Abstract
Since the discovery of cytoglobin (Cygb) a decade ago, growing amounts of data have been gathered to characterise Cygb biochemistry, functioning and implication in human pathologies. Its molecular roles remain under investigation, but nitric oxide dioxygenase and lipid peroxidase activities have been demonstrated. Cygb expression increases in response to various stress conditions including hypoxia, oxidative stress and fibrotic stimulation. When exogenously overexpressed, Cygb revealed cytoprotection against these factors. Cygb was shown to be upregulated in fibrosis and neurodegenerative disorders and downregulated in multiple cancer types. CYGB was also found within the minimal region of a hereditary tylosis with oesophageal cancer syndrome, and its expression was reduced in tylotic samples. Recently, Cygb has been shown to inhibit cancer cell growth in vitro, thus confirming its suggested tumour suppressor role. This article aims to review the biochemical and functional aspects of Cygb, its involvement in various pathological conditions and potential clinical utility.
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References
Hardison R (1998) Hemoglobins from bacteria to man: evolution of different patterns of gene expression. J Exp Biol 201(Pt 8):1099–1117
Weber RE, Fago A (2004) Functional adaptation and its molecular basis in vertebrate hemoglobins, neuroglobins and cytoglobins. Respir Physiol Neurobiol 144(2–3):141–159. doi:10.1016/j.resp.2004.04.018
Wajcman H, Kiger L, Marden MC (2009) Structure and function evolution in the superfamily of globins. C R Biol 332(2–3):273–282. doi:S1631-0691(08)00227-8
Burmester T, Ebner B, Weich B, Hankeln T (2002) Cytoglobin: a novel globin type ubiquitously expressed in vertebrate tissues. Mol Biol Evol 19(4):416–421
Burmester T, Weich B, Reinhardt S, Hankeln T (2000) A vertebrate globin expressed in the brain. Nature 407(6803):520–523. doi:10.1038/35035093
Hankeln T, Ebner B, Fuchs C, Gerlach F, Haberkamp M, Laufs TL, Roesner A, Schmidt M, Weich B, Wystub S, Saaler-Reinhardt S, Reuss S, Bolognesi M, Sanctis DD, Marden MC, Kiger L, Moens L, Dewilde S, Nevo E, Avivi A, Weber RE, Fago A, Burmester T (2005) Neuroglobin and cytoglobin in search of their role in the vertebrate globin family. J Inorg Biochem 99(1):110–119
Pesce A, Bolognesi M, Bocedi A, Ascenzi P, Dewilde S, Moens L, Hankeln T, Burmester T (2002) Neuroglobin and cytoglobin fresh blood for the vertebrate globin family. EMBO Rep 3(12):1146–1151
Trent JT, Hargrove MS (2002) A ubiquitously expressed human hexacoordinate hemoglobin. J Bio Chem 277(22):19538–19545
Gardner PR (2005) Nitric oxide dioxygenase function and mechanism of flavohemoglobin, hemoglobin, myoglobin and their associated reductases. J Inorg Biochem 99(1):247–266. doi:S0162-0134(04)00296-X
Gladwin MT, Grubina R, Doyle MP (2009) The new chemical biology of nitrite reactions with hemoglobin: R-state catalysis, oxidative denitrosylation, and nitrite reductase/anhydrase. Acc Chem Res 42(1):157–167. doi:10.1021/ar800089j
Gladwin MT, Kim-Shapiro DB (2008) The functional nitrite reductase activity of the heme-globins. Blood 112(7):2636–2647. doi:blood-2008-01-115261
Reeder BJ (2010) The redox activity of hemoglobins: from physiologic functions to pathologic mechanisms. Antioxid Redox Signal 13(7):1087–1123. doi:10.1089/ars.2009.2974
Vinogradov SN, Moens L (2008) Diversity of globin function: enzymatic, transport, storage, and sensing. J Biol Chem 283(14):8773–8777. doi:R700029200
Kawada N, Kristensen DB, Asahina K, Nakatani K, Minamiyama Y, Seki S, Yoshizato K (2001) Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells. J Biol Chem 276(27):25318–25323
Hamdane D, Kiger L, Dewilde S, Green BN, Pesce A, Uzan J, Burmester T, Hankeln T, Bolognesi M, Moens L, Marden MC (2003) The redox state of the cell regulates the ligand binding affinity of human neuroglobin and cytoglobin. J Biol Chem 278(51):51713–51721
De Sanctis D, Dewilde S, Pesce A, Moens L, Ascenzi P, Hankeln T, Burmester T, Bolognesi M (2004) Crystal structure of cytoglobin: the fourth globin type discovered in man displays heme hexa-coordination. J Mol Biol 336(4):917–927
Lechauve C, Chauvierre C, Dewilde S, Moens L, Green BN, Marden MC, Celier C, Kiger L (2010) Cytoglobin conformations and disulfide bond formation. FEBS J 277(12):2696–2704. doi:EJB7686
Sugimoto H, Makino M, Sawai H, Kawada N, Yoshizato K, Shiro Y (2004) Structural basis of human cytoglobin for ligand binding. J Mol Biol 339(4):873–885
Burmester T, Haberkamp M, Mitz S, Roesner A, Schmidt M, Ebner B, Gerlach F, Fuchs C, Hankeln T (2004) Neuroglobin and cytoglobin: genes, proteins and evolution. IUBMB Life 56(11–12):703–707
Sawai H, Kawada N, Yoshizato K, Nakajima H, Aono S, Shiro Y (2003) Characterization of the heme environmental structure of cytoglobin, a fourth globin in humans. Biochemistry 42(17):5133–5142. doi:10.1021/bi027067e
Hodges NJ, Innocent N, Dhanda S, Graham M (2008) Cellular protection from oxidative DNA damage by over-expression of the novel globin cytoglobin in vitro. Mutagenesis 23(4):293–298. doi:10.1093/mutage/gen013
Reeder BJ, Svistunenko D, Wilson M (2010) Lipid binding to cytoglobin leads to a change in heme coordination: a role for cytoglobin in lipid signalling of oxidative stress. Biochem J. doi:BJ20101136
Geuens E, Brouns I, Flamez D, Dewilde S, Timmermans J-P, Moens L (2003) A globin in the nucleus. J Biol Chem 278(33):30417–30420
Hundahl CA, Allen GC, Hannibal J, Kjaer K, Rehfeld JF, Dewilde S, Nyengaard JR, Kelsen J, Hay-Schmidt A (2010) Anatomical characterization of cytoglobin and neuroglobin mRNA and protein expression in the mouse brain. Brain Res 1331:58–73. doi:S0006-8993(10)00629-3
Mammen PPA, Shelton JM, Ye Q, Kanatous SB, McGrath AJ, Richardson JA, Garry DJ (2006) Cytoglobin is a stress-responsive hemoprotein expressed in the developing and adult brain. J Histochem Cytochem 54(12):1349–1361. doi:10.1369/jhc.6A7008.2006
Nakatani K, Okuyama H, Shimahara Y, Saeki S, Kim D-H, Nakajima Y, Seki S, Kawada N, Yoshizato K (2003) Cytoglobin//STAP, its unique localization in splanchnic fibroblast-like cells and function in organ fibrogenesis. Lab Invest 84(1):91–101
Schmidt M, Gerlach F, Avivi A, Laufs T, Wystub S, Simpson JC, Nevo E, Saaler-Reinhardt S, Reuss S, Hankeln T, Burmester T (2004) Cytoglobin is a respiratory protein in connective tissue and neurons, which is up-regulated by hypoxia. J Biol Chem 279(9):8063–8069
Shigematsu A, Adachi Y, Matsubara J, Mukaide H, Koike-Kiriyama N, Minamino K, Shi M, Yanai S, Imamura M, Taketani S, Ikehara S (2008) Analyses of expression of cytoglobin by immunohistochemical studies in human tissues. Hemoglobin 32(3):287–296. doi:10.1080/03630260802017261
Fago A, Hundahl C, Malte H, Weber RE (2004) Functional properties of neuroglobin and cytoglobin. Insights into the ancestral physiological roles of globins. IUBMB Life 56(11–12):689–696
Emara M, Turner AR, Allalunis-Turner J (2010) Hypoxic regulation of cytoglobin and neuroglobin expression in human normal and tumor tissues. Cancer Cell Int 10:33. doi:1475-2867-10-33
Man KN, Philipsen S, Tan-Un KC (2008) Localization and expression pattern of cytoglobin in carbon tetrachloride-induced liver fibrosis. Toxicol Lett 183(1–3):36–44. doi:S0378-4274(08)01276-9
Fordel E, Thijs L, Martinet W, Lenjou M, Laufs T, Van Bockstaele D, Moens L, Dewilde S (2006) Neuroglobin and cytoglobin overexpression protects human SH-SY5Y neuroblastoma cells against oxidative stress-induced cell death. Neurosci Lett 410(2):146–151
Li RC, Lee SK, Pouranfar F, Brittian KR, Clair HB, Row BW, Wang Y, Gozal D (2006) Hypoxia differentially regulates the expression of neuroglobin and cytoglobin in rat brain. Brain Res 1096(1):173–179
Ostojic J, Sakaguchi DS, de Lathouder Y, Hargrove MS, Trent JT III, Kwon YH, Kardon RH, Kuehn MH, Betts DM, Grozdanic S (2006) Neuroglobin and cytoglobin: oxygen-binding proteins in retinal neurons. Invest Ophthalmol Vis Sci 47(3):1016–1023. doi:10.1167/iovs.05-0465
Gorr TA, Wichmann D, Pilarsky C, Theurillat JP, Fabrizius A, Laufs T, Bauer T, Koslowski M, Horn S, Burmester T, Hankeln T, Kristiansen G (2010) Old proteins—new locations: myoglobin, haemoglobin, neuroglobin and cytoglobin in solid tumours and cancer cells. Acta Physiol (Oxf). doi:10.1111/j.1748-1716.2010.02205.x
Pacher P, Beckman JS, Liaudet L (2007) Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87(1):315–424. doi:87/1/315
Wystub S, Ebner B, Fuchs C, Weich B, Burmester T, Hankeln T (2004) Interspecies comparison of neuroglobin, cytoglobin and myoglobin: sequence evolution and candidate regulatory elements. Cytogenet Genome Res 105(1):65–78
McRonald FE, Liloglou T, Xinarianos G, Hill L, Rowbottom L, Langan JE, Ellis A, Shaw JM, Field JK, Risk JM (2006) Down-regulation of the cytoglobin gene, located on 17q25, in tylosis with oesophageal cancer (TOC): evidence for trans-allele repression. Hum Mol Genet 15(8):1271–1277. doi:10.1093/hmg/ddl042
Semenza GL, Jiang B-H, Leung SW, Passantino R, Concordet J-P, Maire P, Giallongo A (1996) Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1. J Biol Chem 271(51):32529–32537
Webb JD, Coleman ML, Pugh CW (2009) Hypoxia, hypoxia-inducible factors (HIF), HIF hydroxylases and oxygen sensing. Cell Mol Life Sci 66(22):3539–3554. doi:10.1007/s00018-009-0147-7
Harris AL (2002) Hypoxia—a key regulatory factor in tumour growth. Nat Rev Cancer 2(1):38–47
Swietach P, Vaughan-Jones R, Harris A (2007) Regulation of tumor pH and the role of carbonic anhydrase 9. Cancer Metastasis Rev 26(2):299–310
Denko NC (2008) Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer 8(9):705–713
Mole D (2010) Iron homeostasis and its interaction with prolyl hydroxylases. Antioxid Redox Signal 12(4):445–458
Bristow RG, Hill RP (2008) Hypoxia and metabolism: hypoxia, DNA repair and genetic instability. Nat Rev Cancer 8(3):180–192
Czyzyk-Krzeska MF, Beresh JE (1996) Characterization of the hypoxia-inducible protein binding site within the pyrimidine-rich tract in the 3′-untranslated region of the tyrosine hydroxylase mRNA. J Biol Chem 271(6):3293–3299
Guo X, Philipsen S, Tan-Un K-C (2006) Characterization of human cytoglobin gene promoter region. Biochim Biophys Acta Gene Struct Expr 1759(5):208–215
Cummins E, Taylor C (2005) Hypoxia-responsive transcription factors. Pflugers Arch 450(6):363–371
Cloutier A, Guindi C, Larivee P, Dubois CM, Amrani A, McDonald PP (2009) Inflammatory cytokine production by human neutrophils involves C/EBP transcription factors. J Immunol 182(1):563–571. doi:182/1/563
Glass CK, Saijo K (2008) Immunology: oxysterols hold T cells in check. Nature 455(7209):40–41. doi:455040a
Novo E, Parola M (2008) Redox mechanisms in hepatic chronic wound healing and fibrogenesis. Fibrogenesis Tissue Repair 1(1):5. doi:1755-1536-1-5
Dwyer J, Li H, Xu D, Liu J-P (2007) Ann N Y Acad Sci 1114:36–47 (Healthy Aging and Longevity Third International Conference)
Nakamura Y, Esnault S, Maeda T, Kelly EAB, Malter JS, Jarjour NN (2004) Ets-1 regulates TNF-a-induced matrix metalloproteinase-9 and tenascin expression in primary bronchial fibroblasts. J Immunol 172(3):1945–1952
Guo X, Philipsen S, Tan-Un K-C (2007) Study of the hypoxia-dependent regulation of human CYGB gene. Biochem Biophys Res Commun 364(1):145–150
Singh S, Manda SM, Sikder D, Birrer MJ, Rothermel BA, Garry DJ, Mammen PPA (2009) Calcineurin activates cytoglobin transcription in hypoxic myocytes. J Biol Chem 284(16):10409–10421
De Beuf A, Hou XH, D’Haese PC, Verhulst A (2010) Epoetin-d reduces oxidative stress in primary human renal tubular cells. J Biomed Biotechnol 2010:395785. doi:10.1155/2010/395785
Fago A, Hundahl C, Dewilde S, Gilany K, Moens L, Weber RE (2004) Allosteric regulation and temperature dependence of oxygen binding in human neuroglobin and cytoglobin. J Biol Chem 279(43):44417–44426
Gardner AM, Cook MR, Gardner PR (2010) Nitric-oxide dioxygenase function of human cytoglobin with cellular reductants and in rat hepatocytes. J Biol Chem 285(31):23850–23857. doi:M110.132340
Halligan KE, Jourd’heuil FL, Jourd’heuil D (2009) Cytoglobin is expressed in the vasculature and regulates cell respiration and proliferation via nitric oxide dioxygenation. J Biol Chem 284(13):8539–8547
Gardner PR, Gardner AM, Brashear WT, Suzuki T, Hvitved AN, Setchell KD, Olson JS (2006) Hemoglobins dioxygenate nitric oxide with high fidelity. J Inorg Biochem 100(4):542–550. doi:S0162-0134(05)00372-7
Smagghe BJ, Trent James T, III Hargrove, Mark S (2008) NO dioxygenase activity in hemoglobins in ubiquitous in vitro, but limited by reduction in vivo. PLoS One 3(4):e2039
Thomas DD, Ridnour LA, Isenberg JS, Flores-Santana W, Switzer CH, Donzelli S, Hussain P, Vecoli C, Paolocci N, Ambs S, Colton CA, Harris CC, Roberts DD, Wink DA (2008) The chemical biology of nitric oxide: implications in cellular signaling. Free Radic Biol Med 45(1):18–31. doi:S0891-5849(08)00175-5
Li H, Poulos TL (2005) Structure-function studies on nitric oxide synthases. J Inorg Biochem 99(1):293–305. doi:S0162-0134(04)00321-6
Hill BG, Dranka BP, Bailey SM, Lancaster JR Jr, Darley-Usmar VM (2010) What part of NO don’t you understand? Some answers to the cardinal questions in nitric oxide biology. J Biol Chem 285(26):19699–19704. doi:R110.101618
Berchner-Pfannschmidt U, Yamac H, Trinidad B, Fandrey J (2007) Nitric oxide modulates oxygen sensing by hypoxia-inducible factor 1-dependent induction of prolyl hydroxylase 2. J Biol Chem 282(3):1788–1796. doi:M607065200
Kimura H, Weisz A, Kurashima Y, Hashimoto K, Ogura T, D’Acquisto F, Addeo R, Makuuchi M, Esumi H (2000) Hypoxia response element of the human vascular endothelial growth factor gene mediates transcriptional regulation by nitric oxide: control of hypoxia-inducible factor-1 activity by nitric oxide. Blood 95(1):189–197
Metzen E, Zhou J, Jelkmann W, Fandrey J, Brune B (2003) Nitric oxide impairs normoxic degradation of HIF-1alpha by inhibition of prolyl hydroxylases. Mol Biol Cell 14(8):3470–3481. doi:10.1091/mbc.E02-12-0791E02-12-0791
Erusalimsky JD, Moncada S (2007) Nitric oxide and mitochondrial signaling: from physiology to pathophysiology. Arterioscler Thromb Vasc Biol 27(12):2524–2531. doi:ATVBAHA.107.151167
Li D, Chen X, Li W-J, Yang Y-H, Wang J-Z, Yu A (2007) Cytoglobin up-regulated by hydrogen peroxide plays a protective role in oxidative stress. Neurochem Res 32(8):1375–1380
Chua P-J, Yip GW-C, Bay B-H (2009) Cell cycle arrest induced by hydrogen peroxide is associated with modulation of oxidative stress related genes in breast cancer cells. Exp Biol Med 234(9):1086–1094. doi:10.3181/0903-rm-98
Fordel E, Thijs L, Moens L, Dewilde S (2007) Neuroglobin and cytoglobin expression in mice. FEBS J 274(5):1312–1317
Xu R, Harrison PM, Chen M, Li L, Tsui T-Y, Fung PCW, Cheung P-T, Wang G, Li H, Diao Y, Krissansen GW, Xu S, Farzaneh F (2006) Cytoglobin overexpression protects against damage-induced fibrosis. Mol Ther 13(6):1093–1100
Mimura I, Nangaku M, Nishi H, Inagi R, Tanaka T, Fujita T (2010) Cytoglobin, a novel globin, plays an anti-fibrotic role in the kidney. Am J Physiol Renal Physiol. doi:ajprenal.00145.2010
Trandafir F, Hoogewijs D, Altieri F, Rivetti di Val Cervo P, Ramser K, Van Doorslaer S, Vanfleteren JR, Moens L, Dewilde S (2007) Neuroglobin and cytoglobin as potential enzyme or substrate. Gene 398(1–2):103–113
Fordel E, Thijs L, Martinet W, Schrijvers D, Moens L, Dewilde S (2007) Anoxia or oxygen and glucose deprivation in SH-SY5Y cells: a step closer to the unraveling of neuroglobin and cytoglobin functions. Gene 398(1–2):114–122
Petersen MG, Dewilde S, Fago A (2008) Reactions of ferrous neuroglobin and cytoglobin with nitrite under anaerobic conditions. J Inorg Biochem 102(9):1777–1782
Gardner PR, Gardner AM, Martin LA, Dou Y, Li T, Olson JS, Zhu H, Riggs AF (2000) Nitric-oxide dioxygenase activity and function of flavohemoglobins sensitivity to nitric oxide and carbon monoxide inhibition. J Biol Chem 275(41):31581–31587. doi:10.1074/jbc.M004141200
Wynn TA (2008) Cellular and molecular mechanisms of fibrosis. J Pathol 214(2):199–210. doi:10.1002/path.2277
Zion O, Genin O, Kawada N, Yoshizato K, Roffe S, Nagler A, Iovanna JL, Halevy O, Pines M (2009) Inhibition of transforming growth factor-b signaling by halofuginone as a modality for pancreas fibrosis prevention. Pancreas 38(4):427–435. doi:10.1097/MPA.0b013e3181967670
Shivapurkar N, Stastny V, Okumura N, Girard L, Xie Y, Prinsen C, Thunnissen FB, Wistuba II, Czerniak B, Frenkel E, Roth JA, Liloglou T, Xinarianos G, Field JK, Minna JD, Gazdar AF (2008) Cytoglobin, the newest member of the globin family, functions as a tumor suppressor gene. Cancer Res 68(18):7448–7456. doi:10.1158/0008-5472.can-08-0565
Cao M, Westerhausen-Larson A, Niyibizi C, Kavalkovich K, Georgescu HI, Rizzo CF, Hebda PA, Stefanovic-Racic M, Evans CH (1997) Nitric oxide inhibits the synthesis of type-II collagen without altering Col2A1 mRNA abundance: prolyl hydroxylase as a possible target. Biochem J 324(Pt 1):305–310
Dooley A, Gao B, Shi-Wen X, Abraham DJ, Black CM, Jacobs M, Bruckdorfer KR (2007) Effect of nitric oxide and peroxynitrite on type I collagen synthesis in normal and scleroderma dermal fibroblasts. Free Radic Biol Med 43(2):253–264. doi:S0891-5849(07)00284-5
Urtasun R, Conde de la Rosa L, Nieto N (2008) Oxidative and nitrosative stress and fibrogenic response. Clin Liver Dis 12(4):769–790. doi:S1089-3261(08)00076-7 viii
Murrell GA (2007) Using nitric oxide to treat tendinopathy. Br J Sports Med 41(4):227–231. doi:bjsm.2006.034447
Witte MB, Barbul A (2002) Role of nitric oxide in wound repair. Am J Surg 183(4):406–412. doi:S0002961002008152
Powell FL, Fu Z (2008) HIF-1 and ventilatory acclimatization to chronic hypoxia. Respir Physiol Neurobiol 164(1–2):282–287
Fordel E, Geuens E, Dewilde S, Rottiers P, Carmeliet P, Grooten J, Moens L (2004) Cytoglobin expression is upregulated in all tissues upon hypoxia: an in vitro and in vivo study by quantitative real-time PCR. Biochem Biophys Res Commun 319(2):342–348
Burmester T, Gerlach F, Hankeln T (2007) Regulation and role of neuroglobin and cytoglobin under hypoxia. Adv Exp Med Biol 618:169–180
Shaw RJ, Omar MM, Rokadiya S, Kogera FA, Lowe D, Hall GL, Woolgar JA, Homer J, Liloglou T, Field JK, Risk JM (2009) Cytoglobin is upregulated by tumour hypoxia and silenced by promoter hypermethylation in head and neck cancer. Br J Cancer 101(1):139–144
Stagner JI, Parthasarathy SN, Wyler K, Parthasarathy RN (2005) Protection from ischemic cell death by the induction of cytoglobin. Transplant Proc 37(8):3452–3453
Berchner-Pfannschmidt U, Tug S, Kirsch M, Fandrey J (2010) Oxygen-sensing under the influence of nitric oxide. Cell Signal 22(3):349–356. doi:S0898-6568(09)00321-0
Berchner-Pfannschmidt U, Tug S, Trinidad B, Oehme F, Yamac H, Wotzlaw C, Flamme I, Fandrey J (2008) Nuclear oxygen sensing: induction of endogenous prolyl-hydroxylase 2 activity by hypoxia and nitric oxide. J Biol Chem 283(46):31745–31753. doi:M804390200
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(13):9038–9044
Lundberg JO, Gladwin MT, Ahluwalia A, Benjamin N, Bryan NS, Butler A, Cabrales P, Fago A, Feelisch M, Ford PC, Freeman BA, Frenneaux M, Friedman J, Kelm M, Kevil CG, Kim-Shapiro DB, Kozlov AV, Lancaster JR Jr, Lefer DJ, McColl K, McCurry K, Patel RP, Petersson J, Rassaf T, Reutov VP, Richter-Addo GB, Schechter A, Shiva S, Tsuchiya K, van Faassen EE, Webb AJ, Zuckerbraun BS, Zweier JL, Weitzberg E (2009) Nitrate and nitrite in biology, nutrition and therapeutics. Nat Chem Biol 5(12):865–869. doi:nchembio.260
Igamberdiev AU, Bykova NV, Shah JK, Hill RD (2010) Anoxic nitric oxide cycling in plants: participating reactions and possible mechanisms. Physiol Plant 138(4):393–404. doi:PPL1314
Guzy RD, Schumacker PT (2006) Oxygen sensing by mitochondria at complex III: the paradox of increased reactive oxygen species during hypoxia. Exp Physiol 91(5):807–819
Higgins DF, Kimuro, Kuniko, Iwano, Masayuki, Hasse, Volker H (2008) Hypoxia-inducible factor signaling in the development of tissue fibrosis. Cell Cycle 7(9):1128–1132
Walters DM, Cho HY, Kleeberger SR (2008) Oxidative stress and antioxidants in the pathogenesis of pulmonary fibrosis: a potential role for Nrf2. Antioxid Redox Signal 10(2):321–332
García-Trevijano ER, Iraburu MJ, Fontana L, Domínguez-Rosales JA, Auster A, Covarrubias-Pinedo A, Rojkind M (1999) Transforming growth factor-b induces the expression of al1(i) procollagen mRNA by a hydrogen peroxide-C/EBPbeta-dependent mechanism in rat hepatic stellate cells. Hepatology 29(3):960–970
Powers JM (2006) p53-mediated apoptosis, neuroglobin overexpression, and globin deposits in a patient with hereditary ferritinopathy. J Neuropathol Exp Neurol 65(7):716–721. doi:10.1097/01.jnen.0000228200.27539.19
Hedley-Whyte ET, Goldman JE, Nedergaard M, Friedman A, Han X, Schmidt RE, Powers JM (2009) Hyaline protoplasmic astrocytopathy of neocortex. J Neuropathol Exp Neurol 68(2):136–147
Shaw RJ, Liloglou T, Rogers SN, Brown JS, Vaughan ED, Lowe D, Field JK, Risk JM (2006) Promoter methylation of P16, RARb, E-cadherin, cyclin A1 and cytoglobin in oral cancer: quantitative evaluation using pyrosequencing. Br J Cancer 94(4):561–568
Xinarianos G, McRonald FE, Risk JM, Bowers NL, Nikolaidis G, Field JK, Liloglou T (2006) Frequent genetic and epigenetic abnormalities contribute to the deregulation of cytoglobin in non-small cell lung cancer. Hum Mol Genet 15(13):2038–2044. doi:10.1093/hmg/ddl128
Mozaffarieh M, Grieshaber Matthias C, Flammer Josef (2008) Oxygen and blood flow: players in the pathogenesisof glaucoma. Mol Vis 14:224–233
Adam J, Polivka M, Kaci R, Godfraind C, Gray F (2010) Hyaline astrocytic inclusions in pediatric epilepsy: report of two cases. Clin Neuropathol 29(4):246–253. doi:7715
Patel M (2004) Mitochondrial dysfunction and oxidative stress: cause and consequence of epileptic seizures. Free Radic Biol Med 37(12):1951–1962
Chuang YC (2010) Mitochondrial dysfunction and oxidative stress in seizure-induced neuronal cell death. Acta Neurol Taiwan 19(1):3–15. doi:10196099/1913
Tateaki Y, Ogawa T, Kawada N, Kohashi T, Arihiro K, Tateno C, Obara M, Yoshizato K (2004) Typing of hepatic nonparenchymal cells using fibulin-2 and cytoglobin/STAP as liver fibrogenesis-related markers. Histochem Cell Biol 122(1):41–49
Li JT, Liao ZX, Ping J, Xu D, Wang H (2008) Molecular mechanism of hepatic stellate cell activation and antifibrotic therapeutic strategies. J Gastroenterol 43(6):419–428. doi:10.1007/s00535-008-2180-y
Bosselut N, Housset C, Marcelo P, Rey C, Burmester T, Vinh J, Vaubourdolle M, Cadoret A, Baudin B (2010) Distinct proteomic features of two fibrogenic liver cell populations: hepatic stellate cells and portal myofibroblasts. Proteomics 10(5):1017–1028
Gnainsky Y, Kushnirsky Z, Bilu G, Hagai Y, Genina O, Volpin H, Bruck R, Spira G, Nagler A, Kawada N, Yoshizato K, Reinhardt D, Libermann T, Pines M (2007) Gene expression during chemically induced liver fibrosis: effect of halofuginone on TGF-β signaling. Cell Tissue Res 328(1):153–166
Brown GC (1995) Reversible binding and inhibition of catalase by nitric oxide. Eur J Biochem 232(1):188–191
Farias-Eisner R, Chaudhuri G, Aeberhard E, Fukuto JM (1996) The chemistry and tumoricidal activity of nitric oxide/hydrogen peroxide and the implications to cell resistance/susceptibility. J Biol Chem 271(11):6144–6151
Asahi M, Fujii J, Suzuki K, Seo HG, Kuzuya T, Hori M, Tada M, Fujii S, Taniguchi N (1995) Inactivation of glutathione peroxidase by nitric oxide Implication for cytotoxicity. J Biol Chem 270(36):21035–21039
Rauen U, Li T, Ioannidis I, de Groot H (2007) Nitric oxide increases toxicity of hydrogen peroxide against rat liver endothelial cells and hepatocytes by inhibition of hydrogen peroxide degradation. Am J Physiol Cell Physiol 292(4):C1440–C1449. doi:00366.2006
Kim YM, Bergonia HA, Muller C, Pitt BR, Watkins WD, Lancaster JR Jr (1995) Loss and degradation of enzyme-bound heme induced by cellular nitric oxide synthesis. J Biol Chem 270(11):5710–5713
Lopez-Garcia MP (1998) Endogenous nitric oxide is responsible for the early loss of P450 in cultured rat hepatocytes. FEBS Lett 438(3):145–149. doi:S0014-5793(98)01283-6
Wang J, Lu S, Moenne-Loccoz P, Ortiz de Montellano PR (2003) Interaction of nitric oxide with human heme oxygenase-1. J Biol Chem 278(4):2341–2347. doi:10.1074/jbc.M211131200
Itin PH, Fistarol, Susanna K (2005) Palmoplantar keratodermas. Clin Dermatol 23(1):15–22
Risk JM, Mills H, Garde J, Dunn J, Evans K, Hollstein M, Field J (1999) The tylosis esophageal cancer (TOC) locus: more than just a familial cancer gene. Dis Esophagus 12(3):173–176
Langan J, Cole C, Huckle E, Byrne S, McRonald F, Rowbottom L, Ellis A, Shaw J, Leigh I, Kelsell D, Dunham I, Field J, Risk J (2004) Novel microsatellite markers and single nucleotide polymorphisms refine the tylosis with oesophageal cancer (TOC) minimal region on 17q25 to 42.5 kb: sequencing does not identify the causative gene. Hum Genet 114(6):534–540
Presneau N, Dewar K, Forgetta V, Provencher D, Mes-Masson A-M, Tonin PN (2005) Loss of heterozygosity and transcriptome analyses of a 1.2 Mb candidate ovarian cancer tumor suppressor locus region at 17q25.1-q25.2. Mol Carcinog 43(3):141–154
Shaw RJ, Hall GL, Woolgar JA, Lowe D, Rogers SN, Field JK, Liloglou T, Risk JM (2007) Quantitative methylation analysis of resection margins and lymph nodes in oral squamous cell carcinoma. Br J Oral Maxillofac Surg 45(8):617–622
Hall GL, Shaw RJ, Field EA, Rogers SN, Sutton DN, Woolgar JA, Lowe D, Liloglou T, Field JK, Risk JM (2008) p16 promoter methylation is a potential predictor of malignant transformation in oral epithelial dysplasia. Cancer Epidemiol Biomarkers Prev 17(8):2174–2179
Malik K, Brown KW (2000) Epigenetic gene deregulation in cancer. Br J Cancer 83(12):1583–1588
Klaunig JE, Kamendulis LM, Hocevar BA (2010) Oxidative stress and oxidative damage in carcinogenesis. Toxicol Pathol 38(1):96–109. doi:10.1177/0192623309356453
Yang GY, Taboada S, Liao J (2009) Induced nitric oxide synthase as a major player in the oncogenic transformation of inflamed tissue. Methods Mol Biol 512:119–156. doi:10.1007/978-1-60327-530-9_8
Genin O, Rechavi G, Nagler A, Ben-Itzhak O, Nazemi KJ, Pines M (2008) Myofibroblastin pulmonary and brain metastases of alveolar soft-part sarcoma: a novel target for treatment? Neoplasia 10(9):940–948
Trachootham D, Alexandre J, Huang P (2009) Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 8(7):579–591
Siegel PM, Massague J (2003) Cytostatic and apoptotic actions of TGF-b in homeostasis and cancer. Nat Rev Cancer 3(11):807–820
Lv Y, Wang Qizhao, Diao Yong, Xu Ruian (2008) Cytoglobin: a novel potential gene medicine for fibrosis and cancer therapy. Curr Gene Ther 8(4):287–294
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We would like to acknowledge the Roy Castle Lung Cancer Foundation (Liverpool, UK) for financial support.
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Oleksiewicz, U., Liloglou, T., Field, J.K. et al. Cytoglobin: biochemical, functional and clinical perspective of the newest member of the globin family. Cell. Mol. Life Sci. 68, 3869–3883 (2011). https://doi.org/10.1007/s00018-011-0764-9
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DOI: https://doi.org/10.1007/s00018-011-0764-9