Heme oxygenase in neuroprotection: from mechanisms to therapeutic implications

References

Abraham, N.G. and Kappas, A. (2008). Pharmacological and clinical aspects of heme oxygenase. Pharmacol. Rev. 60, 79–127.10.1124/pr.107.07104Search in Google Scholar PubMed

Adin, C.A., Croker, B.P., and Agarwal, A. (2005). Protective effects of exogenous bilirubin on ischemia-reperfusion injury in the isolated, perfused rat kidney. Am. J. Physiol. Renal. Physiol. 288, F778–784.10.1152/ajprenal.00215.2004Search in Google Scholar PubMed

Ahmad, A.S., Zhuang, H., and Dore, S. (2006). Heme oxygenase-1 protects brain from acute excitotoxicity. Neuroscience 141, 1703–1708.10.1016/j.neuroscience.2006.05.035Search in Google Scholar PubMed

Antonelli, M.C., Guillemin, G.J., Raisman-Vozari, R., Del-Bel, E.A., Aschner, M., Collins, M.A., Tizabi, Y., Moratalla, R., and West, A.K. (2011). New strategies in neuroprotection and neurorepair. Neurotox. Res. 21, 49–56.10.1007/s12640-011-9265-8Search in Google Scholar PubMed PubMed Central

Arai-Gaun, S., Katai, N., Kikuchi, T., Kurokawa, T., Ohta, K., and Yoshimura, N. (2004). Heme oxygenase-1 induced in Muller cells plays a protective role in retinal ischemia-reperfusion injury in rats. Invest. Ophthalmol. Vis. Sci. 45, 4226–4232.10.1167/iovs.04-0450Search in Google Scholar PubMed

Baranano, D.E., Wolosker, H., Bae, B.I., Barrow, R.K., Snyder, S.H., and Ferris, C.D. (2000). A mammalian iron ATPase induced by iron. J. Biol. Chem. 275, 15166–15173.10.1074/jbc.275.20.15166Search in Google Scholar PubMed

Baranano, D.E., Rao, M., Ferris, C.D., and Snyder, S.H. (2002). Biliverdin reductase: a major physiologic cytoprotectant. Proc. Natl. Acad. Sci. USA 99, 16093–16098.10.1073/pnas.252626999Search in Google Scholar PubMed PubMed Central

Barger, S.W., Fiscus, R.R., Ruth, P., Hofmann, F., and Mattson, M.P. (1995). Role of cyclic GMP in the regulation of neuronal calcium and survival by secreted forms of β-amyloid precursor. J. Neurochem. 64, 2087–2096.10.1046/j.1471-4159.1995.64052087.xSearch in Google Scholar PubMed

Barinaga, M. (1998). Stroke-damaged neurons may commit cellular suicide. Science 281, 1302–1303.10.1126/science.281.5381.1302Search in Google Scholar PubMed

Barone, E., Di Domenico, F., Sultana, R., Coccia, R., Mancuso, C., Perluigi, M., and Butterfield, D.A. (2012). Heme oxygenase-1 posttranslational modifications in the brain of subjects with Alzheimer disease and mild cognitive impairment. Free Radic. Biol. Med. 52, 2292–2301.10.1016/j.freeradbiomed.2012.03.020Search in Google Scholar PubMed PubMed Central

Barone, E., Di Domenico, F., Mancuso, C., and Butterfield, D.A. (2013). The Janus face of the heme oxygenase/biliverdin reductase system in Alzheimer disease: It′s time for reconciliation. Neurobiol. Dis. 62C, 144–159.Search in Google Scholar

Barreto, G.E., Gonzalez, J., Capani, F., and Morales, L. (2012). Neuroprotective agents in brain injury: a partial failure? Int. J. Neurosci. 122, 223–226.10.3109/00207454.2011.648292Search in Google Scholar PubMed

Batista-Nascimento, L., Pimentel, C., Menezes, R.A., and Rodrigues-Pousada, C. (2012). Iron and neurodegeneration: from cellular homeostasis to disease. Oxid. Med. Cell Longev. 2012, 128647.10.1155/2012/128647Search in Google Scholar PubMed PubMed Central

Battin, E.E. and Brumaghim, J.L. (2009). Antioxidant activity of sulfur and selenium: a review of reactive oxygen species scavenging, glutathione peroxidase, and metal-binding antioxidant mechanisms. Cell Biochem. Biophys. 55, 1–23.10.1007/s12013-009-9054-7Search in Google Scholar PubMed

Benvenisti-Zarom, L. and Regan, R.F. (2007). Astrocyte-specific heme oxygenase-1 hyperexpression attenuates heme-mediated oxidative injury. Neurobiol. Dis. 26, 688–695.10.1016/j.nbd.2007.03.006Search in Google Scholar PubMed PubMed Central

Bickel, M.H. (2001). [Henry E. Sigerist and Hans Fischer as pioneers of a medical history institute in Zurich]. Gesnerus 58, 215–219.10.1163/22977953-0580304005Search in Google Scholar

Brites, D. (2011). Bilirubin injury to neurons and glial cells: new players, novel targets, and newer insights. Semin. Perinatol. 35, 114–120.10.1053/j.semperi.2011.02.004Search in Google Scholar PubMed

Brito, M.A., Lima, S., Fernandes, A., Falcao, A.S., Silva, R.F., Butterfield, D.A., and Brites, D. (2008). Bilirubin injury to neurons: contribution of oxidative stress and rescue by glycoursodeoxycholic acid. Neurotoxicology 29, 259–269.10.1016/j.neuro.2007.11.002Search in Google Scholar PubMed

Calabrese, V., Scapagnini, G., Ravagna, A., Fariello, R.G., Giuffrida Stella, A.M., and Abraham, N.G. (2002). Regional distribution of heme oxygenase, HSP70, and glutathione in brain: relevance for endogenous oxidant/antioxidant balance and stress tolerance. J. Neurosci. Res. 68, 65–75.10.1002/jnr.10177Search in Google Scholar PubMed

Calabrese, V., Butterfield, D.A., Scapagnini, G., Stella, A.M., and Maines, M.D. (2006). Redox regulation of heat shock protein expression by signaling involving nitric oxide and carbon monoxide: relevance to brain aging, neurodegenerative disorders, and longevity. Antioxid. Redox Signaling 8, 444–477.10.1089/ars.2006.8.444Search in Google Scholar PubMed

Castellani, R.J., Moreira, P.I., Perry, G., and Zhu, X. (2012). The role of iron as a mediator of oxidative stress in Alzheimer disease. Biofactors 38, 133–138.10.1002/biof.1010Search in Google Scholar PubMed

Chang, E.F., Wong, R.J., Vreman, H.J., Igarashi, T., Galo, E., Sharp, F.R., Stevenson, D.K., and Noble-Haeusslein, L.J. (2003). Heme oxygenase-2 protects against lipid peroxidation-mediated cell loss and impaired motor recovery after traumatic brain injury. J. Neurosci. 23, 3689–3696.10.1523/JNEUROSCI.23-09-03689.2003Search in Google Scholar

Chen, J., Zhang, S., Zuo, P., and Tang, L. (1997). Memory-related changes of nitric oxide synthase activity and nitrite level in rat brain. Neuroreport 8, 1771–1774.10.1097/00001756-199705060-00040Search in Google Scholar PubMed

Chen, K., Gunter, K., and Maines, M.D. (2000). Neurons overexpressing heme oxygenase-1 resist oxidative stress-mediated cell death. J. Neurochem. 75, 304–313.10.1046/j.1471-4159.2000.0750304.xSearch in Google Scholar PubMed

Chen, J., Tu, Y., Moon, C., Nagata, E., and Ronnett, G.V. (2003). Heme oxygenase-1 and heme oxygenase-2 have distinct roles in the proliferation and survival of olfactory receptor neurons mediated by cGMP and bilirubin, respectively. J. Neurochem. 85, 1247–1261.10.1046/j.1471-4159.2003.01776.xSearch in Google Scholar PubMed

Chen, J., Tu, Y., Moon, C., Matarazzo, V., Palmer, A.M., and Ronnett, G.V. (2004). The localization of neuronal nitric oxide synthase may influence its role in neuronal precursor proliferation and synaptic maintenance. Dev. Biol. 269, 165–182.10.1016/j.ydbio.2004.01.024Search in Google Scholar PubMed

Chen, J., Tu, Y., Connolly, E.C., and Ronnett, G.V. (2005). Heme oxygenase-2 protects against glutathione depletion-induced neuronal apoptosis mediated by bilirubin and cyclic GMP. Curr. Neurovasc. Res. 2, 121–131.10.2174/1567202053586767Search in Google Scholar PubMed

Cheriyath, P., Gorrepati, V.S., Peters, I., Nookala, V., Murphy, M.E., Srouji, N., and Fischman, D. (2010). High total bilirubin as a protective factor for diabetes mellitus: an analysis of NHANES data from 1999–2006. J. Clin. Med. Res. 2, 201–206.10.4021/jocmr425wSearch in Google Scholar PubMed PubMed Central

Chow, A.M. and Brown, I.R. (2007). Induction of heat shock proteins in differentiated human and rodent neurons by celastrol. Cell Stress Chaperones 12, 237–244.10.1379/CSC-269.1Search in Google Scholar PubMed PubMed Central

Clark, J.E., Foresti, R., Sarathchandra, P., Kaur, H., Green, C.J., and Motterlini, R. (2000). Heme oxygenase-1-derived bilirubin ameliorates postischemic myocardial dysfunction. Am. J. Physiol. Heart Circ. Physiol. 278, H643–H651.10.1152/ajpheart.2000.278.2.H643Search in Google Scholar PubMed

Deguchi, K., Hayashi, T., Nagotani, S., Sehara, Y., Zhang, H., Tsuchiya, A., Ohta, Y., Tomiyama, K., Morimoto, N., Miyazaki, M., et al. (2008). Reduction of cerebral infarction in rats by biliverdin associated with amelioration of oxidative stress. Brain Res. 1188, 1–8.10.1016/j.brainres.2007.07.104Search in Google Scholar PubMed

Di Monte, D.A., Schipper, H.M., Hetts, S., and Langston, J.W. (1995). Iron-mediated bioactivation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in glial cultures. Glia 15, 203–206.10.1002/glia.440150213Search in Google Scholar

Djousse, L., Levy, D., Cupples, L.A., Evans, J.C., D’Agostino, R.B., and Ellison, R.C. (2001). Total serum bilirubin and risk of cardiovascular disease in the Framingham offspring study. Am. J. Cardiol. 87, 1196–1200; A1194, 1197.10.1016/S0002-9149(01)01494-1Search in Google Scholar

Djousse, L., Rothman, K.J., Cupples, L.A., Levy, D., and Ellison, R.C. (2003). Effect of serum albumin and bilirubin on the risk of myocardial infarction (the Framingham Offspring Study). Am. J. Cardiol. 91, 485–488.10.1016/S0002-9149(02)03256-3Search in Google Scholar

Dore, S., Sampei, K., Goto, S., Alkayed, N.J., Guastella, D., Blackshaw, S., Gallagher, M., Traystman, R.J., Hurn, P.D., Koehler, R.C., et al. (1999a). Heme oxygenase-2 is neuroprotective in cerebral ischemia. Mol. Med. 5, 656–663.10.1007/BF03401984Search in Google Scholar

Dore, S., Takahashi, M., Ferris, C.D., Zakhary, R., Hester, L.D., Guastella, D., and Snyder, S.H. (1999b). Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury. Proc. Natl. Acad. Sci. USA 96, 2445–2450.10.1073/pnas.96.5.2445Search in Google Scholar

Dore, S., Goto, S., Sampei, K., Blackshaw, S., Hester, L.D., Ingi, T., Sawa, A., Traystman, R.J., Koehler, R.C., and Snyder, S.H. (2000). Heme oxygenase-2 acts to prevent neuronal death in brain cultures and following transient cerebral ischemia. Neuroscience 99, 587–592.10.1016/S0306-4522(00)00216-5Search in Google Scholar

Dunkel, P., Chai, C.L., Sperlagh, B., Huleatt, P.B., and Matyus, P. (2012). Clinical utility of neuroprotective agents in neurodegenerative diseases: current status of drug development for Alzheimer’s, Parkinson’s and Huntington′s diseases, and amyotrophic lateral sclerosis. Expert Opin. Investig. Drugs 21, 1267–1308.10.1517/13543784.2012.703178Search in Google Scholar PubMed

Dusek, P. and Schneider, S.A. (2012). Neurodegeneration with brain iron accumulation. Curr. Opin. Neurol. 25, 499–506.10.1097/WCO.0b013e3283550cacSearch in Google Scholar PubMed

Elbirt, K. and Bonkovsky, H. (1999). Heme oxygenase : Recent advances in understanding its regulation and role. Proc. Assoc. Am. Phys. 111, 438–447.10.1111/paa.1999.111.5.438Search in Google Scholar

Ewing, J.F. and Maines, M.D. (1991). Rapid induction of heme oxygenase 1 mRNA and protein by hyperthermia in rat brain: heme oxygenase 2 is not a heat shock protein. Proc. Natl. Acad. Sci. USA 88, 5364–5368.10.1073/pnas.88.12.5364Search in Google Scholar PubMed PubMed Central

Ewing, J.F. and Maines, M.D. (1992). In situ hybridization and immunohistochemical localization of heme oxygenase-2 mRNA and protein in normal rat brain: differential distribution of isozyme 1 and 2. Mol. Cell. Neurosci. 3, 559–570.10.1016/1044-7431(92)90068-DSearch in Google Scholar

Ewing, J.F., Haber, S.N., and Maines, M.D. (1992). Normal and heat-induced patterns of expression of heme oxygenase-1 (HSP32) in rat brain: hyperthermia causes rapid induction of mRNA and protein. J. Neurochem. 58, 1140–1149.10.1111/j.1471-4159.1992.tb09373.xSearch in Google Scholar PubMed

Ewing, J.F., Weber, C.M., and Maines, M.D. (1993). Biliverdin reductase is heat resistant and coexpressed with constitutive and heat shock forms of heme oxygenase in brain. J. Neurochem. 61, 1015–1023.10.1111/j.1471-4159.1993.tb03615.xSearch in Google Scholar PubMed

Ewing, J.F., Raju, V.S., and Maines, M.D. (1994). Induction of heart heme oxygenase-1 (HSP32) by hyperthermia: possible role in stress-mediated elevation of cyclic 3′:5′-guanosine monophosphate. J. Pharmacol. Exp. Ther. 271, 408–414.Search in Google Scholar

Farinelli, S.E., Park, D.S., and Greene, L.A. (1996). Nitric oxide delays the death of trophic factor-deprived PC12 cells and sympathetic neurons by a cGMP-mediated mechanism. J. Neurosci. 16, 2325–2334.10.1523/JNEUROSCI.16-07-02325.1996Search in Google Scholar

Ferris, C.D., Jaffrey, S.R., Sawa, A., Takahashi, M., Brady, S.D., Barrow, R.K., Tysoe, S.A., Wolosker, H., Baranano, D.E., Dore, S., et al. (1999). Haem oxygenase-1 prevents cell death by regulating cellular iron. Nat. Cell Biol. 1, 152–157.10.1038/11072Search in Google Scholar PubMed

Fevery, J. (2008). Bilirubin in clinical practice: a review. Liver Int. 28, 592–605.10.1111/j.1478-3231.2008.01716.xSearch in Google Scholar PubMed

Fondevila, C., Shen, X.D., Tsuchiyashi, S., Yamashita, K., Csizmadia, E., Lassman, C., Busuttil, R.W., Kupiec-Weglinski, J.W., and Bach, F.H. (2004). Biliverdin therapy protects rat livers from ischemia and reperfusion injury. Hepatology 40, 1333–1341.10.1002/hep.20480Search in Google Scholar PubMed

Forman, H.J., Zhang, H., and Rinna, A. (2009). Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol. Aspects Med. 30, 1–12.10.1016/j.mam.2008.08.006Search in Google Scholar PubMed PubMed Central

Frandsen, A., Andersen, C.F., and Schousboe, A. (1992). Possible role of cGMP in excitatory amino acid induced cytotoxicity in cultured cerebral cortical neurons. Neurochem. Res. 17, 35–43.10.1007/BF00966863Search in Google Scholar PubMed

Gandhi, S. and Abramov, A.Y. (2012). Mechanism of oxidative stress in neurodegeneration. Oxid. Med. Cell Longev. 2012, 428010.10.1155/2012/428010Search in Google Scholar PubMed PubMed Central

Garthwaite, G. and Garthwaite, J. (1988). Cyclic GMP and cell death in rat cerebellar slices. Neuroscience 26, 321–326.10.1016/0306-4522(88)90148-0Search in Google Scholar

Grochot-Przeczek, A., Dulak, J., and Jozkowicz, A. (2011). Haem oxygenase-1: non-canonical roles in physiology and pathology. Clin. Sci. (Lond.) 122, 93–103.10.1042/CS20110147Search in Google Scholar

Han, S.S., Na, K.Y., Chae, D.W., Kim, Y.S., Kim, S., and Chin, H.J. (2010). High serum bilirubin is associated with the reduced risk of diabetes mellitus and diabetic nephropathy. Tohoku J. Exp. Med. 221, 133–140.10.1620/tjem.221.133Search in Google Scholar

Hayashi, S., Omata, Y., Sakamoto, H., Higashimoto, Y., Hara, T., Sagara, Y., and Noguchi, M. (2004). Characterization of rat heme oxygenase-3 gene. Implication of processed pseudogenes derived from heme oxygenase-2 gene. Gene 336, 241–250.10.1016/j.gene.2004.04.002Search in Google Scholar

Ilzecka, J. and Stelmasiak, Z. (2003). Serum bilirubin concentration in patients with amyotrophic lateral sclerosis. Clin. Neurol. Neurosurg. 105, 237–240.10.1016/S0303-8467(03)00031-3Search in Google Scholar

Ingi, T., Chiang, G., and Ronnett, G.V. (1996). The regulation of heme turnover and carbon monoxide biosynthesis in cultured primary rat olfactory receptor neurons. J. Neurosci. 16, 5621–5628.10.1523/JNEUROSCI.16-18-05621.1996Search in Google Scholar

Iwasaki, Y., Igarashi, O., Iwasa, Y., Hirano, K., Satoh, R., Iwamoto, K., Kawase, Y., Aoyagi, J., Ichikawa, Y., Kawabe, K., et al. (2005). Bilirubin and amyotrophic lateral sclerosis. Clin. Neurol. Neurosurg. 107, 160; author reply 161.10.1016/j.clineuro.2004.07.008Search in Google Scholar PubMed

Jazwa, A. and Cuadrado, A. (2010). Targeting heme oxygenase-1 for neuroprotection and neuroinflammation in neurodegenerative diseases. Curr. Drug Targets 11, 1517–1531.10.2174/1389450111009011517Search in Google Scholar PubMed

Kapitulnik, J. (2004). Bilirubin: an endogenous product of heme degradation with both cytotoxic and cytoprotective properties. Mol. Pharmacol. 66, 773–779.10.1124/mol.104.002832Search in Google Scholar PubMed

Kaplan, M., Bromiker, R., and Hammerman, C. (2011). Severe neonatal hyperbilirubinemia and kernicterus: are these still problems in the third millennium? Neonatology 100, 354–362.10.1159/000330055Search in Google Scholar PubMed

Kim, T.S., Pae, C.U., Yoon, S.J., Jang, W.Y., Lee, N.J., Kim, J.J., Lee, S.J., Lee, C., Paik, I.H., and Lee, C.U. (2006). Decreased plasma antioxidants in patients with Alzheimer′s disease. Int. J. Geriatr. Psychiatry 21, 344–348.10.1002/gps.1469Search in Google Scholar

Kitamura, Y., Furukawa, M., Matsuoka, Y., Tooyama, I., Kimura, H., Nomura, Y., and Taniguchi, T. (1998). In vitro and in vivo induction of heme oxygenase-1 in rat glial cells: possible involvement of nitric oxide production from inducible nitric oxide synthase. Glia 22, 138–148.10.1002/(SICI)1098-1136(199802)22:2<138::AID-GLIA5>3.0.CO;2-3Search in Google Scholar

Kitamura, Y., Ishida, Y., Takata, K., Mizutani, H., Kakimura, J., Inden, M., Nakata, J., Taniguchi, T., Tsukahara, T., Akaike, A., et al. (2003). Hyperbilirubinemia protects against focal ischemia in rats. J. Neurosci. Res. 71, 544–550.10.1002/jnr.10514Search in Google Scholar

Maghzal, G.J., Leck, M.C., Collinson, E., Li, C., and Stocker, R. (2009). Limited role for the bilirubin-biliverdin redox amplification cycle in the cellular antioxidant protection by biliverdin reductase. J. Biol. Chem. 284, 29251–29259.10.1074/jbc.M109.037119Search in Google Scholar

Mailhos, C., Howard, M.K., and Latchman, D.S. (1993). Heat shock protects neuronal cells from programmed cell death by apoptosis. Neuroscience 55, 621–627.10.1016/0306-4522(93)90428-ISearch in Google Scholar

Maines, M.D. and Gibbs, P.E. (2005). 30 some years of heme oxygenase: from a “molecular wrecking ball” to a “mesmerizing” trigger of cellular events. Biochem. Biophys. Res. Commun. 338, 568–577.10.1016/j.bbrc.2005.08.121Search in Google Scholar

Maines, M.D., Trakshel, G.M., and Kutty, R.K. (1986). Characterization of two constitutive forms of rat liver microsomal heme oxygenase: only one molecular species of the enzyme is inducible. J. Biol. Chem. 261, 411.10.1016/S0021-9258(17)42488-4Search in Google Scholar

Maines, M.D., Eke, B.C., and Zhao, X. (1996). Corticosterone promotes increased heme oxygenase-2 protein and transcript expression in the newborn rat brain. Brain Res. 722, 83–94.10.1016/0006-8993(96)00184-9Search in Google Scholar

Mark, J.A. and Maines, M.D. (1992). Tin-protoporphyrin-mediated disruption in vivo of heme oxygenase-2 protein integrity and activity in rat brain. Pediatr. Res. 32, 324–329.10.1203/00006450-199209000-00016Search in Google Scholar

Matsuoka, Y., Kitamura, Y., Okazaki, M., Sakata, M., Tsukahara, T., and Taniguchi, T. (1998). Induction of heme oxygenase-1 and major histocompatibility complex antigens in transient forebrain ischemia. J. Cereb. Blood Flow Metab. 18, 824–832.10.1097/00004647-199808000-00002Search in Google Scholar

Min, K.J., Yang, M.S., Kim, S.U., Jou, I., and Joe, E.H. (2006). Astrocytes induce hemeoxygenase-1 expression in microglia: a feasible mechanism for preventing excessive brain inflammation. J. Neurosci. 26, 1880–1887.10.1523/JNEUROSCI.3696-05.2006Search in Google Scholar

Nakajima, T., Hayakawa, M., Yajima, D., Motani-Saitoh, H., Sato, Y., Kiuchi, M., Ichinose, M., and Iwase, H. (2006). Time-course changes in the expression of heme oxygenase-1 in human subcutaneous hemorrhage. Forensic Sci. Int. 158, 157–163.10.1016/j.forsciint.2005.05.028Search in Google Scholar

Nakamura, T., Cho, D.H., and Lipton, S.A. (2012). Redox regulation of protein misfolding, mitochondrial dysfunction, synaptic damage, and cell death in neurodegenerative diseases. Exp. Neurol. 238, 12–21.10.1016/j.expneurol.2012.06.032Search in Google Scholar

Nicotera, P. and Melino, G. (2004). Regulation of the apoptosis-necrosis switch. Oncogene 23, 2757–2765.10.1038/sj.onc.1207559Search in Google Scholar

Oren, D.A., Desan, P.H., Boutros, N., Anand, A., and Charney, D.S. (2002). Effects of light on low nocturnal bilirubin in winter depression: a preliminary report. Biol. Psychiatry 51, 422–425.10.1016/S0006-3223(01)01254-9Search in Google Scholar

Panahian, N., Yoshiura, M., and Maines, M.D. (1999). Overexpression of heme oxygenase-1 is neuroprotective in a model of permanent middle cerebral artery occlusion in transgenic mice. J. Neurochem. 72, 1187–1203.10.1111/j.1471-4159.1999.721187.xSearch in Google Scholar

Parfenova, H., Leffler, C.W., Basuroy, S., Liu, J., and Fedinec, A.L. (2012). Antioxidant roles of heme oxygenase, carbon monoxide, and bilirubin in cerebral circulation during seizures. J. Cereb. Blood Flow Metab. 32, 1024–1034.10.1038/jcbfm.2012.13Search in Google Scholar

Pivtoraiko, V.N., Stone, S.L., Roth, K.A., and Shacka, J.J. (2009). Oxidative stress and autophagy in the regulation of lysosome-dependent neuron death. Antioxid. Redox Signaling 11, 481–496.10.1089/ars.2008.2263Search in Google Scholar

Poss, K. and Tonegawa, S. (1997). Heme oxygenase 1 is required for mammalian iron reutilization. Proc. Natl. Acad. Sci. USA 94, 10919–10924.10.1073/pnas.94.20.10919Search in Google Scholar

Raju, V.S., McCoubrey, W.K., Jr., and Maines, M.D. (1997). Regulation of heme oxygenase-2 by glucocorticoids in neonatal rat brain: characterization of a functional glucocorticoid response element. Biochim. Biophys. Acta 1351, 89–104.10.1016/S0167-4781(96)00183-2Search in Google Scholar

Rodgers, P.A. and Stevenson, D.K. (1990). Developmental biology of heme oxygenase. Clin. Perinatol. 17, 275–291.10.1016/S0095-5108(18)30568-2Search in Google Scholar

Rosenthal, P., Pincus, M., and Fink, D. (1984). Sex- and age-related differences in bilirubin concentrations in serum. Clin. Chem. 30, 1380–1382.10.1093/clinchem/30.8.1380Search in Google Scholar

Roskams, A.J., Bredt, D.S., Dawson, T.M., and Ronnett, G.V. (1994). Nitric oxide mediates the formation of synaptic connections in developing and regenerating olfactory receptor neurons. Neuron 13, 289–299.10.1016/0896-6273(94)90347-6Search in Google Scholar

Ryter, S.W. and Choi, A.M. (2009). Heme oxygenase-1/carbon monoxide: from metabolism to molecular therapy. Am. J. Respir. Cell Mol. Biol. 41, 251–260.10.1165/rcmb.2009-0170TRSearch in Google Scholar

Ryter, S.W., Otterbein, L.E., Morse, D., and Choi, A.M. (2002). Heme oxygenase/carbon monoxide signaling pathways: regulation and functional significance. Mol. Cell. Biochem. 234–235, 249–263.10.1023/A:1015957026924Search in Google Scholar

Santoro, M.G. (2000). Heat shock factors and the control of the stress response. Biochem. Pharmacol. 59, 55–63.10.1016/S0006-2952(99)00299-3Search in Google Scholar

Scapagnini, G., D’Agata, V., Calabrese, V., Pascale, A., Colombrita, C., Alkon, D., and Cavallaro, S. (2002). Gene expression profiles of heme oxygenase isoforms in the rat brain. Brain Res. 954, 51–59.10.1016/S0006-8993(02)03338-3Search in Google Scholar

Schipper, H.M. (2004a). Brain iron deposition and the free radical-mitochondrial theory of ageing. Ageing Res. Rev. 3, 265–301.10.1016/j.arr.2004.02.001Search in Google Scholar PubMed

Schipper, H.M. (2004b). Heme oxygenase expression in human central nervous system disorders. Free Radic. Biol. Med. 37, 1995–2011.10.1016/j.freeradbiomed.2004.09.015Search in Google Scholar PubMed

Schipper, H.M. (2004c). Heme oxygenase-1: transducer of pathological brain iron sequestration under oxidative stress. Ann. NY Acad. Sci. 1012, 84–93.10.1196/annals.1306.007Search in Google Scholar PubMed

Schipper, H.M. (2011). Neurodegeneration with brain iron accumulation – clinical syndromes and neuroimaging. Biochim. Biophys. Acta 1822, 350–360.10.1016/j.bbadis.2011.06.016Search in Google Scholar

Sedlak, T.W. and Snyder, S.H. (2004). Bilirubin benefits: cellular protection by a biliverdin reductase antioxidant cycle. Pediatrics 113, 1776–1782.10.1542/peds.113.6.1776Search in Google Scholar

Snyder, S.H. and Baranano, D.E. (2001). Heme oxygenase: a font of multiple messengers. Neuropsychopharmacology 25, 294–298.10.1016/S0893-133X(01)00275-5Search in Google Scholar

Song, W., Zukor, H., Lin, S.H., Liberman, A., Tavitian, A., Mui, J., Vali, H., Fillebeen, C., Pantopoulos, K., Wu, T.D., et al. (2012). Unregulated brain iron deposition in transgenic mice over-expressing HMOX1 in the astrocytic compartment. J. Neurochem. 123, 325–336.10.1111/j.1471-4159.2012.07914.xSearch in Google Scholar

Stern, A.J. (1973). Hans Fischer (1881–1945). Ann. NY Acad. Sci. 206, 752–761.10.1111/j.1749-6632.1973.tb43252.xSearch in Google Scholar

Stocker, R., Glazer, A.N., and Ames, B.N. (1987a). Antioxidant activity of albumin-bound bilirubin. Proc. Natl. Acad. Sci. USA 84, 5918–5922.10.1073/pnas.84.16.5918Search in Google Scholar

Stocker, R., Yamamoto, Y., McDonagh, A.F., Glazer, A.N., and Ames, B.N. (1987b). Bilirubin is an antioxidant of possible physiological importance. Science 235, 1043–1046.10.1126/science.3029864Search in Google Scholar

Tenhunen, R., Marver, H.S., and Schmid, R. (1968). The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc. Natl. Acad. Sci. USA 61, 748–755.10.1073/pnas.61.2.748Search in Google Scholar

Verma, A., Hirsch, D.J., Glatt, C.E., Ronnett, G.V., and Snyder, S.H. (1993). Carbon monoxide: a putative neural messenger. Science 259, 381–384.10.1126/science.7678352Search in Google Scholar

Vincent, S.R., Das, S., and Maines, M.D. (1994). Brain heme oxygenase isoenzymes and nitric oxide synthase are co-localized in select neurons. Neuroscience 63, 223–231.10.1016/0306-4522(94)90018-3Search in Google Scholar

Wang, G., Yang, Q., Li, G., Wang, L., Hu, W., Tang, Q., Li, D., and Sun, Z. (2011). Time course of heme oxygenase-1 and oxidative stress after experimental intracerebral hemorrhage. Acta Neurochir. (Wien) 153, 319–325.10.1007/s00701-010-0750-2Search in Google Scholar

Watson, C.J. (1965). Reminiscences of Hans Fischer and his laboratory. Perspect. Biol. Med. 8, 419–435.10.1353/pbm.1965.0052Search in Google Scholar

Weill, C. and Greene, D. (1984). Prevention of natural motoneurone cell death by dibutyryl cyclic GMP. Nature 308, 452–454.10.1038/308452a0Search in Google Scholar

Yachie, A., Niida, Y., Wada, T., Igarashi, N., Kaneda, H., Toma, T., Ohta, K., Kasahara, Y., and Koizumi, S. (1999). Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J. Clin. Invest. 103, 129–135.10.1172/JCI4165Search in Google Scholar

Yamashita, K., McDaid, J., Ollinger, R., Tsui, T.Y., Berberat, P.O., Usheva, A., Csizmadia, E., Smith, R.N., Soares, M.P., and Bach, F.H. (2004). Biliverdin, a natural product of heme catabolism, induces tolerance to cardiac allografts. FASEB J. 18, 765–767.10.1096/fj.03-0839fjeSearch in Google Scholar

Yasuda, M., Kiyohara, Y., Wang, J.J., Arakawa, S., Yonemoto, K., Doi, Y., Ninomiya, T., and Ishibashi, T. (2011). High serum bilirubin levels and diabetic retinopathy: the Hisayama Study. Ophthalmology 118, 1423–1428.10.1016/j.ophtha.2010.12.009Search in Google Scholar

Yenari, M.A., Giffard, R.G., Sapolsky, R.M., and Steinberg, G.K. (1999). The neuroprotective potential of heat shock protein 70 (HSP70). Mol. Med. Today 5, 525–531.10.1016/S1357-4310(99)01599-3Search in Google Scholar

Zeynalov, E., Shah, Z.A., Li, R.C., and Dore, S. (2009). Heme oxygenase 1 is associated with ischemic preconditioning-induced protection against brain ischemia. Neurobiol. Dis. 35, 264–269.10.1016/j.nbd.2009.05.010Search in Google Scholar

Zhang, J. and Piantadosi, C.A. (1992). Mitochondrial oxidative stress after carbon monoxide hypoxia in the rat brain. J. Clin. Invest. 90, 1193–1199.10.1172/JCI115980Search in Google Scholar

Zhang, S., Chen, J., and Wang, S. (1998). Spatial learning and memory induce up-regulation of nitric oxide-producing neurons in rat brain. Brain Res. 801, 101–106.10.1016/S0006-8993(98)00564-2Search in Google Scholar

Zhivotovsky, B. (2004). Apoptosis, necrosis and between. Cell Cycle 3, 64–66.10.4161/cc.3.1.606Search in Google Scholar