxide: the nitric oxide oxidase and peroxynitrite reductase activities of cytochrome oxidase. J Biol Chem 277:13556–13562
Pechanova O, Simko F (2009) Chronic antioxidant therapy fails to ameliorate hypertension: potential mechanisms behind. J Hypertens Suppl 27:S32–S36
Pechanova O, Varga ZV, Cebova M, Giricz Z, Pacher P, Ferdinandy P (2015) Cardiac NO signalling in the metabolic syndrome. Br J Pharmacol 172:1415–1433
Penney DG (1988) Hemodynamic response to carbon monoxide. Environ Health Perspect 77:121–130
Petersen LC (1977) The effect of inhibitors on the oxygen kinetics of cytochrome c oxidase. Biochim Biophys Acta 460:299–307
Piantadosi CA, Carraway MS, Babiker A, Suliman HB (2008) Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via Nrf2-mediated transcriptional control of nuclear respiratory factor-1. Circ Res 103:1232–1240
Picard M, Wallace DC, Burelle Y (2016) The rise of mitochondria in medicine. Mitochondrion 30:105–116
Polhemus DJ, Lefer DJ (2014) Emergence of hydrogen sulfide as an endogenous gaseous signaling molecule in cardiovascular disease. Circ Res 114:730–737
Polhemus DJ, Li Z, Pattillo CB, Gojon G Sr, Gojon G Jr, Giordano T, Krum H (2015) A novel hydrogen sulfide prodrug, SG1002, promotes hydrogen sulfide and nitric oxide bioavailability in heart failure patients. Cardiovasc Ther 33:216–226
Prabhakar NR, Semenza GL (2012) Gaseous messengers in oxygen sensing. J Mol Med (Berl) 90:265–272
Pun PB, Lu J, Kan EM, Moochhala S (2010) Gases in the mitochondria. Mitochondrion 10:83–93
Puranik M, Weeks CL, Lahaye D, Kabil O, Taoka S, Nielsen SB, Groves JT, Banerjee R, Spiro TG (2006) Dynamics of carbon monoxide binding to cystathionine beta-synthase. J Biol Chem 281:13433–13438
Qian Y, Matson JB (2017) Gasotransmitter delivery via self-assembling peptides: treating diseases with natural signaling gases. Adv Drug Deliv Rev 110–111:137–156
Rautio J, Kumpulainen H, Heimbach T, Oliyai R, Oh D, Jarvinen T, Savolainen J (2008) Prodrugs: design and clinical applications. Nat Rev Drug Discov 7:255–270
Retamal MA (2016) Carbon monoxide modulates connexin function through a lipid peroxidation-dependent process: a hypothesis. Front Physiol 7
Retamal MA, Yin S, Altenberg GA, Reuss L (2009) Modulation of Cx46 hemichannels by nitric oxide. Am J Physiol Cell Physiol 296:C1356–C1363
Riccio DA, Malowitz JR, Cotten CM, Murtha AP, McMahon TJ (2016) S-Nitrosylated fetal hemoglobin in neonatal human blood. Biochem Biophys Res Commun 473:1084–1089
Rochette L, Cottin Y, Zeller M, Vergely C (2013) Carbon monoxide: mechanisms of action and potential clinical implications. Pharmacol Ther 137:133–152
Roden DM, Balser JR, George AL Jr, Anderson ME (2002) Cardiac ion channels. Annu Rev Physiol 64:431–475
Rodgers PA, Vreman HJ, Dennery PA, Stevenson DK (1994) Sources of carbon monoxide (CO) in biological systems and applications of CO detection technologies. Semin Perinatol 18:2–10
Rossello X, Yellon DM (2016) A critical review on the translational journey of cardioprotective therapies. Int J Cardiol 220:176–184
Rossoni G, Berti M, Colonna VD, Bernareggi M, Del Soldato P, Berti F (2000) Myocardial protection by the nitroderivative of aspirin, NCX 4016: in vitro and in vivo experiments in the rabbit. Ital Heart J 1:146–155
Rossoni G, Manfredi B, Tazzari V, Sparatore A, Trivulzio S, Del Soldato P, Berti F (2010) Activity of a new hydrogen sulfide-releasing aspirin (ACS14) on pathological cardiovascular alterations induced by glutathione depletion in rats. Eur J Pharmacol 648:139–145
Rothberg BS (2012) The BK channel: a vital link between cellular calcium and electrical signaling. Protein Cell 3:883–892
Salloum FN, Chau VQ, Hoke NN, Abbate A, Varma A, Ockaili RA, Toldo S, Kukreja RC (2009) Phosphodiesterase-5 inhibitor, tadalafil, protects against myocardial ischemia/reperfusion through protein-kinase g-dependent generation of hydrogen sulfide. Circulation 120:S31–S36
Salloum FN, Das A, Samidurai A, Hoke NN, Chau VQ, Ockaili RA, Stasch JP, Kukreja RC (2012) Cinaciguat, a novel activator of soluble guanylate cyclase, protects against ischemia/reperfusion injury: role of hydrogen sulfide. Am J Physiol Heart Circ Physiol 302:H1347–H1354
Sartiani L, Cerbai E, Lonardo G, DePaoli P, Tattoli M, Cagiano R, Carratu MR, Cuomo V, Mugelli A (2004) Prenatal exposure to carbon monoxide affects postnatal cellular electrophysiological maturation of the rat heart: a potential substrate for arrhythmogenesis in infancy. Circulation 109:419–423
Sayed N, Baskaran P, Ma X, van den Akker F, Beuve A (2007) Desensitization of soluble guanylyl cyclase, the NO receptor, by S-nitrosylation. Proc Natl Acad Sci U S A 104:12312–12317
Schwarz K, Siddiqi N, Singh S, Neil CJ, Dawson DK, Frenneaux MP (2014) The breathing heart – mitochondrial respiratory chain dysfunction in cardiac disease. Int J Cardiol 171:134–143
Scragg JL, Dallas ML, Wilkinson JA, Varadi G, Peers C (2008) Carbon monoxide inhibits L-type Ca2+ channels via redox modulation of key cysteine residues by mitochondrial reactive oxygen species. J Biol Chem 283:24412–24419
Semenza GL, Prabhakar NR (2012) Gas biology: small molecular medicine. J Mol Med 90:213–215
Sen N (2017) Functional and molecular insights of hydrogen sulfide signaling and protein sulfhydration. J Mol Biol 429:543–561
Serafim RA, Primi MC, Trossini GH, Ferreira EI (2012) Nitric oxide: state of the art in drug design. Curr Med Chem 19:386–405
Shao M, Zhuo C, Jiang R, Chen G, Shan J, Ping J, Tian H, Wang L, Lin C, Hu L (2017) Protective effect of hydrogen sulphide against myocardial hypertrophy in mice. Oncotarget 8:22344–22352
Sharma HS, Das DK, Verdouw PD (1999) Enhanced expression and localization of heme oxygenase-1 during recovery phase of porcine stunned myocardium. Mol Cell Biochem 196:133–139
Shen Y, Shen Z, Miao L, Xin X, Lin S, Zhu Y, Guo W, Zhu YZ (2015) miRNA-30 family inhibition protects against cardiac ischemic injury by regulating cystathionine-gamma-lyase expression. Antioxid Redox Signal 22:224–240
Shesely EG, Maeda N, Kim HS, Desai KM, Krege JH, Laubach VE, Sherman PA, Sessa WC, Smithies O (1996) Elevated blood pressures in mice lacking endothelial nitric oxide synthase. Proc Natl Acad Sci U S A 93:13176–13181
Shibahara S, Nakayama M, Kitamuro T, Udono-Fujimori R, Takahashi K (2003) Repression of heme oxygenase-1 expression as a defense strategy in humans. Exp Biol Med (Maywood) 228:472–473
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 4:1366
Shieh CC, Coghlan M, Sullivan JP, Gopalakrishnan M (2000) Potassium channels: molecular defects, diseases, and therapeutic opportunities. Pharmacol Rev 52:557–594
Shimizu I, Minamino T (2016) Physiological and pathological cardiac hypertrophy. J Mol Cell Cardiol 97:245–262
Shimizu S, Takahashi N, Mori Y (2014) TRPs as chemosensors (ROS, RNS, RCS, gasotransmitters). Handb Exp Pharmacol 223:767–794
Shintani T, Iwabuchi T, Soga T, Kato Y, Yamamoto T, Takano N, Hishiki T, Ueno Y, Ikeda S, Sakuragawa T, Ishikawa K, Goda N, Kitagawa Y, Kajimura M, Matsumoto K, Suematsu M (2009) Cystathionine beta-synthase as a carbon monoxide-sensitive regulator of bile excretion. Hepatology 49:141–150
Sikora M, Drapala A, Ufnal M (2014) Exogenous hydrogen sulfide causes different hemodynamic effects in normotensive and hypertensive rats via neurogenic mechanisms. Pharmacol Rep 66:751–758
Sjoberg F, Singer M (2013) The medical use of oxygen: a time for critical reappraisal. J Intern Med 274:505–528
Snijder PM, Frenay AR, de Boer RA, Pasch A, Hillebrands JL, Leuvenink HG, van Goor H (2015) Exogenous administration of thiosulfate, a donor of hydrogen sulfide, attenuates angiotensin II-induced hypertensive heart disease in rats. Br J Pharmacol 172:1494–1504
Soni H, Patel P, Rath AC, Jain M, Mehta AA (2010) Cardioprotective effect with carbon monoxide releasing molecule-2 (CORM-2) in isolated perfused rat heart: role of coronary endothelium and underlying mechanism. Vasc Pharmacol 53:68–76
Srinivasan S, Avadhani NG (2012) Cytochrome c oxidase dysfunction in oxidative stress. Free Radic Biol Med 53:1252–1263
Stram AR, Payne RM (2016) Post-translational modifications in mitochondria: protein signaling in the powerhouse. Cell Mol Life Sci 73:4063–4073
Sugishima M, Sakamoto H, Noguchi M, Fukuyama K (2003) Crystal structures of ferrous and CO-, CN(−)-, and NO-bound forms of rat heme oxygenase-1 (HO-1) in complex with heme: structural implications for discrimination between CO and O2 in HO-1. Biochemistry 42:9898–9905
Suliman HB, Carraway MS, Tatro LG, Piantadosi CA (2007) A new activating role for CO in cardiac mitochondrial biogenesis. J Cell Sci 120:299–308
Sun J, Picht E, Ginsburg KS, Bers DM, Steenbergen C, Murphy E (2006) Hypercontractile female hearts exhibit increased S-nitrosylation of the L-type Ca2+ channel alpha1 subunit and reduced ischemia/reperfusion injury. Circ Res 98:403–411
Sun J, Morgan M, Shen RF, Steenbergen C, Murphy E (2007) Preconditioning results in S-nitrosylation of proteins involved in regulation of mitochondrial energetics and calcium transport. Circ Res 101:1155–1163
Sun YG, Cao YX, Wang WW, Ma SF, Yao T, Zhu YC (2008) Hydrogen sulphide is an inhibitor of L-type calcium channels and mechanical contraction in rat cardiomyocytes. Cardiovasc Res 79:632–641
Szabo C (2010) Gaseotransmitters: new frontiers for translational science. Sci Transl Med 2:59ps54
Szabo C, Coletta C, Chao C, Modis K, Szczesny B, Papapetropoulos A, Hellmich MR (2013) Tumor-derived hydrogen sulfide, produced by cystathionine-beta-synthase, stimulates bioenergetics, cell proliferation, and angiogenesis in colon cancer. Proc Natl Acad Sci U S A 110:12474–12479
Takahashi S, Lin H, Geshi N, Mori Y, Kawarabayashi Y, Takami N, Mori MX, Honda A, Inoue R (2008) Nitric oxide-cGMP-protein kinase G pathway negatively regulates vascular transient receptor potential channel TRPC6. J Physiol 586:4209–4223
Takahashi N, Kozai D, Mori Y (2012) TRP channels: sensors and transducers of gasotransmitter signals. Front Physiol 3:324
Takahashi K, Kakimoto Y, Toda K, Naruse K (2013) Mechanobiology in cardiac physiology and diseases. J Cell Mol Med 17:225–232
Takano N, Yamamoto T, Adachi T, Suematsu M (2010) Assessing a shift of glucose biotransformation by LC-MS/MS-based metabolome analysis in carbon monoxide-exposed cells. Adv Exp Med Biol 662:101–107
Talavera K, Nilius B (2006) Biophysics and structure-function relationship of T-type Ca2+ channels. Cell Calcium 40:97–114
Tang XD, Xu R, Reynolds MF, Garcia ML, Heinemann SH, Hoshi T (2003) Haem can bind to and inhibit mammalian calcium-dependent Slo1 BK channels. Nature 425:531–535
Tang G, Wu L, Liang W, Wang R (2005) Direct stimulation of K(ATP) channels by exogenous and endogenous hydrogen sulfide in vascular smooth muscle cells. Mol Pharmacol 68:1757–1764
Tang G, Wu L, Wang R (2010) Interaction of hydrogen sulfide with ion channels. Clin Exp Pharmacol Physiol 37:753–763
Taniguchi S, Kimura T, Umeki T, Kimura Y, Kimura H, Ishii I, Itoh N, Naito Y, Yamamoto H, Niki I (2012) Protein phosphorylation involved in the gene expression of the hydrogen sulphide producing enzyme cystathionine gamma-lyase in the pancreatic beta-cell. Mol Cell Endocrinol 350:31–38
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
Taoka S, Ohja S, Shan X, Kruger WD, Banerjee R (1998) Evidence for heme-mediated redox regulation of human cystathionine beta-synthase activity. J Biol Chem 273:25179–25184
Teng H, Wu B, Zhao K, Yang G, Wu L, Wang R (2013) Oxygen-sensitive mitochondrial accumulation of cystathionine β-synthase mediated by Lon protease. Proc Natl Acad Sci 110:12679–12684
Teodoro RO, O’Farrell PH (2003) Nitric oxide-induced suspended animation promotes survival during hypoxia. EMBO J 22:580–587
Thomas DD, Heinecke JL, Ridnour LA, Cheng RY, Kesarwala AH, Switzer CH, McVicar DW, Roberts DD, Glynn S, Fukuto JM, Wink DA, Miranda KM (2015) Signaling and stress: the redox landscape in NOS2 biology. Free Radic Biol Med 87:204–225
Thorup C, Jones CL, Gross SS, Moore LC, Goligorsky MS (1999) Carbon monoxide induces vasodilation and nitric oxide release but suppresses endothelial NOS. Am J Physiol Ren Physiol 277:F882–F889
Tomasova L, Dobrowolski L, Jurkowska H, Wrobel M, Huc T, Ondrias K, Ostaszewski R, Ufnal M (2016) Intracolonic hydrogen sulfide lowers blood pressure in rats. Nitric Oxide 60:50–58
Tonks NK (2013) Protein tyrosine phosphatases – from housekeeping enzymes to master regulators of signal transduction. FEBS J 280:346–378
Toohey JI (2011) Sulfur signaling: is the agent sulfide or sulfane? Anal Biochem 413:1–7
Traylor TG, Sharma VS (1992) Why NO? Biochemistry 31:2847–2849
Tsai AL, Martin E, Berka V, Olson JS (2012) How do heme-protein sensors exclude oxygen? Lessons learned from cytochrome c′, Nostoc puntiforme heme nitric oxide/oxygen-binding domain, and soluble guanylyl cyclase. Antioxid Redox Signal 17:1246–1263
Ulker SN, Kocer G, Senturk UK (2017) Carbon monoxide does not contribute to vascular tonus improvement in exercise-trained rats with chronic nitric oxide synthase inhibition. Nitric Oxide 65:60–67
Untereiner AA, Fu M, Modis K, Wang R, Ju Y, Wu L (2016) Stimulatory effect of CSE-generated H2S on hepatic mitochondrial biogenesis and the underlying mechanisms. Nitric Oxide 58:67–76
Valerio A, Nisoli E (2015) Nitric oxide, interorganelle communication, and energy flow: a novel route to slow aging. Front Cell Dev Biol 3:6
Vandiver M, Snyder SH (2012) Hydrogen sulfide: a gasotransmitter of clinical relevance. J Mol Med 90:255–263
Vasquez-Trincado C, Garcia-Carvajal I, Pennanen C, Parra V, Hill JA, Rothermel BA, Lavandero S (2016) Mitochondrial dynamics, mitophagy and cardiovascular disease. J Physiol 594:509–525
Vega RB, Konhilas JP, Kelly DP, Leinwand LA (2017) Molecular mechanisms underlying cardiac adaptation to exercise. Cell Metab 25:1012–1026
Vicente JB, Colaco HG, Mendes MI, Sarti P, Leandro P, Giuffre A (2014) NO* binds human cystathionine beta-synthase quickly and tightly. J Biol Chem 289:8579–8587
Vicente JB, Malagrino F, Arese M, Forte E, Sarti P, Giuffre A (2016) Bioenergetic relevance of hydrogen sulfide and the interplay between gasotransmitters at human cystathionine beta-synthase. Biochim Biophys Acta 1857:1127–1138
Victorino VJ, Mencalha AL, Panis C (2015) Post-translational modifications disclose a dual role for redox stress in cardiovascular pathophysiology. Life Sci 129:42–47
Villanueva C, Kross RD (2012) Antioxidant-induced stress. Int J Mol Sci 13:2091–2109
Volpato MD, Gian P, Searles BAR, Yu PDB, Scherrer-Crosbie MDPDM, Bloch MD, Kenneth D, Ichinose MDF, Zapol MD, Warren M (2008a) Inhaled hydrogen sulfide: a rapidly reversible inhibitor of cardiac and metabolic function in the mouse. Anesthesiology 108:659–668
Volpato GP, Searles R, Yu B, Scherrer-Crosbie M, Bloch KD, Ichinose F, Zapol WM (2008b) Inhaled hydrogen sulfide: a rapidly reversible inhibitor of cardiac and metabolic function in the mouse. Anesthesiology 108:659–668
Walter A, Gutknecht J (1986) Permeability of small nonelectrolytes through lipid bilayer membranes. J Membr Biol 90:207–217
Wang R (2003) The gasotransmitter role of hydrogen sulfide. Antioxid Redox Signal 5:493–501
Wang R (2012) Shared signaling pathways among gasotransmitters. Proc Natl Acad Sci U S A 109:8801–8802
Wang R (2014) Gasotransmitters: growing pains and joys. Trends Biochem Sci 39:227–232
Wang CY, Chau LY (2010) Heme oxygenase-1 in cardiovascular diseases: molecular mechanisms and clinical perspectives. Chang Gung Med J 33:13–24
Wang R, Wu L, Wang Z (1997) The direct effect of carbon monoxide on KCa channels in vascular smooth muscle cells. Pflugers Arch 434:285–291
Wang PG, Xian M, Tang X, Wu X, Wen Z, Cai T, Janczuk AJ (2002) Nitric oxide donors: chemical activities and biological applications. Chem Rev 102:1091–1134
Wang YY, Chang RB, Liman ER (2010) TRPA1 is a Component of the Nociceptive Response to CO(2) (CO(2) Sensing by TRPA1). J Neurosci 30:12958–12963
Wang R, Szabo C, Ichinose F, Ahmed A, Whiteman M, Papapetropoulos A (2015a) The role of H2S bioavailability in endothelial dysfunction. Trends Pharmacol Sci 36:568–578
Wang L, Tang ZP, Zhao W, Cong BH, JQ L, Tang XL, Li XH, Zhu XY, Ni X (2015b) MiR-22/Sp-1 links estrogens with the up-regulation of cystathionine gamma-lyase in myocardium, which contributes to estrogenic cardioprotection against oxidative stress. Endocrinology 156:2124–2137
Watanabe M, Osada J, Aratani Y, Kluckman K, Reddick R, Malinow MR, Maeda N (1995) Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia. Proc Natl Acad Sci 92:1585–1589
Webb AJ, Patel N, Loukogeorgakis S, Okorie M, Aboud Z, Misra S, Rashid R, Miall P, Deanfield J, Benjamin N, MacAllister R, Hobbs AJ, Ahluwalia A (2008) Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. Hypertension 51:784–790
Wedmann R, Ivanovic-Burmazovic I, Filipovic MR (2017) Nitrosopersulfide (SSNO-) decomposes in the presence of sulfide, cyanide or glutathione to give HSNO/SNO-: consequences for the assumed role in cell signalling. Interface Focus 7:20160139
Wegiel B, Nemeth Z, Correa-Costa M, Bulmer AC, Otterbein LE (2014) Heme oxygenase-1: a metabolic nike. Antioxid Redox Signal 20:1709–1722
Wegiel B, Hauser CJ, Otterbein LE (2015) Heme as a danger molecule in pathogen recognition. Free Radic Biol Med 89:651–661
Wesseling S, Fledderus JO, Verhaar MC, Joles JA (2015) Beneficial effects of diminished production of hydrogen sulfide or carbon monoxide on hypertension and renal injury induced by NO withdrawal. Br J Pharmacol 172:1607–1619
Whiteman M, Li L, Kostetski I, Chu SH, Siau JL, Bhatia M, Moore PK (2006) Evidence for the formation of a novel nitrosothiol from the gaseous mediators nitric oxide and hydrogen sulphide. Biochem Biophys Res Commun 343:303–310
Whiteman M, Gooding KM, Whatmore JL, Ball CI, Mawson D, Skinner K, Tooke JE, Shore AC (2010) Adiposity is a major determinant of plasma levels of the novel vasodilator hydrogen sulphide. Diabetologia 53:1722–1726
Whiteman M, Perry A, Zhou Z, Bucci M, Papapetropoulos A, Cirino G, Wood ME (2015) Phosphinodithioate and phosphoramidodithioate hydrogen sulfide donors. Handb Exp Pharmacol 230:337–363
Wilkinson WJ, Kemp PJ (2011) Carbon monoxide: an emerging regulator of ion channels. J Physiol 589:3055–3062
Williams SE, Wootton P, Mason HS, Bould J, Iles DE, Riccardi D, Peers C, Kemp PJ (2004) Hemoxygenase-2 is an oxygen sensor for a calcium-sensitive potassium channel. Science 306:2093–2097
Wong CM, Marcocci L, Das D, Wang X, Luo H, Zungu-Edmondson M, Suzuki YJ (2013) Mechanism of protein decarbonylation. Free Radic Biol Med 65:1126–1133
Woo J, Iyer S, Cornejo MC, Mori N, Gao L, Sipos I, Maines M, Buelow R (1998) Stress protein-induced immunosuppression: inhibition of cellular immune effector functions following overexpression of haem oxygenase (HSP 32). Transpl Immunol 6:84–93
Wu L, Wang R (2005) Carbon monoxide: endogenous production, physiological functions, and pharmacological applications. Pharmacol Rev 57:585–630
Wu L, Cao K, Lu Y, Wang R (2002) Different mechanisms underlying the stimulation of K(Ca) channels by nitric oxide and carbon monoxide. J Clin Invest 110:691–700
Wu ML, Ho YC, Lin CY, Yet SF (2011) Heme oxygenase-1 in inflammation and cardiovascular disease. Am J Cardiovasc Dis 1:150–158
Xu L, JP E, Meissner G, Stamler JS (1998) Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation. Science 279:234–237
Yamamoto T, Takano N, Ishiwata K, Suematsu M (2011) Carbon monoxide stimulates global protein methylation via its inhibitory action on cystathionine beta-synthase. J Clin Biochem Nutr 48:96–100
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 gamma-lyase. Science 322:587–590
Yet SF, Pellacani A, Patterson C, Tan L, Folta SC, Foster L, Lee WS, Hsieh CM, Perrella MA (1997) Induction of heme oxygenase-1 expression in vascular smooth muscle cells. A link to endotoxic shock. J Biol Chem 272:4295–4301
Yet SF, Tian R, Layne MD, Wang ZY, Maemura K, Solovyeva M, Ith B, Melo LG, Zhang L, Ingwall JS, Dzau VJ, Lee ME, Perrella MA (2001) Cardiac-specific expression of heme oxygenase-1 protects against ischemia and reperfusion injury in transgenic mice. Circ Res 89:168–173
Yong QC, Pan TT, LF H, Bian JS (2008) Negative regulation of beta-adrenergic function by hydrogen sulphide in the rat hearts. J Mol Cell Cardiol 44:701–710
Yoshida M, Muneyuki E, Hisabori T (2001) ATP synthase – a marvellous rotary engine of the cell. Nat Rev Mol Cell Biol 2:669–677
Yoshida T, Inoue R, Morii T, Takahashi N, Yamamoto S, Hara Y, Tominaga M, Shimizu S, Sato Y, Mori Y (2006) Nitric oxide activates TRP channels by cysteine S-nitrosylation. Nat Chem Biol 2:596–607
Yu W, Jin H, Tang C, Du J, Zhang Z (2017a) Sulfur-containing gaseous signal molecules, ion channels and cardiovascular diseases. Br J Pharmacol https://doi.org/10.1111/bph.13829 [Epub ahead of print]
Yu L, Li S, Tang X, Li Z, Zhang J, Xue X, Han J, Liu Y, Zhang Y, Zhang Y, Xu Y, Yang Y, Wang H (2017b) Diallyl trisulfide ameliorates myocardial ischemia-reperfusion injury by reducing oxidative stress and endoplasmic reticulum stress-mediated apoptosis in type 1 diabetic rats: role of SIRT1 activation. Apoptosis 22:942–954
Yuan S, Pardue S, Shen X, Alexander JS, Orr AW, Kevil CG (2016) Hydrogen sulfide metabolism regulates endothelial solute barrier function. Redox Biol 9:157–166
Zhang R, Sun Y, Tsai H, Tang C, Jin H, Du J (2012) Hydrogen sulfide inhibits L-type calcium currents depending upon the protein sulfhydryl state in rat cardiomyocytes. PLoS One 7:10
Zhao W, Zhang J, Lu Y, Wang R (2001) The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener. EMBO J 20:6008–6016
Zhao W, Ndisang JF, Wang R (2003) Modulation of endogenous production of H2S in rat tissues. Can J Physiol Pharmacol 81:848–853
Zhao Y, Biggs TD, Xian M (2014) Hydrogen sulfide (H2S) releasing agents: chemistry and biological applications. Chem Commun (Camb) 50:11788–11805
Ziolo MT, Katoh H, Bers DM (2001) Positive and negative effects of nitric oxide on Ca(2+) sparks: influence of beta-adrenergic stimulation. Am J Physiol Heart Circ Physiol 281:H2295–H2303
Zobi F (2013) CO and CO-releasing molecules in medicinal chemistry. Future Med Chem 5:175–188
Zuckerbraun BS, Chin BY, Wegiel B, Billiar TR, Czsimadia E, Rao J, Shimoda L, Ifedigbo E, Kanno S, Otterbein LE (2006) Carbon monoxide reverses established pulmonary hypertension. J Exp Med 203:2109–2119
Acknowledgments
The authors apologize for the vast number of outstanding publications that could not be cited owing to space limitations. This work was supported by the Priority Research Centers Program (2010-0020224) and the Basic Science Research Program (2015R1A2A1A13001900 and 2015R1D1A3A01015596) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology.
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Lee, S.R., Nilius, B., Han, J. (2018). Gaseous Signaling Molecules in Cardiovascular Function: From Mechanisms to Clinical Translation. In: Nilius, B., de Tombe, P., Gudermann, T., Jahn, R., Lill, R., Petersen, O. (eds) Reviews of Physiology, Biochemistry and Pharmacology Vol. 174. Reviews of Physiology, Biochemistry and Pharmacology, vol 174. Springer, Cham. https://doi.org/10.1007/112_2017_7
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