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Alpha-synuclein deficiency leads to increased glyoxalase I expression and glycation stress

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Kurz, Alexander, Rabbani, Naila, Walter, Michael, Bonin, Michael, Thornalley, Paul J., Auburger, Georg and Gispert, Suzana. (2011) Alpha-synuclein deficiency leads to increased glyoxalase I expression and glycation stress. Cellular and Molecular Life Sciences, Vol.68 (No.4). pp. 721-733. ISSN 1420-682X

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Official URL: http://dx.doi.org/10.1007/s00018-010-0483-7

Abstract

The presynaptic protein alpha-synuclein has received much attention because its gain-of-function is associated with Parkinson’s disease. However, its physiological function is still poorly understood. We studied brain regions of knock-out mice at different ages with regard to consistent upregulations of the transcriptome and focused on glyoxalase I (GLO1). The microarray data were confirmed in qPCR, immunoblot, enzyme activity, and behavior analyses. GLO1 induction is a known protective cellular response to glucose stress, representing efforts to decrease toxic levels of methylglyoxal (MG), glyoxal and advanced glycation endproducts (AGEs). Mass spectrometry quantification demonstrated a ubiquitous increase in MG and fructosyl-lysine as consequences of glucose toxicity, and consistent enhancement of certain AGEs. Thus, GLO1 induction in KO brain seems insufficient to prevent AGE formation. In conclusion, the data demonstrate GLO1 expression and glycation damage to be induced by alphasynuclein ablation. We propose that wild-type alpha-synuclein modulates brain glucose metabolism.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Medicine > Warwick Medical School > Clinical Sciences Research Institute (CSRI) Faculty of Medicine > Warwick Medical School > Metabolic and Vascular Health Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Presynaptic receptors, Glyoxalase, Glycosylation, Glucose -- Metabolism
Journal or Publication Title:	Cellular and Molecular Life Sciences
Publisher:	Springer
ISSN:	1420-682X
Date:	February 2011
Volume:	Vol.68
Number:	No.4
Page Range:	pp. 721-733
Identification Number:	10.1007/s00018-010-0483-7
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	Deutsche Forschungsgemeinschaft (DFG), Germany. Bundesministerium für Gesundheit [Ministry of Health]
Grant number:	GI342/1-1 (DFG), GI342/3-1 (DFG), AU96/10-1 (DFG), 01GS0472 (MoH), 01GS08138 (MoH), 0315584A (MoH)
References:	1. Ma QL, Chan P, Yoshii M, Ueda K (2003) Alpha-synuclein aggregation and neurodegenerative diseases. J Alzheimers Dis 5:139–148 2. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276: 2045–2047 3. Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K (2003) Alpha-synuclein locus triplication causes Parkinson’s disease. Science 302:841 4. Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388:839–840 5. Braak H, Del Tredici K, Bratzke H, Hamm-Clement J, Sandmann- Keil D, Rub U (2002) Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson’s disease (preclinical and clinical stages). J Neurol 249(Suppl 3): III/1–5 6. Jenner P (1993) Altered mitochondrial function, iron metabolism and glutathione levels in Parkinson’s disease. Acta Neurol Scand Suppl 146:6–13 7. Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, Jaros E, Hersheson JS, Betts J, Klopstock T, Taylor RW, Turnbull DM (2006) High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 38:515–517 8. Gandhi S, Wood NW (2005) Molecular pathogenesis of Parkinson’s disease. Hum Mol Genet 14:2749–2755 9. Pavese N, Brooks DJ (2009) Imaging neurodegeneration in Parkinson’s disease. Biochim Biophys Acta 1792:722–729 10. Kahle PJ, Neumann M, Ozmen L, Haass C (2000) Physiology and pathophysiology of alpha-synuclein. Cell culture and transgenic animal models based on a Parkinson’s disease-associated protein. Ann NY Acad Sci 920:33–41 11. Cooper AA, Gitler AD, Cashikar A, Haynes CM, Hill KJ, Bhullar B, Liu K, Xu K, Strathearn KE, Liu F, Cao S, Caldwell KA, Caldwell GA, Marsischky G, Kolodner RD, Labaer J, Rochet JC, Bonini NM, Lindquist S (2006) Alpha-synuclein blocks ERGolgi traffic and Rab1 rescues neuron loss in Parkinson’s models. Science 313:324–328 12. Liang J, Clark-Dixon C, Wang S, Flower TR, Williams-Hart T, Zweig R, Robinson LC, Tatchell K, Witt SN (2008) Novel suppressors of alpha-synuclein toxicity identified using yeast. Hum Mol Genet 17:3784–3795 13. van Ham TJ, Thijssen KL, Breitling R, Hofstra RM, Plasterk RH, Nollen EA (2008) C. elegans model identifies genetic modifiers of alpha-synuclein inclusion formation during aging. PLoS Genet 4:e1000027 14. Yeger-Lotem E, Riva L, Su LJ, Gitler AD, Cashikar AG, King OD, Auluck PK, Geddie ML, Valastyan JS, Karger DR, Lindquist S, Fraenkel E (2009) Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity. Nat Genet 41:316–323 15. Waxman EA, Giasson BI (2009) Molecular mechanisms of alpha-synuclein neurodegeneration. Biochim Biophys Acta 1792: 616–624 16. Chandra S, Gallardo G, Fernandez-Chacon R, Schluter OM, Sudhof TC (2005) Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell 123:383–396 17. Thayanidhi N, Helm JR, Nycz DC, Bentley M, Liang Y, Hay JC (2010) Alpha-synuclein delays endoplasmic reticulum (ER)-to- Golgi transport in mammalian cells by antagonizing ER/Golgi SNAREs. Mol Biol Cell 21:1850–1863 18. Al-Wandi A, Ninkina N, Millership S, Williamson SJ, Jones PA, Buchman VL (2010) Absence of alpha-synuclein affects dopamine metabolism and synaptic markers in the striatum of aging mice. Neurobiol Aging 31:796–804 19. Cabin DE, Shimazu K, Murphy D, Cole NB, Gottschalk W, McIlwain KL, Orrison B, Chen A, Ellis CE, Paylor R, Lu B, Nussbaum RL (2002) Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein. J Neurosci 22:8797–8807 20. Gureviciene I, Gurevicius K, Tanila H (2007) Role of alphasynuclein in synaptic glutamate release. Neurobiol Dis 28:83–89 21. Liu S, Ninan I, Antonova I, Battaglia F, Trinchese F, Narasanna A, Kolodilov N, Dauer W, Hawkins RD, Arancio O (2004) Alpha-synuclein produces a long-lasting increase in neurotransmitter release. EMBO J 23:4506–4516 22. Abeliovich A, Schmitz Y, Farinas I, Choi-Lundberg D, Ho WH, Castillo PE, Shinsky N, Verdugo JM, Armanini M, Ryan A, Hynes M, Phillips H, Sulzer D, Rosenthal A (2000) Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25:239–252 23. Senior SL, Ninkina N, Deacon R, Bannerman D, Buchman VL, Cragg SJ, Wade-Martins R (2008) Increased striatal dopamine release and hyperdopaminergic-like behaviour in mice lacking both alpha-synuclein and gamma-synuclein. Eur J Neurosci 27:947–957 24. Chandra S, Fornai F, Kwon HB, Yazdani U, Atasoy D, Liu X, Hammer RE, Battaglia G, German DC, Castillo PE, Sudhof TC (2004) Double-knockout mice for alpha- and beta-synucleins: effect on synaptic functions. Proc Natl Acad Sci USA 101:14966–14971 25. Liu S, Fa M, Ninan I, Trinchese F, Dauer W, Arancio O (2007) Alpha-synuclein involvement in hippocampal synaptic plasticity: role of NO, cGMP, cGK and CaMKII. Eur J Neurosci 25:3583–3596 26. Ellis CE, Murphy EJ, Mitchell DC, Golovko MY, Scaglia F, Barcelo-Coblijn GC, Nussbaum RL (2005) Mitochondrial lipid abnormality and electron transport chain impairment in mice lacking alpha-synuclein. Mol Cell Biol 25:10190–10201 27. Edgar R, Domrachev M, Lash AE (2002) Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30:207–210 28. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang JY, Zhang J (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5:R80 29. Gautier L, Cope L, Bolstad BM, Irizarry RA (2004) affy— analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20:307–315 30. Smyth GK (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3. (Article3) 31. Smyth GK (2005) Limma: linear models for microarray data. In: Gentleman RC et al (eds) Bioinformatics and computational biology solutions using R and bioconductor. Springer, Berlin Heidelberg New York, pp 397–420 32. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408 33. Clelland JD, Thornalley PJ (1991) S-2-Hydroxyacylglutathionederivates: enzymatic preparation, purification and characterisation. J Chem Soc Perkin Trans I, 3009–3015 34. Ahmed N, Thornalley PJ, Luthen R, Haussinger D, Sebekova K, Schinzel R, Voelker W, Heidland A (2004) Processing of protein glycation, oxidation and nitrosation adducts in the liver and the effect of cirrhosis. J Hepatol 41:913–919 35. Ahmed N, Argirov OK, Minhas HS, Cordeiro CA, Thornalley PJ (2002) Assay of advanced glycation endproducts (AGEs): surveying AGEs by chromatographic assay with derivatization by 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate and application to Nepsilon-carboxymethyl-lysine- and Nepsilon-(1-carboxyethyl) lysine-modified albumin. Biochem J 364:1–14 36. Thornalley PJ (2003) Glyoxalase I–structure, function and a critical role in the enzymatic defence against glycation. Biochem Soc Trans 31:1343–1348 37. Basso DM, Beattie MS, Bresnahan JC (1995) A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 12:1–21 38. Kurz A, Wohr M, Walter M, Bonin M, Auburger G, Gispert S, Schwarting RK (2010) Alpha-synuclein deficiency affects brain Foxp1 expression and ultrasonic vocalization. Neuroscience 166:785–795 39. Hovatta I, Tennant RS, Helton R, Marr RA, Singer O, Redwine JM, Ellison JA, Schadt EE, Verma IM, Lockhart DJ, Barlow C (2005) Glyoxalase 1 and glutathione reductase 1 regulate anxiety in mice. Nature 438:662–666 40. Espartero J, Sanchez-Aguayo I, Pardo JM (1995) Molecular characterization of glyoxalase-I from a higher plant; upregulation by stress. Plant Mol Biol 29:1223–1233 41. Hambsch B, Chen BG, Brenndorfer J, Meyer M, Avrabos C, Maccarrone G, Liu RH, Eder M, Turck CW, Landgraf R (2010) Methylglyoxal-mediated anxiolysis involves increased protein modification and elevated expression of glyoxalase 1 in the brain. J Neurochem 113:1240–1251 42. Ueno H, Segawa T, Hasegawa T, Nakamuro K, Maeda H, Hiramatsu Y, Okada S, Sayato Y (1991) Subchronic oral toxicity of glyoxal via drinking water in rats. Fundam Appl Toxicol 16:763–772 43. Thornalley PJ (2008) Protein and nucleotide damage by glyoxal and methylglyoxal in physiological systems—role in ageing and disease. Drug Metabol Drug Interact 23:125–150 44. Morcos M, Du X, Pfisterer F, Hutter H, Sayed AA, Thornalley P, Ahmed N, Baynes J, Thorpe S, Kukudov G, Schlotterer A, Bozorgmehr F, El Baki RA, Stern D, Moehrlen F, Ibrahim Y, Oikonomou D, Hamann A, Becker C, Zeier M, Schwenger V, Miftari N, Humpert P, Hammes HP, Buechler M, Bierhaus A, Brownlee M, Nawroth PP (2008) Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans. Aging Cell 7:260–269 45. Schlotterer A, Kukudov G, Bozorgmehr F, Hutter H, Du X, Oikonomou D, Ibrahim Y, Pfisterer F, Rabbani N, Thornalley P, Sayed A, Fleming T, Humpert P, Schwenger V, Zeier M, Hamann A, Stern D, Brownlee M, Bierhaus A, Nawroth P, Morcos M (2009) C. elegans as model for the study of high glucose-mediated life span reduction. Diabetes 58:2450–2456 46. Delplanque J, Delpierre G, Opperdoes FR, Van Schaftingen E (2004) Tissue distribution and evolution of fructosamine 3-kinase and fructosamine 3-kinase-related protein. J Biol Chem 279: 46606–46613 47. Veiga da-Cunha M, Jacquemin P, Delpierre G, Godfraind C, Theate I, Vertommen D, Clotman F, Lemaigre F, Devuyst O, Van Schaftingen E (2006) Increased protein glycation in fructosamine 3-kinase-deficient mice. Biochem J 399:257–264 48. Dauer W, Kholodilov N, Vila M, Trillat AC, Goodchild R, Larsen KE, Staal R, Tieu K, Schmitz Y, Yuan CA, Rocha M, Jackson-Lewis V, Hersch S, Sulzer D, Przedborski S, Burke R, Hen R (2002) Resistance of alpha-synuclein null mice to the parkinsonian neurotoxin MPTP. Proc Natl Acad Sci USA 99:14524–14529 49. Fountaine TM, Venda LL, Warrick N, Christian HC, Brundin P, Channon KM, Wade-Martins R (2008) The effect of alpha-synuclein knockdown on MPP ? toxicity in models of human neurons. Eur J Neurosci 28:2459–2473 50. Klivenyi P, Siwek D, Gardian G, Yang L, Starkov A, Cleren C, Ferrante RJ, Kowall NW, Abeliovich A, Beal MF (2006) Mice lacking alpha-synuclein are resistant to mitochondrial toxins. Neurobiol Dis 21:541–548 51. Robertson DC, Schmidt O, Ninkina N, Jones PA, Sharkey J, Buchman VL (2004) Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of gamma-synuclein, alpha-synuclein and double alpha/ gamma-synuclein null mutant mice. J Neurochem 89:1126–1136 52. Schluter OM, Fornai F, Alessandri MG, Takamori S, Geppert M, Jahn R, Sudhof TC (2003) Role of alpha-synuclein in 1-methyl-4- phenyl-1, 2, 3, 6-tetrahydropyridine-induced parkinsonism in mice. Neuroscience 118:985–1002 53. Trostchansky A, Rubbo H (2007) Lipid nitration and formation of lipid-protein adducts: biological insights. Amino Acids 32: 517–522 54. Habig K, Walter M, Stappert H, Riess O, Bonin M (2009) Microarray expression analysis of human dopaminergic neuroblastoma cells after RNA interference of SNCA–a key player in the pathogenesis of Parkinson’s disease. Brain Res 1256:19–33 55. Palacino JJ, Sagi D, Goldberg MS, Krauss S, Motz C, Wacker M, Klose J, Shen J (2004) Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem 279:18614–18622 56. Chen F, Wollmer MA, Hoerndli F, Munch G, Kuhla B, Rogaev EI, Tsolaki M, Papassotiropoulos A, Gotz J (2004) Role for glyoxalase I in Alzheimer’s disease. Proc Natl Acad Sci USA 101:7687–7692 57. Munch G, Mayer S, Michaelis J, Hipkiss AR, Riederer P, Muller R, Neumann A, Schinzel R, Cunningham AM (1997) Influence of advanced glycation end-products and AGE-inhibitors on nucleation- dependent polymerization of beta-amyloid peptide. Biochim Biophys Acta 1360:17–29 58. Munch G, Thome J, Foley P, Schinzel R, Riederer P (1997) Advanced glycation endproducts in ageing and Alzheimer’s disease. Brain Res Brain Res Rev 23:134–143 59. Kallhoff V, Peethumnongsin E, Zheng H (2007) Lack of alphasynuclein increases amyloid plaque accumulation in a transgenic mouse model of Alzheimer’s disease. Mol Neurodegener 2:6 60. Krautwald M, Munch G (2010) Advanced glycation end products as biomarkers and gerontotoxins—a basis to explore methylglyoxal- lowering agents for Alzheimer’s disease? Exp Gerontol [Epub ahead of print] 61. Dias WB, Hart GW (2007) O-GlcNAc modification in diabetes and Alzheimer’s disease. Mol Biosyst 3:766–772 62. Leclerc E, Sturchler E, Vetter SW, Heizmann CW (2009) Crosstalk between calcium, amyloid beta and the receptor for advanced glycation endproducts in Alzheimer’s disease. Rev Neurosci 20:95–110 63. Eugene E, Depienne C, Baulac S, Baulac M, Fritschy JM, Le Guern E, Miles R, Poncer JC (2007) GABA(A) receptor gamma 2 subunit mutations linked to human epileptic syndromes differentially affect phasic and tonic inhibition. J Neurosci 27: 14108–14116 64. Thornalley PJ (2003) Protecting the genome: defence against nucleotide glycation and emerging role of glyoxalase I overexpression in multidrug resistance in cancer chemotherapy. Biochem Soc Trans 31:1372–1377 65. Villa T, Guthrie C (2005) The Isy1p component of the NineTeen complex interacts with the ATPase Prp16p to regulate the fidelity of pre-mRNA splicing. Genes Dev 19:1894–1904 66. Jang JH (2004) FIGC, a novel FGF-induced ubiquitin-protein ligase in gastric cancers. FEBS Lett 578:21–25 67. Budd ME, Campbell JL (1995) DNA polymerases required for repair of UV-induced damage in Saccharomyces cerevisiae. Mol Cell Biol 15:2173–2179 68. Syvaoja JE (1990) DNA polymerase epsilon: the latest member in the family of mammalian DNA polymerases. Bioessays 12: 533–536 69. Forch P, Puig O, Kedersha N, Martinez C, Granneman S, Seraphin B, Anderson P, Valcarcel J (2000) The apoptosis-promoting factor TIA-1 is a regulator of alternative pre-mRNA splicing. Mol Cell 6:1089–1098 70. Tian Q, Streuli M, Saito H, Schlossman SF, Anderson P (1991) A polyadenylate binding protein localized to the granules of cytolytic lymphocytes induces DNA fragmentation in target cells. Cell 67:629–639
URI:	http://wrap.warwick.ac.uk/id/eprint/34584