Free radicals: Key to brain aging and heme oxygenase as a cellular response to oxidative stress

Journals of Gerontology - Series A Biological Sciences and Medical Sciences

Volumn 59, Issue 5, 2004, Pages 478-493

  Poon, H Fai ^a   Calabrese, Vittorio ^b   Scapagnini, Giovanni ^b   Butterfield, D Allan ^a  

^a UNIVERSITY OF KENTUCKY   (United States)

^b UNIVERSITY OF CATANIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

3 NITROTYROSINE; BILIRUBIN; BILIVERDIN; CARBON MONOXIDE; CREATINE KINASE; FREE RADICAL; GLUTATHIONE SYNTHASE; HEAT SHOCK PROTEIN 10; HEAT SHOCK PROTEIN 27; HEAT SHOCK PROTEIN 32; HEAT SHOCK PROTEIN 47; HEAT SHOCK PROTEIN 60; HEAT SHOCK PROTEIN 70; HEME OXYGENASE; HEME OXYGENASE 1; HEME OXYGENASE 2; ISOPROSTANE DERIVATIVE; MALONALDEHYDE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; PHOSPHOLIPID; REACTIVE OXYGEN METABOLITE; UBIQUITIN;

AGING; BRAIN FUNCTION; DEGENERATIVE DISEASE; ELECTRON SPIN RESONANCE; ENZYME ACTIVITY; HUMAN; LIPID COMPOSITION; LIPID PEROXIDATION; NEUROMODULATION; NEUROTOXICITY; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN DEGRADATION; REVIEW; SYSTEMATIC REVIEW;

EID: 2442482592     PISSN: 10795006     EISSN: None     Source Type: Journal    
DOI: 10.1093/gerona/59.5.m478     Document Type: Review

References (233)

1. Ashok BT, Ali R. The aging paradox: free radical theory of aging. Exp Gerontol. 1999;34:293-303.
2. Harman D. The aging process: major risk factor for disease and death. Proc Natl Acad Sci U S A. 1991;88:5360-5363.
3. Sohal RS, Mockett RJ, Orr WC. Mechanisms of aging: an appraisal of the oxidative stress hypothesis. Free Radic Biol Med. 2002;33:575-586.
4. Gilgun-Sherki Y, Melamed E, Offen D. Oxidative stress induced-neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier. Neuropharmacology. 2001;40:959-975.
5. Floyd RA. Antioxidants, oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med. 1999;222:236-245.
6. Halliwell B, Gutteridge JM. Biologically relevant metal ion-dependent hydroxyl radical generation. An update. FEBS Lett. 1992;307:108-112.
7. Frankel EN. Chemistry of free radical and singlet oxidation of lipids. Prog Lipid Res. 1984;23:197-221.
8. Spiteller G. Peroxidation of linoleic acid and its relation to aging and age dependent diseases. Mech Ageing Dev. 2001;122:617-657.
9. Esterbauer H, Schaur RJ, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med. 1991;11:81-128.
10. Delsal JL. Nouveau procede d'extraction des lipids du serum per le methylal. Applications aux, icrodpsages du chlesterol total, des phosphoaminolipides et des proteines. Bull Soc Chim Biol. 1944;26: 99-105.
11. Vitiello F, Zanetta JP. Thin-layer chromatography of phospholipids. J Chromatogr. 1978;166:637-640.
12. Hedegaard E, Jensen B. Nano-scale densitometric quantitation of phospholipids. J Chromatogr. 1981;225:450-454.
13. Lanza E, Zyren J, Slover HT. Fatty acid analysis on short glass capillary columns. J Agric Food Chem. 1980;28:1182-1186.
14. Murphy EJ, Stephens R, Jurkowitz-Alexander M, Horrocks LA. Acidic hydrolysis of plasmalogens followed by high-performance liquid chromatography. Lipids. 1993;28:565-568.
15. Schroeder F, Goetz I, Roberts E. Sex and age alter plasma membranes of cultured fibroblasts. Eur J Biochem. 1984;142:183-191.
16. Lopez GH, Ilincheta de Boschero MG, Castagnet PI, Giusto NM. Age-associated changes in the content and fatty acid composition of brain glycerophospholipids. Comp Biochem Physiol B Biochem Mol Biol. 1995;112:331-343.
17. Giusto NM, Salvador GA, Castagnet PI, Pasquare SJ, Ilincheta de Boschero MG. Age-associated changes in central nervous system glycerolipid composition and metabolism. Neurochem Res. 2002;27: 1513-1523.
18. Ulmann L, Mimouni V, Roux S, Porsolt R, Poisson JP. Brain and hippocampus fatty acid composition in phospholipid classes of aged-relative cognitive deficit rats. Prostagl Leukot Essent Fatty Acids. 2001;64:189-195.
19. Lynch MA. Analysis of the mechanisms underlying the age-related impairment in long-term potentiation in the rat. Rev Neurosci. 1998;9: 169-201.
20. Butterfield DA, Stadtman ER. Protein oxidation processes in aging brain. Adv Cell Aging Gerontol. 1997;2:161-191.
21. Pizzimenti S, Barrera G, Dianzani MU, Brusselbach S. Inhibition of D1, D2, and A-cyclin expression in HL-60 cells by the lipid peroxydation product 4-hydroxynonenal. Free Radic Biol Med. 1999; 26:1578-1586.
22. Uchida K, Stadtman ER. Modification of histidine residues in proteins by reaction with 4-hydroxynonenal. Proc Natl Acad Sci U S A. 1992; 89:4544-4548.
23. Guichardant M, Taibi-Tronche P, Fay LB, Lagarde M. Covalent modifications of aminophospholipids by 4-hydroxynonenal. Free Radic Biol Med. 1998;25:1049-1056.
24. Del Corso A, Dal Monte M, Vilardo PG, et al. Site-specific inactivation of aldose reductase by 4-hydroxynonenal. Arch Biochem Biophys. 1998;350:245-248.
25. Boschi-Muller S, Azza S, Sanglier-Cianferani S, Talfournier F, Van Dorsselear A, Branlant G. A sulfenic acid enzyme intermediate is involved in the catalytic mechanism of peptide methionine sulfoxide reductase from Escherichia coli. J Biol Chem. 2000;275:35908-35913.
26. Siems WG, Hapner SJ, van Kuijk FJ. 4-hydroxynonenal inhibits Na(+)-K(+)-ATPase. Free Radic Biol Med. 1996;20:215-223.
27. Butterfield DA, Lauderback CM. 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. 2002;32:1050-1060.
28. Mark RJ, Lovell MA, Markesbery WR, Uchida K, Mattson MP. A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide. J Neurochem. 1997;68:255-264.
29. Uchida K, Kanematsu M, Sakai K, et al. Protein-bound acrolein: potential markers for oxidative stress. Proc Natl Acad Sci U S A. 1998; 95:4882-4887.
30. Lovell MA, Xie C, Markesbery WR. Acrolein is increased in Alzheimer's disease brain and is toxic to primary hippocampal cultures. Neurobiol Aging. 2001;22:187-194.
31. Pocernich CB, Cardin AL, Racine CL, Lauderback CM, Butterfield DA. Glutathione elevation and its protective role in acrolein-induced protein damage in synaptosomal membranes: relevance to brain lipid peroxidation in neurodegenerative disease. Neurochem Int. 2001;39: 141-149.
32. Lovell MA, Xie C, Markesbery WR. Acrolein, a product of lipid peroxidation, inhibits glucose and glutamate uptake in primary neuronal cultures. Free Radic Biol Med. 2000;29:714-720.
33. Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman ER, Mizuno Y. Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci U S A. 1996;93: 2696-2701.
34. Papaioannou N, Tooten PC, van Ederen AM, et al. Immunohistochemical investigation of the brain of aged dogs. I. Detection of neurofibrillary tangles and of 4-hydroxynonenal protein, an oxidative damage product, in senile plaques. Amyloid. 2001;8:11-21.
35. Markesbery WR, Lovell MA. Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer's disease. Neurobiol Aging. 1998;19:33-36.
36. Sayre LM, Zelasko DA, Harris PL, Perry G, Salomon RG, Smith MA. 4-Hydroxynonenal-derived advanced lipid peroxidation end products are increased in Alzheimer's disease. J Neurochem. 1997;68:2092-2097.
37. Michiels C, Remacle J. Cytotoxicity of linoleic acid peroxide, malondialdehyde and 4-hydroxynonenal towards human fibroblasts. Toxicology. 1991;66:225-234.
38. Esterbauer H. Cytotoxicity and genotoxicity of lipid-oxidation products. Am J Clin Nutr. 1993;57:779S-785S; discussion 785S-786S.
39. Basu AK, Marnett LJ. Unequivocal demonstration that malondialdehyde is a mutagen. Carcinogenesis. 1983;4:331-333.
40. Nair V, Offerman RJ, Turner GA, Pryor AN. Fluorescent 1,4-dihydropyridines-the malondialdehyde connection. Tetrahedron. 1988;44:2793-2803.
41. Nair V, Vietti DE, Cooper CS. Degenerative chemistry of malondialdehyde. Structure, stereochemistry, and kinetics of formation of enaminals from reaction with amino acids. J Am Chem Soc. 1981;103: 3030-3036.
42. Slatter DA, Murray M, Bailey AJ. Formation of a dihydropyridine derivative as a potential cross-link derived from malondialdehyde in physiological systems. FEBS Lett. 1998;421:180-184.
43. King TP. Selective chemical modification of arginyl residues. Biochemistry. 1966;5:3454-3459.
44. Slatter DA, Paul RG, Murray M, Bailey AJ. Reactions of lipid-derived malondialdehyde with collagen. J Biol Chem. 1999;274:19661-19669.
45. Xu D, Thiele GM, Beckenhauer JL, Klassen LW, Sorrell MF, Tuma DJ. Detection of circulating antibodies to malondialdehyde-acetaldehyde adducts in ethanol-fed rats. Gastroenterology. 1998;115:686-692.
46. Slatter DA, Bolton CH, Bailey AJ. The importance of lipid-derived malondialdehyde in diabetes mellitus. Diabetologia. 2000;43:550-557.
47. Agarwal S, Draper HH. Isolation of a malondialdehyde-deoxyguanosine adduct from rat liver DNA. Free Radic Biol Med. 1992;13:695-699.
48. Ji C, Rouzer CA, Marnett LJ, Pietenpol JA. Induction of cell cycle arrest by the endogenous product of lipid peroxidation, malondialdehyde. Carcinogenesis. 1998;19:1275-1283.
49. Yagi K. Lipid peroxides and related radicals in clinical medicine. Adv Exp Med Biol. 1994;366:1-15.
50. Yagi K. Assay for serum lipid peroxide level and its clinical significance. In: K Yagi, ed. Lipid Peroxides in Biology and Medicine. New York: Academic; 1982:223-241.
51. Fukunaga K, Yoshida M, Nakazono N. A simple, rapid, highly sensitive and reproducible quantification method for plasma malondialdehyde by high-performance liquid chromatography. Biomed Chromatogr. 1998;12:300-303.
52. Wong SH, Knight JA, Hopfer SM, Zaharia O, Leach CN Jr, Sunderman FW Jr. Lipoperoxides in plasma as measured by liquid-chromatographic separation of malondialdehyde-thiobarbituric acid adduct. Clin Chem. 1987;33:214-220.
53. Young IS, Trimble ER. Measurement of malondialdehyde in plasma by high performance liquid chromatography with fluorimetric detection. Ann Clin Biochem. 1991;28(Pt 5):504-508.
54. Palinski W, Yla-Herttuala S, Rosenfeld ME, et al. Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein. Arteriosclerosis. 1990;10:325-335.
55. Dei R, Takeda A, Niwa H, et al. Lipid peroxidation and advanced glycation end products in the brain in normal aging and in Alzheimer's disease. Acta Neuropathol (Berl). 2002;104:113-122.
56. Head E, Liu J, Hagen TM, et al. Oxidative damage increases with age in a canine model of human brain aging. J Neurochem. 2002;82:375-381.
57. Mooradian AD, Lung CC, Shah G, Mahmoud S, Pinnas JL. Age-related changes in tissue content of malondialdehyde-modified proteins. Life Sci. 1994;55:1561-1566.
58. Cini M, Moretti A. Studies on lipid peroxidation and protein oxidation in the aging brain. Neurobiol Aging. 1995;16:53-57.
59. Cai Q, Tian L, Wei H. Age-dependent increase of indigenous DNA adducts in rat brain is associated with a lipid peroxidation product. Exp Gerontol. 1996;31:373-385.
60. Randerath K, Li D, Moorthy B, Randerath E. I-compounds-endogenous DNA markers of nutritional status, ageing, tumour promotion and carcinogenesis. IARC Sci Publ. 1993;124:157-165.
61. Randerath K, Li DH, Randerath E. Age-related DNA modifications (I-compounds): modulation by physiological and pathological processes. Mutat Res. 1990;238:245-253.
62. Randerath K, Eiehr JG, Gladek A, Randerath E. Age-dependent covalent DNA alterations (I-compounds) in rodent tissues: species, tissue and sex specificities. Mutat Res. 1989;219:121-133.
63. Gupta KP, van Golen KL, Randerath E, Randerath K. Age-dependent covalent DNA alterations (I-compounds) in rat liver mitochondrial DNA. Mutat Res. 1990;237:17-27.
64. Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJ II. A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci U S A. 1990;87:9383-9387.
65. Chen Y, Morrow JD, Roberts LJ II. Formation of reactive cyclopentenone compounds in vivo as products of the isoprostane pathway. J Biol Chem. 1999;274:10863-10868.
66. Morrow JD, Minton TA, Mukundan CR, et al. Free radical-induced generation of isoprostanes in vivo. Evidence for the formation of D-ring and E-ring isoprostanes. J Biol Chem. 1994;269:4317-4326.
67. Morrow JD, Awad JA, Wu A, Zackert WE, Daniel VC, Roberts LJ II. Nonenzymatic free radical-catalyzed generation of thromboxane-like compounds (isothromboxanes) in vivo. J Biol Chem. 1996;271: 23185-23190.
68. Taber DF, Herr RJ, Gleave DM. Diastereoselective synthesis of an isoprostane: (+/-)-8-epi-PGF(2)(alpha) ethyl ester. J Org Chem. 1997; 62:194-198.
69. Morrow JD, Roberts LJ. The isoprostanes: unique bioactive products of lipid peroxidation. Prog Lipid Res. 1997;36:1-21.
70. Brame CJ, Salomon RG, Morrow JD, Roberts LJ II. Identification of extremely reactive gamma-ketoaldehydes (isolevuglandins) as products of the isoprostane pathway and characterization of their lysyl protein adducts. J Biol Chem. 1999;274:13139-13146.
71. Roberts LJ II, Morrow JD. The generation and actions of isoprostanes. Biochim Biophys Acta. 1997;1345:121-135.
72. Roberts LJ II, Reckelhoff JF. Measurement of F(2)-isoprostanes unveils profound oxidative stress in aged rats. Biochem Biophys Res Commun. 2001;287:254-256.
73. Roberts LJ, Morrow JD. Measurement of F(2)-isoprostanes as an index of oxidative stress in vivo. Free Radic Biol Med. 2000;28:505-513.
74. Morrow JD, Awad JA, Kato T, et al. Formation of novel noncyclooxygenase-derived prostanoids (F2-isoprostanes) in carbon tetrachloride hepatotoxicity. An animal model of lipid peroxidation, J Clin Invest. 1992;90:2502-2507.
75. Granstrom E, Kindahl H. Radioimmunoassay of prostaglandins and thromboxanes. Adv Prostaglandin Thromboxane Res. 1978;5:119-210.
76. Proudfoot J, Barden A, Mori TA, Burke V, Croft KD, Beilin LJ, Puddey IB. Measurement of urinary F(2)-isoprostanes as markers of in vivo lipid peroxidation-A comparison of enzyme immunoassay with gas chromatography/mass spectrometry. Anal Biochem. 1999;272: 209-215.
77. Morrow JD, Roberts LJ II. Mass spectrometric quantification of F2-isoprostanes in biological fluids and tissues as measure of oxidant stress. Methods Enzymol. 1999;300:3-12.
78. Reich EE, Zackert WE, Brame CJ, et al. Formation of novel D-ring and E-ring isoprostane-like compounds (D4/E4-neuroprostanes) in vivo from docosahexaenoic acid. Biochemistry. 2000;39:2376-2383.
79. Roberts LJ II, Montine TJ, Markesbery WR, et al. Formation of isoprostane-like compounds (neuroprostanes) in vivo from docosahexaenoic acid. J Biol Chem. 1998;273:13605-13612.
80. Moore SA, Yoder E, Murphy S, Dutton GR, Spector AA. Astrocytes, not neurons, produce docosahexaenoic acid (22:6 omega-3) and arachidonic acid (20:4 omega-6). J Neurochem. 1991;56:518-524.
81. Bernoud-Hubac N, Davies SS, Boutaud O, Montine TJ, Roberts LJ II. Formation of highly reactive gamma-ketoaldehydes (neuroketals) as products of the neuroprostane pathway. J Biol Chem. 2001;276: 30964-30970.
82. Davies SS, Amarnath V, Montine KS, et al. Effects of reactive gamma-ketoaldehydes formed by the isoprostane pathway (isoketals) and cyclooxygenase pathway (levuglandins) on proteasome function. FASEB J. 2002;16:715-717.
83. Youssef JA, Birnbaum LS, Swift LL, Morrow JD, Badr MZ. Age-independent, gray matter-localized, brain-enhanced oxidative stress in male fischer 344 rats: brain levels of F(2)-isoprostanes and F(4)-neuroprostanes. Free Radic Biol Med. 2003;34:1631-1635.
84. Liu J, Mori A. Age-associated changes in superoxide dismutase activity, thiobarbituric acid reactivity and reduced glutathione level in the brain and liver in senescence accelerated mice (SAM): a comparison with ddY mice. Mech Ageing Dev. 1993;71:23-30.
85. Hussain S, Slikker W Jr, Ali SF. Age-related changes in antioxidant enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione in different regions of mouse brain. Int J Dev Neurosci. 1995;13:811-817.
86. Morrow JD, Roberts LJ, Daniel VC, et al. Comparison of formation of D2/E2-isoprostanes and F2-isoprostanes in vitro and in vivo-effects of oxygen tension and glutathione. Arch Biochem Biophys. 1998;353: 160-171.
87. Benzi G, Pastoris O, Marzatico F, Villa RF. Age-related effect induced by oxidative stress on the cerebral glutathione system. Neurochem Res. 1989;14:473-481.
88. Balazs L, Leon M. Evidence of an oxidative challenge in the Alzheimer's brain. Neurochem Res. 1994;19:1131-1137.
89. Perry TL, Yong VW, Bergeron C, Hansen S, Jones K. Amino acids, glutathione, and glutathione transferase activity in the brains of patients with Alzheimer's disease. Ann Neurol. 1987;21:331-336.
90. Montine TJ, Markesbery WR, Morrow JD, Roberts LJ II. Cerebrospinal fluid F2-isoprostane levels are increased in Alzheimer's disease. Ann Neurol. 1998;44:410-413.
91. Pratico D, Rokach J, Tangirala RK. Brains of aged apolipoprotein E-deficient mice have increased levels of F2-isoprostanes, in vivo markers of lipid peroxidation. J Neurochem. 1999;73:736-741.
92. Pratico D, Uryu K, Leight S, Trojanoswki JQ, Lee VM. Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. J Neurosci. 2001;21:4183-4187.
93. Yamamoto S. Mammalian lipoxygenases: molecular structures and functions. Biochim Biophys Acta. 1992;1128:117-131.
94. Spiteller G. Lipid peroxidation in aging and age-dependent diseases. Exp Gerontol. 2001;36:1425-1457.
95. Hazen SL, Ford DA, Gross RW. Activation of a membrane-associated phospholipase A2 during rabbit myocardial ischemia which is highly selective for plasmalogen substrate. J Biol Chem. 1991;266:5629-5633.
96. Parthasarathy S, Steinbrecher UP, Barnett J, Witztum JL, Steinberg D. Essential role of phospholipase A2 activity in endothelial cell-induced modification of low density lipoprotein. Proc Natl Acad Sci U S A. 1985;82:3000-3004.
97. Sapirstein A, Spech RA, Witzgall R, Bonventre JV. Cytosolic phospholipase A2 (PLA2), but not secretory PLA2, potentiates hydrogen peroxide cytotoxicity in kidney epithelial cells. J Biol Chem. 1996;271:21505-21513.
98. Golconda MS, Ueda N, Shah SV. Evidence suggesting that iron and calcium are interrelated in oxidant-induced DNA damage. Kidney Int. 1993;44:1228-1234.
99. Levine RL, Stadtman ER. Oxidative modification of proteins during aging. Exp Gerontol. 2001;36:1495-1502.
100. Stadtman ER. Metal ion-catalyzed oxidation of proteins: biochemical mechanism and biological consequences. Free Radic Biol Med. 1990; 9:315-325.
101. Smith CD, Carney JM, Starke-Reed PE, et al. Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc Natl Acad Sci U S A. 1991;88:10540-10543.
102. Aksenova MV, Aksenov MY, Carney JM, Butterfield DA. Protein oxidation and enzyme activity decline in old brown Norway rats are reduced by dietary restriction. Mech Ageing Dev. 1998;100:157-168.
103. Dubey A, Forster MJ, Sohal RS. Effect of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone on protein oxidation and life span. Arch Biochem Biophys. 1995;324:249-254.
104. Cakatay U, Telci A, Kayali R, Tekeli F, Akcay T, Sivas A. Relation of oxidative protein damage and nitrotyrosine levels in the aging rat brain. Exp Gerontol. 2001;36:221-229.
105. Nicolle MM, Gonzalez J, Sugaya K, et al. Signatures of hippocampal oxidative stress in aged spatial learning-impaired rodents. Neuroscience. 2001;107:415-431.
106. Agarwal S, Sohal RS. Aging and proteolysis of oxidized proteins. Arch Biochem Biophys. 1994;309:24-28.
107. Butterfield DA, Howard BJ, Yatin S, Allen KL, Carney JM. Free radical oxidation of brain proteins in accelerated senescence and its modulation by N-tert-butyl-alpha-phenylnitrone. Proc Natl Acad Sci U S A. 1997;94:674-678.
108. Farr SA, Poon HF, Dogrukol-Ak D, et al. The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. J Neurochem. 2003;84: 1173-1183.
109. Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol. 1996;271:C1424-C1437.
110. Butterfield DA, Kanski J. Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins. Mech Ageing Dev. 2001;122:945-962.
111. Althaus JS, Schmidt KR, Fountain ST, Tseng MT, Carroll RT, Galatsis P, Hall ED. LC-MS/MS detection of peroxynitrite-derived 3-nitrotyrosine in rat microvessels. Free Radic Biol Med. 2000;29: 1085-1095.
112. Shin CM, Chung YH, Kim MJ, Lee EY, Kim EG, Cha CI. Age-related changes in the distribution of nitrotyrosine in the cerebral cortex and hippocampus of rats. Brain Res. 2002;931:194-199.
113. Tohgi H, Abe T, Yamazaki K, Murata T, Ishizaki E, Isobe C. Alterations of 3-nitrotyrosine concentration in the cerebrospinal fluid during aging and in patients with Alzheimer's disease. Neurosci Lett. 1999;269:52-54.
114. Sloane JA, Hollander W, Moss MB, Rosene DL, Abraham CR. Increased microglial activation and protein nitration in white matter of the aging monkey. Neurobiol Aging. 1999;20:395-405.
115. Chung YH, Shin CM, Joo KM, Kim MJ, Cha CI. Immunohistochemical study on the distribution of nitrotyrosine and neuronal nitric oxide synthase in aged rat cerebellum. Brain Res. 2002;951:316-321.
116. Hensley K, Maidt ML, Yu Z, Sang H, Markesbery WR, Floyd RA. Electrochemical analysis of protein nitrotyrosine and dityrosine in the Alzheimer brain indicates region-specific accumulation. J Neurosci. 1998;18:8126-8132.
117. Smith MA, Richey Harris PL, Sayre LM, Beckman JS, Perry G. Widespread peroxynitrite-mediated damage in Alzheimer's disease. J Neurosci. 1997;17:2653-2657.
118. Castegna A, Thongboonkerd V, Klein JB, Lynn B, Markesbery WR, Butterfield DA. Proteomic identification of nitrated proteins in Alzheimer's disease brain. J Neurochem. 2003;85:1994-1401.
119. Koppal T, Drake J, Yatin S, et al. Peroxynitrite-induced alterations in synaptosomal membrane proteins: insight into oxidative stress in Alzheimer's disease. J Neurochem. 1999;72:310-317.
120. Hall NC, Carney JM, Cheng MS, Butterfield DA. Ischemia/reperfusion-induced changes in membrane proteins and lipids of gerbil cortical synaptosomes. Neuroscience. 1995;64:81-89.
121. Hall NC, Carney JM, Plante OJ, Cheng M, Butterfield DA. Effect of 2-cyclohexene-1-one-induced glutathione diminution on ischemia/reperfusion-induced alterations in the physical state of brain synaptosomal membrane proteins and lipids. Neuroscience. 1997;77:283-290.
122. Subramaniam R, Koppal T, Green M, et al. The free radical antioxidant vitamin E protects cortical synaptosomal membranes from amyloid beta-peptide(25-35) toxicity but not from hydroxynonenal toxicity: relevance to the free radical hypothesis of Alzheimer's disease. Neurochem Res. 1998;23:1403-1410.
123. Pocemich CB, La Fontaine M, Butterfield DA. In-vivo glutathione elevation protects against hydroxyl free radical-induced protein oxidation in rat brain. Neurochem Int. 2000;36:185-191.
124. Hensley K, Carney J, Hall N, Shaw W, Butterfield DA. Electron paramagnetic resonance investigations of free radical-induced alterations in neocortical synaptosomal membrane protein infrastructure. Free Radic Biol Med. 1994;17:321-331.
125. Hensley K, Howard BJ, Carney JM, Butterfield DA. Membrane protein alterations in rodent erythrocytes and synaptosomes due to aging and hyperoxia. Biochim Biophys Acta. 1995;1270:203-206.
126. Aksenov MY, Aksenova MV, Carney JM, Butterfield DA. Oxidative modification of glutamine synthetase by amyloid beta peptide. Free Radic Res. 1997;27:267-281.
127. Hensley K, Hall N, Subramaniam R, et al. Brain regional correspondence between Alzheimer's disease histopathology and biomarkers of protein oxidation. J Neurochem. 1995;65:2146-2156.
128. Howard BJ, Yatin S, Hensley K, Allen KL, Kelly JP, Carney J, Butterfield DA. Prevention of hyperoxia-induced alterations in synaptosomal membrane-associated proteins by N-tert-butyl-alpha-phenylnitrone and 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (Tempol). J Neurochem. 1996;67:2045-2050.
129. Floyd RA. Role of oxygen free radicals in carcinogenesis and brain ischemia. FASEB J. 1990;4:2587-2597.
130. Carney JM, Starke-Reed PE, Oliver CN, et al. 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-alpha-phenylnitrone. Proc Natl Acad Sci U S A. 1991;88:3633-3636.
131. Yatin SM, Aksenov M, Butterfield DA. The antioxidant vitamin E modulates amyloid beta-peptide-induced creatine kinase activity inhibition and increased protein oxidation: implications for the free radical hypothesis of Alzheimer's disease. Neurochem Res. 1999;24: 427-435.
132. Gibson GE, Park LC, Zhang H, Sorbi S, Calingasan NY. Oxidative stress and a key metabolic enzyme in Alzheimer brains, cultured cells, and an animal model of chronic oxidative deficits. Ann N Y Acad Sci. 1999;893:79-94.
133. Vitorica J, Andres A, Satrustegui J, Machado A. Age-related quantitative changes in enzyme activities of rat brain. Neurochem Res. 1981;6:127-136.
134. Deloulme JC, Lucas M, Gaber C, Bouillon P, Keller A, Eclancher F, Sensenbrenner M. Expression of the neuron-specific enolase gene by rat oligodendroglial cells during their differentiation. J Neurochem. 1996;66:936-945.
135. Ferrante F, Amenta F. Enzyme histochemistry of the choroid plexus in old rats. Mech Ageing Dev. 1987;41:65-72.
136. Agrawal A, Shukla R, Tripathi LM, Pandey VC, Srimal RC. Permeability function related to cerebral microvessel enzymes during ageing in rats. Int J Dev Neurosci. 1996;14:87-91.
137. Hrachovina V, Mourek J. [Lactate dehydrogenase and malate dehydrogenase activity in the glial and neuronal fractions of the brain tissue in rats of various ages]. Sb Lek. 1990;92:39-44.
138. Mizuno Y, Ohta K. Regional distributions of thiobarbituric acid-reactive products, activities of enzymes regulating the metabolism of oxygen free radicals, and some of the related enzymes in adult and aged rat brains. J Neurochem. 1986;46:1344-1352.
139. Sandhu SK, Kaur G. Mitochondrial electron transport chain complexes in aging rat brain and lymphocytes. Biogerontology. 2003;4:19-29.
140. Kocak H, Oner P, Oztas B. Comparison of the activities of Na(+), K(+)-ATPase in brains of rats at different ages. Gerontology. 2002;48: 279-281.
141. Gorini A, Canosi U, Devecchi E, Geroldi D, Villa RF. ATPases enzyme activities during ageing in different types of somatic and synaptic plasma membranes from rat frontal cerebral cortex. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26:81-90.
142. Vohra BP, Sharma SP, Kansal VK. Age-dependent variations in mitochondrial and cytosolic antioxidant enzymes and lipid peroxidation in different regions of central nervous system of guinea pigs. Indian J Biochem Biophys. 2001;38:321-326.
143. Sandhu SK, Kaur G. Alterations in oxidative stress scavenger system in aging rat brain and lymphocytes. Biogerontology. 2002;3: 161-173.
144. Tsay HJ, Wang P, Wang SL, Ku HH. Age-associated changes of superoxide dismutase and catalase activities in the rat brain. J Biomed Sci. 2000;7:466-474.
145. Castegna A, Aksenov M, Aksenova M, et al. Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part I: creatine kinase BB, glutamine synthase, and ubiquitin carboxyterminal hydrolase L-1. Free Radic Biol Med. 2002;33:562-571.
146. Castegna A, Aksenov M, Thongboonkerd V, et al. Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part II: dihydropyrimidinase-related protein 2, alpha-enolase and heat shock cognate 71. J Neurochem. 2002;82:1524-1532.
147. Butterfield DA, Boyd-Kimball DL, Castegna A. Proteomics in Alzheimer's disease: insights into mechanisms of neurodegenation. J Neurochem. 203;86:1313-1327.
148. Ropeleski MJ, Tang J, Walsh-Reitz MM, Musch MW, Chang EB. Interleukin-11-induced heat shock protein 25 confers intestinal epithelial-specific cytoprotection from oxidant stress. Gastroenterology. 2003;124:1358-1368.
149. Ozawa T, Tanaka M, Ikebe S, Ohno K, Kondo T, Mizuno Y. Quantitative determination of deleted mitochondrial DNA relative to normal DNA in parkinsonian striatum by a kinetic PCR analysis. Biochem Biophys Res Commun. 1990;172:483-489.
150. Strauss E. Longevity research. Single signal unites treatments that prolong life. Science. 2003;300:881-883.
151. Calabrese V, Scapagnini G, Ravagna A, Giuffrida Stella AM, Butterfield DA. Molecular chaperones and their roles in neural cell differentiation. Dev Neurosci. 2002;24:1-13.
152. Calabrese V, Renis M, Calderone A, Russo A, Reale S, Barcellona ML, Rizza V. Stress proteins and SH-groups in oxidant-induced cellular injury after chronic ethanol administration in rat. Free Radic Biol Med. 1998;24:1159-1167.
153. Calabrese V, Scapagnini G, Catalano C, et al. 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. 2001;23:51-58.
154. Wheeler DS, Dunsmore KE, Wong HR, Intracellular delivery of HSP70 using HIV-1 Tat protein transduction domain. Biochem Biophys Res Commun. 2003;301:54-59.
155. Meldrum KK, Burnett AL, Meng X, Misseri R, Shaw MB, Gearhart JP, Meldrum DR. Liposomal delivery of heat shock protein 72 into renal tubular cells blocks nuclear factor-kappaB activation, tumor necrosis factor-alpha production, and subsequent ischemia-induced apoptosis. Circ Res. 2003;92:293-299.
156. Goodman R, Blank M. Insights into electromagnetic interaction mechanisms. J Cell Physiol. 2002;192:16-22.
157. Calabrese V, Scapagnini G, Giuffrida Stella AM, Bates TE, Clark JB. Mitochondrial involvement in brain function and dysfunction: relevance to aging, neurodegenerative disorders and longevity. Neurochem Res. 2001;26:739-764.
158. Kelly S, Yenari MA. Neuroprotection: heat shock proteins. Curr Med Res Opin. 2002;18(Suppl 2):S55-S60.
159. Kelly S, Zhang ZJ, Zhao H, et al. Gene transfer of HSP72 protects cornu ammonis 1 region of the hippocampus neurons from global ischemia: influence of Bcl-2. Ann Neurol. 2002;52:160-167.
160. Yenari MA. Heat shock proteins and neuroprotection. Adv Exp Med Biol. 2002;513:281-299.
161. Hata R, Gass P, Mies G, Wiessner C, Hossmann KA. Attenuated c-fos mRNA induction after middle cerebral artery occlusion in CREB knockout mice does not modulate focal ischemic injury. J Cereb Blood Flow Metab. 1998;18:1325-1335.
162. Narasimhan P, Swanson RA, Sagar SM, Sharp FR. Astrocyte survival and HSP70 heat shock protein induction following heat shock and acidosis. Glia. 1996;17:147-159.
163. Fink SL, Chang LK, Ho DY, Sapolsky RM. Defective herpes simplex virus vectors expressing the rat brain stress-inducible heat shock protein 72 protect cultured neurons from severe heat shock. J Neurochem. 1997;68:961-969.
164. Mosser DD, Caron AW, Bourget L, Denis-Larose C, Massie B. Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis. Mol Cell Biol. 1997;17:5317-5327.
165. McLaughlin B, Hartnett KA, Erhardt JA, et al. Caspase 3 activation is essential for neuroprotection in preconditioning. Proc Natl Acad Sci U S A. 2003;100:715-720.
166. Calabrese V, Copani A, Testa D, et al. Nitric oxide synthase induction in astroglial cell cultures: effect on heat shock protein 70 synthesis and oxidant/antioxidant balance. J Neurosci Res. 2000;60:613-622.
167. Calabrese V, Testa G, Ravagna A, Bates TE, Stella AM. HSP70 induction in the brain following ethanol administration in the rat: regulation by glutathione redox state. Biochem Biophys Res Commun. 2000;269:397-400.
168. Mayer RJ. From neurodegeneration to neurohomeostasis: the role of ubiquitin. Drug News Perspect. 2003;16:103-108.
169. Valentim LM, Rodnight R, Geyer AB, et al. Changes in heat shock protein 27 phosphorylation and immunocontent in response to preconditioning to oxygen and glucose deprivation in organotypic hippocampal cultures. Neuroscience. 2003;118:379-386.
170. Turner CP, Panter SS, Sharp FR. 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. 1999;65:87-102.
171. Izaki K, Kinouchi H, Watanabe K, et al. Induction of mitochondrial heat shock protein 60 and 10 mRNAs following transient focal cerebral ischemia in the rat. Brain Res Mol Brain Res. 2001;88:14-25.
172. Sahlas DJ, Liberman A, Schipper HM. Role of heme oxygenase-I in the biogenesis of corpora amylacea. Biogerontology. 2002;3:223-231.
173. Goldbaum O, Richter-Landsberg C. Stress proteins in oligodendrocytes: differential effects of heat shock and oxidative stress. J Neurochem. 2001;78:1233-1242.
174. Schipper HM. Heme oxygenase-1: role in brain aging and neurodegeneration. Exp Gerontol. 2000;35:821-830.
175. Shibahara S, Muller R, Taguchi H, Yoshida T. Cloning and expression of cDNA for rat heme oxygenase. Proc Natl Acad Sci U S A. 1985;82:7865-7869.
176. Maines MD, Trakshel GM, Kutty RK. Characterization of two constitutive
177. McCoubrey WK Jr, Huang TJ, Maines MD. Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3. Eur J Biochem. 1997;247:725-732.
178. Maines MD. The heme oxygenase system: a regulator of second messenger gases. Ann Rev Pharmacol Toxicol. 1997;37:517-554.
179. Abraham NG, Drummond GS, Lutton JD, Kappas A. The biological significance and physiological role of heme oxygenase. Cell Physiol Biochem. 1996;6:129-168.
180. Calabrese V, Scapagnini G, Ravagna A, Fariello RG, Giuffrida Stella AM, Abraham NG. Regional distribution of heme oxygenase, HSP70, and glutathione in brain: relevance for endogenous oxidant/antioxidant balance and stress tolerance. J Neurosci Res. 2002;68:65-75.
181. Ewing JF, Maines MD. 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. 1992;3:559-570.
182. Scapagnini G, D'Agata V, Calabrese V, et al. Gene expression profiles of heme oxygenase isoforms in the rat brain. Brain Res. 2002;954: 51-59.
183. Colombrita C, Calabrese V, Stella AM, Mattei F, Alkon DL, Scapagnini G. Regional rat brain distribution of heme oxygenase-1 and manganese superoxide dismutase mRNA: relevance of redox homeostasis in the aging processes. Exp Biol Med (Maywood). 2003; 228:517-524.
184. Verma A, Hirsch DJ, Glatt CE, Ronnett GV, Snyder SH. Carbon monoxide: a putative neural messenger. Science. 1993;259:381-384.
185. Hon T, Hach A, Lee HC, Cheng T, Zhang L. Functional analysis of heme regulatory elements of the transcriptional activator Hap1. Biochem Biophys Res Commun. 2000;273:584-591.
186. McCoubrey WK Jr, Huang TJ, Maines MD. Heme oxygenase-2 is a hemoprotein and binds heme through heme regulatory motifs that are not involved in heme catalysis. J Biol Chem. 1997;272:12568-12574.
187. Maines MD. The heme oxygenase system and its functions in the brain. Cell Mol Biol (Noisy-le-grand). 2000;46:573-585.
188. Kazazian HH Jr. Genetics. L1 retrotransposons shape the mammalian genome. Science. 2000;289:1152-1153.
189. Mighell AJ, Smith NR, Robinson PA, Markham AF. Vertebrate pseudogenes. FEBS Lett. 2000;468:109-114.
190. Raju VS, McCoubrey WK Jr, Maines MD. Regulation of heme oxygenase-2 by glucocorticoids in neonatal rat brain: characterization of a functional glucocorticoid response element. Biochim Biophys Acta. 1997;1351:89-104.
191. Liu N, Wang X, McCoubrey WK, Maines MD. 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. 2000;241:175-183.
192. Tyrrell R. Redox regulation and oxidant activation of heme oxygenase-1. Free Radic Res. 1999;31:335-340.
193. Motterlini R, Foresti R, Bassi R, Calabrese V, Clark JE, Green CJ. Endothelial heme oxygenase-1 induction by hypoxia. Modulation by inducible nitric-oxide synthase and S-nitrosothiols. J Biol Chem. 2000;275:13613-13620.
194. Hill-Kapturczak N, Sikorski E, Voakes C, Garcia J, Nick HS, Agarwal A. An internal enhancer regulates heme- and cadmium-mediated induction of human heme oxygenase-1. Am J Physiol Renal Physiol. 2003;285:F515-F523.
195. Fogg S, Agarwal A, Nick HS, Visner GA. Iron regulates hyperoxia-dependent human heme oxygenase 1 gene expression in pulmonary endothelial cells. Am J Respir Cell Mol Biol. 1999;20:797-804.
196. Scapagnini G, Foresti R, Calabrese V, Giuffrida Stella AM, Green CJ, Motterlini R. Caffeic acid phenethyl ester and curcumin: a novel class of heme oxygenase-1 inducers. Mol Pharmacol. 2002;61:554-561.
197. Balogun E, Hoque M, Gong P, et al. Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem J. 2003;371:887-895.
198. Chen K, Gunter K, Maines MD. Neurons overexpressing heme oxygenase-1 resist oxidative stress-mediated cell death. J Neurochem. 2000;75:304-313.
199. Dore S, Takahashi M, Ferris CD, Zakhary R, Hester LD, Guastella D, Snyder SH. Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury. Proc Natl Acad Sci U S A. 1999;96:2445-2450.
200. Le WD, Xie WJ, Appel SH. Protective role of heme oxygenase-1 in oxidative stress-induced neuronal injury. J Neurosci Res. 1999;56: 652-658.
201. Dore S. Decreased activity of the antioxidant heme oxygenase enzyme: implications in ischemia and in Alzheimer's disease. Free Radic Biol Med. 2002;32:1276-1282.
202. Beschorner R, Adjodah D, Schwab JM, et al. Long-term expression of heme oxygenase-1 (HO-1, HSP-32) following focal cerebral infarctions and traumatic brain injury in humans. Acta Neuropathol (Berl). 2000;100:377-384.
203. Takeda A, Perry G, Abraham NG, et al. Overexpression of heme oxygenase in neuronal cells, the possible interaction with tau. J Biol Chem. 2000;275:5395-5399.
204. Takahashi M, Dore S, Ferris CD, et al. Amyloid precursor proteins inhibit heme oxygenase activity and augment neurotoxicity in Alzheimer's disease. Neuron. 2000;28:461-473.
205. Premkumar DR, Smith MA, Richey PL, et al. Induction of heme oxygenase-1 mRNA and protein in neocortex and cerebral vessels in Alzheimer's disease. J Neurochem. 1995;65:1399-1402.
206. Schipper HM, Chertkow H, Mehindate K, Frankel D, Melmed C, Bergman H. Evaluation of heme oxygenase-1 as a systemic biological marker of sporadic AD. Neurology. 2000;54:1297-1304.
207. Schipper HM, Liberman A, Stopa EG. Neural heme oxygenase-1 expression in idiopathic Parkinson's disease. Exp Neurol. 1998;150: 60-68.
208. Yoo MS, Chun HS, Son JJ, et al. Oxidative stress regulated genes in nigral dopaminergic neuronal cells: correlation with the known pathology in Parkinson's disease. Brain Res Mol Brain Res. 2003; 110:76-84.
209. Liu Y, Zhu B, Luo L, Li P, Paty DW, Cynader MS. Heme oxygenase-1 plays an important protective role in experimental autoimmune encephalomyelitis. Neuroreport. 2001;12:1841-1845.
210. Butterfield D, Castegna A, Pocemich C, Drake J, Scapagnini G, Calabrese V. Nutritional approaches to combat oxidative stress in Alzheimer's disease. J Nutr Biochem. 2002;13:444-461.
211. Piantadosi CA, Zhang J, Levin ED, Folz RJ, Schmechel DE. Apoptosis and delayed neuronal damage after carbon monoxide poisoning in the rat. Exp Neurol. 1997;147:103-114.
212. Graser T, Vedernikov YP, Li DS. Study on the mechanism of carbon monoxide induced endothelium-independent relaxation in porcine coronary artery and vein. Biomed Biochim Acta. 1990;49: 293-296.
213. Glaum SR, Miller RJ. Zinc protoporphyrin-IX blocks the effects of metabotropic glutamate receptor activation in the rat nucleus tractus solitarii. Mol Pharmacol. 1993;43:965-969.
214. White KA, Marletta MA. Nitric oxide synthase is a cytochrome P-450 type hemoprotein. Biochemistry. 1992;31:6627-6631.
215. Foresti R, Motterlini R. The heme oxygenase pathway and its interaction with nitric oxide in the control of cellular homeostasis. Free Radic Res. 1999;31:459-475.
216. Turcanu V, Dhouib M, Poindron P. Nitric oxide synthase inhibition by haem oxygenase decreases macrophage nitric-oxide-dependent cytotoxicity: a negative feedback mechanism for the regulation of nitric oxide production. Res Immunol. 1998;149:741-744.
217. Wang R, Wu L. Interaction of selective amino acid residues of K(ca) channels with carbon monoxide. Exp Biol Med (Maywood). 2003;228: 474-480.
218. Coceani F, Kelsey L, Seidlitz E, et al. Carbon monoxide formation in the ductus arteriosus in the lamb: implications for the regulation of muscle tone. Br J Pharmacol. 1997;120:599-608.
219. Vijayasarathy C, Damle S, Lenka N, Avadhani NG. Tissue variant effects of heme inhibitors on the mouse cytochrome c oxidase gene expression and catalytic activity of the enzyme complex. Eur J Biochem. 1999;266:191-200.
220. Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN. Bilirubin is an antioxidant of possible physiological importance. Science. 1987;235:1043-1046.
221. Clark JE, Foresti R, Green CJ, Motterlini R. Dynamics of haem oxygenase-1 expression and bilirubin production in cellular protection against oxidative stress. Biochem J. 2000;348 Pt 3:615-619.
222. Dore S, Goto S, Sampei K, et al. Heme oxygenase-2 acts to prevent neuronal death in brain cultures and following transient cerebral ischemia. Neuroscience. 2000;99:587-592.
223. Kimpara T, Takeda A, Yamaguchi T, et al. Increased bilirubins and their derivatives in cerebrospinal fluid in Alzheimer's disease. Neurobiol Aging. 2000;21:551-554.
224. Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A. 1993; 90:7915-7922.
225. Rustin P, von Kleist-Retzow JC, Vajo Z, Rotig A, Munnich A. For debate: defective mitochondria, free radicals, cell death, aging-reality or myth-ochondria? Mech Ageing Dev. 2000;114:201-206.
226. Koubova J, Guarente L. How does calorie restriction work? Genes Dev. 2003;17:313-321.
227. Kaeberlein M, McVey M, Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 1999;13:2570-2580.
228. Dilman VM. Growth hormone, age and the endometrium. N Engl J Med. 1970;283:375.
229. Herrling T, Fuchs J, Rehberg J, Groth N. UV-induced free radicals in the skin detected by ESR spectroscopy and imaging using nitroxides. Free Radic Biol Med. 2003;35:59-67.
230. Weismann A. Ueber die Dauer des Lebens. Jena, Germany: Verlag von Gustav Fisher; 1982.
231. Olovnikov AM. Telomeres, telomerase, and aging: origin of the theory. Exp Gerontol. 1996;31:443-448.
232. Johnson S. The possible crucial role of iron accumulation combined with low tryptophan, zinc and manganese in carcinogenesis. Med Hypotheses. 2001;57:539-543.
233. Butterfield DA, Castegna A, Lauderback CM, Drake J. Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer's disease brain contribute to neuronal death. Neurobiol Aging. 2002;23:655-664.