Neuroprotection through stimulation of mitochondrial antioxidant protein expression

Journal of Alzheimer's Disease

Volumn 20, Issue SUPPL.2, 2010, Pages

  Greco, Tiffany ^a   Fiskum, Gary ^a  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

Antioxidant; bioenergetics; calcium; cerebral ischemia; neurodegeneration; Nrf2; oxidative stress; permeability transition pore

Indexed keywords

BUTYLATED HYDROXYANISOLE; COPPER ZINC SUPEROXIDE DISMUTASE; HYDROQUINONE; KELCH LIKE ECH ASSOCIATED PROTEIN 1; PEROXIREDOXIN 3; SULFORAPHANE; TRANSCRIPTION FACTOR NRF2;

BRAIN INJURY; ENZYME INDUCTION; GENE EXPRESSION; NEUROPROTECTION; PHOSPHORYLATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW;

EID: 77956202732     PISSN: 13872877     EISSN: None     Source Type: Journal    
DOI: 10.3233/JAD-2010-100519     Document Type: Review

References (110)

1. Keeney PM, Xie J, Capaldi RA, Bennett JP, Jr. (2006) Parkinson's disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misas- sembled. J Neurosci 26, 5256-5264.
2. Brown GC, Borutaite V (2004) Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S- nitrosothiols. Biochim Biophys Acta 1658, 44-49.
3. Richards EM, Rosenthal RE, Kristian T, Fiskum (2006) Postischemic hyperoxia reduces hippocampal pyruvate de- hydrogenase activity. Free Radic Biol Med 40, 1960-1970.
4. Poon HF, Shepherd HM, Reed TT, Calabrese V, Stella AM, Pennisi G, Cai J, Pierce WM, Klein JB, Butterfield DA (2006) Proteomics analysis provides insight into caloric restriction mediated oxidation and expression of brain proteins associated with age-related impaired cellular processes: Mito- chondrial dysfunction, glutamate dysregulation and impaired protein synthesis. Neurobiol Aging 27, 1020-1034.
5. Park LC, Zhang H, Sheu KF, Calingasan NY, Kristal BS, Lindsay JG, Gibson GE (1999) Metabolic impairment induces oxidative stress, compromises inflammatory responses, and inactivates a key mitochondrial enzyme in microglia. JNeurochem 72, 1948-1958.
6. Battaglia V, Grancara S, Satriano J, Saccoccio S, Agostinel- li E, Toninello A (2010) Agmatine prevents the Ca(2+)- dependent induction of permeability transition in rat brain mitochondria. Amino Acids 38, 431-437.
7. Petronilli V, Costantini P, Scorrano L, Colonna R, Passamon- ti S, Bernardi P (1994) The voltage sensor of the mitochon- drial permeability transition pore is tuned by the oxidation- reduction state of vicinal thiols. Increase of the gating potential by oxidants and its reversal by reducing agents. J Biol Chem 269, 16638-16642.
8. Ott M, Gogvadze V, Orrenius S, Zhivotovsky B (2007) Mitochondria, oxidative stress and cell death. Apoptosis 12, 913922.
9. Bayir H, Fadeel B, Palladino MJ, Witasp E, Kurnikov IV, Tyurina YY, Tyurin VA, Amoscato AA, Jiang J, Kochanek PM, DeKosky ST, Greenberger JS, Shvedova AA, Kagan VE (2006) Apoptotic interactions of cytochrome c: Redox flirting with anionic phospholipids within and outside of mitochondria. Biochim Biophys Acta 1757, 648-659.
10. Nunomura A, Hofer T, Moreira PI, Castellani RJ, Smith MA, Perry G (2009) RNA oxidation in Alzheimer disease and related neurodegenerative disorders. Acta Neuropathol 118, 151-166.
11. Lovell MA, Markesbery WR (2007) Oxidative DNA damage in mild cognitive impairment and late-stage Alzheimer's disease. Nucleic Acids Res 35, 7497-7504.
12. Wang Y, Dawson VL, Dawson TM (2009) Poly(ADP-ribose) signals to mitochondrial AIF: a key event in parthanatos. Exp Neurol 218, 193-202.
13. Mattson MP (2003) Excitotoxic and excitoprotective mechanisms: abundant targets for the prevention and treatment of neurodegenerative disorders. Neuromolecular Med 3, 65-94.
14. Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M, Green DR (2004) Direct activation of Bax by p53 mediates mitochondrial membrane per- meabilization and apoptosis. Science 303, 1010-1014.
15. Lai Y, Chen Y, Watkins SC, Nathaniel PD, Guo F, Kochanek PM, Jenkins LW, Szabo C, Clark RS (2008) Identification of poly-ADP-ribosylated mitochondrial proteins after traumatic brain injury. J Neurochem 104, 1700-1711.
16. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443, 787-795.
17. Moreira PI, Zhu X, Wang X, Lee HG, Nunomura A, Petersen RB, Perry G, Smith MA (2010) Mitochondria: a therapeutic target in neurodegeneration. Biochim Biophys Acta 1802, 212-220.
18. Yap LP, Garcia JV, Han D, Cadenas E (2009) The energy- redox axis in aging and age-related neurodegeneration. Adv DrugDelivRev 61, 1283-1298.
19. Swerdlow RH (2009) The neurodegenerative mitochondri- opathies. J Alzheimers Dis 17, 737-751.
20. Gogvadze V, Orrenius S, Zhivotovsky B (2009) Mitochondria as targets for chemotherapy. Apoptosis 14, 624-640.
21. Knott AB, Bossy-Wetzel E (2008) Impairing the mitochon- drial fission and fusion balance: a new mechanism of neu- rodegenerationAnn N Y Acad Sci 1147, 283-292.
22. de la Monte SM, Wands JR (2006) Molecular indices of oxidative stress and mitochondrial dysfunction occur early and often progress with severity of Alzheimer's disease. J Alzheimers Dis 9,167-181.
23. Niizuma K, Endo H, Chan PH (2009) Oxidative stress and mitochondrial dysfunction as determinants of ischemic neu- ronal death and survival. J Neurochem 109,133-138.
24. Pope S, Land JM, Heales SJ (2008) Oxidative stress and mitochondrial dysfunction in neurodegeneration; cardiolipin a critical target? Biochim Biophys Acta 1777, 794-799.
25. Kauppinen TM, Swanson RA (2007) The role of poly (ADP- ribose) polymerase-1 in CNS disease. Neuroscience 45, 1267-1272.
26. Murphy MP (2008) Targeting lipophilic cations to mitochondria. Biochim Biophys Acta 1777, 1028-1031.
27. Sheu SS, Nauduri D, Anders MW (2006) Targeting antioxi- dants to mitochondria: a new therapeutic direction. BiochimBiophys Acta 1762, 256-265.
28. Richards EM, Fiskum G, Rosenthal RE, Hopkins I, McKen- na MC (2007) Hyperoxic reperfusion after global ischemia decreases hippocampal energy metabolism. Stroke 38, 15781584.
29. Balan IS, Fiskum G, Hazelton J, Cotto-Cumba C, Rosenthal RE (2006) Oximetry-guided reoxygenation improves neurological outcome after experimental cardiac arrest. Stroke 37, 3008-3013.
30. Fiskum G, Danilov CA, Mehrabian Z, Bambrick LL, Kristian T, McKenna MC, Hopkins I, Richards EM, Rosenthal RE (2008) Postischemic oxidative stress promotes mitochondrial metabolic failure in neurons and astrocytes. Ann N Y Acad Sci 1147, 129-138
31. Allen BW, Demchenko IT, Piantadosi CA (2009) Two faces ofnitric oxide: implications for cellular mechanisms ofoxy- gen toxicity. J Appl Physiol 106, 662-667.
32. Moncada S, Bolanos JP (2006) Nitric oxide, cell bioenerget- ics and neurodegeneration. J Neurochem 97, 1676-1689.
33. Kim-Han JS, Dugan LL (2005) Mitochondrial uncoupling proteins in the central nervous system. Antioxid Redox Signal 7, 1173-1181.
34. Conti B, Sugama S, Lucero J, Winsky-Sommerer R, Wirz SA, Maher P, Andrews Z, Barr AM, Morale MC, Paneda C, Pemberton J, Gaidarova S, Behrens MM, Beal F, San- na PP, Horvath T, Bartfai T (2005) Uncoupling protein 2 protects dopaminergic neurons from acute 1,2,3,6-methyl- phenyl-tetrahydropyridine toxicity. J Neurochem 93, 493501.
35. Sullivan PG, Springer JE, Hall ED, Scheff SW (2004) Mito- chondrial uncoupling as a therapeutic target following neu- ronal injury. JBioenerg Biomembr 36, 353-356.
36. Mattiasson G, Shamloo M, Gido G, Mathi K, Tomasevic G, Yi S, Warden CH, Castilho RF, Melcher T, Gonzalez-Zulueta M, Nikolich K, Wieloch T (2003) Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma. Nat Med 9, 1062-1068.
37. Johnson-Cadwell LI, Jekabsons MB, Wang A, Polster BM, Nicholls DG (2007) 'Mild Uncoupling' does not decrease mi- tochondrial superoxide levels in cultured cerebellar granule neurons but decreases spare respiratory capacity and increases toxicity to glutamate and oxidative stress. J Neurochem 101, 1619-1631.
38. Chan PH (2005) Mitochondrial dysfunction and oxidative stress as determinants of cell death/survival in stroke. AnnN Y Acad Sci 1042, 203-209.
39. Esposito L, Raber J, Kekonius L, Yan F, Yu GQ, Bien-Ly N, Puolivali J, Scearce-Levie K, Masliah E, Mucke L (2006) Reduction in mitochondrial superoxide dismutase modulates Alzheimer's disease-like pathology and accelerates the onset of behavioral changes in human amyloid precursor protein transgenic mice. J Neurosci 26, 5167-5179.
40. Andreassen OA, Ferrante RJ, Dedeoglu A, Albers DW, Klivenyi P, Carlson EJ, Epstein CJ, Beal MF (2001) Mice with a partial deficiency of manganese superoxide dismu- tase show increased vulnerability to the mitochondrial toxins malonate, 3-nitropropionic acid, and MPTP. Exp Neurol 167, 189-195.
41. Murakami K, Kondo T, Kawase M, Li Y, Sato S, Chen SF, Chan PH (1998) Mitochondrial susceptibility to oxidative stress exacerbates cerebral infarction that follows permanent focal cerebral ischemia in mutant mice with manganese su- peroxide dismutase deficiency. J Neurosci 18, 205-213.
42. Mazzeo AT, Beat A, Singh A, Bullock MR (2009) The role of mitochondrial transition pore, and its modulation, in traumatic brain injury and delayed neurodegeneration after TBI. Exp Neurol 218, 363-370.
43. Schinzel AC, Takeuchi O, Huang Z, Fisher JK, Zhou Z, Rubens J, Hetz C, Danial NN, Moskowitz MA, Korsmeyer SJ (2005) Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia. ProcNatl Acad Sci U SA 102, 1200512010.
44. Forte M, Gold BG, Marracci G, Chaudhary P, Basso E, Johnsen D, Yu X, Fowlkes J, Rahder M, Stem K, Bernardi P, Bourdette D (2007) Cyclophilin D inactivation protects ax- ons in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Proc Natl Acad Sci U S A 104, 7558-7563.
45. Jaiswal AK (2004) Nrf2 signaling in coordinated activation of antioxidant gene expression. Free Radic Biol Med 36, 1199-1207.
46. Li W, Kong AN (2009) Molecular mechanisms of Nrf2- mediated antioxidant response. Mol Carcinog 48, 91-104.
47. Li W, Yu S, Liu T, Kim JH, Blank V, Li H, Kong AN (2008) Heterodimerization with small Maf proteins enhances nuclear retention of Nrf2 via masking the NESzip motif.Biochim Biophys Acta 1783, 1847-1856.
48. Yu X, Kensler T (2005) Nrf2 as a target for cancer chemo- prevention. Mutat Res 591, 93-102.
49. Jain AK, Jaiswal AK (2007) GSK-3beta acts upstream of Fyn kinase in regulation of nuclear export and degradation of NF-E2 related factor 2. J Biol Chem 282, 16502-16510.
50. Thimmulappa RK, Mai KH, Srisuma S, Kensler TW, Ya- mamoto M, Biswal S (2002) Identification ofNrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res 62, 5196-5203.
51. Hu R, Xu C, Shen G, Jain MR, Khor TO, Gopalkrishnan A, Lin W, Reddy B, Chan JY, Kong AN (2006) Identification of Nrf2-regulated genes induced by chemopreventive isoth- iocyanate PEITC by oligonucleotide microarray. Life Sci 79, 1944-1955.
52. Wattenberg LW, Coccia JB, Lam LK (1980) Inhibitory effects of phenolic compounds on benzo(a)pyrene-induced neopla- sia. Cancer Res 40, 2820-2823.
53. Ramos-Gomez M, Kwak MK, Dolan PM, Itoh K, Yamamoto M, Talalay P, Kensler TW (2001) Sensitivity to carcinogen- esis is increased and chemoprotective efficacy of enzyme in- ducers is lost in nrf2 transcription factor-deficient mice. Proc Natl Acad Sci USA 98, 3410-3415.
54. Fahey JW, Talalay P (1999) Antioxidant functions of sul- foraphane: a potent inducer of Phase II detoxication enzymes. Food Chem Toxicol 37, 973-979.
55. Dinkova-Kostova AT, Holtzclaw WD, Cole RN, Itoh K, Wak- abayashi N, Katoh Y, Yamamoto M, Talalay P (2002) Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc Natl Acad Sci U S A 99, 11908-11913.
56. Satoh T, Kosaka K, Itoh K, Kobayashi A, Yamamoto M, Shimojo Y, Kitajima C, Cui J, Kamins J, Okamoto S, Izumi M, Shirasawa T, Lipton SA (2008) Carnosic acid, a catechol- type electrophilic compound, protects neurons both in vitro and in vivo through activation of the Keap1/Nrf2 pathway via S-alkylation of targeted cysteines on Keap1. J Neurochem 104, 1116-1131.
57. Pugazhenthi S, Akhov L, Selvaraj G, Wang M, Alam J (2007) Regulation of heme oxygenase-1 expression by demethoxy curcuminoids through Nrf2 by a PI3-kinase/Akt-mediated pathway in mouse beta-cells. Am J Physiol EndocrinolMetab 293, E645-E655.
58. Gharavi N, Haggarty S, El Kadi AO (2007) Chemoprotective and carcinogenic effects of tert-butylhydroquinone and its metabolites. Curr Drug Metab 8, 1-7.
59. Son TG, Camandola S, Arumugam TV, Cutler RG, Telljo- hann RS, Mughal MR, Moore TA, Luo W, Yu QS, Johnson DA, Johnson JA, Greig NH, Mattson MP (2010) Plumba- gin, a novel Nrf2/ARE activator, protects against cerebral ischemia. J Neurochem 112, 1316-1326.
60. Wang L, Chen Y, Sternberg P, Cai J (2008) Essential roles ofthe PI3 kinase/Akt pathway in regulating Nrf2-dependent antioxidant functions in the RPE. Invest Ophthalmol Vis Sci 49, 1671-1678.
61. Kaspar JW, Niture SK, Jaiswal AK (2009) Nrf2:INrf2 (Keap1) signaling in oxidative stress. Free Radic Biol Med 47, 1304-1309.
62. Niture SK, Kaspar JW, Shen J, Jaiswal AK (2009) Nrf2 signaling and cell survival. Toxicol Appl Pharmacol 244, 37-42.
63. Zhao X, Sun G, Zhang J, Strong R, Dash PK, Kan YW, Grotta JC, Aronowski J (2007) Transcription Factor Nrf2 Protects the Brain From Damage Produced by Intracerebral Hemorrhage. Stroke 38, 3280-3286.
64. Wang J, Fields J, Zhao C, Langer J, Thimmulappa RK, Kensler TW, Yamamoto M, Biswal S, Dore S (2007) Role of Nrf2 in protection against intracerebral hemorrhage injury in mice. Free Radic Biol Med 43, 408-414.
65. Zhao J, Kobori N, Aronowski J, Dash PK (2006) Sul- foraphane reduces infarct volume following focal cerebral ischemia in rodents. Neurosci Lett 393, 108-112.
66. Shah ZA, Li RC, Thimmulappa RK, Kensler TW, Yamamoto M, Biswal S, Dore S (2007) Role of reactive oxygen species in modulation of Nrf2 following ischemic reperfusion injury. Neuroscience 147, 53-59.
67. Shih AY, Li P, Murphy TH (2005) A small-molecule- inducible Nrf2-mediated antioxidant response provides effective prophylaxis against cerebral ischemia in vivo. J Neurosci 25, 10321-10335.
68. Dash PK, Zhao J, Orsi SA, Zhang M, Moore AN (2009) Sul- foraphane improves cognitive function administered following traumatic brain injury. Neurosci Lett 460, 103-107.
69. Zhao J, Moore AN, Clifton GL, Dash PK (2005) Sul- foraphane enhances aquaporin-4 expression and decreases cerebral edema following traumatic brain injury. J Neurosci Res 82, 499-506.
70. Zhao J, Moore AN, Redell JB, Dash PK (2007) Enhancing expression of Nrf2-driven genes protects the blood brain barrier after brain injury. J Neurosci 27, 10240-10248.
71. Fiskum G, Greco T, Hazelton J, Balan I, Racz J, Cotto-Cumba C, Rosenthal RE (2010) Sulforaphane inhibits redox regulated mitochondrial permeability transition and provides neu- roprotection after cardiac arrest. Abstr Am Soc Neurochem Meet, 156.
72. Soane L, Li DW, Fiskum G, Bambrick LL (2009) Sul- foraphane protects immature hippocampal neurons against death caused by exposure to hemin or to oxygen and glucose deprivation. J Neurosci Res 88, 1355-1363.
73. Danilov CA, Chandrasekaran K, Racz J, Soane L, Zielke C, Fiskum G: Sulforaphane protects astrocytes against oxida- tive stress and delayed death caused by oxygen and glucose deprivation. Glia 57, 645-656.
74. Liu XY, Li CY, Bu H, Li Z, Li B, Sun MM, Guo YS, Zhang L, Ren WB, Fan ZL, Wu DX, Wu SY: The neuroprotective potential of phase II enzyme inducer on motor neuron survival in traumatic spinal cord injury in vitro. Cell Mol Neurobiol 28, 769-779.
75. Eftekharzadeh B, Maghsoudi N, Khodagholi F (2010) Stabilization of transcription factor Nrf2 by tBHQ prevents oxida- tive stress-induced amyloid beta formation in NT2N neurons. Biochimie 92, 245-253.
76. Kanninen K, Heikkinen R, Malm T, Rolova T, Kuhmonen S, Leinonen H, Yla-Herttuala S, Tanila H, Levonen AL, Koisti- naho M, Koistinaho J (2009) Intrahippocampal injection of a lentiviral vector expressing Nrf2 improves spatial learning in a mouse model of Alzheimer's disease. Proc Natl Acad Sci USA 106, 16505-16510.
77. Calkins MJ, Jakel RJ, Johnson DA, Chan K, Kan YW, Johnson JA (2005) Protection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcription. Proc Natl Acad Sci USA 102, 244-249.
78. Siebert A, Desai V, Chandrasekaran K, Fiskum G, Jafri MS (2009) Nrf2 activators provide neuroprotection against 6- hydroxydopamine toxicity in rat organotypic nigrostriatal co- cultures. J Neurosci Res 87, 1659-1669.
79. Tarozzi A, Morroni F, Merlicco A, Hrelia S, Angeloni C, Cantelli-Forti G, Hrelia P (2009) Sulforaphane as an inducer of glutathione prevents oxidative stress-induced cell death in a dopaminergic-like neuroblastoma cell line. J Neurochem 111, 1161-1171.
80. Chen PC, Vargas MR, Pani AK, Smeyne RJ, Johnson DA, Kan YW, Johnson JA (2009) Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson's disease: Critical role for the astrocyte. Proc Natl Acad Sci USA 106, 29332938.
81. Vargas MR, Johnson DA, Sirkis DW, Messing A, Johnson JA (2008) Nrf2 activation in astrocytes protects against neurode- generation in mouse models of familial amyotrophic lateral sclerosis. J Neurosci 28, 13574-13581.
82. Burton NC, Kensler TW, Guilarte TR (2006) In vivo modulation of the Parkinsonian phenotype by Nrf2. Neurotoxicology 27, 1094-1100.
83. Kraft AD, Lee JM, Johnson DA, Kan YW, Johnson JA (2006) Neuronal sensitivity to kainic acid is dependent on the Nrf2- mediated actions of the antioxidant response element. J Neurochem 98, 1852-1865.
84. Nimura T, Weinstein PR, Massa SM, Panter S, Sharp FR (1996) Heme oxygenase-1 (HO-1) protein induction in rat brain following focal ischemia. Mol Brain Res 37, 201-208.
85. Mattson MP (1997) Neuroprotective signal transduction: relevance to stroke. Neurosci Biobehav Rev 21, 193-206.
86. Shukla PK, Khanna VK, Ali MM, Khan MY, Srimal RC (2008) Anti-ischemic effect of curcumin in rat brain. Neurochem Res 33, 1036-1043.
87. Valdivia A, Perez-Alvarez S, roca-Aguilar JD, Ikuta I, Jordan J (2009) Superoxide dismutases: a physiopharmacological update. J Physiol Biochem 65, 195-208.
88. Dohare P, Garg P, Jain V, Nath C, Ray M (2008) Dose dependence and therapeutic window for the neuroprotective effects of curcumin in thromboembolic model of rat. Behav Brain Res 193, 289-297.
89. Al-Omar FA, Nagi MN, Abdulgadir MM, Al Joni KS, Al-Majed AA (2006) Immediate and delayed treatments with curcumin prevents forebrain ischemia-induced neuronal damage and oxidative insult in the rat hippocampus. Neu- rochem Res 31, 611-618.
90. Dringen R, Pawlowski PG, Hirrlinger J (2005) Peroxide detoxification by brain cells. J Neurosci Res 79, 157-165.
91. Lavoie S, Chen Y, Dalton TP, Gysin R, Cuenod M, Steullet P, Do KQ (2009) Curcumin, quercetin, and tBHQ modulate glutathione levels in astrocytes and neurons: importance of the glutamate cysteine ligase modifier subunit. J Neurochem 108, 1410-1422.
92. Piantadosi CA, Carraway MS, Babiker A, Suliman HB (2008) Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via Nrf2-mediated transcriptional control of nuclear respiratory factor-1. Circ Res 103, 1232-1240.
93. Lee JM, Calkins MJ, Chan K, Kan YW, Johnson JA (2003) Identification ofthe NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis. J Biol Chem 278, 12029-12038.
94. Lambert AJ, Brand MD (2009) Reactive oxygen species production by mitochondria. Methods Mol Biol 554, 165- 81.:165-181.
95. Stowe DF, Camara AK (2009) Mitochondrial reactive oxygen species production in excitable cells: modulators of mito- chondrial and cell function. Antioxid Redox Signal 11, 13731414.
96. Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417, 1-13.
97. Starkov AA (2008) The role of mitochondria in reactive oxygen species metabolism and signaling. Ann N Y Acad Sci 1147, 37-52.
98. Starkov AA, Fiskum G, Chinopoulos C, Lorenzo BJ, Browne SE, Patel MS, Beal MF (2004) Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen species. J Neurosci 24, 7779-7788.
99. Tretter L, Adam-Vizi V (2004) Generation of reactive oxygen species in the reaction catalyzed by alpha-ketoglutarate dehydrogenase. J Neurosci 24, 7771-7778.
100. Alves E, Summavielle T, Alves CJ, Gomes-da-Silva J, Barata JC, Fernandes E, Bastos ML, Tavares MA, Carvalho F (2007) Monoamine oxidase-B mediates ecstasy-induced neurotoxic effects to adolescent rat brain mitochondria. J Neurosci 27, 10203-10210.
101. Sinet PM, Heikkila RE, Cohen G (1980) Hydrogen peroxide production by rat brain in vivo. J Neurochem 34, 1421-1428.
102. Hogberg J, Orrenius S, Larson RE (1975) Lipid peroxidation in isolated hepatocytes. Eur J Biochem 50, 595-602.
103. Zhu H, Jia Z, Strobl JS, Ehrich M, Misra HP, Li Y (2008) Potent induction of total cellular and mitochondrial antioxi- dants and phase 2 enzymes by cruciferous sulforaphane in rat aortic smooth muscle cells: cytoprotection against oxidative and electrophilic stress. Cardiovasc Toxicol 8, 115-125.
104. Zhu H, Jia Z, Zhou K, Misra H, Santo A, Gabrielson KL, Li Y (2009) Cruciferous dithiolethione-mediated coordinated induction of total cellular and mitochondrial antioxidants and phase 2 enzymes in human primary cardiomyocytes: cy- toprotection against oxidative/electrophilic stress and dox- orubicin toxicity. Exp Biol Med (Maywood) 234, 418-429.
105. Fiskum G, Pease A(1986) Hydroperoxide-stimulated release of calcium from rat liver and AS-30D hepatoma mitochondria. Cancer Res 46, 3459-3463.
106. Mukherjee S, Gangopadhyay H, Das DK (2008) Broccoli: a unique vegetable that protects mammalian hearts through the redox cycling of the thioredoxin superfamily. J Agric Food Chem 56,609-617.
107. Kowaltowski AJ, Vercesi AE, Fiskum G (2000) Bcl-2 prevents mitochondrial permeability transition and cytochrome c release via maintenance of reduced pyridine nucleotides. Cell Death Differ 7, 903-910.
108. Robertson CL, Scafidi S, McKenna MC, Fiskum G (2009) Mitochondrial mechanisms ofcell death and neuroprotection in pediatric ischemic and traumatic brain injury. Exp Neurol 218, 371-380.
109. Halestrap AP (2009) Mitochondria and reperfusion injury of the heart - a holey death but not beyond salvation. JBioenerg Biomembr 41, 113-121.
110. Bernardi P, Rasola A (2007) Calcium and cell death: the mitochondrial connection. Subcell Biochem 45, 481-506.