Soluble oligomers of amyloid-β cause changes in redox state, DNA methylation, and gene transcription by inhibiting EAAT3 mediated cysteine uptake

Journal of Alzheimer's Disease

Volumn 36, Issue 1, 2013, Pages 197-209

  Hodgson, Nathaniel ^a   Trivedi, Malav ^a   Muratore, Christina ^b   Li, Shaomin ^b   Deth, Richard ^a  

^a NORTHEASTERN UNIVERSITY   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Alzheimer's disease; epigenomics; glutathione; insulin like growth factor 1,5 methyltetrahydrofolate homocysteine s methyltransferase

Indexed keywords

AMYLOID BETA PROTEIN; CYSTEINE; EXCITATORY AMINO ACID TRANSPORTER 3; GLUTATHIONE; HOMOCYSTEINE; METHIONINE SYNTHASE; S ADENOSYLHOMOCYSTEINE; S ADENOSYLMETHIONINE; SOMATOMEDIN C; THIOL;

ALZHEIMER DISEASE; ARTICLE; CONTROLLED STUDY; DNA METHYLATION; ENZYME ACTIVITY; GENETIC TRANSCRIPTION; HUMAN; HUMAN CELL; NERVE CELL CULTURE; OXIDATION REDUCTION STATE; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TRANSPORT;

EID: 84878856081     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-130101     Document Type: Article

References (71)

1. Li S, Hong S, Shepardson NE, Walsh DM, Shankar GM, Selkoe D (2009) Soluble oligomers of amyloid [beta] protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron 62, 788-801.
2. Benilova I, Karran E, Strooper BD (2012) The toxic A-oligomer and Alzheimer's disease: An emperor in need of clothes. Nat Neurosci 15, 349-357.
3. Nieoullon A, Canolle B, Masmejean F, Guillet B, Pisano P, Lortet S (2006) The neuronal excitatory amino acid transporter EAAC1/EAAT3: Does it represent a major actor at the brain excitatory synapse? J Neurochem 98, 1007-1018.
4. Watabe M, Aoyama K, Nakaki T (2007) Regulation of glutathione synthesis via interaction between glutamate transport-associated protein 3-18 (GTRAP3-18) and excitatory amino acid carrier-1 (EAAC1) at plasma membrane. Mol Pharmacol 72, 1103-1110.
5. Sultana R, Perluigi M, Butterfield DA (2009) Oxidatively modified proteins in Alzheimer's disease (AD), mild cognitive impairment and animal models of AD: Role of Abeta in pathogenesis. Acta Neuropathol 118, 131-150.
6. Himi T, Ikeda M,Yasuhara T, Nishida M, Morita I (2003) Role of neuronal glutamate transporter in the cysteine uptake and intracellular glutathione levels in cultured cortical neurons. J Neural Transm 110, 1337-1348.
7. Chen Y, Swanson RA (2003) The glutamate transporters EAAT2 and EAAT3 mediate cysteine uptake in cortical neuron cultures. J Neurochem 84, 1332-1339.
8. Aoyama K, Watabe M, Nakaki T (2008) Regulation of neuronal glutathione synthesis. J Pharmacol Sci 108, 227-238.
9. Esslinger CS, Agarwal S, Gerdes J, Wilson PA, Davis ES, Awes AN, O'Brien E, Mavencamp T, Koch HP, Poulsen DJ, Rhoderick JF, Chamberlin AR, Kavanaugh MP, Bridges RJ (2005) The substituted aspartate analogue L-betathreo-benzyl- aspartate preferentially inhibits the neuronal excitatory amino acid transporter EAAT3. Neuropharmacology 49, 850-861.
10. Leary GP, Stone EF, Holley DC, Kavanaugh MP (2007) The glutamate and chloride permeation pathways are colocalized in individual neuronal glutamate transporter subunits. J Neurosci 27, 2938-2942.
11. Tallan HH, Moore S, Stein WH (1958) L-cystathionine in human brain. J Biol Chem 230, 707-716.
12. Sheldon A, Gonzalez M, Robinson M (2006) A carboxylterminal determinant of the neuronal glutamate transporter, EAAC1, is required for platelet-derived growth factordependent trafficking. J Biol Chem 281, 4876-4886.
13. Watabe M, Aoyama K, Nakaki T (2008) A dominant role of GTRAP3-18 in neuronal glutathione synthesis. J Neurosci 28, 9404-9413.
14. Talbot K, Wang H-Y, Kazi H, Han L-Y, Bakshi KP, Stucky A, Fuino RL, Kawaguchi KR, Samoyedny AJ, Wilson RS, Arvanitakis Z, Schneider JA, Wolf BA, Bennett DA, Trojanowski JQ, Arnold SE (2012) Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J Clin Invest 122, 1316-1338.
15. Bollati V, Galimberti D, Pergoli L, Dalla Valle E, Barretta F, Cortini F, Scarpini E, Bertazzi PA, Baccarelli A (2011) DNA methylation in repetitive elements and Alzheimer disease. Brain Behav Immun 25, 1078-1083.
16. Zawia NH, Lahiri DK, Cardozo-Pelaez F (2009) Epigenetics, oxidative stress, and Alzheimer disease. Free Radic Biol 46, 1241-1249.
17. Brohede J, Rinde M, Winblad B, Graff C (2010) A DNA methylation study of the amyloid precursor protein gene in several brain regions from patients with familial Alzheimer disease. J Neurogenet 24, 179-181.
18. Chen K-L, Wang SS-S, Yang Y-Y, Yuan R-Y, Chen R-M, Hu C-J (2009) The epigenetic effects of amyloid-beta(1-40) on global DNA and neprilysin genes in murine cerebral endothelial cells. Biochem Biophys Res Commun 378, 57-61.
19. Siegmund KD, Connor CM, Campan M, Long TI, Weisenberger DJ, Biniszkiewicz D, Jaenisch R, Laird PW, Akbarian S (2007) DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons. PloS One 2, e895.
20. Silva PNO, Gigek CO, Leal MF, Bertolucci PHF, de Labio RW, Payão SLM, Smith M de AC (2008) Promoter methylation analysis of SIRT3, SMARCA5, HTERT and CDH1 genes in aging and Alzheimer's disease. J Alzheimers Dis 13, 173-176.
21. Wang S-C, Oelze B, Schumacher A (2008) Age-specific epigenetic drift in late-onset Alzheimer's disease. PloS One 3, e2698.
22. Beyer K, Lao JI, Latorre P, Riutort N, Matute B, Fernández- Figueras MT, Mate JL, Ariza A (2003) Methionine synthase polymorphism is a risk factor for Alzheimer disease. Neuroreport 14, 1391-1394.
23. Wang B, Jin F, Kan R, Ji S, Zhang C, Lu Z, Zheng C, Yang Z, Wang L (2005) Association of MTHFR gene polymorphism C677T with susceptibility to late-onset Alzheimer's disease. J Mol Neurosci 27, 23-27.
24. Waly M, Olteanu H, Banerjee R, Choi S-W,Mason JB, Parker BS, Sukumar S, Shim S, Sharma A, Benzecry JM, Power-Charnitsky V-A, Deth RC (2004) Activation of methionine synthase by insulin-like growth factor-1 and dopamine: A target for neurodevelopmental toxins and thimerosal. Mol Psychiatry 9, 358-370.
25. Martin C, Zhang Y (2007) Mechanisms of epigenetic inheritance. Curr Opin Cell Biol 19, 266-272.
26. Santos F, Dean W (2004) Epigenetic reprogramming during early development in mammals. Reproduction 127, 643-651.
27. Weir DG, Scott JM (1999) Brain function in the elderly: Role of vitamin B12 and folate. Br Med Bull 55, 669-682.
28. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB,Wilson PWF,Wolf PA (2002) Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. New Engl J Med 346, 476-483.
29. Chiang E-PI, Wang Y-C, Chen W-W, Tang F-Y (2009) Effects of insulin and glucose on cellular metabolic fluxes in homocysteine transsulfuration, remethylation, Sadenosylmethionine synthesis, and global deoxyribonucleic acid methylation. J Clin Endocr Metab 94, 1017-1025.
30. Pogribny I, Beland F (2009) DNA hypomethylation in the origin and pathogenesis of human diseases. Cell Mol Life Sci 66, 2249-2261.
31. West RL, Lee JM,Maroun LE (1995) Hypomethylation of the amyloid precursor protein gene in the brain of an Alzheimer's disease patient. J Mol Neurosci 6, 141-146.
32. Fuso A, Cavallaroa RA, Nicolia V, Scarpa S (2012) PSEN1 promoter demethylation in hyperhomocysteinemic TgCRND8 mice is the culprit, not the consequence. Curr Alzheimer Res 9, 527-535.
33. McCaddon A, Regland B, Hudson P, Davies G (2002) Functional vitamin B(12) deficiency and Alzheimer disease. Neurology 58, 1395-1399.
34. Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM(1998) Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol-Chicago 55, 1449-1455.
35. Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G, Oulhaj A, Bradley KM, Jacoby R, Refsum H (2010) Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: A randomized controlled trial. PLoS One 5, e12244.
36. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193, 265-275.
37. Shanker G, Allen JW, Mutkus LA, Aschner M (2001) The uptake of cysteine in cultured primary astrocytes and neurons. Brain Res 902, 156-163.
38. Kavanagh TJ, McConnachie LA, Mohar I, Hudson FN, Ware CB, Ladiges WC, Fernandez C, Chatterton-Kirchmeier S, White CC, Pierce RH (2007) Glutamate cysteine ligase modifier subunit deficiency and gender as determinants of acetaminophen-induced hepatotoxicity in mice. Toxicol Sci 99, 628-636.
39. Aoyama K, Suh SW, Hamby AM, Liu J, Chan WY, Chen Y, SwansonRA(2006) Neuronal glutathione deficiency and agedependent neurodegeneration in the EAAC1 deficient mouse. Nat Neurosci 9, 119-126.
40. Podlisny MB, Ostaszewski BL, Squazzo SL, Koo EH, Rydell RE, Teplow DB, Selkoe DJ (1995) Aggregation of secreted amyloid beta-protein into sodium dodecyl sulfatestable oligomers in cell culture. J Biol Chem 270, 9564-9570.
41. Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535-539.
42. Holmseth S, Dehnes Y, Huang YH, Follin-Arbelet VV, Grutle NJ, Mylonakou MN, Plachez C, ZhouY, Furness DN, Bergles DE, Lehre KP, Danbolt NC (2012) The density of EAAC1 (EAAT3) glutamate transporters expressed by neurons in the mammalian CNS. J Neurosci 32, 6000-6013.
43. Bendahan A, Armon A, Madani N, Kavanaugh MP, Kanner BI (2000) Arginine 447 plays a pivotal role in substrate interactions in a neuronal glutamate transporter. J Biol Chem 275, 37436-37442.
44. Danbolt N (2001) Glutamate uptake. Prog Neurobiol 65, 1-105.
45. Kruman II (2004) Why do neurons enter the cell cycle? Cell Cycle 3, 769-773.
46. Castagna A, Le Grazie C, Accordini A, Giulidori P, Cavalli G, Bottiglieri T, Lazzarin A (1995) Cerebrospinal fluid Sadenosylmethionine (SAMe) and glutathione concentrations in HIV infection: Effect of parenteral treatment with SAMe. Neurology 45, 1678-1683.
47. Vitvitsky V, Thomas M, Ghorpade A, Gendelman HE, Banerjee R (2006) A functional transsulfuration pathway in the brain links to glutathione homeostasis. J Biol Chem 281, 35785-35793.
48. Currais A, Hortobagyi T, Soriano S (2009) The neuronal cell cycle as a mechanism of pathogenesis in Alzheimer's disease. Aging 1, 363-371.
49. Brewer GJ (2010) Epigenetic oxidative redox shift (EORS) theory of aging unifies the free radical and insulin signaling theories. Exp Gerontol 45, 173-179.
50. Chen Z, Chakraborty S, Banerjee R (1995) Demonstration that mammalian methionine synthases are predominantly cobalamin-loaded. J Biol Chem 270, 19246-19249.
51. Drummond JT, Huang S, Blumenthal RM, Matthews RG (1993) Assignment of enzymatic function to specific protein regions of cobalamin-dependent methionine synthase from Escherichia coli. Biochemistry 32, 9290-9295.
52. Jensen KP (2005) Electronic structure of Cob(I)alamin: The story of an unusual nucleophile. J Phys Chem B 109, 10505-10512.
53. Bosco P, Guéant-Rodríguez R-M, Anello G, Romano A, Namour B, Spada RS, Caraci F, Tringali G, Ferri R, Guéant J-L (2004) Association of IL-1 RN*2 allele and methionine synthase 2756 AA genotype with dementia severity of sporadic Alzheimer's disease. J Neurol Neurosurg Psychiatry 75, 1036-1038.
54. Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE (2007) Systematic meta-analyses of Alzheimer disease genetic association studies: The AlzGene database. Nat Genet 39, 17-23.
55. Kageyama M, Hiraoka M, Kagawa Y (2008) Relationship between genetic polymorphism, serum folate and homocysteine in Alzheimer's disease. Asia Pac J Public Health 20, 111-117.
56. Bi X-H, Zhao H-L, Zhang Z-X, Zhang J-W (2009) Association of RFC1 A80G andMTHFRC677T polymorphisms with Alzheimer's disease. Neurobiol Aging 30, 1601-1607.
57. Morrison LD, Smith DD, Kish SJ (1996) Brain Sadenosylmethionine levels are severely decreased in Alzheimer's disease. J Neurochem 67, 1328-1331.
58. Serot J-M, Barbé F, Arning E, Bottiglieri T, Franck P, Montagne P, Nicolas J-P (2005) Homocysteine and methylmalonic acid concentrations in cerebrospinal fluid: Relation with age and Alzheimer's disease. J Neurol Neuros Ps 76, 1585-1587.
59. Oulhaj A, Refsum H, Beaumont H,Williams J, King E, Jacoby R, Smith AD (2010) Homocysteine as a predictor of cognitive decline in Alzheimer's disease. Int J Geriatr Psych 25, 82-90.
60. Bottiglieri T, Godfrey P, Flynn T, Carney MW, Toone BK, Reynolds EH (1990) Cerebrospinal fluid S-adenosylmethionine in depression and dementia: Effects of treatment with parenteral and oral S-adenosylmethionine. J Neurol Neurosurg Psychiatry 53, 1096-1098.
61. Bottiglieri T, Hyland K (1994) S-adenosylmethionine levels in psychiatric and neurological disorders: A review. Acta Neurol Scand Supp 154, 19-26.
62. Fleming JL, Phiel CJ, Toland AE(2012) The role for oxidative stress in aberrant DNA methylation in alzheimer's disease. Curr Alzheimer Res 9, 1077-1096.
63. Tchantchou F, Graves M, Shea TB (2006) Expression and activity of methionine cycle genes are altered following folate and vitamin E deficiency under oxidative challenge: Modulation by apolipoprotein E-deficiency. Nutr Neurosci 9, 17-24.
64. Chan A, Shea TB (2007) Folate deprivation increases presenilin expression, gamma-secretase activity, and Abeta levels in murine brain: Potentiation by ApoE deficiency and alleviation by dietary S-adenosyl methionine. J Neurochem 102, 753-760.
65. Fuso A, NicoliaV, Ricceri L, Cavallaro RA, Isopi E, Mangia F, FiorenzaMT, Scarpa S (2012) S-adenosylmethionine reduces the progress of the Alzheimer-like features induced by Bvitamin deficiency in mice. Neurobiol Aging 33, 1-16.
66. Vafai SB, Stock JB (2002) Protein phosphatase 2A methylation: A link between elevated plasma homocysteine and Alzheimer's disease. FEBS Lett 518, 1-4.
67. Sontag E, Nunbhakdi-Craig V, Sontag J-M, Diaz-Arrastia R, Ogris E, Dayal S, Lentz SR, Arning E, Bottiglieri T (2007) Protein phosphatase 2A methyltransferase links homocysteine metabolism with tau and amyloid precursor protein regulation. J Neurosci 27, 2751-2759.
68. Chan AY, Alsaraby A, Shea TB (2008) Folate deprivation increases tau phosphorylation by homocysteine-induced calcium influx and by inhibition of phosphatase activity: Alleviation by S-adenosyl methionine. Brain Res 1199, 133-137.
69. Sims KD, Straff DJ, Robinson MB (2000) Platelet-derived growth factor rapidly increases activity and cell surface expression of the EAAC1 subtype of glutamate transporter through activation of phosphatidylinositol 3-kinase. J Biol Chem 275, 5228-5237.
70. Xia P, Pei G, Schwarz W (2006) Regulation of the glutamate transporter EAAC1 by expression and activation of deltaopioid receptor. Eur J Neurosci 24, 87-93.
71. Bomfim TR, Forny-Germano L, Sathler LB, Brito-Moreira J, Houzel J-C, Decker H, Silverman MA, Kazi H, Melo HM, McClean PL, Holscher C, Arnold SE, Talbot K, Klein WL, Munoz DP, Ferreira ST,De Felice FG (2012) An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease-associated A-oligomers. J Clin Invest 122, 1339-1353.