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Gasotransmitters: Physiology and Pathophysiology pp 37–70Cite as

The Role of Carbon Monoxide as a Gasotransmitter in Cardiovascular and Metabolic Regulation

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Abstract

Carbon monoxide (CO) is produced endogenously through the oxidative catabolism of heme by heme oxygenase (HO). First described as a putative neuronal signaling messenger, CO is now also known to be involved in a variety of physiological and pathophysiological processes in the cardiovascular system, including regulating blood pressure, smooth muscle cell proliferation, anti-inflammatory, anti-apoptotic, and anti-coagulation effects. CO contributes substantially to the protective effects of HO enzymes as a mediator of cell and tissue protection. The diverse actions of this diatomic gas mainly depend on the stimulation of soluble guanylate cyclase, opening of BKCa channels as well as activation of mitogen-activated protein kinases, and/or Akt signaling pathways. The cellular and molecular consequences of CO signaling are only partially characterized and appear to differ depending on cell types and circumstances. This chapter provides an overview of the many roles CO plays as a gasotransmitter in the cardiovascular system.

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Abbreviations

AMPK:

AMP-activated protein kinase

BKCa :

Big-conductance calcium-activated potassium channels

C/EBP:

CCAATT-enhancer-binding protein

cGMP:

Cyclic guanosine 3′, 5′-monophosphate

CO:

Carbon monoxide

CoPP:

Cobalt protoporphyrin

CORM:

Carbon monoxide releasing molecule

EDRF:

Endothelium-derived relaxing factor

ENaC:

Epithelial Na+ channel

eNOS:

Endothelial nitric oxide synthase

ER:

Endoplasmic reticulum

ERK:

Extracellular regulated kinases

ETC:

Electron transport chain

GC:

Guanylate cyclase

H2O2 :

Hydrogen peroxide

H2S:

Hydrogen sulfide

HEK293:

Human embryonic kidney

HIF-1α:

Hypoxia-inducible factor-1α

HO:

Heme oxygenase

HUVEC:

Human umbilical vein endothelial cells

ICAM-1:

Intracellular adhesion molecule-1

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

JNK:

Jun-activated kinases

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinases

NF-κB:

Nuclear factor-κB

NO:

Nitric oxide

NOS:

Nitric oxide synthase

Nox:

Nicotinamide adenine dinucleotide phosphate oxidase

O2 − :

Superoxide anion

PAH:

Pulmonary arterial hypertension

PI3K:

Phosphatidylinositol 3-kinase

PPARγ:

Peroxisome proliferator-activated receptor-γ

ROS:

Reactive oxygen species

sGC:

Soluble guanylate cyclase

SHRs:

Spontaneously hypertensive rats

STATs:

Signal transducers and activators of transcription

STZ:

Streptozotocin

TLR:

Toll-like receptor

VEGF:

Vascular endothelial growth factor

VSMCs:

Vascular smooth muscle cells

ZDF:

Zucker diabetic fatty

References

  • Abraham NG, Kappas A (2008) Pharmacological and clinical aspects of heme oxygenase. Pharm Rev 60:79–127. doi:10.1124/pr.107.07104

    PubMed  CAS  Google Scholar 

  • Abraham NG, Jiang H, Balazy M, Goodman AI (2003) Methods for measurements of heme oxygenase (HO) isoforms-mediated synthesis of carbon monoxide and HO-1 and HO-2 proteins. Methods Mol Med 86:399–411. doi:10.1385/1-59259-392-5:399

    PubMed  CAS  Google Scholar 

  • Achouh PE, Simonet S, Fabiani JN, Verbeuren TJ (2008) Carbon monoxide induces relaxation of human internal thoracic and radial arterial grafts. Interact Cardiovasc Thorac Surg 7:959–962. doi:10.1510/icvts.2008.180489

    PubMed  Google Scholar 

  • Akamatsu Y, Haga M, Tyagi S, Yamashita K, Graca-Souza AV, Ollinger R, Czismadia E, May GA, Ifedigbo E, Otterbein LE, Bach FH, Soares MP (2004) Heme oxygenase-1-derived carbon monoxide protects hearts from transplant associated ischemic rerfusion injury. FASEB J 18:771–772. doi:10.1096/fj.03-0921fje

    PubMed  CAS  Google Scholar 

  • Alexander SP, Mathie A, Peters JA (2008) Guide to receptors and channels (GRAC), 3rd edn. Br J Pharmacol 153:Suppl 2:S1-209. doi:10.1038/sj.bjp.0707746

  • Alonso R, Cardellach F, Lopez S, Casademont J, Miro O (2003) Carbon monoxide specifically inhibits cytochrome c oxidase of human mitochondrial respiratory chain. Pharmacol Toxicol 93:142–146. doi:10.1034/j.1600-0773.2003.930306.x

    PubMed  CAS  Google Scholar 

  • Althaus M, Fronius M, Buchäckert Y, Vadász I, Clauss WG, Seeger W, Motterlini R, Morty RE (2009) Carbon monoxide rapidly impairs alveolar fluid clearance by inhibiting epithelial sodium channels. Am J Respir Cell Mol Biol 41:639–650. doi:10.1165/rcmb.2008-0458OC

    PubMed  CAS  Google Scholar 

  • Amersi F, Buelow R, Kato H, Ke B, Coito AJ, Shen XD, Zhao D, Zaky J, Melinek J, Lassman CR, Kolls JK, Alam J, Ritter T, Volk HD, Farmer DG, Ghobrial RM, Busuttil RW, Kupiec-Weglinski JW (1999) Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury. J Clin Invest 104:1631–1639. doi:10.1172/JCI17903

    PubMed  CAS  Google Scholar 

  • André L, Gouzi F, Thireau J, Meyer G, Boissiere J, Delage M, Abdellaoui A, Feillet-Coudray C, Fouret G, Cristol JP, Lacampagne A, Obert P, Reboul C, Fauconnier J, Hayot M, Richard S, Cazorla O (2011) Carbon monoxide exposure enhances arrhythmia after cardiac stress: involvement of oxidative stress. Basic Res Cardiol 106:1235–1246. doi:10.1007/s00395-011-0211-y

    PubMed  Google Scholar 

  • Antuni JD, Kharitonov SA, Hughes D, Hodson ME, Barnes PJ (2000) Increase in exhaled carbon monoxide during exacerbations of cystic fibrosis. Thorax 55:138–142. doi:10.1136/thorax.55.2.138

    PubMed  CAS  Google Scholar 

  • Barinaga M (1993) Carbon monoxide: killer to brain messenger in one step. Science 259:309. doi:10.1126/science.8093563

    PubMed  CAS  Google Scholar 

  • Battle TE, Frank DA (2002) The role of STATs in apoptosis. Curr Mol Med 2:381–392. doi:10.2174/1566524023362456

    PubMed  CAS  Google Scholar 

  • Bergstraesser C, Hoeger S, Song H, Ermantraut L, Hottenrot M, Czymai T, Schmidt M, Goebeler M, Ponelies N, Stich C, Loesel R, Molema G, Seelen M, van Son W, Yard BA, Rafat N (2011) Inhibition of VCAM-1 expression in endothelial cells by CORM-3: The role of the ubiquitin-proteasome system, p38, and mitochondrial respiration. Free Radic Biol Med. doi:10.1016/j.freeradbiomed.2011.11.035

    PubMed  Google Scholar 

  • Biernacki WA, Kharitonov SA, Barnes PJ (2001) Exhaled carbon monoxide in patients with lower respiratory tract infection. Respir Med 95(12):1003–1005. doi:10.1053/rmed.2001.1196

    PubMed  CAS  Google Scholar 

  • Bilban M, Bach F, Otterbein S, Ifedigboe E, deCosta d’Avila J, Esterbauer H, Chin B, Usheva A, Robson S, Wagner O, Otterbein LE (2006) Carbon monoxide orchestrates a protective response through PPARgamma. Immunity 24:601–610. doi:10.1016/j.immuni.2006.03.012

    PubMed  CAS  Google Scholar 

  • Bilban M, Haschemi A, Wegiel B, Chin BY, Wagner O, Otterbein LE (2008) Heme oxygenase and carbon monoxide initiate homeostatic signaling. J Mol Med 86:267–279. doi:10.1007/s00109-007-0276-0

    PubMed  CAS  Google Scholar 

  • Boczkowski J, Poderoso JJ, Motterlini R (2006) CO-metal interaction: vital signaling from a lethal gas. Trends Biochem Sci 31:614–621. doi:10.1016/j.tibs.2006.09.001

    PubMed  CAS  Google Scholar 

  • Boehning D, Moon C, Sharma S, Hurt KJ, Hester LD, Ronnett GV, Shugar D, Snyder SH (2003) Carbon monoxide neurotransmission activated by CK2 phosphorylation of heme oxygenase-2. Neuron 40:129–137. doi:10.1016/S0896-6273(03)00596-8

    PubMed  CAS  Google Scholar 

  • Boehning D, Sedaghat L, Sedlak TW, Snyder SH (2004) Heme oxygenase-2 is activated by calcium-calmodulin. J Biol Chem 279:30927–30930. doi:10.1074/jbc.C400222200

    PubMed  CAS  Google Scholar 

  • Botros FT, Navar LG (2006) Interaction between endogenously produced carbon monoxide and nitric oxide in regulation of renal afferent arterioles. Am J Physiol Heart Circ Physiol 291:H2772–H2778. doi:10.1152/ajpheart.00528.2006

    PubMed  CAS  Google Scholar 

  • Brouard S, Otterbein LE, Anrather J, Tobiasch E, Bach FH, Choi AM, Soares MP (2000) Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis. J Exp Med 192:1015–1026

    PubMed  CAS  Google Scholar 

  • Brown D, Piantadosi A (1990) In vivo binding of carbon monoxide to cytochrome c oxidase in rat brain. J Appl Physiol 68:604–610

    PubMed  CAS  Google Scholar 

  • Brugger J, Schick MA, Brock RW, Baumann A, Muellenbach RM, Roewer N, Wunder C (2010) Carbon monoxide has antioxidative properties in the liver involving p38 MAP kinase pathway in a murine model of systemic inflammation. Microcirculation 17:504–513. doi:10.1111/j.1549-8719.2010.00044.x

    PubMed  CAS  Google Scholar 

  • Brüne B, Ullrich V (1987) Inhibition of platelet aggregation by carbon monoxide is mediated by activation of guanylate cyclase. Mol Pharmacol 32:497–504

    PubMed  Google Scholar 

  • Cantley LC (2002) The phosphoinositide 3-kinase pathway. Science 296:1655–1657. doi:10.1126/science.296.5573.1655

    PubMed  CAS  Google Scholar 

  • Cargnello M, Roux PP (2011) Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev 75:50–83. doi:10.1128/MMBR.00031-10

    PubMed  CAS  Google Scholar 

  • Cepinskas G, Katada K, Bihari A, Potter RF (2008) Carbon monoxide liberated from carbon monoxide-releasing molecule CORM-2 attenuates inflammation in the liver of septic mice. Am J Physiol 294:G184–G191. doi:10.1152/ajpgi.00348.2007

    CAS  Google Scholar 

  • Chang T, Wu L, Wang R (2008) Inhibition of vascular smooth muscle cell proliferation by chronic hemin treatment. Am J Physiol Heart Circ Physiol 295(3):H999–H1007. doi:10.1152/ajpheart.01289.2007

    PubMed  CAS  Google Scholar 

  • Cheng S, Lyass A, Massaro JM, O’Connor GT, Keaney JF Jr, Vasan RS (2010) Exhaled carbon monoxide and risk of metabolic syndrome and cardiovascular disease in the community. Circulation 122:1470–1477. doi:10.1161/CIRCULATIONAHA.110.941013

    PubMed  CAS  Google Scholar 

  • Chin BY, Jiang G, Wegiel B, Wang HJ, Macdonald T, Zhang XC, Gallo D, Cszimadia E, Bach FH, Lee PJ, Otterbein LE (2007) Hypoxia-inducible factor 1alpha stabilization by carbon monoxide results in cytoprotective preconditioning. Proc Natl Acad Sci USA 104:5109–5114. doi:10.1073/pnas.0609611104

    PubMed  CAS  Google Scholar 

  • Choi BM, Pae HO, Kim YM, Chung HT (2003) Nitric oxide-mediated cytoprotection of hepatocytes from glucose deprivation-induced cytotoxicity: involvement of heme oxygenase-1. Hepatology 37:810–823. doi:10.1053/jhep.2003.50114

    PubMed  CAS  Google Scholar 

  • Choi YK, Kim CK, Lee H, Jeoung D, Ha KS, Kwon YG, Kim KW, Kim YM (2010) Carbon monoxide promotes VEGF expression by increasing HIF-1alpha protein level via two distinct mechanisms, translational activation and stabilization of HIF-1alpha protein. J Biol Chem 285:32116–32125. doi:10.1074/jbc.M110.131284

    PubMed  CAS  Google Scholar 

  • 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. doi:10.1161/01.res.0000084381.86567.08

    PubMed  CAS  Google Scholar 

  • Coburn RF, Blakemore WS, Forster RE (1963) Endogenous carbon monoxide production in man. J Clin Invest 42:1172–1178. doi:10.1172/jci104802

    PubMed  CAS  Google Scholar 

  • Dallas ML, Scragg JL, Peers C (2009) Inhibition of L-type Ca(2+) channels by carbon monoxide. Adv Exp Med Biol 648:89–95. doi: 10.1007/978-90-481-2259-2_10

    PubMed  CAS  Google Scholar 

  • Datta PK, Gross EJ, Lianos EA (2002) Interactions between inducible nitric oxide synthase and heme oxygenase-1 in glomerulonephritis. Kidney Int 61:847–850. doi:10.1046/j.1523-1755.2002.00231.x

    PubMed  CAS  Google Scholar 

  • Di Pascoli M, Rodella L, Sacerdoti D, Bolognesi M, Turkseven S, Abraham NG (2006) Chronic CO levels have [corrected] a beneficial effect on vascular relaxation in diabetes. Biochem Biophys Res Commun 340:935–943. doi:10.1016/j.bbrc.2005.12.082

    PubMed  Google Scholar 

  • Dijkstra G, Blokzijl H, Bok L, Homan M, van Goor H, Faber KN, Jansen PL, Moshage H (2004) Opposite effect of oxidative stress on inducible nitric oxide synthase and haem oxygenase-1 expression in intestinal inflammation: anti-inflammatory effect of carbon monoxide. J Pathol 204:296–303. doi:10.1002/path.1656

    PubMed  CAS  Google Scholar 

  • Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM (1999) Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 399:601–605. doi:10.1038/21224

    PubMed  CAS  Google Scholar 

  • Dioum EM, Rutter J, Tuckerman J, Gonzalez G, Gilles-Gonzalez M, McKnight S (2002) NPAS2: a gas-responsive transcription factor. Science 298:2385–2387. doi:10.1126/science.1078456

    PubMed  CAS  Google Scholar 

  • 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. doi:10.1161/HYPERTENSIONAHA.107.096057

    PubMed  CAS  Google Scholar 

  • Douglas CG, Haldane JS, Haldane JB (1912) The laws of combination of haemoglobin with carbon monoxide and oxygen. J Physiol 44:275–304

    PubMed  CAS  Google Scholar 

  • Dubuis E, Potier M, Wang R, Vandier C (2005) Continuous inhalation of carbon monoxide attenuates hypoxic pulmonary hypertension development presumably through activation of BKCa channels. Cardiovasc Res 65:751–761. doi:10.1016/j.cardiores.2004.11.007

    PubMed  CAS  Google Scholar 

  • Dulak J, Józkowicz A, Foresti R, Kasza A, Frick M, Huk I, Green CJ, Pachinger O, Weidinger F, Motterlini R (2002) Heme oxygenase activity modulates vascular endothelial growth factor synthesis in vascular smooth muscle cells. Antioxid Redox Signal 4(2):229–240. doi:10.1089/152308602753666280

    PubMed  CAS  Google Scholar 

  • Durante W (2011) Protective role of heme oxygenase-1 against inflammation in atherosclerosis. Front Biosci 17:2372–2388. doi:10.2741/3860

    Google Scholar 

  • Estabrook RW, Franklin MR, Hildebrandt AG (1970) Factors influencing the inhibitory effect of carbon monoxide on cytochrome P-450-catalyzed mixed function oxidation reactions. Ann N Y Acad Sci 174:218–232

    PubMed  CAS  Google Scholar 

  • Fearon IM, Varadi G, Koch S, Isaacsohn I, Ball SG, Peers C (2000) Splice variants reveal the region involved in oxygen sensing by recombinant human L-type Ca(2+) channels. Circ Res 87:537–539. doi:10.1161/01.RES.87.7.537

    PubMed  CAS  Google Scholar 

  • Ferrándiz ML, Maicas N, Garcia-Arnandis I, Terencio MC, Motterlini R, Devesa I (2008) Treatment with a CO-releasing molecule (CORM-3) reduces joint inflammation and erosion in murine collagen-induced arthritis. Ann Rheum Dis 67:1211–1217. doi:10.1136/ard.2007.082412

    PubMed  Google Scholar 

  • Finkel T (1998) Oxygen radicals and signaling. Curr Opin Cell Biol 10:248–253. doi:10.1016/S0955-0674(98)80147-6

    PubMed  CAS  Google Scholar 

  • Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247. doi:10.1038/35041687

    PubMed  CAS  Google Scholar 

  • Foresti R, Motterlini R (1999) The heme oxygenase pathway and its interaction with nitric oxide in the control of cellular homeostasis. Free Radic Res 31:459–475. doi:10.1080/10715769900301031

    PubMed  CAS  Google Scholar 

  • Foresti R, Hoque M, Bains S, Green CJ, Motterlini R (2003) Haem and nitric oxide: synergism in the modulation of the endothelial haem oxygenase-1 pathway. Biochem J 372:381–390. doi:10.1042/BJ20021516

    PubMed  CAS  Google Scholar 

  • Foresti R, Hammad J, Clark JE, Johnson TR, Mann BE, Friebe A, Green CJ, Motterlini R (2004) Vasoactive properties of CORM-3, a novel water-soluble carbon monoxide-releasing molecule. Br J Pharmacol 142:453–460. doi:10.1038/sj.bjp.0705825

    PubMed  CAS  Google Scholar 

  • Freitas A, Alves-Filho JC, Secco DD, Neto AF, Ferreira SH, Barja-Fidalgo C, Cunha FQ (2006) Heme oxygenase/carbon monoxide-biliverdin pathway down regulates neutrophil rolling, adhesion and migration in acute inflammation. Br J Pharmacol 149:345–354. doi:10.1038/sj.bjp.0706882

    PubMed  CAS  Google Scholar 

  • Frolkis JP, Pothier CE, Blackstone EH, Lauer MS (2003) Frequent ventricular ectopy after exercise as a predictor of death. N Engl J Med 348:781–790. doi:10.1056/NEJMoa022353

    PubMed  Google Scholar 

  • Fujimoto H, Ohno M, Ayabe S, Kobayashi H, Ishizaka N, Kimura H, Yoshida K, Nagai R (2004) Carbon monoxide protects against cardiac ischemia-reperfusion injury in vivo via MAPK and Akt-eNOS pathways. Arterioscler Thromb Vasc Biol 24:1–7. doi:10.1161/01.ATV.0000142364.85911.0e

    Google Scholar 

  • Fujita T, Toda K, Karimova A, Yan SF, Naka Y, Yet SF, Pinsky DJ (2001) Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by derepression of fibrinolysis. Nat Med 7:598–604. doi:10.1038/87929

    PubMed  CAS  Google Scholar 

  • Furchgott RF, Jothianandan D (1991) Endothelium-dependent and -independent vasodilation involving cyclic GMP: relaxation induced by nitric oxide, carbon monoxide and light. Blood Vessels 28:52–61

    PubMed  CAS  Google Scholar 

  • Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376. doi:10.1038/288373a0

    PubMed  CAS  Google Scholar 

  • Gorman D, Drewry A, Huang YL, Sames C (2003) The clinical toxicology of carbon monoxide. Toxicology 187:25–38. doi:10.1016/S0300-483X(03)00005-2

    PubMed  CAS  Google Scholar 

  • Guo Y, Stein AB, Wu WJ, Tan W, Zhu X, Li QH, Dawn B, Motterlini R, Bolli R (2004) Administration of a CO-releasing molecule at the time of reperfusion reduced infarct size in vivo. Am J Physiol Heart Circ Physiol 286:H1649–H1653. doi:10.1152/ajpheart.00971.2003

    PubMed  CAS  Google Scholar 

  • Haldane JB (1927) Carbon monoxide as a tissue poison. Biochem J 21:1068–1075

    PubMed  CAS  Google Scholar 

  • Haschemi A, Chin BY, Jeitler M, Esterbauer H, Wagner O, Bilban M, Otterbein LE (2011) Carbon monoxide induced PPARγ SUMOylation and UCP2 block inflammatory gene expression in macrophages. PLoS ONE 6:e26376. doi:10.1371/journal.pone.0026376

    PubMed  CAS  Google Scholar 

  • 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. doi:10.1016.j.gene.2004.04.002

    PubMed  CAS  Google Scholar 

  • Henningsson R, Alm P, Ekström P, Lundquist I (1999) Heme oxygenase and carbon monoxide: regulatory roles in islet hormone release: a biochemical, immunohistochemical, and confocal microscopic study. Diabetes 48:66–76. doi:10.2337/diabetes.48.1.66

    PubMed  CAS  Google Scholar 

  • Hoetzel A, Dolinay T, Vallbracht S, Zhang Y, Kim HP, Ifedigbo E, Alber S, Kaynar AM, Schmidt R, Ryter SW, Choi AM (2008) Carbon monoxide protects against ventilator-induced lung injury via PPAR-gamma and inhibition of Egr-1. Am J Respir Crit Care Med 177:1223–1232. doi:10.1164/rccm.200708-1265OC

    PubMed  CAS  Google Scholar 

  • Horvath I, Donnelly LE, Kiss A, Paredi P, Kharitonov SA, Barnes PJ (1998a) Elevated levels of exhaled carbon monoxide are associated with an increased expression of heme oxygenase-1 in airway macrophages in asthma: a new marker of chronic inflammation. Thorax 53:668–672

    PubMed  CAS  Google Scholar 

  • Horvath I, Loukides S, Wodehouse T, Kharitonov SA, Cole PJ, Barnes PJ (1998b) Increased levels of exhaled carbon monoxide in bronchiectasis: a new marker of oxidative stress. Thorax 53(867–870):867

    PubMed  CAS  Google Scholar 

  • Hou S, Xu R, Heinemann SH, Hoshi T (2008) The RCK1 high-affinity Ca2+ sensor confers carbon monoxide sensitivity to Slo1 BK channels. Proc Natl Acad Sci USA 105:4039–4043. doi:10.1073/pnas.0800304105

    PubMed  CAS  Google Scholar 

  • Huang LE, Willmore WG, Gu J, Goldberg MA, Bunn HF (1999) Inhibition of hypoxia-inducible factor 1 activation by carbon monoxide and nitric oxide. Implications for oxygen sensing and signaling. J Biol Chem 274:9038–9044. doi:10.1074/jbc.274.13.9038

    PubMed  CAS  Google Scholar 

  • Johnson FK, Durante W, Peyton KJ, Johnson RA (2003) Heme oxygenase inhibitor restores arteriolar nitric oxide function in Dahl rats. Hypertension 41:149–155. doi:10.1161/01.HYP.0000046923.52222.58

    PubMed  CAS  Google Scholar 

  • Johnson FK, Johnson RA, Durante W, Jackson KE, Stevenson BK, Peyton KJ (2006) Metabolic syndrome increases endogenous carbon monoxide production to promote hypertension and endothelial dysfunction in obese Zucker rats. J Physiol Regul Integr Comp Physiol 290:R601–R608. doi:10.1152/ajpregu.00308.2005

    CAS  Google Scholar 

  • Jones RH, Ellicott MF, Cadigan JB, Gaensler EA (1958) The relationship between alveolar and blood carbon monoxide concentrations during breathholding; simple estimation of COHb saturation. J Lab Clin Med 51:553–564

    PubMed  CAS  Google Scholar 

  • Józkowicz A, Huk I, Nigisch A, Weigel G, Dietrich W, Motterlini R, Dulak J (2004) Heme oxygenase and angiogenic activity of endothelial cells: stimulation by carbon monoxide and inhibition by Tin protoporphyrin-IX. Antioxid Redox Signal 5(2):155–162. doi:10.1089/152308603764816514

    Google Scholar 

  • Kaide J, Zhang F, Wei Y, Wang W, Gopal VR, Falck JR, Laniado-Schwartzman M, Nasjletti A (2004) Vascular CO counterbalances the sensitizing influence of 20-HETE on agonist-induced vasoconstriction. Hypertension 44:210–216. doi:10.1161/01.HYP.0000135658.57547.bb

    PubMed  CAS  Google Scholar 

  • Kharitonov SA, Barnes PJ (2001) Exhaled markers of pulmonary disease. Am J Respir Crit Care Med 163:1693–1722

    PubMed  CAS  Google Scholar 

  • Kim KM, Pae HO, Zheng M, Park R, Kim YM, Chung HT (2007) Carbon monoxide induces heme oxygenase-1 via activation of protein kinase R-like endoplasmic reticulum kinase and inhibits endothelial cell apoptosis triggered by endoplasmic reticulum stress. Circ Res 101:919–927. doi:10.1161/circresaha.107.154781

    PubMed  CAS  Google Scholar 

  • Kim HS, Loughran PA, Rao J, Billiar TR, Zuckerbraun BS (2008a) Carbon monoxide activates NF-kappaB via ROS generation and Akt pathways to protect against cell death of hepatocytes. Am J Physiol Gastrointest Liver Physiol 295:G146–G152. doi:10.1152/ajpgi.00105.2007

    PubMed  CAS  Google Scholar 

  • Kim HS, Loughran PA, Billiar TR (2008b) Carbon monoxide decreases the level of iNOS protein and active dimer in IL-1beta-stimulated hepatocytes. Nitric Oxide 18:256–265. doi:10.1016/j.niox.2008.02.002

    PubMed  CAS  Google Scholar 

  • Kobayashi A, Ishikawa K, Matsumoto H, Kimura S, Kamiyama Y, Maruyama Y (2007) Synergetic antioxidant and vasodilatory action of carbon monoxide in angiotension II-induced cardiac hypertrophy. Hypertension 50:1040–1048. doi:10.1161/HYPERTENSIONAHA.107.097006

    PubMed  CAS  Google Scholar 

  • Kreck TC, Shade ED, Lamm WJ, McKinney SE, Hlastala MP (2001) Isocapnic hyperventilation increases carbon monoxide elimination and oxygen delivery. Am J Respir Crit Care Med 163(2):458–462

    PubMed  CAS  Google Scholar 

  • Kruger AL, Peterson SJ, Schwartzman ML, Fusco H, McClung JA, Weiss M, Shenouda S, Goodman AI, Goligorsky MS, Kappas A, Abraham NG (2006) Up-regulation of heme oxygenase provides vascular protection in an animal model of diabetes through its antioxidant and antiapoptotic effects. J Pharmacol Exp Ther 319:1144–1152. doi:10.1124/jpet.106.107482

    PubMed  CAS  Google Scholar 

  • Kubo S, Kurokawa Y, Doe I, Masuko T, Sekiguchi F, Kawabata A (2007) Hydrogen sulfide inhibits activity of three isoforms of recombinant nitric oxide synthase. Toxicology 241:92–97. doi:10.1016/j.tox.2007.08.087

    PubMed  CAS  Google Scholar 

  • Kunisada K, Negoro S, Tone E, Funamoto M, Osugi T, Yamada S, Okabe M, Kishimoto T, Yamauchi-Takihara K (2000) Signal transducer and activator of transcription 3 in the heart transduces not only a hypertrophic signal but a protective signal against doxorubicin-induced cardiomyopathy. Proc Natl Acad Sci USA 97:315–319. doi:10.1073/pnas.97.1.315

    PubMed  CAS  Google Scholar 

  • Kurth-Kraczek EJ, Hirshman MF, Goodyear LJ, Winder WW (1999) 5’ AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. Diabetes 48:1667–1671. doi:10.2337/diabetes.48.8.1667

    PubMed  CAS  Google Scholar 

  • Lakkisto P, Kytö V, Forsten H, Siren JM, Segersvärd H, Voipio-Pulkki LM, Laine M, Pulkki K, Tikkanen I (2010) Heme oxygenase-1 and carbon monoxide promote neovascularization after myocardial infarction by modulating the expression of HIF-1alpha, SDF-1alpha and VEGF-B. Eur J Pharmacol 635:156–164. doi:10.1016/j.ejphar.2010.02.050

    PubMed  CAS  Google Scholar 

  • Lamon BD, Zhang FF, Puri N, Brodsky SV, Goligorsky MS, Nasjletti A (2009) Dual pathways of carbon monoxide-mediated vasoregulation: modulation by redox mechanisms. Circ Res 105:775–783. doi:10.1161/CIRCRESAHA.109.197434

    PubMed  CAS  Google Scholar 

  • Lavitrano M, Smolesnki RT, Musumeci A, Maccherini M, Slominska E, Di Florio E, Bracco A, Mancini A, Stassi G, Patti M, Giovannoni R, Froio A, Simeone F, Forni M, Bacci ML, D’Alise G, Cozzi E, Otterbein LE, Yacoub MH, Bach FH, Calise F (2004) Carbon monoxide improves cardiac energetics and safeguards the heart during reperfusion after cardiopulmonary bypass in pigs. FASEB J 1(8):1093–1095

    Google Scholar 

  • Lee YC, Martin E, Murad F (2000) Human recombinant soluble guanylyl cyclase: expression, purification, and regulation. Proc Natl Acad Sci USA 97:10763–10768. doi:10.1073/pnas.190333697

    PubMed  CAS  Google Scholar 

  • Lee SR, Yang KS, Kwon J, Lee C, Jeong W, Rhee SG (2002) Reversible inactivation of the tumor suppressor PTEN by H2O2. J Biol Chem 277:20336–203342. doi:10.1074/jbc.M111899200

    PubMed  CAS  Google Scholar 

  • Leffler CW, Parfenova H, Jaggar JH, Wang R (2006) Carbon monoxide and hydrogen sulfide: gaseous messengers in cerebrovascular circulation. J Appl Physiol 100(3):1065–1076. doi:10.1152/japplphysiol.00793.2005

    PubMed  CAS  Google Scholar 

  • Leslie NR, Bennett D, Lindsay YE, Stewart H, Gray A, Downes CP (2003) Redox regulation of PI 3-kinase signalling via inactivation of PTEN. EMBO J 22:5501–5510. doi:10.1093/emboj/cdg513

    PubMed  CAS  Google Scholar 

  • Li Volti G, Sacerdoti D, Sangras B, Vanella A, Mezentsev A, Scapagnini G, Falck JR, Abraham NG (2005) Carbon monoxide signaling in promoting angiogenesis in human microvessel endothelial cells. Antioxid Redox Signal 7(5–6):704–710. doi:10.1089/ars.2005.7.704

    PubMed  CAS  Google Scholar 

  • Li A, Xi Q, Umstot ES, Bellner L, Schwartzman ML, Jaggar JH, Leffler CW (2008) Astrocyte-derived CO is a diffusible messenger that mediates glutamate-induced cerebral arteriolar dilation by activating smooth muscle Cell KCa channels. Circ Res 102:234–241. doi:10.1161/CIRCRESAHA.107.164145

    PubMed  CAS  Google Scholar 

  • Li L, Hsu A, Moore PK (2009) Actions and interactions of nitric oxide, carbon monoxide and hydrogen sulphide in the cardiovascular system and in inflammation–a tale of three gases! Pharmacol Ther 123(3):386–400. doi:10.1016/j.pharmthera.2009.05.005

    PubMed  CAS  Google Scholar 

  • Lim I, Gibbons SJ, Lyford GL, Miller SM, Strege PR, Sarr MG, Chatterjee S, Szurszewski JH, Shah VH, Farrugia G (2005) Carbon monoxide activates human intestinal smooth muscle L-type Ca2+ channels through a nitric oxide-dependent mechanism. Am J Physiol Gastrointest Liver Physiol 288:G7–G14. doi:10.1152/ajpgi.00205.2004

    PubMed  CAS  Google Scholar 

  • Lin HY, Juan SH, Shen SC, Hsu FL, Chen YC (2003) Inhibition of lipopolysaccharide-induced nitric oxide production by flavonoids in RAW264.7 macrophages involves heme oxygenase-1. Biochem Pharmacol 66:1821–1832. doi:10.1016/S0006-2952(03)00422-2

    PubMed  CAS  Google Scholar 

  • Lin HH, Lai SC, Chau LY (2011) Heme oxygenase-1/carbon monoxide induces vascular endothelial growth factor expression via p38 kinase-dependent activation of Sp1. J Biol Chem 286(5):3829–3838. doi:10.1074/jbc.M110.168831

    PubMed  CAS  Google Scholar 

  • Liu DN, Fang Y, Wu LR, Liu XD, Li P, He ZY (2010) Effect of the haeme oxygenase-1/endogenous carbon monoxide system on atherosclerotic plaque formation in rabbits. Cardiovasc J Afr 21(5):257–262. doi:CVJ-21.001

    PubMed  Google Scholar 

  • Lo Iacono L, Boczkowski J, Zini R, Salouage I, Berdeaux A, Motterlini R, Morin D (2011) A carbon monoxide-releasing molecule (CORM-3) uncouples mitochondrial respiration and modulates the production of reactive oxygen species. Free Radic Biol Med 50:1556–1564. doi:10.1016/j.freeradbiomed.2011.02.033

    PubMed  CAS  Google Scholar 

  • Lutter R, van Schaik ML, van Zwieten R, Wever R, Roos D, Hamers MN (1985) Purification and partial characterization of the b-type cytochrome from human polymorphonuclear leukocytes. J Biol Chem 260:2237–2244

    PubMed  CAS  Google Scholar 

  • Maines MD (1997) The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 37:517–554. doi:10.1146/annurev.pharmtox.37.1.517

    PubMed  CAS  Google Scholar 

  • Marks GS, Brien JF, Nakatsu K, McLaughlin BE (1991) Does carbon monoxide have a physiological function? Trends Pharmacol Sci 12:185–188. doi:10.1016/0165-6147(91)90544-3

    PubMed  CAS  Google Scholar 

  • Mayr FB, Spiel A, Leitner J, Marsik C, Germann P, Ullrich R, Wanger O, Jilma B (2005) Effects of carbon monoxide inhalation during experimental endotoxemia in humans. Am J Respir Crit Care Med 171:354–360. doi:10.1164/rccm.200404-446OC

    PubMed  Google Scholar 

  • 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. doi:10.1111/j.1432-1033.1997.00725.x

    PubMed  CAS  Google Scholar 

  • McDonagh AF (1990) Is bilirubin good for you? Clin Perinatol 17:359–369

    PubMed  CAS  Google Scholar 

  • Miller TW, Isenberg JS, Roberts DD (2009) Molecular regulation of tumor angiogenesis and perfusion via redox signaling. Chem Rev 109(7):3099–3124. doi:10.1021/cr8005125

    PubMed  CAS  Google Scholar 

  • Mishra S, Fujita T, Lama VN, Nam D, Liao H, Okada M, Minamoto K, Yoshikawa Y, Harada H, Pinsky DJ (2006) Carbon monoxide rescues ischemic lungs by interrupting MAPK-driven expression of early growth response 1 gene and its downstream target genes. Proc Natl Acad Sci USA 103:5191–5196. doi:10.1073/pnas.0600241103

    PubMed  CAS  Google Scholar 

  • Monma M, Yamaya M, Sekizawa K, Ikeda K, Suzuki N, Kikuchi T, Takasaka T, Sasaki H (1999) Increased carbon monoxide in exhaled air of patients with seasonal allergic rhinitis. Clin Exp Allergy 29:1537–1541. doi:10.1046/j.1365-2222.1999.00684.x

    PubMed  CAS  Google Scholar 

  • Morita T, Kourembanas S (1995) Endothelial cell expression of vasoconstrictors and growth factors is regulated by smooth muscle cell-derived carbon monoxide. J Clin Invest 96:2676–2682. doi:10.1172/jci118334

    PubMed  CAS  Google Scholar 

  • Morita T, Mitsialis SA, Koike H, Liu Y, Kourembanas S (1997) Carbon monoxide controls the proliferation of hypoxic vascular smooth muscle cells. J Biol Chem 272:32804–32809. doi:10.1074/jbc.272.52.32804

    PubMed  CAS  Google Scholar 

  • Mortia T, Kourembanas S (1995) Endothelial cell expression of vasoconstrictors and growth factors is regulated by smooth muscle cell-derived carbon monoxide. J Clin Invest 96:2676–2682. doi:10.1172/jci118334

    Google Scholar 

  • Mosén H, Salehi A, Alm P, Henningsson R, Jimenez-Feltström J, Ostenson CG, Efendic S, Lundquist I (2004) Defective glucose-stimulated insulin release in the diabetic Goto-Kakizaki (GK) rat coincides with reduced activity of the islet carbon monoxide signaling pathway. Endocrinology 146:1553–1558. doi:10.1210/en.2004-0851

    PubMed  Google Scholar 

  • Mosén H, Salehi A, Henningsson R, Lundquist I (2006) Nitric oxide inhibits, and carbon monoxide activates, islet acid alpha-glucoside hydrolase activities in parallel with glucose-stimulated insulin secretion. J Endocrinol 190:681–693. doi:10.1677/joe.1.06890

    PubMed  Google Scholar 

  • Motterlini R, Otterbein LE (2010) The therapeutic potential of carbon monoxide. Nat Rev Drug Discov 9(9):728–743. doi:10.1038/nrd3228

    PubMed  CAS  Google Scholar 

  • Motterlini R, Foresti R, Intaglietta M, Winslow RM (1997) NO-mediated activation of heme oxygenase: endogenous cytoprotection against oxidative stress to endothelium. Am J Physiol 270:H107–H114

    Google Scholar 

  • Motterlini R, Clark JE, Foresti R, Sarathchandra P, Mann BE, Green CJ (2002a) Carbon monoxide-releasing molecules: characterization of biochemical and vascular activities. Circ Res 90:E17–E24. doi:10.1161/hh0202.104530

    PubMed  CAS  Google Scholar 

  • Motterlini R, Green CJ, Foresti R (2002b) Regulation of heme oxygenase-1 by redox signals involving nitric oxid. Antioxid Redox Signal 4:615–624. doi:10.1089/15230860260220111

    PubMed  CAS  Google Scholar 

  • Mustafa AK, Gadalla MM, Snyder SH (2009) Signaling by gasotransmitters. Sci Signal 2:re2. doi:10.1126/scisignal.268re2

  • Nakahira K, Kim HP, Geng XH, Nakao A, Wang X, Murase N, Drain PF, Wang X, Sasidhar M, Nabel EG, Takahashi T, Lukacs NW, Ryter SW, Morita K, Choi AM (2006) Carbon monoxide differentially inhibits TLR signaling pathways by regulating ROS-induced trafficking of TLRs to lipid rafts. J Exp Med 203:2377–2389. doi:10.1084/jem.20060845

    PubMed  CAS  Google Scholar 

  • Nakao A, Faleo G, Nalesnik MA, Seda-Neto J, Kohmoto J, Murase N (2009) Low-dose carbon monoxide inhibits progressive chronic allograft nephropathy and restores renal allograft function. Am J Physiol Renal Physiol 297:F19–F26. doi:10.1152/ajprenal.90728.2008

    PubMed  CAS  Google Scholar 

  • Nakao A, Huang CS, Stolz DB, Wang Y, Franks JM, Tochigi N, Billiar TR, Toyoda Y, Tzeng E, McCurry KR (2011) Ex vivo carbon monoxide delivery inhibits intimal hyperplasia in arterialized vein grafts. Cardiovasc Res 89:457–463. doi:10.1093/cvr/cvq298

    PubMed  CAS  Google Scholar 

  • Naughton P, Hoque M, Green CJ, Foresti R, Motterlini R (2002) Interaction of heme with nitroxyl or nitric oxide amplifies heme oxygenase-1 induction: involvement of the transcription factor Nrf2. Cell Mol Biol (Noisy-le-grand) 48:885–894

    CAS  Google Scholar 

  • Ndisang JF, Zhao W, Wang R (2002) Selective regulation of blood pressure by heme oxygenase-1 in hypertension. Hypertension 40(3):315–321. doi:10.1161/01.HYP.0000028488.71068.16

    PubMed  CAS  Google Scholar 

  • Ndisang JF, Wu L, Zhao W, Wang R (2003) Induction of heme oxygenase-1 and stimulation of cGMP production by hemin in aortic tissues from hypertensive rats. Blood 101(10):3893–3900. doi:10.1182/blood-2002-08-2608

    PubMed  CAS  Google Scholar 

  • Ndisang JF, Tabien HE, Wang R (2004) Carbon monoxide and hypertension. J Hypertens 22:1057–1074

    PubMed  CAS  Google Scholar 

  • Negoro S, Kunisada K, Fujio Y, Funamoto M, Darville MI, Eizirik DL, Osugi T, Izumi M, Oshima Y, Nakaoka Y, Hirota H, Kishimoto T, Yamauchi-Takihara K (2001) Activation of signal transducer and activator of transcription 3 protects cardiomyocytes from hypoxia/reoxygenation-induced oxidative stress through the upregulation of manganese superoxide dismutase. Circulation 104:979–981. doi:10.1161/hc3401.095947

    PubMed  CAS  Google Scholar 

  • Nicolai A, Li M, Kim DH, Peterson SJ, Vanella L, Positano V, Gastaldelli A, Rezzani R, Rodella LF, Drummond G, Kusmic C, L’Abbatet A, Kappas A, Abraham NG (2009) Heme oxygenase-1 induction remodels adipose tissue and improves insulin sensitivity in obesity-induced diabetic rats. Hypertension 53:508–515. doi:10.1161/HYPERTENSIONAHA.108.124701

    PubMed  CAS  Google Scholar 

  • Nikberg II, Murashko VA, Leonenko IN (1972) Carbon monoxide concentration in the air exhaled by the healthy and the ill. Vrach Delo 12:112–114

    PubMed  CAS  Google Scholar 

  • Nisimoto Y, Otsuka-Murakami H, Iwata S (1994) NADPH-cytochrome c reductase from human neutrophil membranes: purification, characterization and localization. Biochem J 297(Pt 3):585–593

    PubMed  CAS  Google Scholar 

  • Nizamutdinova IT, Kim YM, Kim HJ, Seo HG, Lee JH, Chang KC (2009) Carbon monoxide (from CORM-2) inhibits high glucose-induced ICAM-1 expression via AMP-activated protein kinase and PPAR-gamma activations in endothelial cells. Atherosclerosis 207:405–411. doi:10.1016/j.atherosclerosis.2009.05.008

    PubMed  CAS  Google Scholar 

  • Oh GS, Pae HO, Lee BS, Kim BN, Kim JM, Kim HR, Jeon SB, Jeon WK, Chae HJ, Chung HT (2006) Hydrogen sulfide inhibits nitric oxide production and nuclear factor-kappaB via heme oxygenase-1 expression in RAW264.7 macrophages stimulated with lipopolysaccharide. Free Radic Biol Med 41:106–119. doi:10.1016/j.freeradbiomed.2006.03.021

    PubMed  CAS  Google Scholar 

  • Okinaga S, Shibahara S (1993) Identification of a nuclear protein that constitutively recognizes the sequence containing a heat-shock element. Its binding properties and possible function modulating heat-shock induction of the rat heme oxygenase gene. Eur J Biochem 212(1):167–175. doi:10.1111/j.1432-1033.1993.tb17647.x

    PubMed  CAS  Google Scholar 

  • Otterbein LE, Mantell LL, Choi AM (1999) Carbon monoxide provides protection against hyperoxic lung injury. Am J Physiol 276:L688–L694

    PubMed  CAS  Google Scholar 

  • Otterbein LE, Bach FH, Alam J, Soares M, Tao LuH, Wysk M, Davis RJ, Flavell RA, Choi AM (2000) Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 6:422–428. doi:10.1038/74680

    PubMed  CAS  Google Scholar 

  • Otterbein LE, Otterbein SL, Ifedigbo E, Liu F, Morse DE, Fearns C, Ulevitch RJ, Knickelbein R, Flavell RA, Choi AM (2003a) MKK3 mitogen-activated protein kinase pathway mediates carbon monoxide-induced protection against oxidant-induced lung injury. Am J Pathol 163:2555–2563. doi:10.1016/S0002-9440(10)63610-3

    PubMed  CAS  Google Scholar 

  • Otterbein LE, Zuckerbraun BS, Haga M, Liu F, Song R, Usheva A, Stachulak C, Bodyak N, Smith RN, Csizmadia E, Tyagi S, Akamatsu Y, Flavell RJ, Billiar TR, Tzeng E, Bach FH, Choi AM, Soares MP (2003b) Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury. Nat Med 9:183–190. doi:10.1038/nm817

    PubMed  CAS  Google Scholar 

  • Otterbein LE, May A, Chin BY (2005) Carbon monoxide increases macrophage bacterial clearance through Toll-like receptor (TLR)4 expression. Cell Mol Biol (Noisy-le-grand) 51(5):433–440

    CAS  Google Scholar 

  • Pae HO, Oh GS, Choi BM, Chae SC, Kim YM, Chung KR, Chung HT (2004) Carbon monoxide produced by heme oxygenase-1 suppresses T cell proliferation via inhibition of IL-2 production. J Immunol 172:4744–4751

    PubMed  CAS  Google Scholar 

  • Paredi P, Biernacki W, Invernizzi G, Kharitonov SA, Barnes PJ (1999) Exhaled carbon monoxide levels elevated in diabetes and correlated with glucose concentration in blood: a new test for monitoring the disease? Chest 116:1007–1111. doi:10.1378/chest.116.4.1007

    PubMed  CAS  Google Scholar 

  • Paredi P, Kharitonov SA, Leak D, Shah PL, Cramer D, Hodson ME, Barnes PJ (2000) Exhaled ethane is elevated in cystic fibrosis and correlates with carbon monoxide levels and airway obstruction. Am J Respir Crit Care Med 161:1247–1251

    PubMed  CAS  Google Scholar 

  • Peyton KJ, Reyna SV, Chapman GB, Ensenat D, Liu XM, Wang H, Schafer AI, Durante W (2002) Heme oxygenase-1-derived carbon monoxide is an autocrine inhibitor of vascular smooth muscle cell growth. Blood 99:4443–4448. doi:10.1182/blood.V99.12.4443

    PubMed  CAS  Google Scholar 

  • Piantadosi CA (2008) Carbon monoxide, reactive oxygen signaling, and oxidative stress. Free Radic Biol Med 45:562–569. doi:10.1016/j.freeradbiomed.2008.05.013

    PubMed  CAS  Google Scholar 

  • Polizio AH, Santa-Cruz DM, Balestrasse KB, Gironacci MM, Bertera FM, Höcht C, Taira CA, Tomaro ML, Gorzalczany SB (2011) Heme oxygenase-1 overexpression fails to attenuate hypertension when the nitric oxide synthase system is not fully operative. Pharmacology 87:341–349. doi:10.1159/000327939

    PubMed  CAS  Google Scholar 

  • Polte T, Abata A, Dennery PA, Schröder H (2000) Heme oxygenase-1 is a cGMP-inducible endothelial protein and mediates the cytoprotective action of nitric oxide. Arterioscler Thromb Vasc Biol 20:1209–1215. doi:10.1161/01.atv.20.5.1209

    PubMed  CAS  Google Scholar 

  • Qingyou Z, Junbao D, Weijin Z, Hui Y, Chaoshu T, Chunyu Z (2004) Impact of hydrogen sulfide on carbon monoxide/heme oxygenase pathway in the pathogenesis of hypoxic pulmonary hypertension. Biochem Biophys Res Commun 317:30–37. doi:10.1016/j.bbrc.2004.02.176

    PubMed  Google Scholar 

  • Queiroga CS, Almeida AS, Alves PM, Brenner C, Vieira HL (2011) Carbon monoxide prevents hepatic mitochondrial membrane permeabilization. BMC Cell Biol 12:10. doi:10.1186/1471-2121-12-10

    PubMed  CAS  Google Scholar 

  • Raman KG, Barbato JE, Ifedigbo E, Ozanich BA, Zenati MS, Otterbein LE, Tzeng E (2006) Inhaled carbon monoxide inhibits intimal hyperplasia and provides added benefit with nitric oxide. J Vasc Surg 44:151–158. doi:10.1016/j.jvs.2006.04.004

    PubMed  Google Scholar 

  • Ramlawi B, Scott JR, Feng J, Mieno S, Raman KG, Gallo D, Csizmadia E, Yoke Chin B, Bach FH, Otterbein LE, Selke FW (2007) Inhaled carbon monoxide prevents graft-induced intimal hyperplasia in swine. J Surg Res 138:121–127. doi:10.1016/j.jss.2006.08.031

    PubMed  CAS  Google Scholar 

  • Ramos KS, Lin H, McGrath JJ (1989) Modulation of cyclic guanosine monophosphate levels in cultured aortic smooth muscle cells by carbon monoxide. Biochem Pharmacol 38:1368–1370

    PubMed  CAS  Google Scholar 

  • Rémy S, Blancou P, Tesson L, Tardif V, Brion R, Royer PJ, Motterlini R, Foresti R, Painchaut M, Pogu S, Gregoire M, Bach JM, Anegon I, Chauveau C (2009) Carbon monoxide inhibits TLR-induced dendritic cell immunogenicity. J Immunol 182:1877–1884. doi:10.4049/jimmunol.0802436

    PubMed  Google Scholar 

  • Ricote M, Li A, Willson T, Kelly C, Glass C (1998) The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391:79–82. doi:10.1038/34178

    PubMed  CAS  Google Scholar 

  • Riesco-Fagundo AM, Pérez-García MT, González C, López-López JR (2001) O(2) modulates large-conductance Ca(2+)-dependent K(+) channels of rat chemoreceptor cells by a membrane-restricted and CO-sensitive mechanism. Circ Res 89:430–436. doi:10.1161/hh1701.095632

    PubMed  CAS  Google Scholar 

  • Roberts P, Youn H, Kerby R (2004) CO-sensing mechanisms. Microbiol Mol Biol Rev 68:453–473. doi:10.1128/MMBR.68.3.453-473.2004

    PubMed  CAS  Google Scholar 

  • Ryter SW, Choi AM (2007) Cytoprotective and anti-inflammatory actions of carbon monoxide in organ injury and sepsis models. Novartis Found Symp 280:165–181. doi:10.1124/jpet.108.148049

    PubMed  CAS  Google Scholar 

  • Ryter SW, Otterbein LE (2004) Carbon monoxide in biology and medicine. BioEssays 26:270–280. doi:10.1002/bies.20005

    PubMed  CAS  Google Scholar 

  • Sato K, Balla J, Otterbein L, Smith RN, Brouard S, Lin Y, Csizmadia E, Sevigny J, Robson SC, Vercellotti G, Choi AM, Bach FH, Soares MP (2001) Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants. J Immunol 166:4185–4194

    PubMed  CAS  Google Scholar 

  • Sawle P, Foresti R, Mann BE, Johnson TR, Green CJ, Motterlini R (2005) Carbon monoxide-releasing molecules (CO-RMs) attenuate the inflammatory response elicited by lipopolysaccharide in RAW264.7 murine macrophages. Br J Pharmacol 145:800–810. doi:10.1038/sj.bjp.0706241

    PubMed  CAS  Google Scholar 

  • 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. doi:10.1074/jbc.M803037200

    PubMed  CAS  Google Scholar 

  • Semenza GL (2007) Hypoxia-inducible factor 1 (HIF-1) pathway. Sci STKE 2007:cm8. doi:10.1126/stke.4072007cm8

  • Shamloul R, Wang R (2005) Monitoring circulatory heme level in hemin therapy for lowering blood pressure in rats. Cell Mol Biol (Noisy-le-grand) 51(5):507–512

    CAS  Google Scholar 

  • Shibahara S, Müller RM (1987) Taguchi H (Transcriptional control of rat heme oxygenase by heat shock). J Biol Chem 262(27):12889–12892

    PubMed  CAS  Google Scholar 

  • Sjöstrand T (1949) Endogenous formation of carbon monoxide in man under normal and pathological conditions. Scand J Clin Lab Invest 1:201–214

    Google Scholar 

  • Sjöstrand T (1951) Endogenous formation of carbon monoxide; the CO concentration in the inspired and expired air of hospital patients. Acta Physiol Scand 22:137–141

    PubMed  Google Scholar 

  • Song R, Mahidhara RS, Liu F, Ning W, Otterbein LE, Choi AM (2002) Carbon monoxide inhibits human airway smooth muscle cell proliferation via mitogen-activated protein kinase pathway. Am J Respir Cell Mol Biol 27:603–610. doi:10.1165/rcmb.4851

    PubMed  CAS  Google Scholar 

  • Stein AB, Guo Y, Tan W, Wu WJ, Zhu X, Li Q, Luo C, Dawn B, Johnson TR, Motterlini R, Bolli R (2005) Administration of a CO-releasing molecule induces late preconditioning against myocardial infarction. J Mol Cell Cardiol 38:127–134. doi:10.1016/j.yjmcc.2004.10.006

    PubMed  CAS  Google Scholar 

  • Stephanou A, Latchman DS (1999) Transcriptional regulation of the heat shock protein genes by STAT family transcription factors. Gene Exp 7:311–319

    CAS  Google Scholar 

  • Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN (1987) Bilirubin is an antioxidant of possible physiological importance. Science 235:1043–1046. doi:10.1126/science.3029864

    PubMed  CAS  Google Scholar 

  • Stone JR, Marletta MA (1994) Soluble guanylate cyclase from bovine lung: activation with nitric oxide and carbon monoxide and spectral characterization of the ferrous and ferric states. Biochemistry 33:5636–5640. doi:10.1021/bi00184a036

    PubMed  CAS  Google Scholar 

  • Stoppani J, Hildebrandt AL, Sakamoto K, Cameron-Smith D, Goodyear LJ, Neufer PD (2002) AMP-activated protein kinase activates transcription of the UCP3 and HKII genes in rat skeletal muscle. Am J Physiol 283:E1239–E1248. doi:10.1152/ajpendo.00278.2002

    CAS  Google Scholar 

  • Suematsu M, Goda N, Santo T, Kashiwagi S, Egawa T, Shinoda Y, Ishimura Y (1995) Carbon monoxide: an endogenous modulator of sinusoidal tone in the perfused rat liver. J Clin Invest 96:2431–2437. doi:10.1172/JCI118300

    PubMed  CAS  Google Scholar 

  • Suh GY, Jin Y, Yi AK, Wang XM, Choi AM (2006) CCAAT/enhancer-binding protein mediates carbon monoxide-induced suppression of cyclooxygenase-2. Am J Respir Cell Mol Biol 35:220–226. doi:10.1165/rcmb.2005-0154OC

    PubMed  CAS  Google Scholar 

  • 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. doi:10.1242/jcs.03318

    PubMed  CAS  Google Scholar 

  • Taillé C, El-Benna J, Lanone S, Boczkowski J, Motterlini R (2005) Mitochondrial respiratory chain and NAD(P)H oxidase are targets for the antiproliferative effect of carbon monoxide in human airway smooth muscle. J Biol Chem 280:25350–25360. doi:10.1074/jbc.M503512200

    PubMed  Google Scholar 

  • Telezhkin V, Brazier SP, Mears R, Müller CT, Riccardi D, Kemp PJ (2011) Cysteine residue 911 in C-terminal tail of human BK(Ca)α channel subunit is crucial for its activation by carbon monoxide. Pflugers Arch 461:665–675. doi:10.1007/s00424-011-0924-7

    PubMed  CAS  Google Scholar 

  • Tenhunen R, Marver HS, Schmid R (1968) The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci USA 61:748–755

    PubMed  CAS  Google Scholar 

  • Tenhunen R, Marver HS, Schmid R (1969) Microsomal heme oxygenase. Characterization of the enzyme. J Biol Chem 244:6388–6394

    PubMed  CAS  Google Scholar 

  • Tsoyi K, Ha YM, Kim YM, Lee YS, Kim HJ, Kim HJ, Seo HG, Lee JH, Chang KC (2009) Activation of PPAR-gamma by carbon monoxide from CORM-2 leads to the inhibition of iNOS but not COX-2 expression in LPS-stimulated macrophages. Inflammation 32:364–371. doi:10.1007/s10753-009-9144-0

    PubMed  CAS  Google Scholar 

  • Turcanu V, Dhouib M, Poindron P (1998) Nitric oxide synthase inhibition by haem oxygenase decreases macrophage nitric-oxide-dependent cytotoxicity: a negative feedback mechanism for the regulation of nitric oxide production. Res Immunol 149:741–744

    PubMed  CAS  Google Scholar 

  • Uemura K, Adachi-Akahane S, Shintani-Ishida K, Yoshida K (2005) Carbon monoxide protects cardiomyogenic cells against ischemic death through L-type Ca2+ channel inhibition. Biochem Biophys Res Commun 334:661–668. doi:10.1016/j.bbrc.2005.06.142

    PubMed  CAS  Google Scholar 

  • Urquhart P, Rosignoli G, Cooper D, Motterlini R, Perretti M (2007) Carbon monoxide-releasing molecules modulate leukocyte-endothelial interactions under flow. J Pharmacol Exp Ther 321:656–662. doi:10.1124/jpet.106.117218

    PubMed  CAS  Google Scholar 

  • Van Landeghem L, Laleman W, Vander Elst I, Zeegers M, Van Pelt J, Cassiman D, Nevens F (2009) Carbon monoxide produced by intrasinusoidally located haem-oxygenase-1 regulates the vascular tone in cirrhotic rat liver. Liver Int 29:650–660. doi:10.1111/j.1478-3231.2008.01857.x

    PubMed  Google Scholar 

  • Verma A, Hirsch DJ, Glatt CE, Ronnett GV, Snyder SH (1993) Carbon monoxide: a putative neural messenger. Science 259:381–384. doi:10.1126/science.7678352

    PubMed  CAS  Google Scholar 

  • Vicente AM, Guillen MI, Alcaraz MJ (2001) Modulation of haem oxygenase-1 expression by nitric oxide and leukotrienes in zymosan-activated macrophages. Br J Pharmacol 133:920–926. doi:10.1038/sj.bjp.0704145

    PubMed  CAS  Google Scholar 

  • Von Berg R (1999) Toxicology update: carbon monoxide. J Appl Toxicol 19:379–386. doi:10.1002/(SICI)1099-1263(199909/10)19:5<379:AID-JAT563>3.0.CO;2-8

    Google Scholar 

  • Vreman HJ, Wong RJ, Stevenson DK (2001) Carbon monoxide and cardiovascular functions. Chapter 15. Sources, Sinks, and Measurement of Carbon Monoxide. CRC Press, Boca Raton

    Google Scholar 

  • Wagner CT, Durante W, Christodoulides N, Hellums JD, Schafer AI (1997) Hemodynamic forces induce the expression of heme oxygenase in cultured vascular smooth muscle cells. J Clin Invest 100:589–596. doi:10.1172/JCI119569

    PubMed  CAS  Google Scholar 

  • Wang R (1998) Resurgence of carbon monoxide: an endogenous gaseous vasorelaxing factor. Can J Physiol Pharmacol 76:1–15

    PubMed  Google Scholar 

  • Wang R (2002) Two’s company, three’s a crowd: can H2S be the third endogenous gaseous transmitter? FASEB J 16(13):1792–1798. doi:10.1096/fj.02-0211hyp

    PubMed  CAS  Google Scholar 

  • Wang R, Wu L (1997) The chemical modification of KCa channels by carbon monoxide in vascular smooth muscle cells. J Biol Chem 272:8222–8226. doi:10.1074/jbc.272.13.8222

    PubMed  CAS  Google Scholar 

  • Wang R, Wu L, Wang Z (1997a) The direct effect of carbon monoxide on KCa channels in vascular smooth muscle cells. Pflugers Arch 434:285–291

    PubMed  CAS  Google Scholar 

  • Wang R, Wang Z, Wu L (1997b) Carbon monoxide-induced vasorelaxation and the underlying mechanisms. Br J Pharmacol 121(5):927–934. doi:10.1038/sj.bjp.0701222

    PubMed  CAS  Google Scholar 

  • Wang R, Wang Z, Wu L, Hanna ST, Peterson-Wakeman R (2001) Reduced vasorelaxant effect of carbon monoxide in diabetes and the underlying mechanisms. Diabetes 50(1):166–174. doi:10.2337/diabetes.50.1.166

    PubMed  CAS  Google Scholar 

  • Wang R, Shamloul R, Wang X, Meng Q, Wu L (2006) Sustained normalization of high blood pressure in spontaneously hypertensive rats by implanted hemin pump. Hypertension 48(4):685–692. doi:10.1161/0​1.HYP.0000239673.80332.2f

    PubMed  CAS  Google Scholar 

  • Wang X, Wang Y, Kim HP, Nakahira K, Ryter SW, Choi AM (2007) Carbon monoxide protects against hyperoxia-induced endothelial cell apoptosis by inhibiting reactive oxygen species formation. J Biol Chem 282:1718–1726. doi:10.1074/jbc.M607610200

    PubMed  CAS  Google Scholar 

  • Wang S, Publicover S, Gu Y (2009) An oxygen-sensitive mechanism in regulation of epithelial sodium channel. Proc Natl Acad Sci USA 106:2957–2962. doi:10.1073/pnas.0809100106

    PubMed  CAS  Google Scholar 

  • Weaver LK (1999) Carbon monoxide poisoning. Crit Care Clin 15:297–317

    PubMed  CAS  Google Scholar 

  • Wegiel B, Gallo DJ, Raman KG, Karlsson JM, Ozanich B, Chin BY, Tzeng E, Ahmad S, Ahmed A, Baty CJ, Otterbein LE (2010) Nitric oxide-dependent bone marrow progenitor mobilization by carbon monoxide enhances endothelial repair after vascular injury. Circulation 121:537–548. doi:10.1161/CIRCULATIONAHA.109.887695

    PubMed  CAS  Google Scholar 

  • Wei Y, Chen P, de Bruyn M, Zhang W, Bremer E, Helfrich W (2010) Carbon monoxide-releasing molecule-2 (CORM-2) attenuates acute hepatic ischemia reperfusion injury in rats. BMC Gastroenterol 10:42. doi:10.1186/1471-230X-10-42

    PubMed  Google Scholar 

  • Wilkinson WJ, Kemp PJ (2011a) Carbon monoxide: an emerging regulator of ion channels. J Physiol 589:3055–3062. doi:10.1113/jphysiol.2011.206706

    PubMed  CAS  Google Scholar 

  • Wilkinson WJ, Kemp PJ (2011b) The carbon monoxide donor, CORM-2, is an antagonist of ATP-gated, human P2X4 receptors. Purinergic Signal 7:57–64. doi:10.1007/s11302-010-9213-8

    PubMed  CAS  Google Scholar 

  • Wilkinson WJ, Gadeberg HC, Harrison AW, Allen ND, Riccardi D, Kemp PJ (2009) Carbon monoxide is a rapid modulator of recombinant and native P2X(2) ligand-gated ion channels. Br J Pharmacol 158:862–871. doi:10.1111/j.1476-5381.2009.00354.x

    PubMed  CAS  Google Scholar 

  • 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. doi:10.1126/science.1105010

    PubMed  CAS  Google Scholar 

  • Woo CH, Massett MP, Shishido T, Itoh S, Ding B, McClain C, Che W, Vulapalli SR, Yan C, Abe J (2006) ERK5 activation inhibits inflammatory responses via peroxisome proliferator-activated receptor delta (PPARdelta) stimulation. J Biol Chem 281:32164–32174. doi:10.1074/jbc.M602369200

    PubMed  CAS  Google Scholar 

  • Wu L, Wang R (2005) Carbon monoxide: endogenous production, physiological functions, and pharmacological applications. Pharmacol Rev 57(4):585–630. doi:10.1124/pr.57.4.3

    PubMed  CAS  Google Scholar 

  • Wu L, Cao K, Lu Y, Wang R (2002) Different mechanisms underlying the stimulation of KCa channels by nitric oxide and carbon monoxide. J Clin Invest 110(5):691–700. doi:10.1172/JCI0215316

    PubMed  CAS  Google Scholar 

  • Yamaya M, Sekizawa K, Ishizuka S, Monma M, Mizuta K, Sasaki H (1998) Increased carbon monoxide in exhaled air of subjects with upper respiratory tract infections. Am J Respir Crit Care Med 158(1):311–314

    PubMed  CAS  Google Scholar 

  • Yamaya M, Hosoda M, Ishizuka S, Monma M, Matsui T, Suzuki T, Sekizawa K, Saskai H (2001) Relation between exhaled carbon monoxide levels and clinical severity of asthma. Clin Exp Allergy 31:417–422. doi:10.1046/j.1365-2222.2001.01013.x

    PubMed  CAS  Google Scholar 

  • Zakhary R, Gaine SP, Dinerman JL, Ruat M, Flavahan NA, Snyder SH (1996) Heme oxygenase 2: endothelial and neuronal localization and role in endothelium-dependent relaxation. Proc Natl Acad Sci USA 93:795–798. doi:10.1073/pnas.93.2.795

    PubMed  CAS  Google Scholar 

  • Zakhary R, Poss KD, Jaffrey SR, Ferris CD, Tonegawa S, Snyder SH (1997) Targeted gene deletion of heme oxygenase 2 reveals neural role for carbon monoxide. Proc Natl Acad Sci USA 94:14848–14853. doi:10.1073/pnas.94.26.14848

    PubMed  CAS  Google Scholar 

  • Zayasu K, Sekizawa K, Okinaga S, Yamaya M, Ohrui T, Sasaki H (1997) Increased carbon monoxide in exhaled air of asthmatic patients. Am J Respir Crit Care Med 156:1140–1143

    PubMed  CAS  Google Scholar 

  • Zhang X, Shan P, Alam J, Fu XY, Lee PL (2005) Carbon monoxide differentially modulates STAT1 and STAT3 and inhibits apoptosis via a phosphatidylinositol 3-kinase/Akt and p38 kinase-dependent STAT3 pathway during anoxia-reoxygenation injury. J Biol Chem 280:8714–8721. doi:10.1074/jbc.M408092200

    PubMed  CAS  Google Scholar 

  • Zhang X, Shan P, Jiang G, Zhang SS, Otterbein LE, Fu XY, Lee PJ (2006) Endothelial STAT3 is essential for the protective effects of HO-1 in oxidant-induced lung injury. FASEB J 20:2156–2158. doi:10.1096/fj.06-5668fje

    PubMed  CAS  Google Scholar 

  • Zheng L, Zhou Z, Lin L, Alber S, Watkins S, Kaminski N, Choi AM, Morse D (2009) Carbon monoxide modulates alpha-smooth muscle actin and small proline rich-1a expression in fibrosis. Am J Respir Cell Mol Biol 41:85–92. doi:10.1165/rcmb.2007-0401OC

    PubMed  CAS  Google Scholar 

  • Zhou Z, Song R, Fattman CL, Greenhill S, Alber S, Oury TD, Choi AM, Morse D (2005) Carbon monoxide suppresses bleomycin-induced lung fibrosis. Am J Pathol 166:27–37. doi:10.1016/S0002-9440(10)62229-8

    PubMed  CAS  Google Scholar 

  • Zuckerbraun BS, Billiar TR, Otterbein SL, Kim PK, Liu F, Choi AM, Bach FH, Otterbein LE (2003) Carbon monoxide protects against liver failure through nitric oxide-induced heme oxygenase 1. J Exp Med 198:1707–1716. doi:10.1084/jem.20031003

    PubMed  CAS  Google Scholar 

  • Zuckerbraun BS, Chin BY, Wegiel B, Billiar TR, Csizmadia E, Rao J, Shimoda L, Ifedigbo E, Kanno S, Otterbein LE (2006) Carbon monoxide reverses established pulmonary hypertension. J Exp Med 203:2109–2119. doi:10.1084/jem.20052267

    PubMed  CAS  Google Scholar 

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Acknowledgments

This study has been supported by a Discovery Grant from Natural Sciences and Engineering Research Council of Canada

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Authors and Affiliations

  1. Department of Health Sciences, Lakehead University, Thunder Bay, ON, P7B 5E1, Canada

    Ashley A. Untereiner & Lingyun Wu

  2. Thunder Bay Regional Research Institute, Thunder Bay, ON, Canada

    Ashley A. Untereiner & Lingyun Wu

  3. Department of Biology, Lakehead University, 955 Oliver Road, Thunder Bay, ON, P7B 5E1, Canada

    Rui Wang

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  1. Ashley A. Untereiner
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  2. Lingyun Wu
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  3. Rui Wang
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Correspondence to Rui Wang .

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Editors and Affiliations

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

    Anton Hermann

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

    Guzel F. Sitdikova

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

    Thomas M. Weiger

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Untereiner, A.A., Wu, L., Wang, R. (2012). The Role of Carbon Monoxide as a Gasotransmitter in Cardiovascular and Metabolic Regulation. In: Hermann, A., Sitdikova, G., Weiger, T. (eds) Gasotransmitters: Physiology and Pathophysiology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30338-8_2

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