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Aging and Oxidative Stress Response in the CNS

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Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

Cellular oxidant/antioxidant balance has become the subject of intense study, particularly focused on brain aging and neurodegenerative disorders. There is now evidence to suggest that reduction of cellular expression and activity of antioxidant proteins and the resulting increase of oxidative stress are fundamental causes for both the aging processes and neurodegenerative diseases. However, to survive different types of injuries, brain cells have evolved networks of different responses, which detect and control diverse forms of stress. Efficient functioning of maintenance and repair process seems to be crucial for both survival and physical quality of life. This is accomplished by a complex network of the so-called longevity assurance processes, which are composed of several genes termed “vitagenes.” Among these, heat-shock proteins (Hsps), proteasome, and mitochondrial uncoupling protein systems are highly conserved mechanisms responsible for the preservation and repair of the correct conformation of cellular macromolecules, such as proteins, RNA, and DNA.

Recent studies have shown that the heat-shock response contributes to establishing a cytoprotective state in a wide variety of human diseases, including ischemia and reperfusion damage, inflammation, metabolic disorders, cancer, infection, trauma, and aging. Among the various Hsps, Hsp32 also known as heme oxygenase I (HO-1), has received considerable attention, as it has been recently demonstrated that HO-1 induction, by generating the vasoactive molecule carbon monoxide (CO) and the potent antioxidant bilirubin, could represent a protective system potentially active against brain oxidative injury. The major neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and Friedreich's ataxia (FA), are all associated with the presence of abnormal proteins. Given the broad cytoprotective properties of the heat-shock response, there is now strong interest in discovering and developing pharmacological agents capable of inducing the heat-shock response. These findings have opened up new perspectives in medicine and pharmacology, as molecules inducing this defense mechanism appear to be possible candidates for novel cytoprotective strategies. Particularly, modulation of endogenous cellular defense mechanisms such as the heat-shock response, and the proteasomal system, through nutritional antioxidants or pharmacological compounds may represent an innovative approach to therapeutic intervention in diseases causing tissue damage, such as neurodegeneration. Moreover, by maintaining or recovering the activity of vitagenes, it would be possible to delay the aging process and decrease the occurrence of age-related diseases with resulting prolongation of a healthy life span.

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Abbreviations

AD:

Alzheimer's disease

AP-1:

activator protein-1

Aβ:

amyloid beta-peptide

CNS:

central nervous system

GSH:

reduced glutathione

GSSG:

oxidized glutathione

Hsp:

heat-shock protein

JAK:

janus kinase

JNK:

c-jun N-terminal kinase

MAPK:

mitogen-activated protein kinase

NF-κB:

nuclear factor kappa-B

NFT:

intraneuronal fibrillary tangles

NOS:

nitric oxide synthase

PD:

Parkinson's disease

PLA2 :

phospholipase A2

RNS:

reactive nitrogen species

ROS:

reactive oxygen species

SAPK:

stress-activated protein kinase

STAT:

signal transducer and transcription activator

TNF:

tumor necrosis factor

References

  • Akamatsu Y, Haga M, Tyagi S, Yamashita K, Graca-Souza AV, et al. 2004. Heme oxygenase-1-derived carbon monoxide protects hearts from transplant associated ischemia reperfusion injury. FASEB J 18: 771–772.

    CAS  PubMed  Google Scholar 

  • Alam J. 2002. Heme oxygenase-1: Past, present, and future. Antioxid Redox Signal 4: 559–562.

    Article  CAS  PubMed  Google Scholar 

  • Alam J, Cook JL. 2003. Transcriptional regulation of the heme oxygenase-1 gene via the stress response element pathway. Curr Pharm Des 9: 2499–2511.

    Article  CAS  PubMed  Google Scholar 

  • Anisimov VN, Alimova IN, Baturin DA, Popovich IG, Zabezhinski MA, et al. 2003. Dose-dependent effect of melatonin on life span and spontaneous tumor incidence in female SHR mice. Exp Gerontol 38: 449–461.

    Article  CAS  PubMed  Google Scholar 

  • Aquino DA, Capello E, Weisstein J, Sanders V, Lopez C, et al. 1977. Multiple sclerosis: Altered expression of 70-and 27-kDa heat shock proteins in lesions and myelin. J Neuropathol Exp Neurol 56: 664–672.

    Google Scholar 

  • Aviv A, Levy D, Mangel M. 2003. Growth, telomere dynamics and successful and unsuccessful human aging. Mech Ageing Dev 124: 829–837.

    Article  CAS  PubMed  Google Scholar 

  • Babcock M, de Silva D, Oaks R, Davis-Kaplan S, Jiralerspong S, et al. 1997. Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science 276: 1709–1712.

    Article  CAS  PubMed  Google Scholar 

  • Bagasra O, Michaels FH, Zheng YM, Bobroski LE, Spitsin SV, et al. 1995. Activation of the inducible form of nitric oxide synthase in the brains of patients with multiple sclerosis. Proc Natl Acad Sci USA 92: 12041–12045.

    Article  CAS  PubMed  Google Scholar 

  • Balogun E, Hoque M, Gong P, Killeen E, Green CJ, et al. 2003. Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem J 371: 887–895.

    Article  CAS  PubMed  Google Scholar 

  • Beal MF. 1998. Excitotoxicity and nitric oxide in Parkinson's disease pathogenesis. Ann Neurol 44: S110–S114.

    Article  CAS  PubMed  Google Scholar 

  • Beal MF. 2003. Mitochondria, oxidative damage, and inflammation in Parkinson's disease. Ann NY Acad Sci 991: 120–131.

    Article  CAS  PubMed  Google Scholar 

  • Beal MF, Ferrante RJ, Browne SE, Matthews RT, Kowall NW, et al. 1997. Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis. Ann Neurol 42: 644–654.

    Article  CAS  PubMed  Google Scholar 

  • Bechtold DA, Brown IR. 2003. Induction of Hsp27 and Hsp32 stress proteins and vimentin in glial cells of the rat hippocampus following hyperthermia. Neurochem Res 28: 1163–1173.

    Article  CAS  PubMed  Google Scholar 

  • Beckman JS, Carlson M, Smith CD, Koppenol WH. 1993. ALS, SOD and peroxynitrite. Nature 364: 584–586.

    Article  CAS  PubMed  Google Scholar 

  • Beckman KB, Ames BN. 1998. Mitochondrial aging: Open questions. Ann NY Acad Sci 854: 118–127.

    Article  CAS  PubMed  Google Scholar 

  • Beschorner R, Adjodah D, Schwab JM, Mittelbronn M, Pedal I, et al. 2000. Long-term expression of heme oxygenase-1 (HO-1, HSP32) following focal cerebral infarctions and traumatic brain injury in humans. Acta Neuropathol 100: 377–384.

    Article  CAS  PubMed  Google Scholar 

  • Biesalski HK. 2002. Free radical theory of aging. Curr Opin Clin Nutr Metab Care 5: 5–10.

    Article  CAS  PubMed  Google Scholar 

  • Bohr VA, Dianov GL. 1999. Oxidative DNA damage processing in nuclear and mitochondrial DNA. Biochimie 81: 155–160.

    Article  CAS  PubMed  Google Scholar 

  • Bolanos JP, Almeida A, Medina JM. 1998. Nitric oxide mediates brain mitochondrial damage during perinatal anoxia. Brain Res 787: 117–122.

    Article  CAS  PubMed  Google Scholar 

  • Bradley JL, Blake JC, Chamberlain S, Thomas PK, Cooper JM, et al. 2000. Clinical, biochemical and molecular genetic correlations in Friedreich's ataxia. Hum Mol Genet 9: 275–282.

    Article  CAS  PubMed  Google Scholar 

  • Bredt DS. 1999. Endogenous nitric oxide synthesis: Biological functions and pathophysiology. Free Radic Res 31: 577–596.

    Article  CAS  PubMed  Google Scholar 

  • Brooks KJ, Hargreaves I, Bhakoo K, Sellwood M, O' Brien F, et al. 2002. Delayed hypothermia prevents decreases in N-acetylaspartate and reduced glutathione in the cerebral cortex of the neonatal pig following transient hypoxia-ischaemia. Neurochem Res 27: 1599–1604.

    Article  CAS  PubMed  Google Scholar 

  • Browne SE. 1997. Mitochondrial dysfunction and oxidative damage in Huntington's disease. Mitochondria and Free Radicals in Neurodegenerative Diseases. Flint Beal M, Howell N, Bodis-Wollner I, editors. New York: Wiley-Liss.

    Google Scholar 

  • Brwon RH. 1994. Clinical implications of basic research: A transgenic-mouse model of amyotrophic lateral sclerosis. N Engl J Med 331: 1091–1092.

    Article  Google Scholar 

  • Butterfield DA. 2002. Amyloid β-peptide1–42-induced oxidative stress and neurotoxicity: Implications for neurodegeneration in Alzheimer's disease brain. A review. Free Radic Res 36: 1307–1313.

    Article  CAS  PubMed  Google Scholar 

  • Butterfield DA. 2004. Proteomics: A new approach to investigate oxidative stress in Alzheimer's disease brain. Brain Res 1000: 1–7.

    Article  CAS  PubMed  Google Scholar 

  • Butterfield DA, Kanski J. 2002. Methionine residue 35 is critical for the oxidative stress and neurotoxic properties of Alzheimer's amyloid-peptide 1–42. Review Peptides 23: 1299–1309.

    Article  CAS  Google Scholar 

  • Butterfield DA, Castegna A, Drake J, Scapagnini G, Calabrese V. 2002a. Vitamin E and neurodegenerative disorders associated with oxidative stress. Nutr Neurosci 5: 229–239.

    Article  CAS  Google Scholar 

  • Butterfield DA, Castagna A, Pocernich CB, Drake J, Scapagnini G, et al. 2002b. Nutritional approaches to combat oxidative stress in Alzheimer's disease. J Nutr Biochem 13: 444–461.

    Article  CAS  Google Scholar 

  • Butterfield DA, Lauderback CM 2002. Lipid peroxidation and protein oxidation in Alzheimer's disease brain: Potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Radic Biol Med 32: 1050–1060.

    Article  CAS  PubMed  Google Scholar 

  • Butterfield DA, Howard BJ, Yatin S, Allen KL, Carney JM. 1997. Free radical oxidation of brain proteins in accelerated senescence and its modulation by N-tert-butyl-α-phenylnitrone. Proc Natl Acad Sci USA 94: 674–678.

    Article  CAS  PubMed  Google Scholar 

  • Butterfield DA, Koppal T, Subramaniam R, Yatin S. 1999. Vitamin E as an antioxidant/free radical scavenger against amyloid β-peptide-induced oxidative stress in neocortical synaptosomal membranes and hippocampal neurons in culture: Insights into Alzheimer's disease. Rev Neurosci 10: 141–149.

    CAS  PubMed  Google Scholar 

  • Calabrese V, Rizza V. 1999. Formation of propionate after short-term ethanol treatment and its interaction with the carnitine pool in rat. Alcohol 19: 169–176.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese V, Bates TE, Giuffrida Stella AM. 2000a. NO synthase and NO-dependent signal pathways in brain aging and neurodegenerative disorders: The role of oxidant/antioxidant balance. Neurochem Res 65: 1315–1341.

    Article  Google Scholar 

  • Calabrese V, Copani A, Testa D, Ravagna A, Spadaro F, et al. 2000b. Nitric oxide synthase induction in astroglial cell cultures: Effect on heat shock protein 70 synthesis and oxidant/antioxidant balance. J Neurosc Res 60: 613–622.

    Article  CAS  Google Scholar 

  • Calabrese V, Testa D, Ravagna A, Bates TE, Giuffrida Stella AM. 2000c. Hsp70 induction in the brain following ethanol administration in the rat: Regulation by glutathione redox state. Biochem Biophys Res Commun 269: 397–400.

    Article  CAS  Google Scholar 

  • Calabrese V, Bella R, Testa D, Spadaro F, Scorfani A, et al. 1998. Increased cerebrospinal fluid and plasma levels of ultraweak chemiluminescence are associated with changes in the thiol pool and lipid-soluble fluorescence in multiple sclerosis: The pathogenic role of oxidative stress. Drugs Exp Clin Res 24: 125–131.

    CAS  PubMed  Google Scholar 

  • Calabrese V, Raffaele R, Casentino E, Rizza V. 1994. Changes in cerebrospinal fluid levels of malonaldehyde and glutathione reductase activity in multiple sclerosis. J Clin Pharmacol Res 4: 119–123.

    Google Scholar 

  • Calabrese V, Ravagna A, Colombrita C, Guagliano E, Scapagnini G, et al. 2005. Acetylcarnitine induces heme oxygenase in rat astrocytes and protects against oxidative stress: Involvement of the transcription factor Nrf2. J Neurosci Res 79: 509–521.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese V, Scapagnini G, Colombrita C, Ravagna A, Pennisi G, et al. 2003a. Redox regulation of heat shock protein expression in aging and neurodegenerative disorders associated with oxidative stress: A nutritional approach. Amino acids 27: 15–23.

    Google Scholar 

  • Calabrese V, Scapagnini G, Ravagna A, Bella R, Butterfield DA, et al. 2003b. Disruption of thiol homeostasis and nitrosative stress in the cerebrospinal fluid of patients with active multiple sclerosis: Evidence for a protective role of acetylcarnitine. Neurochem Res 28: 1321–1328.

    Article  CAS  Google Scholar 

  • Calabrese V, Butterfield DA, Giuffrida Stella AM. 2003c. Nutritional antioxidants and the hem oxygenase pathway of stress tolerance: Novel targets for neuroprotection in Alzheimer's disease. It J Biochem 52: 177–181.

    CAS  Google Scholar 

  • Calabrese V, Scapagnini G, Giuffrida Stella AM, Bates TE, Clark JB. 2001a. Mitochondrial involvement in brain function and dysfunction: Relevance to aging, neurodegenerative disorders and longevity. Neurochem Res 26: 739–764.

    Article  CAS  Google Scholar 

  • Calabrese V, Scapagnini G, Catalano C, Bates TE, Dirotta F, et al. 2001b. Induction of heat shock protein synthesis in human skin fibroblasts in response to oxidative stress: Regulation by a natural antioxidant from rosemary extract. Int J Tissue React 23: 121–128.

    Google Scholar 

  • Calabrese V, Scapagnini G, Ravagna A, Bella R, Foresti R, et al. 2002a. Nitric oxide synthase is present in the cerebrospinal fluid of patients with active multiple sclerosis and is associated with increases in CSF protein nitrotyrosine, S-nitrosothiols and with changes in glutathione levels. J Neurosci Res 70: 580–587.

    Article  CAS  Google Scholar 

  • Calabrese V, Scapagnini G, Ravagna A, Fardello RG, Giuffrida Stella AM, et al. 2002b. 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.

    Article  CAS  Google Scholar 

  • Calabrese V, Scapagnini G, Ravagna A, Giuffrida Stella AM, Butterfield DA. 2002c. Molecular chaperones and their roles in neural cell differentiation. Dev Neurosci 24: 1–13.

    Article  CAS  Google Scholar 

  • Calabrese V, Scapagnini G, Latteri S, Colombrita C, Ravagna A, et al. 2002d. Long-term ethanol administration enhances age-dependent modulation of redox state in different brain regions in the rat: Protection by acetyl carnitine. Int J Tissue React 24: 97–104.

    CAS  Google Scholar 

  • Calabrese V, Scapagnini G, Ravagna A, Colombrita C, Spadaro F, et al. 2004a. Increased expression of heat shock proteins in rat brain during aging: Relationship with mitochondrial function and glutathione redox state. Mech Age Dev 125: 325–335.

    Article  CAS  Google Scholar 

  • Calabrese V, Boyd-Kimball D, Scapagnini G, Butterfield DA. 2004b. Nitric oxide and cellular stress response in brain aging and neurodegenerative disorders: The role of vitagenes. In vivo 18: 23–45.

    Google Scholar 

  • Calabrese V, Giuffrida Stella, AM, Butterfield DA, Scapagnini G. 2004c. Redox regulation in neurodegeneration and longevity: Role of the heme oxygenase and Hsp70 systems in brain stress tolerance. Antiox Redox Signal 5: 895–913.

    Google Scholar 

  • Campuzano V, Contermini L, Molto’ MD, Pianese L, Cassee M, et al. 1996. Friedreich's ataxia: Autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271: 1423–1427.

    Article  CAS  PubMed  Google Scholar 

  • Carney JM, Starke-Reed PE, Oliver CN, Landum RW, Cheng MS, et al. 1991. Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-α-phenylnitrone. Proc Natl Acad Sci USA 88: 3633–3636.

    Article  CAS  PubMed  Google Scholar 

  • Castegna A, Lauderback CM, Mohmmad-Abdul H, Butterfield DA. 2004. Modulation of phospholipid asymmetry in synaptosomal membranes by the lipid peroxidation products, 4-hydroxynonenal and acrolein: Implications for Alzheimer's disease. Brain Res 1004: 193–197.

    Article  CAS  PubMed  Google Scholar 

  • Catania MV, Giuffrida R, Seminara G, Barbagallo G, Aronica E, et al. 2003. Upregulation of neuronal nitric oxide synthase in vitro stellate astrocytes and in vivo reactive astrocytes after electrically induced status epilepticus. Neurochem Res 28: 607–615.

    Article  PubMed  Google Scholar 

  • Chakrabarty A, Emerson MR, Le Vine SM. 2003. Heme oxygenase-1 in SJL mice with experimental allergic encephalomyelitis. Mult Scler 9: 372–381.

    Article  CAS  PubMed  Google Scholar 

  • Chen K, Gunter K, Maines MD. 2000. Neurons overexpressing heme oxygenase-1 resist oxidative stress-mediated cell death. J Neurochem 75: 304–312.

    Article  CAS  PubMed  Google Scholar 

  • Chou SM, Wang HS, Komai K. 1996. Co-localisation of NOS and SOD-1 in neurofilament accumulation within motor neurones of amyotrophic lateral sclerosis—an immunohistochemical study. J Chem Neuroanat 10: 249–258.

    Article  CAS  PubMed  Google Scholar 

  • Christen Y. 2000. Oxidative stress and Alzheimer disease. Am J Clin Nutr 71: 621S–629S.

    CAS  PubMed  Google Scholar 

  • Coceani F, Kelsey L, Seidlitz E, Marks GS, McLaughlin BE, et al. 1997. Carbon monoxide formation in the ductus arteriosus in the lamb: Implications for the regulation of muscle tone. Br J Pharmacol 120: 599–608.

    Article  CAS  PubMed  Google Scholar 

  • Collard JF, Cote F, Julien JP. 1995. Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis. Nature 375: 61–64.

    Article  CAS  PubMed  Google Scholar 

  • Colombrita C, Calabrese V, Giuffrida Stella AM, Mattei F, Alkon DL, et al. 2003. Regional rat brain distribution of heme oxygenase-1 and manganese superoxide dismutase mRNA: Relevance of redox homeostasis in the aging processes. Exp Biol Med 228: 517–524.

    CAS  Google Scholar 

  • Corregidor C, De Pasamonte J. 1996. Cerebrospinal fluid nitrate levels in patients with Alzheimer's disease. Acta Neurol Scand 94: 411–414.

    Google Scholar 

  • Cottrell DA, Turnbull DM. 2000. Mitochondria and ageing. Curr Opin Clin Nutr Metab Care 3: 473–478.

    Article  CAS  PubMed  Google Scholar 

  • Cottrell DA, Blakely EL, Johnson MA, Ince PG, Borthwick GM, et al. 2001. Cytochrome c oxidase deficient cells accumulate in the hippocampus and choroid plexus with age. Neurobiol Aging 22: 265–272.

    Article  CAS  PubMed  Google Scholar 

  • Cross AH, Manning PT, Keeling RM, Schmidt RE, Misko TP. 1998. Peroxynitrite formation within the central nervous system in active multiple sclerosis. J Neuroimmunol 88: 45–56.

    Article  CAS  PubMed  Google Scholar 

  • Cross AH, Manning PT, Stern MK, Misko TP. 1997. Evidence for the production of peroxynitrite in inflammatory CNS demyelination. J Neuroimmunol 80: 121–130.

    Article  CAS  PubMed  Google Scholar 

  • Dawson TM, Dawson VL. 2002. Neuroprotective and neurorestorative strategies for Parkinson's disease. Nat Neurosci 5: 1058–1061.

    Article  CAS  PubMed  Google Scholar 

  • Dawson VL, Dawson TM. 1995. Physiological and toxicological actions of nitric oxide in the central nervous system. Adv Pharmacol 34: 323–342.

    Article  CAS  PubMed  Google Scholar 

  • Demple B, Harrison L. 1994. Repair of oxidative damage to DNA: Enzymology and biology. Annu Rev Biochem 63: 915–948.

    Article  CAS  PubMed  Google Scholar 

  • Dexter DT, Carayon A, Javoy-Agid F, Agid Y, Wells FR, et al. 1991. Alterations in the levels of iron ferritin and other trace metals in Parkinson's diseases affecting the basal ganglia. Brain 114: 1953–1975.

    Article  PubMed  Google Scholar 

  • Dinkova-Kostova AT, Massiah MA, Bozak RE, Hicks RJ, Talalay P. 2001. Potency of Michael reaction acceptors as inducers of enzymes that protect against carcinogenesis depends on their reactivity with sulfhydryl groups. Proc Natl Acad Sci USA 98: 3404–3409.

    Article  CAS  PubMed  Google Scholar 

  • Dore S. 2002. Decreased activity of the antioxidant heme oxygenase enzyme: Implications in ischemia and in Alzheimer's disease. Free Radic Biol Med 32: 1276–1282.

    Article  CAS  PubMed  Google Scholar 

  • Dore S, Goto S, Sampei K, Blackshaw S, Hester LD, et al. 2000. Heme oxygenase-2 acts to prevent neuronal death in brain cultures and following transient cerebral ischemia. Neuroscience 99: 587–592.

    Article  CAS  PubMed  Google Scholar 

  • Drake J, Link CD, Butterfield DA. 2003a. Oxidative stress precedes fibrillar deposition of Alzheimer's disease amyloid β-peptide1–42 in a transgenic Caenorhabditis elegans model. Neurobiol Aging 24: 415–420.

    Article  CAS  Google Scholar 

  • Drake J, Sultana R, Aksenova M, Calabrese V, Butterfield DA. 2003b. Elevation of mitochondrial glutathione by γ-glutamylcysteine ethyl ester protects mitochondria against peroxynitrite-induced oxidative stress. J Neurosci Res 74: 917–927.

    Article  CAS  Google Scholar 

  • Drake J, Petroze R, Castegna A, Ding Q, Keller JN, et al. 2004. 4-Hydroxynonenal oxidatively modifies histones: Implications for Alzheimer's disease. Neurosci Lett 356: 155–158.

    Article  CAS  PubMed  Google Scholar 

  • Dringen R, Hirrlinger J. 2003. Glutathione pathways in the brain. Biol Chem 384: 505–516.

    Article  CAS  PubMed  Google Scholar 

  • Durr A, Cossee M, Agid Y, Campuzano V, Mignard C, et al. 1996. Clinical and genetic abnormalities in patients with Friedreich's ataxia. N Engl J Med 335: 1169–1175.

    Article  CAS  PubMed  Google Scholar 

  • El Khoury J, Hickman SE, Thomas CA, Loike JD, Silverstein SC. 1998. Microglia, scavenger receptors, and the pathogenesis of Alzheimer's disease. Neurobiol Aging 19: S81–S84.

    Article  CAS  PubMed  Google Scholar 

  • Ewing JF, Maines MD. 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.

    Article  CAS  PubMed  Google Scholar 

  • Ferri P, Cecchini T, Ciarloni S, Ambrogini P, Cuppini R, et al. 2003. Vitamin E affects cell death in adult rat dentate gyrus. J Neurocytol 32: 1155–1164.

    Article  CAS  PubMed  Google Scholar 

  • Fink SL, Chang LK, Ho DY, Sapolsky RM. 1997. Defective herpes simplex virus vectors expressing the rat brain stress-inducible heat shock protein 72 protect cultured neurons from severe heat shock. J Neurochem 68: 961–969.

    Article  CAS  PubMed  Google Scholar 

  • Floyd RA, Hensley K. 2002. Oxidative stress in brain aging. Implications for therapeutics of neurodegenerative diseases. Neurobiol Aging 23: 795–807.

    Article  CAS  PubMed  Google Scholar 

  • Foresti R, Motterlini R. 1999. The heme oxygenase pathway and its interaction with nitric oxide in the control of cellular homeostasis. Free Rad Res 31: 459–475.

    Article  CAS  Google Scholar 

  • Foresti R, Clark JE, Green CJ, Motterlini R. 1997. Thiol compounds interact with nitric oxide in regulating heme oxygenase-1 induction in endothelial cells. Involvement of superoxide and peroxynitrite anions. J Biol Chem 272: 18411–18417.

    Article  CAS  PubMed  Google Scholar 

  • Foresti R, Goatly H, Green CJ, Motterlini R. 2001. Role of heme oxygenase-1 in hypoxia-reoxygenation: Requirement of substrate heme to promote cardioprotection. Am J Physiol Heart Circ Physiol 281: H1976–H1984.

    CAS  PubMed  Google Scholar 

  • Forster MJ, Dubey A, Dawson KM, Stutts WA, Lal H, et al. 1996. Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain. Proc Natl Acad Sci USA 93: 4765–4769.

    Article  CAS  PubMed  Google Scholar 

  • Foury F, Talibi D. 2000. Mitochondrial control of iron homeostasis. A genome wide analysis of gene expression in a yeast frataxin deficient mutant. J Biol Chem 276: 7762–7768.

    Article  PubMed  Google Scholar 

  • France-Lanord V, Brugg B, Michel PP, Agid Y, Ruberg M. 1997. Mitochondrial free radical signal in ceramide-dependent apoptosis: A putative mechanism for neuronal death in Parkinson's disease. J Neurochem 69: 1612–1621.

    Article  CAS  PubMed  Google Scholar 

  • Fries JF. 2002. Successful aging—an emerging paradigm of gerontology. Clin Geriatr Med 18: 371–382.

    Article  PubMed  Google Scholar 

  • Friguet B. 2002. Protein repair and degradation during aging. Scientific World Journal 2: 248–254.

    CAS  PubMed  Google Scholar 

  • Fujita K, Yamaucji M, Shibayama M, Ando M, Honda M, et al. 1996. Decreased cytochrome c oxidase activity but unchanged superoxide dismutase and glutathione peroxidase activities in the spinal cords of patients with amyotrophic lateral sclerosis. J Neurosci Res 45: 276–281.

    Article  CAS  PubMed  Google Scholar 

  • Ganguli M, Chandra V, Kamboh MI, Johnston JM, Dodge HH, et al. 2000. Apolipoprotein E polymorphism and Alzheimer disease: The Indo-US Cross-National Dementia Study. Arch Neurol 57: 824–830.

    Article  CAS  PubMed  Google Scholar 

  • Garthwaite G, Goodwin DA, Batchelor AM, Leeming K, Garthwaite J. 2002. Nitric oxide toxicity in CNS white matter: An in vitro study using rat optic nerve. Neuroscience 109: 145–155.

    Article  CAS  PubMed  Google Scholar 

  • Gaubatz JW, Tan BH. 1993. Age-related studies on the removal of 7-methylguanine from DNA of mouse kidney tissue following N-methyl-N-nitrosourea treatment. Mutat Res 295: 81–91.

    CAS  PubMed  Google Scholar 

  • Gaubatz JW, Tan BH. 1994. Aging affects the levels of DNA damage in postmitotic cells. Ann NY Acad Sci 719: 97–107.

    Article  CAS  PubMed  Google Scholar 

  • Gegg ME, Beltran B, Salas-Pino S, Bolanos JP, Clark JB, et al. 2003. Differential effect of nitric oxide on glutathione metabolism and mitochondrial function in astrocytes and neurones: Implications for neuroprotection/neurodegeneration? J Neurochem 86: 228–237.

    Article  CAS  PubMed  Google Scholar 

  • Genova ML, Pich MM, Biondi A, Pernacchia A, Falasca A, et al. 2003. Mitochondrial production of oxygen radical species and the role of coenzyme Q as an antioxidant. Exp Biol Med 228: 506–513.

    CAS  Google Scholar 

  • Genova ML, Pich MM, Pernacchia A, Bianchi C, Biondi A, et al. 2004. The mitochondrial production of reactive oxygen species in relation to aging and pathology. Ann NY Acad Sci 1011: 86–100.

    Article  CAS  PubMed  Google Scholar 

  • Giovannoni G. 1998. Cerebrospinal fluid and serum nitric oxide metabolites in patients with multiple sclerosis. Mult Scler 4: 27–30.

    Article  CAS  PubMed  Google Scholar 

  • Glaum SR, Miller RJ. 1993. Zinc protoporphyrin-IX blocks the effects of metabotropic glutamate receptor activation in the rat nucleus tractus solitarii. Mol Pharmacol 43: 965–969.

    CAS  PubMed  Google Scholar 

  • Gong P, Stewart D, Hu B, Vinson C, Alam J. 2002. Multiple basic-leucine zipper proteins regulate induction of the mouse heme oxygenase-1 gene by arsenite. Arch Biochem Biophys 405: 265–274.

    Article  CAS  PubMed  Google Scholar 

  • Graser T, Vedernikov YP, Li DS. 1990. Study on the mechanism of carbon monoxide induced endothelium-independent relaxation in porcine coronary artery and vein. Biomed Biochim Acta 49: 293–296.

    CAS  PubMed  Google Scholar 

  • Grehan N. 1894. Le Gas du Sang. Paris.

    Google Scholar 

  • Hagen TM, Wehr CM, Ames BN. 1998a. Mitochondrial decay in aging. Reversal through supplementation of acetyl-l-carnitine and N-tert-butyl-α-phenyl-nitrone. Ann NY Acad Sci 854: 214–223.

    Article  CAS  Google Scholar 

  • Hagen TM, Ingersoll RT, Wehr CM, Lykkesfeldt J, Vinarsky V, et al. 1998b. Acetyl-l-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Proc Natl Acad Sci USA 95: 9562–9566.

    Article  CAS  Google Scholar 

  • Halliwell B. 1999. Oxygen and nitrogen are pro-carcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: Measurement, mechanism and the effects of nutrition. Mutat Res 443: 37–52.

    CAS  PubMed  Google Scholar 

  • Halliwell B. 2001. Role of free radicals in the neurodegenerative diseases: Therapeutic implications for antioxidant treatment. Drugs Aging 18: 685–716.

    Article  CAS  PubMed  Google Scholar 

  • Halliwell B. 2002. Hypothesis: Proteasomal dysfunction: A primary event in neurogeneration that leads to nitrative and oxidative stress and subsequent cell death. Ann NY Acad Sci 962: 182–194.

    Article  CAS  PubMed  Google Scholar 

  • Harding AE. 1981. Friedreich's ataxia: A clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain 104: 598–620.

    Article  Google Scholar 

  • Harman D. 1981. The aging process. Proc Natl Acad Sci USA 78: 7124–7128.

    Article  CAS  PubMed  Google Scholar 

  • Harman DA. 1956. A theory based on free radical and radiation chemistry. J Gerontol 11: 298–300.

    CAS  PubMed  Google Scholar 

  • Harris N, Costa V, Mac Lean M, Mollapour M, Moradas-Ferreira P, et al. 2003. MnSOD overexpression extends the yeast chronological (G0) life span but acts independently of Sir2p histone deacetylase to shorten the replicative life span of dividing cells. Free Radic Biol Med 34: 1599–1606.

    Article  CAS  PubMed  Google Scholar 

  • Hausladen A, Privalle CT, Keng T, Deangelo J, Stamler JS. 1996. Nitrosative stress: Activation of the transcription factor OxyR. Cell 86: 719–729.

    Article  CAS  PubMed  Google Scholar 

  • Heales SJR, Bolanos JP, Stewart VC, Brookes PS, Land JM, et al. 1999. Nitric oxide, mitochondria and neurological disease. Biochim Biophys Acta 1410: 215–228.

    Article  CAS  PubMed  Google Scholar 

  • Hill-Kapturczak N, Sikorski EM, Voakes C, Garcia J, Nick HS, et al. 2003. An internal enhancer regulates heme and cadmium-mediated induction of human heme oxygenase-1. Am J Physiol Renal Physiol 285: F515–F523.

    PubMed  Google Scholar 

  • Hon T, Hach A, Lee HC, Cheng T, Zhang L. 2000. Functional analysis of heme regulatory elements of the transcriptional activator Hap1. Biochem Biophys Res Commun 273: 584–591.

    Article  CAS  PubMed  Google Scholar 

  • Hu JR, Ferreira A, Van Eldik LJ. 1997. S100 β induces neuronal cell death through nitric oxide release from astrocytes. J Neurochem 69: 2294–2301.

    Article  CAS  PubMed  Google Scholar 

  • Hunot S, Brugg B, Richard D, Michel PP, Muriel MP, et al. 1997. Nuclear translocation of NF-κB is increased in dopaminergic neurons of patients with Parkinson's disease. Proc Natl Acad Sci USA 94: 7531–7536.

    Article  CAS  PubMed  Google Scholar 

  • Hursting SD, Lavigne JA, Berrigan D, Perkins SN, Barrett JC. 2003. Calorie restriction, aging, and cancer prevention: Mechanisms of action and applicability to humans. Annu Rev Med 54: 131–152.

    Article  CAS  PubMed  Google Scholar 

  • Hyun DH, Lee MH, Halliwell B, Jenner P. 2002. Proteasomal dysfunction induced by 4-hydroxy-2,3-trans-nonenal, an end-product of lipid peroxidation: A mechanism contributing to neurodegeneration? J Neurochem 83: 360–370.

    Article  CAS  PubMed  Google Scholar 

  • Hyun DH, Lee M, Halliwell B, Jenner P. 2003. Proteasomal inhibition causes the formation of protein aggregates containing a wide range of proteins, including nitrated proteins. J Neurochem 86: 363–373.

    Article  CAS  PubMed  Google Scholar 

  • Ignarro LJ. 2002. Nitric oxide as a unique signaling molecule in the vascular system: A historical overview. J Physiol Pharmacol 53: 503–514.

    CAS  PubMed  Google Scholar 

  • Izaki K, Kinouchim H, Watanabem K, Owada Y, Okubo A, et al. 2001. Induction of mitochondrial heat shock protein 60 and 10 mRNAs following transient focal cerebral ischemia in the rat. Brain Res Mol Brain Res 88: 14–25.

    Article  CAS  PubMed  Google Scholar 

  • Jauslin ML, Meier T, Smith RA, Murphy MP. 2003. Mitochondria-targeted antioxidants protect Friedreich ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants. FASEB J 17: 1972–1974.

    CAS  PubMed  Google Scholar 

  • Jenkins B, Koroshetz W, Beal MF, Rosen B. 1993. Evidence for an energy metabolism defect in Huntington's disease using localized proton spectroscopy. Neurology 43: 2689–2695.

    CAS  PubMed  Google Scholar 

  • Kalyuzhny AE. 2002. Simultaneous in situ detection of DNA fragmentation and RNA/DNA oxidative damage using TUNEL assay and immunohistochemical labeling for 8-hydroxy-2′-deoxyguanosine (8-OHdG). Methods Mol Biol 203: 219–234.

    CAS  PubMed  Google Scholar 

  • Kanakiriya SK, Croatt AJ, Haggard JJ, Ingelfinger JR, Tang SS, et al. 2003. Heme: A novel inducer of MCP-1 through HO-dependent and HO-independent mechanisms. Am J Physiol Renal Physiol 284: F546–F554.

    CAS  PubMed  Google Scholar 

  • Kaur H, Hughes MN, Green CJ, Naughton P, Foresti R, et al. 2003. Interaction of bilirubin and biliverdin with reactive nitrogen species. FEBS Lett 543: 113–119.

    Article  CAS  PubMed  Google Scholar 

  • Kazazian HH. 2000. Genetics. L1 retrotransposons shape the mammalian genome. Science 289: 1152–1153.

    Article  CAS  PubMed  Google Scholar 

  • Kelly S, Zhang ZJ, Zhao H, Xu L, Giffard RG, et al. 2002. Gene transfer of HSP72 protects cornu ammonis 1 region of the hippocampus neurons from global ischemia: Influence of Bcl-2. Ann Neurol 52: 160–167.

    Article  CAS  PubMed  Google Scholar 

  • Keyse SM, Tyrrell RM. 1989. Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide and sodium arsenite. Proc Natl Acad Sci USA 86: 99–103.

    Article  CAS  PubMed  Google Scholar 

  • Kimpara T, Takeda A, Yamaguchi T, Arai H, Okita N, et al. 2000. Increased bilirubins and their derivatives in cerebrospinal fluid in Alzheimer's disease. Neurobiol Aging 21: 551–554.

    Article  CAS  PubMed  Google Scholar 

  • Kirkwood TB. 1977. Evolution of ageing. Nature 270: 301–304.

    Article  CAS  PubMed  Google Scholar 

  • Kish SJ, Bergeron C, Rajput A, Dozic S, Mastrogiacomo F, et al. 1992. Brain cytochrome oxidase in Alzheimer's disease. J Neurochem 59: 776–779.

    Article  CAS  PubMed  Google Scholar 

  • Knight JA. 2000. The biochemistry of aging. Adv Clin Chem 35: 1–62.

    Article  CAS  PubMed  Google Scholar 

  • Koppal T, Subramaniam R, Drake J, Prasad RP, Dhillon H, et al. 1998. Vitamin E protects against Alzheimer's amyloid peptide25–35-induced changes in neocortical synaptosomal membrane lipid structure and composition. Brain Res 786: 270–273.

    Article  CAS  PubMed  Google Scholar 

  • Lauderback CM, Hackett JM, Keller JN, Varadarajan S, Szweda L, et al. 2001. Vulnerability of synaptosomes from apoE knock-out mice to structural and oxidative modifications induced by Aβ1–40: Implications for Alzheimer's disease. Biochemistry 40: 2548–2554.

    Article  CAS  PubMed  Google Scholar 

  • Lauderback CM, Kanski J, Hackett JM, Maeda N, Kindy MS, et al. 2002. Apolipoprotein E modulates Alzheimer's Aβ1–42-induced oxidative damage to synaptosomes in an allele-specific manner. Brain Research 924: 90–97.

    Article  CAS  PubMed  Google Scholar 

  • Lee TS, Chau LY. 2002. Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat Med 8: 240–248.

    Article  CAS  PubMed  Google Scholar 

  • Li H, Dryhurst G. 1997. Irreversible inhibition of mitochondrial complex I by 2-aminoethyl-3,4-dyhydro-5-hydroxy-2-benzothiazine-3-carboxylic acid (DHBT): A putative nigral endotoxin of relevance to Parkinson's disease. J Neurochem 69: 1530–1541.

    Article  CAS  PubMed  Google Scholar 

  • Lim GP, Chu T, Yang F, Beech W, Frautschy SA, et al. 2001. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 21: 8370–8377.

    CAS  PubMed  Google Scholar 

  • Lindsey JW, Kerman RH, Wolinsky JS. 1997. T cell-T cell activation in multiple sclerosis. Mult Scler 3: 238–242.

    Article  CAS  PubMed  Google Scholar 

  • Liu N, Wang X, McCoubrey WK, Maines MD. 2000. Developmentally regulated expression of two transcripts for heme oxygenase-2 with a first exon unique to rat testis: Control by corticosterone of the oxygenase protein expression. Gene 241: 175–183.

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Zhu B, Luo L, Li P, Paty DW, et al. 2001. Heme oxygenase-1 plays an important protective role in experimental autoimmune encephalomyelitis. Neuroreport 12: 1841–1845.

    Article  CAS  PubMed  Google Scholar 

  • Lodi R, Rajagopalan B, Bradley JL, Taylor DJ, Crilley JG, et al. 2002. Mitochondrial dysfunction in Friedreich's ataxia: From pathogenesis to treatment perspectives. Free Radic Res 36: 461–466.

    Article  CAS  PubMed  Google Scholar 

  • Lodi R, Rajagopalan B, Schapira AHV, Hart PE, Crilley JG, et al. 2003. Coenzyme Q10 and vitamin E treatment of patients with Friedreich ataxia. A 4 year clinical and 31P-MRS follow up study. International Society for Magnetic Resonance in Medicine. 11th Scientific Meeting and Exhibition. Toronto, Ontario, Canada. 10–16 page 638.

    Google Scholar 

  • Maines MD. 1997. The heme oxygenase system: A regulator of second messenger gases. Annu Rev Pharmacol Toxicol 37: 517–554.

    Article  CAS  PubMed  Google Scholar 

  • Maines MD. 2000. The heme oxygenase system and its functions in the brain. Cell Mol Biol 46: 573–585.

    CAS  PubMed  Google Scholar 

  • Mancuso C, Bonsignore A, Di Stasio E, Mordente A, Motterlini R. 2003. Bilirubin and S-nitrosothiols interaction: Evidence for a possible role of bilirubin as a scavenger of nitric oxide. Biochem Pharmacol 66: 2355–2366.

    Article  CAS  PubMed  Google Scholar 

  • Mandavilli BS, Rao KS. 1996. Accumulation of DNA damage in aging neurons occurs through a mechanism other than apoptosis. J Neurochem 67: 1559–1565.

    Article  CAS  PubMed  Google Scholar 

  • Markesbery WR. 1997. Oxidative stress hypothesis in Alzheimer's disease. Free Radic Biol Med 23: 134–147.

    Article  CAS  PubMed  Google Scholar 

  • Martin D, Rojo AI, Salinas M, Diaz R, Gallardo G, et al. 2004. Regulation of heme oxygenase-1 expression through the phosphatidylinositol-3-kinase/Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. J Biol Chem 279: 8919–8929.

    Article  CAS  PubMed  Google Scholar 

  • Martin GM, La Marco K, Strauss E, Kelner KL. 2003. Research on aging: The end of the beginning. Science 299: 1339–1341.

    Article  CAS  PubMed  Google Scholar 

  • Mattson MP. 2003. Will caloric restriction and folate protect against AD and PD? Neurology 60: 690–695.

    Article  CAS  PubMed  Google Scholar 

  • Mattson MP, Duan W, Guo Z. 2003. Meal size and frequency affect neuronal plasticity and vulnerability to disease: Cellular and molecular mechanisms. J Neurochem 84: 417–431.

    Article  CAS  PubMed  Google Scholar 

  • Mattson MP, Duan W, Chan SL, Cheng A, Haughey N, et al. 2002. Neuroprotective and neurorestorative signal transduction mechanisms in brain aging: Modification by genes, diet and behavior. Neurobiol Aging 23: 695–705.

    Article  CAS  PubMed  Google Scholar 

  • Mautes AE, Bergeron M, Sharp FR, Panter SS, Weinzierl M, et al. 2000. Sustained induction of heme oxygenase-1 in the traumatized spinal cord. Exp Neurol 166: 254–265.

    Article  CAS  PubMed  Google Scholar 

  • Mayer RJ. 2003. From neurodegeneration to neurohomeostasis: The role of ubiquitin. Drug News Perspect 16: 103–108.

    Article  CAS  PubMed  Google Scholar 

  • McLaughlin B, Hartnett KA, Erhardt JA, Legos JJ, White RF, et al. 2003. Caspase 3 activation is essential for neuroprotection in preconditioning. Proc Natl Acad Sci USA 100: 715–720.

    Article  CAS  PubMed  Google Scholar 

  • Mc Naught KS, Olanow CW, Halliwell B, Isacson O, Jenner P. 2001. Failure of the ubiquitin-proteasome system in Parkinson disease. Nat Rev Neurosci 2: 589–594.

    Article  CAS  Google Scholar 

  • Mecocci P, Beal MF, Cecchetti R, Polidori MC, Cherubini A, et al. 1997. Mitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged and AD human brain. Mol Chem Neuropathol 31: 53–64.

    Article  CAS  PubMed  Google Scholar 

  • Mecocci P, Polidori MC, Ingegni T, Cherubini A, Chionne F, et al. 1998. Oxidative damage to DNA in lymphocytes from AD patients. Neurology 51: 1014–1017.

    CAS  PubMed  Google Scholar 

  • Moore DJ, Dawson VL, Dawson TM. 2003. Role for the ubiquitin-proteasome system in Parkinson's disease and other neurodegenerative brain amyloidoses. Neuromolecular Med 4: 95–108.

    Article  PubMed  Google Scholar 

  • Mosser DD, Caron AW, Bourget L, Denis-Larose D. 1997. Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis. Mol Cell Biol 17: 5317–5327.

    CAS  PubMed  Google Scholar 

  • Motterlini R, Foresti R, Bassi R, Calabrese V, Clark JE, et al. 2000a. Endothelial heme oxygenase-1 induction by hypoxia. Modulation by inducible nitric-oxide synthase and S-nitrosothiols. J Biol Chem 275: 13613–13620.

    Article  CAS  Google Scholar 

  • Motterlini R, Foresti R, Bassi R, Green CJ. 2000b. Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radic Biol Med 28: 1303–1312.

    Article  CAS  Google Scholar 

  • Motterlini R, Green CJ, Foresti R. 2002a. Regulation of heme oxygenase-1 by redox signals involving nitric oxide. Antioxid Redox Signal 4: 615–624.

    Article  CAS  Google Scholar 

  • Motterlini R, Clark JE, Foresti R, Sarathchandra P, Mann BE, et al. 2002b. Carbon monoxide-releasing molecules: Characterization of biochemical and vascular activities. Circ Res 92: 17–24.

    Article  Google Scholar 

  • Motterlini R, Mann BE, Johnson TR, Clark JE, Foresti R, et al. 2003. Bioactivity and pharmacological actions of carbon monoxide-releasing molecules. Curr Pharm Des 9: 2525–2539.

    Article  CAS  PubMed  Google Scholar 

  • Narasimhan P, Swanson RA, Sagar SM, Sharp FR. 1996. Astrocyte survival and HSP70 heat shock protein induction following heat shock and acidosis. Glia 17: 147–159.

    Article  CAS  PubMed  Google Scholar 

  • Ojaimi J, Masters CL, McLean C, Opeskin K, McKelvie P, et al. 1999. Irregular distribution of cytochrome c oxidase protein subunits in aging and Alzheimer's disease. Ann Neurol 46: 656–660.

    Article  CAS  PubMed  Google Scholar 

  • Okubo A, Kinouchi H, Owada Y, Kunizuka H, Itoh H, et al. 2000. Simultaneous induction of mitochondrial heat shock protein mRNAs in rat forebrain ischemia. Brain Res Mol Brain Res 84: 127–134.

    Article  CAS  PubMed  Google Scholar 

  • Otterbein LE. 2002. Carbon monoxide: Innovative anti-inflammatory properties of an age-old gas molecule. Antioxid Redox Signal 4: 309–319.

    Article  CAS  PubMed  Google Scholar 

  • Otterbein LE, Soares MP, Yamashita K, Bach F. 2003a. Heme oxygenase-1: Unleashing the protective properties of heme. Trends Immunol 24: 449–466.

    Article  CAS  Google Scholar 

  • Otterbein LE, Zuckerbraun BS, Haga M, Liu F, Song R, et al. 2003b. Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury. Nat Med 9: 183–190.

    Article  CAS  Google Scholar 

  • Papa S, Skulachev VP. 1997. Reactive oxygen species, mitochondria, apoptosis and aging. Mol Cell Biochem 174: 305–319.

    Article  CAS  PubMed  Google Scholar 

  • Paradies G, Petrosillo G, Gadaleta MN, Ruggiero FM. 1999. The effect of aging and acetyl-l-carnitine on the pyruvate transport and oxidation in rat heart mitochondria. FEBS Lett 454: 207–209.

    Article  CAS  PubMed  Google Scholar 

  • Paradies G, Petrosillo G, Pistolese M, Ruggiero FM. 2002. Reactive oxygen species affect mitochondrial electron transport complex I activity through oxidative cardiolipin damage. Gene 286: 135–141.

    Article  CAS  PubMed  Google Scholar 

  • Perluigi M, Poon FH, Hensley K, Pierce WM, Klein JB, et al. 2005. Proteomic analysis of 4-hydroxy-2-nonenal-modified proteins in G93A-SOD1 transgenic mice-A model of familial amyotrophic lateral sclerosis. Free Radic Biol Med 38: 960–968.

    Article  CAS  PubMed  Google Scholar 

  • Perry G, Taddeo MA, Petersen RB, Castellani RJ, Harris PL, et al. 2003. Adventiously-bound redox active iron and copper are at the center of oxidative damage in Alzheimer disease. Biometals 16: 77–81.

    Article  CAS  PubMed  Google Scholar 

  • Perry TL, Godin DV, Hansen S. 1982. Parkinson's disease: A disorder due to nigral glutathione deficiency? Neurosci Lett 33: 305–310.

    Article  CAS  PubMed  Google Scholar 

  • Piantadosi CA, Zhang J, Levin ED, Folz RJ, Schmechel DE. 1997. Apoptosis and delayed neuronal damage after carbon monoxide poisoning in the rat. Exp Neurol 147: 103–114.

    Article  CAS  PubMed  Google Scholar 

  • Pocernich C, Boyd-Kimball D, Poon F, Thongboonkerd V, Lynn BC, et al. 2005. Proteomic analysis of human astrocytes expressing the HIV protein TAT. Brain Res Mol Brain Res 133: 307–316.

    Article  CAS  PubMed  Google Scholar 

  • Poon F, Calabrese V, Scapagnini G, Butterfield DA. 2004a. Free radicals: Key to brain aging and heme oxygenase as a cellular response to oxidative stress. J Gerontol 59: 478–493.

    Google Scholar 

  • Poon HF, Calabrese V, Scapagnini G, Butterfield DA. 2004b. Free radicals and brain aging. Clin Geriatr Med 20: 329–359.

    Article  Google Scholar 

  • Poon FH, Frasier M, Shreve N, Calabrese V, Wolozin B, et al. 2005. Mitochondrial associated metabolic proteins are selectively oxidized in A30P α-synuclein transgenic mice—a model of familial Parkinson's disease. Neurobiol Dis 18: 492–498.

    Article  CAS  PubMed  Google Scholar 

  • Portero-Otin M, Bellmunt MJ, Ruiz MC, Barja G, Pamplona R. 2001. Correlation of fatty acid unsaturation of the major liver mitochondrial phospholipid classes in mammals to their maximum life span potential. Lipids 236: 491–498.

    Article  Google Scholar 

  • Powell CS, Jackson RM. 2003. Mitochondrial complex I, aconitase, and succinate dehydrogenase during hypoxia-reoxygenation: Modulation of enzyme activities by MnSOD. Am J Physiol Lung Cell Mol Physiol 285: L189–L198.

    CAS  PubMed  Google Scholar 

  • Premkumar DR, Smith MA, Richey PL, Petersen RB, Castellani R, et al. 1995. Induction of heme oxygenase-1 mRNA and protein in neocortex and cerebral vessels in Alzheimer's disease. J Neurochem 65: 1399–1402.

    Article  CAS  PubMed  Google Scholar 

  • Quiles JL, Martinez E, Ibanez S, Ochoa JJ, Martin Y, et al. 2002. Ageing-related tissue-specific alterations in mitochondrial composition and function are modulated by dietary fat type in the rat. J Bioenerg Biomembr 34: 517–524.

    Article  CAS  PubMed  Google Scholar 

  • Radisky DC, Babcock MC, Kaplan J. 1999. The yeast frataxin homologue mediates mitochondrial iron efflux. Evidence for a mitochondrial iron cycle. J Biol Chem 274: 4497–4499.

    Article  CAS  PubMed  Google Scholar 

  • Raju VS, McCoubrey WK, Maines MD. 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.

    CAS  PubMed  Google Scholar 

  • Risch N, Merikangas K. 1996. The future of genetic studies of complex human diseases. Science 273: 1516–1517.

    Article  CAS  PubMed  Google Scholar 

  • Rosenberg PA, Li Y, Ali S, Altiok N, Back SA, et al. 1999. Intracellular redox state determines whether nitric oxide is toxic or protective to rat oligodendrocytes in culture. J Neurochem 73: 476–484.

    Article  CAS  PubMed  Google Scholar 

  • Roses AD. 1996. Apolipoprotein E alleles as risk factors in Alzheimer's disease. Annu Rev Med 47: 387–400.

    Article  CAS  PubMed  Google Scholar 

  • Rothschild H, Jazwinski S. 1988. Human longevity determinant genes. J La State Med Soc 150: 272–274.

    Google Scholar 

  • Sastre J, Pallardo FV, Vina J. 2003. The role of mitochondrial oxidative stress in aging. Free Radic Biol Med 35: 1–8.

    Article  CAS  PubMed  Google Scholar 

  • Sayre LM, Perry G, Harris PL, Liu Y, Schubert KA, et al. 2000. In situ oxidative catalysis by neurofibrillary tangles and senile plaques in Alzheimer's disease: A central role for bound transition metals. J Neurochem 74: 270–279.

    Article  CAS  PubMed  Google Scholar 

  • Scapagnini G, Butterfield DA, Colombrita C, Sultana R, Pascale A, et al. 2004. Ethyl ferulate, a lipophilic polyphenol, induces HO-1 and protects rat neurons against oxidative stress. Antioxid Redox Signal 6: 811–818.

    CAS  PubMed  Google Scholar 

  • Scapagnini G, Giuffrida Stella AM, Abraham NG, Alkon D, Calabrese V. 2002a. Differential expression of Heme oxygenase-1 in rat brain by endotoxin (LPS). Heme Oxygenase in Biology and Medicine. Abraham et al. editors. New York: Kluwer Academic/Plenum Publishers; pp. 121–134.

    Google Scholar 

  • Scapagnini G, D'Agata V, Calabrese V, Pascal A, Colombrita C, et al. 2002b. Gene expression profiles of heme oxygenase isoforms in the rat brain. Brain Res 954: 51–59.

    Article  CAS  Google Scholar 

  • Scapagnini G, Foresti R, Calabrese V, Giuffirida Stella AM, Green CJ, et al. 2002c. Caffeic acid phenethyl ester and curcumin: A novel class of heme oxygenase-1 inducers. Mol Pharmacol 61: 554–561.

    Article  CAS  Google Scholar 

  • Scapagnini G, Ravagna A, Bella R, Colombrita C, Pennisi G, et al. 2002d. Long-term ethanol administration enhances age-dependent modulation of redox state in brain and peripheral organs of rat: Protection by acetyl carnitine. Int J Tissue React 24: 89–96.

    CAS  Google Scholar 

  • Schapira AH. 1998. Mitochondrial dysfunction in neurodegenerative disorders. Biochim Biophys Acta 1366: 225–233.

    Article  CAS  PubMed  Google Scholar 

  • Schapira AHV, Cooper JM, Dexter D. 1990. Mitochondrial complex I deficiency in Parkinson disease. J Neurochem 54: 823–827.

    Article  CAS  PubMed  Google Scholar 

  • Schipper HM, Chertkow H, Mehindate K, Frankel D, Melmed C, et al. 2000. Evaluation of heme oxygenase-1 as a systemic biological marker of sporadic AD. Neurology 54: 1297–1304.

    CAS  PubMed  Google Scholar 

  • Sellebjerg F, Giovannoni G, Hand A, Madsen HO, Jensen CV, et al. 2002. Cerebrospinal fluid levels of nitric oxide metabolites predict response to methylprednisolone treatment in multiple sclerosis and optic neuritis. J Neuroimmunol 125: 198–203.

    Article  CAS  PubMed  Google Scholar 

  • Selman C, Gredilla R, Phaneuf S, Kendaiah S, Barja G, et al. 2003. Short-term caloric restriction and regulatory proteins of apoptosis in heart, skeletal muscle and kidney of Fischer 344 rats. Biogerontology 4: 141–147.

    Article  CAS  PubMed  Google Scholar 

  • Sergent O, Griffon B, Morel I, Chevanne M, Dubos MP, et al. 1977. Effect of nitric oxide on iron-mediated oxidative stress in primary rat hepatocyte culture. Hepatology 25: 122–127.

    Article  Google Scholar 

  • Sharman EH, Bondy SC. 2001. Effects of age and dietary antioxidants on cerebral electron transport chain activity. Neurobiol Aging 22: 629–634.

    Article  CAS  PubMed  Google Scholar 

  • Sian J, Dexter DT, Lees AJ. 1994. Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting the basal ganglia. Ann Neurol 36: 348–355.

    Article  CAS  PubMed  Google Scholar 

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

    Article  Google Scholar 

  • Smith MA, Harris PRL, Sayre LM, Beckman JS, Perry G. 1997. Widespread peroxynitrite mediated damage in Alzheimer's disease. J Neurosci 17: 2653–2657.

    CAS  PubMed  Google Scholar 

  • Soares MP, Seldon MP, Gregoire IP, Vassilevskaia T, Berberat PO, et al. 2004. Heme oxygenase-1 modulates the expression of adhesion molecules associated with endothelial cell activation. J Immunol 172: 3553–3563.

    CAS  PubMed  Google Scholar 

  • Soti C, Csermely P. 2002. Chaperones and aging: Role in neurodegeneration and in other civilizational diseases. Neurochem Int 41: 383–389.

    Article  CAS  PubMed  Google Scholar 

  • Spencer J, Jenner A, Aruoma O, Evans P, Jenner P, et al. 1994. Intense oxidative DNA damage promoted by l-DOPA and its metabolites. Implication for neurodegenerative diseases. FEBS Lett 353: 246–250.

    Article  CAS  PubMed  Google Scholar 

  • Spencer JP, Whiteman M, Jenner P, Halliwell B. 2002. 5-S-cysteinyl-conjugates of catecholamines induce cell damage, extensive DNA base modification and increase in caspase-3 activity in neurons. J Neurochem 81: 122–129.

    Article  CAS  PubMed  Google Scholar 

  • Stadtman ER. 2001. Protein oxidation in aging and age-related diseases. Ann NY Acad Sci 928: 22–38.

    Article  CAS  PubMed  Google Scholar 

  • Stamler JS, Hausladen A. 1998. Oxidative modifications in nitrosative stress. Cell 78: 931–936.

    Article  Google Scholar 

  • Stamler JS, Singel DI, Loscalzo J. 1992. Biochemistry of nitric oxide and its redox activated forms. Science 258: 1898–1902.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Strauss E. 2003. Longevity research. Single signal unites treatments that prolong life. Science 300: 881–883.

    Article  CAS  PubMed  Google Scholar 

  • Sultana R, Ravagna A, Mohmmad-Abdul H, Calabrese V, Butterfield DA. 2005. Ferulic acid ethyl ester protects neurons against amyloid β-peptide1–42-induced oxidative stress and neurotoxicity: Relationship to antioxidant activity. J Neurochem 92: 749–758.

    Article  CAS  PubMed  Google Scholar 

  • Sun J, Hoshino O, Takaku K, Nakajima O, Muto A, et al. 2002. Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene. EMBO J 21: 5216–5224.

    Article  CAS  PubMed  Google Scholar 

  • Szilard L. 1977. On the nature of the aging process. Proc Natl Acad Sci USA 45: 35–45.

    Google Scholar 

  • Takeda A, Perry G, Abraham NG, Dwyer BE, Kutty RK, et al. 2000. Overexpression of heme oxygenase in neuronal cells, the possible interaction with Tau. J Biol Chem 275: 5395–5399.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Thompson EJ. 1988. The CSF Proteins: A Biochemical Approach. London: Elsevier; pp. 16–24.

    Google Scholar 

  • Toshniwal PK, Zarling EJ. 1992. Evidence for increased lipid peroxidation in multiple sclerosis. Neurochem Res 17: 205–207.

    Article  CAS  PubMed  Google Scholar 

  • Tran EH, Hardin PH, Verge G, Owens T. 1997. Astrocytes and microglia express inducible nitric oxide synthase in mice with experimental allergic encephalomyelitis. J Neuroimmunol 74: 121–129.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Turner CP, Panter SS, Sharp FR. 1999. Anti-oxidants prevent focal rat brain injury as assessed by induction of heat shock proteins (Hsp70, HO-1/Hsp32, Hsp47) following subarachnoid injections of lysed blood. Brain Res Mol Brain Res 65: 87–102.

    Article  CAS  PubMed  Google Scholar 

  • Tyrrell R. 1999. Redox regulation and oxidant activation of heme oxygenase-1. Free Radic Res 31: 335–340.

    Article  CAS  PubMed  Google Scholar 

  • Valentim LM, Rodnight R, Geyer AB, Horn AP, Tavares A, et al. 2003. Changes in heat shock protein 27 phosphorylation and immunocontent in response to preconditioning to oxygen and glucose deprivation in organotypic hippocampal cultures. Neuroscience 118: 379–386.

    Article  CAS  PubMed  Google Scholar 

  • Veinbergs I, Mallory M, Sagara Y, Masliah E. 2000. Vitamin E supplementation prevents spatial learning deficits and dendritic alterations in aged apolipoprotein E-deficient mice. Eur J Neurosci 12: 4541–4546.

    CAS  PubMed  Google Scholar 

  • Verma A, Hirsch DJ, Glatt CE, Ronnett GV, Snyder SH. 1993. Carbon monoxide: A putative neural messenger. Science 259: 381–384.

    Article  CAS  PubMed  Google Scholar 

  • Wang R, Wu L. 2003. Interaction of selective amino acid residues of K(Ca) channels with carbon monoxide. Exp Biol Med 228: 474–480.

    CAS  Google Scholar 

  • Weng YH, Yang G, Weiss S, Dennery PA. 2003. Interaction between heme oxygenase-1 and -2 proteins. J Biol Chem 278: 50999–51005.

    Article  CAS  PubMed  Google Scholar 

  • Wheeler DS, Dunsmore KE, Wong HR. 2003. Intracellular delivery of HSP70 using HIV-1 Tat protein transduction domain. Biochem Biophys Res Commun 301: 54–59.

    Article  CAS  PubMed  Google Scholar 

  • Xin W, Chen XM, Li H, Dryhurst G. 2000. Oxidative metabolites of 5-S-cysteinylnorepinephrine are irreversible inhibitors of mitochondrial complex I and the α-ketoglutarate dehydrogenase and pyruvate dehydrogenase complexes: Possible implications for neurodegenerative brain disorders. Chem Res Toxicol 13: 749–760.

    Article  CAS  PubMed  Google Scholar 

  • Yamashita K, McDaid J, Ollinger R, Tsui TY, Berberat PO, et al. 2004. Biliverdin, a natural product of heme catabolism, induces tolerance to cardiac allografts. FASEB J 18: 765–767.

    CAS  PubMed  Google Scholar 

  • Yatin SM, Kink CD, Butterfield DA. 1999. In-vitro and in-vivo oxidative stress associated with Alzheimer's amyloid β-peptide1–42. Neurobiol Aging 20: 325–330.

    Article  CAS  PubMed  Google Scholar 

  • Yuceyar N, Taskiran D, Sagduyu A. 2001. Serum and cerebrospinal fluid nitrite and nitrate levels in relapsing-remitting and secondary progressive multiple sclerosis patients. Clin Neurol Neurosurg 103: 206–211.

    Article  CAS  PubMed  Google Scholar 

  • Zhang HX, Du GH, Zhang JT. 2003. Ischemic pre-conditioning preserves brain mitochondrial functions during the middle cerebral artery occlusion in rat. Neurol Res 25: 471–476.

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported in part by grants from the Wellcome Trust, MIUR-Cluster Biomedicine, and FIRB RBNE01ZK8F, and by grants from the National Institute of Health (D.A.B.). The authors acknowledge helpful discussions with John Clark (Institute of Neurology, UCL, London, UK) and with Roberto Motterlini (Northwick Park Institute for Medical Research, Harrow, UK); Enrico Rizzarelli and Eduardo Puleo (Department of Chemistry, University of Catania).

Authors
  1. V. Calabrese
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  2. D. A. Butterfield
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  3. A. M. Giuffrida Stella
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Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 10962, 140 Old Orangeburg Road, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, 301 University Blvd., TX, 77555, Galveston, USA

    J. Regino Perez-Polo (I. H. Kempner Professor and Chair Dept. Biochemistry & Molecular Biology Senior Scientist Sealy Center for Molecular Medicine Staff Scientist Shriner's Hospital for Children) (I. H. Kempner Professor and Chair Dept. Biochemistry & Molecular Biology Senior Scientist Sealy Center for Molecular Medicine Staff Scientist Shriner's Hospital for Children)

  3. Universität Leipzig Medizinische Fakultät, Paul-Flechsig-Institut für Hirnforschung, Jahnallee 59, 04109, Leipzig, Germany

    Steffen Rossner

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Calabrese, V., Butterfield, D.A., Stella, A.M.G. (2008). Aging and Oxidative Stress Response in the CNS. In: Lajtha, A., Perez-Polo, J.R., Rossner, S. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-32671-9_6

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