{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T16:20:47Z","timestamp":1772209247050,"version":"3.50.1"},"reference-count":98,"publisher":"Springer Science and Business Media LLC","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Mol Med"],"published-print":{"date-parts":[[2008,10]]},"DOI":"10.1007\/s00109-008-0368-5","type":"journal-article","created":{"date-parts":[[2008,7,18]],"date-time":"2008-07-18T08:15:53Z","timestamp":1216368953000},"page":"1097-1111","source":"Crossref","is-referenced-by-count":173,"title":["A central role for free heme in the pathogenesis of severe malaria: the missing link?"],"prefix":"10.1007","volume":"86","author":[{"given":"Ana","family":"Ferreira","sequence":"first","affiliation":[]},{"given":"J\u00f3zsef","family":"Balla","sequence":"additional","affiliation":[]},{"given":"Vikt\u00f3ria","family":"Jeney","sequence":"additional","affiliation":[]},{"given":"Gy\u00f6rgy","family":"Balla","sequence":"additional","affiliation":[]},{"given":"Miguel P.","family":"Soares","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2008,7,19]]},"reference":[{"key":"368_CR1","unstructured":"WHO (2000) Expert Committee on Malaria: 20th Report. http:\/\/www.rbm.who.int\/docs\/ecr20.pdf"},{"key":"368_CR2","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/nrmicro1529","volume":"4","author":"M Prudencio","year":"2006","unstructured":"Prudencio M, Rodriguez A, Mota MM (2006) The silent path to thousands of merozoites: the Plasmodium liver stage. Nat Rev Microbiol 4:849\u2013856","journal-title":"Nat Rev Microbiol"},{"key":"368_CR3","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/nri1686","volume":"5","author":"L Schofield","year":"2005","unstructured":"Schofield L, Grau GE (2005) Immunological processes in malaria pathogenesis. Nat Rev Immunol 5:722\u2013735","journal-title":"Nat Rev Immunol"},{"key":"368_CR4","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1146\/annurev.pathol.2.010506.091913","volume":"2","author":"K Haldar","year":"2007","unstructured":"Haldar K, Murphy SC, Milner DA, Taylor TE (2007) Malaria: mechanisms of erythrocytic infection and pathological correlates of severe disease. Annu Rev Pathol 2:217\u2013249","journal-title":"Annu Rev Pathol"},{"key":"368_CR5","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/S1474-4422(05)70247-7","volume":"4","author":"R Idro","year":"2005","unstructured":"Idro R, Jenkins NE, Newton CR (2005) Pathogenesis, clinical features, and neurological outcome of cerebral malaria. Lancet Neurol 4:827\u2013840","journal-title":"Lancet Neurol"},{"key":"368_CR6","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/415673a","volume":"415","author":"LH Miller","year":"2002","unstructured":"Miller LH, Baruch DI, Marsh K, Doumbo OK (2002) The pathogenic basis of malaria. Nature 415:673\u2013679","journal-title":"Nature"},{"key":"368_CR7","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1056\/NEJM199505253322102","volume":"332","author":"K Marsh","year":"1995","unstructured":"Marsh K, Forster D, Waruiru C et al (1995) Indicators of life-threatening malaria in African children. N Engl J Med 332:1399\u20131404","journal-title":"N Engl J Med"},{"key":"368_CR8","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nm1586","volume":"13","author":"A Pamplona","year":"2007","unstructured":"Pamplona A, Ferreira A, Balla J et al (2007) Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria. Nat Med 13:703\u2013710","journal-title":"Nat Med"},{"key":"368_CR9","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1038\/nm1499","volume":"12","author":"I Gramaglia","year":"2006","unstructured":"Gramaglia I, Sobolewski P, Meays D et al (2006) Low nitric oxide bioavailability contributes to the genesis of experimental cerebral malaria. Nat Med 12:1417\u20131422","journal-title":"Nat Med"},{"key":"368_CR10","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/nri1978","volume":"6","author":"RT Gazzinelli","year":"2006","unstructured":"Gazzinelli RT, Denkers EY (2006) Protozoan encounters with Toll-like receptor signalling pathways: implications for host parasitism. Nat Rev Immunol 6:895\u2013906","journal-title":"Nat Rev Immunol"},{"key":"368_CR11","doi-asserted-by":"crossref","first-page":"8606","DOI":"10.1074\/jbc.M413541200","volume":"280","author":"G Krishnegowda","year":"2005","unstructured":"Krishnegowda G, Hajjar AM, Zhu J et al (2005) Induction of proinflammatory responses in macrophages by the glycosylphosphatidylinositols of Plasmodium falciparum: cell signaling receptors, glycosylphosphatidylinositol (GPI) structural requirement, and regulation of GPI activity. J Biol Chem 280:8606\u20138616","journal-title":"J Biol Chem"},{"key":"368_CR12","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1073\/pnas.0608745104","volume":"104","author":"P Parroche","year":"2007","unstructured":"Parroche P, Lauw FN, Goutagny N et al (2007) Malaria hemozoin is immunologically inert but radically enhances innate responses by presenting malaria DNA to Toll-like receptor 9. Proc Natl Acad Sci U S A 104:1919\u20131924","journal-title":"Proc Natl Acad Sci U S A"},{"key":"368_CR13","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/intimm\/dxl123","volume":"19","author":"C Coban","year":"2007","unstructured":"Coban C, Ishii KJ, Uematsu S et al (2007) Pathological role of Toll-like receptor signaling in cerebral malaria. Int Immunol 19:67\u201379","journal-title":"Int Immunol"},{"key":"368_CR14","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1073\/pnas.0506803102","volume":"103","author":"FP Mockenhaupt","year":"2006","unstructured":"Mockenhaupt FP, Cramer JP, Hamann L et al (2006) Toll-like receptor (TLR) polymorphisms in African children: common TLR-4 variants predispose to severe malaria. Proc Natl Acad Sci U S A 103:177\u2013182","journal-title":"Proc Natl Acad Sci U S A"},{"key":"368_CR15","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1086\/505152","volume":"194","author":"FP Mockenhaupt","year":"2006","unstructured":"Mockenhaupt FP, Hamann L, von Gaertner C et al (2006) Common polymorphisms of toll-like receptors 4 and 9 are associated with the clinical manifestation of malaria during pregnancy. J Infect Dis 194:184\u2013188","journal-title":"J Infect Dis"},{"key":"368_CR16","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/ng1976","volume":"39","author":"CC Khor","year":"2007","unstructured":"Khor CC, Chapman SJ, Vannberg FO et al (2007) A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis. Nat Genet 39:523\u2013528","journal-title":"Nat Genet"},{"key":"368_CR17","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.2353\/ajpath.2007.060889","volume":"170","author":"D Togbe","year":"2007","unstructured":"Togbe D, Schofield L, Grau GE et al (2007) Murine cerebral malaria development is independent of toll-like receptor signaling. Am J Pathol 170:1640\u20131648","journal-title":"Am J Pathol"},{"key":"368_CR18","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00430-007-0057-y","volume":"197","author":"B Lepenies","year":"2008","unstructured":"Lepenies B, Cramer JP, Burchard GD, Wagner H, Kirschning CJ, Jacobs T (2008) Induction of experimental cerebral malaria is independent of TLR2\/4\/9. Med Microbiol Immunol 197:39\u201344","journal-title":"Med Microbiol Immunol"},{"key":"368_CR19","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev.immunol.23.021704.115638","volume":"23","author":"MF Good","year":"2005","unstructured":"Good MF, Xu H, Wykes M, Engwerda CR (2005) Development and regulation of cell-mediated immune responses to the blood stages of malaria: implications for vaccine research. Annu Rev Immunol 23:69\u201399","journal-title":"Annu Rev Immunol"},{"key":"368_CR20","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1126\/science.1148526","volume":"318","author":"L Raberg","year":"2007","unstructured":"Raberg L, Sim D, Read AF (2007) Disentangling genetic variation for resistance and tolerance to infectious diseases in animals. Science 318:812\u2013814","journal-title":"Science"},{"key":"368_CR21","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1146\/annurev.micro.51.1.97","volume":"51","author":"SE Francis","year":"1997","unstructured":"Francis SE, Sullivan DJ Jr, Goldberg DE (1997) Hemoglobin metabolism in the malaria parasite Plasmodium falciparum. Annu Rev Microbiol 51:97\u2013123","journal-title":"Annu Rev Microbiol"},{"key":"368_CR22","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1126\/science.7027441","volume":"214","author":"AU Orjih","year":"1981","unstructured":"Orjih AU, Banyal HS, Chevli R, Fitch CD (1981) Hemin lyses malaria parasites. Science 214:667\u2013669","journal-title":"Science"},{"key":"368_CR23","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1001\/jama.293.13.1653","volume":"293","author":"RP Rother","year":"2005","unstructured":"Rother RP, Bell L, Hillmen P, Gladwin MT (2005) The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA 293:1653\u20131662","journal-title":"JAMA"},{"key":"368_CR24","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1182\/blood.V100.3.879","volume":"100","author":"V Jeney","year":"2002","unstructured":"Jeney V, Balla J, Yachie A et al (2002) Pro-oxidant and cytotoxic effects of circulating heme. Blood 100:879\u2013887","journal-title":"Blood"},{"key":"368_CR25","doi-asserted-by":"crossref","first-page":"3442","DOI":"10.1182\/blood.V95.11.3442","volume":"95","author":"J Balla","year":"2000","unstructured":"Balla J, Balla G, Jeney V, Kakuk G, Jacob HS, Vercellotti GM (2000) Ferriporphyrins and endothelium: a 2-edged sword-promotion of oxidation and induction of cytoprotectants. Blood 95:3442\u20133450","journal-title":"Blood"},{"key":"368_CR26","doi-asserted-by":"crossref","first-page":"9285","DOI":"10.1073\/pnas.90.20.9285","volume":"90","author":"J Balla","year":"1993","unstructured":"Balla J, Jacob HS, Balla G, Nath K, Eaton JW, Vercellotti GM (1993) Endothelial-cell heme uptake from heme proteins: induction of sensitization and desensitization to oxidant damage. Proc Natl Acad Sci U S A 90:9285\u20139289","journal-title":"Proc Natl Acad Sci U S A"},{"key":"368_CR27","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1002\/mnfr.200500076","volume":"49","author":"J Balla","year":"2005","unstructured":"Balla J, Vercellotti GM, Jeney V et al (2005) Heme, heme oxygenase and ferritin in vascular endothelial cell injury. Mol Nutr Food Res 49:1030\u20131043","journal-title":"Mol Nutr Food Res"},{"key":"368_CR28","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1073\/pnas.61.2.748","volume":"61","author":"R Tenhunen","year":"1968","unstructured":"Tenhunen R, Marver HS, Schmid R (1968) The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci U S A 61:748\u2013755","journal-title":"Proc Natl Acad Sci U S A"},{"key":"368_CR29","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/nri1372","volume":"4","author":"S-Y Seong","year":"2004","unstructured":"Seong S-Y, Matzinger P (2004) Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses. Nat Rev Immunol 4:469\u2013478","journal-title":"Nat Rev Immunol"},{"key":"368_CR30","doi-asserted-by":"crossref","first-page":"20221","DOI":"10.1074\/jbc.M610737200","volume":"282","author":"RT Figueiredo","year":"2007","unstructured":"Figueiredo RT, Fernandez PL, Mourao-Sa DS et al (2007) Characterization of heme as activator of Toll-like receptor 4. J Biol Chem 282:20221\u201320229","journal-title":"J Biol Chem"},{"key":"368_CR31","doi-asserted-by":"crossref","first-page":"24430","DOI":"10.1074\/jbc.M703570200","volume":"282","author":"BN Porto","year":"2007","unstructured":"Porto BN, Alves LS, Fernandez PL et al (2007) Heme induces neutrophil migration and reactive oxygen species generation through signaling pathways characteristic of chemotactic receptors. J Biol Chem 282:24430\u201324436","journal-title":"J Biol Chem"},{"key":"368_CR32","doi-asserted-by":"crossref","first-page":"4160","DOI":"10.1182\/blood.V99.11.4160","volume":"99","author":"AV Graca-Souza","year":"2002","unstructured":"Graca-Souza AV, Arruda MA, de Freitas MS, Barja-Fidalgo C, Oliveira PL (2002) Neutrophil activation by heme: implications for inflammatory processes. Blood 99:4160\u20134165","journal-title":"Blood"},{"key":"368_CR33","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.4049\/jimmunol.173.3.2023","volume":"173","author":"MA Arruda","year":"2004","unstructured":"Arruda MA, Rossi AG, de Freitas MS, Barja-Fidalgo C, Graca-Souza AV (2004) Heme inhibits human neutrophil apoptosis: involvement of phosphoinositide 3-kinase, MAPK, and NF-kappaB. J Immunol 173:2023\u20132030","journal-title":"J Immunol"},{"key":"368_CR34","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1126\/science.3306918","volume":"237","author":"GE Grau","year":"1987","unstructured":"Grau GE, Fajardo LF, Piguet PF, Allet B, Lambert PH, Vassalli P (1987) Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science 237:1210\u20131212","journal-title":"Science"},{"key":"368_CR35","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/355167a0","volume":"355","author":"AF Slater","year":"1992","unstructured":"Slater AF, Cerami A (1992) Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites. Nature 355:167\u2013169","journal-title":"Nature"},{"key":"368_CR36","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/ni1501","volume":"8","author":"N Jiang","year":"2007","unstructured":"Jiang N, Tan NS, Ho B, Ding JL (2007) Respiratory protein-generated reactive oxygen species as an antimicrobial strategy. Nat Immunol 8:1114\u20131122","journal-title":"Nat Immunol"},{"key":"368_CR37","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/35051594","volume":"409","author":"M Kristiansen","year":"2001","unstructured":"Kristiansen M, Graversen JH, Jacobsen C et al (2001) Identification of the haemoglobin scavenger receptor. Nature 409:198\u2013201","journal-title":"Nature"},{"key":"368_CR38","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/309131a0","volume":"309","author":"N Maeda","year":"1984","unstructured":"Maeda N, Yang F, Barnett DR, Bowman BH, Smithies O (1984) Duplication within the haptoglobin Hp2 gene. Nature 309:131\u2013135","journal-title":"Nature"},{"key":"368_CR39","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1086\/511868","volume":"44","author":"SH Atkinson","year":"2007","unstructured":"Atkinson SH, Mwangi TW, Uyoga SM et al (2007) The haptoglobin 2-2 genotype is associated with a reduced incidence of Plasmodium falciparum malaria in children on the coast of Kenya. Clin Infect Dis 44:802\u2013809","journal-title":"Clin Infect Dis"},{"key":"368_CR40","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/0035-9203(85)90053-7","volume":"79","author":"JF Trape","year":"1985","unstructured":"Trape JF, Fribourg-Blanc A, Bosseno MF, Lallemant M, Engler R, Mouchet J (1985) Malaria, cause of ahaptoglobinaemia in Africans. Trans R Soc Trop Med Hyg 79:430\u2013434","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"368_CR41","first-page":"94","volume":"12","author":"EK Uko","year":"2003","unstructured":"Uko EK, Udoh AE, Etukudoh MH (2003) Methaemoglobin profile in malaria infected children in Calabar. Niger J Med 12:94\u201397","journal-title":"Niger J Med"},{"key":"368_CR42","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0035-9203(96)90118-2","volume":"90","author":"NM Anstey","year":"1996","unstructured":"Anstey NM, Hassanali MY, Mlalasi J, Manyenga D, Mwaikambo ED (1996) Elevated levels of methaemoglobin in Tanzanian children with severe and uncomplicated malaria. Trans R Soc Trop Med Hyg 90:147\u2013151","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"368_CR43","doi-asserted-by":"crossref","first-page":"2572","DOI":"10.1182\/blood-2005-03-1185","volume":"106","author":"V Hvidberg","year":"2005","unstructured":"Hvidberg V, Maniecki MB, Jacobsen C, Hojrup P, Moller HJ, Moestrup SK (2005) Identification of the receptor scavenging hemopexin\u2013heme complexes. Blood 106:2572\u20132579","journal-title":"Blood"},{"key":"368_CR44","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1126\/science.3029864","volume":"235","author":"R Stocker","year":"1987","unstructured":"Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN (1987) Bilirubin is an antioxidant of possible physiological importance. Science 235:1043\u20131046","journal-title":"Science"},{"key":"368_CR45","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1152\/physiol.00029.2005","volume":"20","author":"MD Maines","year":"2005","unstructured":"Maines MD (2005) New insights into biliverdin reductase functions: linking heme metabolism to cell signaling. Physiology (Bethesda) 20:382\u2013389","journal-title":"Physiology (Bethesda)"},{"key":"368_CR46","doi-asserted-by":"crossref","first-page":"18148","DOI":"10.1016\/S0021-9258(19)37165-0","volume":"267","author":"G Balla","year":"1992","unstructured":"Balla G, Jacob HS, Balla J et al (1992) Ferritin: a cytoprotective antioxidant strategem of endothelium. J Biol Chem 267:18148\u201318153","journal-title":"J Biol Chem"},{"key":"368_CR47","doi-asserted-by":"crossref","first-page":"25122","DOI":"10.1074\/jbc.M003797200","volume":"275","author":"A Cozzi","year":"2000","unstructured":"Cozzi A, Corsi B, Levi S, Santambrogio P, Albertini A, Arosio P (2000) Overexpression of wild type and mutated human ferritin H-chain in HeLa cells\u2014in vivo role of ferritin ferroxidase activity. J Biol Chem 275:25122\u201325129","journal-title":"J Biol Chem"},{"key":"368_CR48","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1096\/fj.03-0229fje","volume":"17","author":"PO Berberat","year":"2003","unstructured":"Berberat PO, Katori M, Kaczmarek E et al (2003) Heavy chain ferritin acts as an antiapoptotic gene that protects livers from ischemia reperfusion injury. FASEB J 17:1724\u20131726","journal-title":"FASEB J"},{"key":"368_CR49","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0005-2728(96)00022-9","volume":"1275","author":"PM Harrison","year":"1996","unstructured":"Harrison PM, Arosio P (1996) Ferritins\u2014molecular properties, iron storage function and cellular regulation. Biochimica et Biophysica Acta\u2013Bioenergetics 1275:161\u2013203","journal-title":"Biochimica et Biophysica Acta\u2013Bioenergetics"},{"key":"368_CR50","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.cell.2004.10.017","volume":"119","author":"CG Pham","year":"2004","unstructured":"Pham CG, Bubici C, Zazzeroni F et al (2004) Ferritin heavy chain upregulation by NF-kappaB inhibits TNFalpha-induced apoptosis by suppressing reactive oxygen species. Cell 119:529\u2013542","journal-title":"Cell"},{"key":"368_CR51","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S1471-4906(03)00181-9","volume":"24","author":"LE Otterbein","year":"2003","unstructured":"Otterbein LE, Soares MP, Yamashita K, Bach FH (2003) Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol 24:449\u2013455","journal-title":"Trends Immunol"},{"key":"368_CR52","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s004010000250","volume":"101","author":"HJ Schluesener","year":"2001","unstructured":"Schluesener HJ, Kremsner PG, Meyermann R (2001) Heme oxygenase-1 in lesions of human cerebral malaria. Acta Neuropathol (Berl) 101:65\u201368","journal-title":"Acta Neuropathol (Berl)"},{"key":"368_CR53","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1046\/j.0305-1846.2001.00360.x","volume":"27","author":"IM Medana","year":"2001","unstructured":"Medana IM, Mai NT, Day NP et al (2001) Cellular stress and injury responses in the brains of adult Vietnamese patients with fatal Plasmodium falciparum malaria. Neuropathol Appl Neurobiol 27:421\u2013433","journal-title":"Neuropathol Appl Neurobiol"},{"key":"368_CR54","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1475-2875-2-41","volume":"2","author":"IA Clark","year":"2003","unstructured":"Clark IA, Awburn MM, Harper CG, Liomba NG, Molyneux ME (2003) Induction of HO-1 in tissue macrophages and monocytes in fatal falciparum malaria and sepsis. Malar J 2:41","journal-title":"Malar J"},{"key":"368_CR55","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1182\/blood-2003-08-2760","volume":"104","author":"ML Jison","year":"2004","unstructured":"Jison ML, Munson PJ, Barb JJ et al (2004) Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease. Blood 104:270\u2013280","journal-title":"Blood"},{"key":"368_CR56","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1172\/JCI4165","volume":"103","author":"A Yachie","year":"1999","unstructured":"Yachie A, Niida Y, Wada T et al (1999) Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J Clin Invest 103:129\u2013135","journal-title":"J Clin Invest"},{"key":"368_CR57","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.freeradbiomed.2004.07.008","volume":"37","author":"M Exner","year":"2004","unstructured":"Exner M, Minar E, Wagner O, Schillinger M (2004) The role of heme oxygenase-1 promoter polymorphisms in human disease. Free Radic Biol Med 37:1097\u20131104","journal-title":"Free Radic Biol Med"},{"key":"368_CR58","doi-asserted-by":"crossref","first-page":"268","DOI":"10.7883\/yoken.JJID.2005.268","volume":"58","author":"M Takeda","year":"2005","unstructured":"Takeda M, Kikuchi M, Ubalee R et al (2005) Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to cerebral malaria in Myanmar. Jpn J Infect Dis 58:268\u2013271","journal-title":"Jpn J Infect Dis"},{"key":"368_CR59","doi-asserted-by":"crossref","unstructured":"Epiphanio S, Mikolajczak SA, Goncalves et al (2008) Heme oxygenase-1 is an anti-inflammatory host factor that promotes murine plasmodium liver infection. Cell Host Microbe 3, 331\u2013338","DOI":"10.1016\/j.chom.2008.04.003"},{"key":"368_CR60","doi-asserted-by":"crossref","first-page":"4185","DOI":"10.4049\/jimmunol.166.6.4185","volume":"166","author":"K Sato","year":"2001","unstructured":"Sato K, Balla J, Otterbein L et al (2001) Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse to rat cardiac transplants. J Immunol 166:4185\u20134194","journal-title":"J Immunol"},{"key":"368_CR61","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/74680","volume":"6","author":"LE Otterbein","year":"2000","unstructured":"Otterbein LE, Bach FH, Alam J et al (2000) Carbon monoxide mediates anti-inflammatory effects via the mitogen activated protein kinase pathway. Nat Med 6:422\u2013428","journal-title":"Nat Med"},{"key":"368_CR62","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/nm817","volume":"9","author":"LE Otterbein","year":"2003","unstructured":"Otterbein LE, Zuckerbraun BS, Haga M et al (2003) Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury. Nat Med 9:183\u2013190","journal-title":"Nat Med"},{"key":"368_CR63","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1172\/JCI28844","volume":"117","author":"AA Chora","year":"2007","unstructured":"Chora AA, Fontoura P, Cunha A et al (2007) Heme oxygenase-1 and carbon monoxide suppress autoimmune neuroinflammation. J Clin Invest 117:438\u2013447","journal-title":"J Clin Invest"},{"key":"368_CR64","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1161\/CIRCULATIONAHA.104.528802","volume":"112","author":"R Ollinger","year":"2005","unstructured":"Ollinger R, Bilban M, Erat A et al (2005) Bilirubin: a natural inhibitor of vascular smooth muscle cell proliferation. Circulation 112:1030\u20131039","journal-title":"Circulation"},{"key":"368_CR65","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1084\/jem.192.7.1015","volume":"192","author":"S Brouard","year":"2000","unstructured":"Brouard S, Otterbein LE, Anrather J et al (2000) Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis. J Exp Med 192:1015\u20131026","journal-title":"J Exp Med"},{"key":"368_CR66","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00109-007-0276-0","volume":"86","author":"M Bilban","year":"2008","unstructured":"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\u2013279","journal-title":"J Mol Med"},{"key":"368_CR67","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.1021\/bi952386+","volume":"35","author":"JR Stone","year":"1996","unstructured":"Stone JR, Sands RH, Dunham WR, Marletta MA (1996) Spectral and ligand-binding properties of an unusual hemoprotein, the ferric form of soluble guanylate cyclase. Biochemistry 35:3258\u20133262","journal-title":"Biochemistry"},{"key":"368_CR68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.ph.52.030190.000245","volume":"52","author":"MF Perutz","year":"1990","unstructured":"Perutz MF (1990) Mechanisms regulating the reactions of human hemoglobin with oxygen and carbon monoxide. Annu Rev Physiol 52:1\u201325","journal-title":"Annu Rev Physiol"},{"key":"368_CR69","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1073\/pnas.92.7.2568","volume":"92","author":"VG Kharitonov","year":"1995","unstructured":"Kharitonov VG, Sharma VS, Pilz RB, Magde D, Koesling D (1995) Basis of guanylate cyclase activation by carbon monoxide. Proc Natl Acad Sci U S A 92:2568\u20132571","journal-title":"Proc Natl Acad Sci U S A"},{"key":"368_CR70","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1006\/meth.1999.0892","volume":"19","author":"VS Sharma","year":"1999","unstructured":"Sharma VS, Magde D (1999) Activation of soluble guanylate cyclase by carbon monoxide and nitric oxide: a mechanistic model. Methods 19:494\u2013505","journal-title":"Methods"},{"key":"368_CR71","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1146\/annurev.pharmtox.46.120604.141053","volume":"46","author":"HP Kim","year":"2005","unstructured":"Kim HP, Ryter SW, Choi AM (2005) CO as a cellular signaling molecule. Annu Rev Pharmacol Toxicol 46:411\u2013449","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"368_CR72","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/S0021-9258(17)45261-6","volume":"240","author":"QH Gibson","year":"1965","unstructured":"Gibson QH, Palmer G, Wharton DC (1965) The binding of carbon monoxide by cytochrome c oxidase and the ratio of the cytochromes a and A3. J Biol Chem 240:915\u2013920","journal-title":"J Biol Chem"},{"key":"368_CR73","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nrm762","volume":"3","author":"S Moncada","year":"2002","unstructured":"Moncada S, Erusalimsky JD (2002) Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nat Rev Mol Cell Biol 3:214\u2013220","journal-title":"Nat Rev Mol Cell Biol"},{"key":"368_CR74","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1096\/fj.06-6644com","volume":"21","author":"BS Zuckerbraun","year":"2007","unstructured":"Zuckerbraun BS, Chin BY, Bilban M et al (2007) Carbon monoxide signals via inhibition of cytochrome c oxidase and generation of mitochondrial reactive oxygen species. FASEB J 21:1099\u20131106","journal-title":"FASEB J"},{"key":"368_CR75","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.immuni.2006.03.012","volume":"24","author":"M Bilban","year":"2006","unstructured":"Bilban M, Bach FH, Otterbein SL et al (2006) Carbon monoxide orchestrates a protective response through PPARgamma. Immunity 24:601\u2013610","journal-title":"Immunity"},{"key":"368_CR76","doi-asserted-by":"crossref","first-page":"5109","DOI":"10.1073\/pnas.0609611104","volume":"104","author":"BY Chin","year":"2007","unstructured":"Chin BY, Jiang G, Wegiel B et al (2007) Hypoxia-inducible factor 1 alpha stabilization by carbon monoxide results in cytoprotective preconditioning. Proc Natl Acad Sci U S A 104:5109\u20135114","journal-title":"Proc Natl Acad Sci U S A"},{"key":"368_CR77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0898-6568(99)00071-6","volume":"12","author":"K Ono","year":"2000","unstructured":"Ono K, Han J (2000) The p38 signal transduction pathway: activation and function. Cell Signal 12:1\u201313","journal-title":"Cell Signal"},{"key":"368_CR78","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.4049\/jimmunol.177.3.1894","volume":"177","author":"G Silva","year":"2006","unstructured":"Silva G, Cunha A, Gregoire IP, Seldon MP, Soares MP (2006) The antiapoptotic effect of heme oxygenase-1 in endothelial cells involves the degradation of p38{alpha} MAPK isoform. J Immunol 177:1894\u20131903","journal-title":"J Immunol"},{"key":"368_CR79","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.4049\/jimmunol.175.4.2622","volume":"175","author":"HP Kim","year":"2005","unstructured":"Kim HP, Wang X, Zhang J et al (2005) Heat shock protein-70 mediates the cytoprotective effect of carbon monoxide: involvement of p38 beta MAPK and heat shock factor-1. J Immunol 175:2622\u20132629","journal-title":"J Immunol"},{"key":"368_CR80","doi-asserted-by":"crossref","first-page":"11319","DOI":"10.1073\/pnas.0501345102","volume":"102","author":"HP Kim","year":"2005","unstructured":"Kim HP, Wang X, Nakao A et al (2005) Caveolin-1 expression by means of p38beta mitogen-activated protein kinase mediates the antiproliferative effect of carbon monoxide. Proc Natl Acad Sci U S A 102:11319\u201311324","journal-title":"Proc Natl Acad Sci U S A"},{"key":"368_CR81","doi-asserted-by":"crossref","first-page":"6712","DOI":"10.1073\/pnas.1031789100","volume":"100","author":"JS Welch","year":"2003","unstructured":"Welch JS, Ricote M, Akiyama TE, Gonzalez FJ, Glass CK (2003) PPARgamma and PPARdelta negatively regulate specific subsets of lipopolysaccharide and IFN-gamma target genes in macrophages. Proc Natl Acad Sci U S A 100:6712\u20136717","journal-title":"Proc Natl Acad Sci U S A"},{"key":"368_CR82","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1126\/science.1078456","volume":"298","author":"EM Dioum","year":"2002","unstructured":"Dioum EM, Rutter J, Tuckerman JR, Gonzalez G, Gilles-Gonzalez MA, McKnight SL (2002) NPAS2: a gas-responsive transcription factor. Science 298:2385\u20132387","journal-title":"Science"},{"key":"368_CR83","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/S0140-6736(68)91469-4","volume":"1","author":"F Hawking","year":"1968","unstructured":"Hawking F, Worms MJ, Gammage K (1968) Host temperature and control of 24-hour and 48-hour cycles in malaria parasites. Lancet 1:506\u2013509","journal-title":"Lancet"},{"key":"368_CR84","doi-asserted-by":"crossref","first-page":"43","DOI":"10.4269\/ajtmh.2004.71.43","volume":"71","author":"AJ Cunnington","year":"2004","unstructured":"Cunnington AJ, Kendrick SF, Wamola B, Lowe B, Newton CR (2004) Carboxyhemoglobin levels in Kenyan children with Plasmodium falciparum malaria. Am J Trop Med Hyg 71:43\u201347","journal-title":"Am J Trop Med Hyg"},{"key":"368_CR85","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1212\/WNL.55.1.104","volume":"55","author":"HC Brown","year":"2000","unstructured":"Brown HC, Chau TT, Mai NT et al (2000) Blood-brain barrier function in cerebral malaria and CNS infections in Vietnam. Neurology 55:104\u2013111","journal-title":"Neurology"},{"key":"368_CR86","doi-asserted-by":"crossref","first-page":"4941","DOI":"10.1128\/IAI.73.8.4941-4947.2005","volume":"73","author":"SM Potter","year":"2005","unstructured":"Potter SM, Mitchell AJ, Cowden WB et al (2005) Phagocyte-derived reactive oxygen species do not influence the progression of murine blood-stage malaria infections. Infect Immun 73:4941\u20134947","journal-title":"Infect Immun"},{"key":"368_CR87","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/0169-4758(94)90237-2","volume":"10","author":"IA Clark","year":"1994","unstructured":"Clark IA, Rockett KA (1994) The cytokine theory of human cerebral malaria. Parasitol Today 10:410\u2013412","journal-title":"Parasitol Today"},{"key":"368_CR88","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1084\/jem.20060845","volume":"203","author":"K Nakahira","year":"2006","unstructured":"Nakahira K, Kim HP, Geng XH et al (2006) Carbon monoxide differentially inhibits TLR signaling pathways by regulating ROS-induced trafficking of TLRs to lipid rafts. J Exp Med 203:2377\u20132389","journal-title":"J Exp Med"},{"key":"368_CR89","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.4049\/jimmunol.127.6.2469","volume":"127","author":"KH Stenzel","year":"1981","unstructured":"Stenzel KH, Rubin AL, Novogrodsky A (1981) Mitogenic and co-mitogenic properties of hemin. J Immunol 127:2469\u20132473","journal-title":"J Immunol"},{"key":"368_CR90","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.4049\/jimmunol.143.12.3981","volume":"143","author":"A Novogrodsky","year":"1989","unstructured":"Novogrodsky A, Suthanthiran M, Stenzel KH (1989) Immune stimulatory properties of metalloporphyrins. J Immunol 143:3981\u20133987","journal-title":"J Immunol"},{"key":"368_CR91","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.1084\/jem.20070819","volume":"204","author":"TW Yeo","year":"2007","unstructured":"Yeo TW, Lampah DA, Gitawati R et al (2007) Impaired nitric oxide bioavailability and l-arginine reversible endothelial dysfunction in adults with falciparum malaria. J Exp Med 204:2693\u20132704","journal-title":"J Exp Med"},{"key":"368_CR92","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1038\/nm1202-799","volume":"8","author":"CD Reiter","year":"2002","unstructured":"Reiter CD, Wang X, Tanus-Santos JE et al (2002) Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med 8:1383\u20131389","journal-title":"Nat Med"},{"key":"368_CR93","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/0003-9861(90)90596-Q","volume":"277","author":"KR Maples","year":"1990","unstructured":"Maples KR, Kennedy CH, Jordan SJ, Mason RP (1990) In vivo thiyl free radical formation from hemoglobin following administration of hydroperoxides. Arch Biochem Biophys 277:402\u2013409","journal-title":"Arch Biochem Biophys"},{"key":"368_CR94","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/BF01024768","volume":"9","author":"DJ McCormick","year":"1990","unstructured":"McCormick DJ, Atassi MZ (1990) Hemoglobin binding with haptoglobin: delineation of the haptoglobin binding site on the alpha-chain of human hemoglobin. J Protein Chem 9:735\u2013742","journal-title":"J Protein Chem"},{"key":"368_CR95","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S0021-9258(18)93628-8","volume":"243","author":"HF Bunn","year":"1968","unstructured":"Bunn HF, Jandl JH (1968) Exchange of heme among hemoglobins and between hemoglobin and albumin. J Biol Chem 243:465\u2013475","journal-title":"J Biol Chem"},{"key":"368_CR96","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1038\/13294","volume":"6","author":"M Paoli","year":"1999","unstructured":"Paoli M, Anderson BF, Baker HM, Morgan WT, Smith A, Baker EN (1999) Crystal structure of hemopexin reveals a novel high-affinity heme site formed between two beta-propeller domains. Nat Struct Biol 6:926\u2013931","journal-title":"Nat Struct Biol"},{"key":"368_CR97","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/188913a0","volume":"188","author":"HN Little","year":"1960","unstructured":"Little HN, Neilands JB (1960) Binding of haematin by human serum albumin. Nature 188:913\u2013915","journal-title":"Nature"},{"key":"368_CR98","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1080\/15216540701474523","volume":"59","author":"M Fasano","year":"2007","unstructured":"Fasano M, Fanali G, Leboffe L, Ascenzi P (2007) Heme binding to albuminoid proteins is the result of recent evolution. IUBMB Life 59:436\u2013440","journal-title":"IUBMB Life"}],"container-title":["Journal of Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-008-0368-5.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T12:13:55Z","timestamp":1709122435000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00109-008-0368-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7,19]]},"references-count":98,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2008,10]]}},"alternative-id":["368"],"URL":"https:\/\/doi.org\/10.1007\/s00109-008-0368-5","relation":{},"ISSN":["0946-2716","1432-1440"],"issn-type":[{"value":"0946-2716","type":"print"},{"value":"1432-1440","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,7,19]]}}}