Artículo

Borsarelli, C.D.; Falomir-Lockhart, L.J.; Ostatná, V.; Fauerbach, J.A.; Hsiao, H.-H.; Urlaub, H.; Paleček, E.; Jares-Erijman, E.A.; Jovin, T.M. "Biophysical properties and cellular toxicity of covalent crosslinked oligomers of α-synuclein formed by photoinduced side-chain tyrosyl radicals" (2012) Free Radical Biology and Medicine. 53(4):1004-1015
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Abstract:

Alpha-synuclein (αS), a 140 amino acid presynaptic protein, is the major component of the fibrillar aggregates (Lewy bodies) observed in dopaminergic neurons of patients affected by Parkinson's disease. It is currently believed that noncovalent oligomeric forms of αS, arising as intermediates in its aggregation, may constitute the major neurotoxic species. However, attempts to isolate and characterize such oligomers in vitro, and even more so in living cells, have been hampered by their transient nature, low concentration, polymorphism, and inherent instability. In this work, we describe the preparation and characterization of low molecular weight covalently bound oligomeric species of αS obtained by crosslinking via tyrosyl radicals generated by blue-light photosensitization of the metal coordination complex ruthenium (II) tris-bipyridine in the presence of ammonium persulfate. Numerous analytical techniques were used to characterize the αS oligomers: biochemical (anion-exchange chromatography, SDS-PAGE, and Western blotting); spectroscopic (optical: UV/Vis absorption, steady state, dynamic fluorescence, and dynamic light scattering); mass spectrometry; and electrochemical. Light-controlled protein oligomerization was mediated by formation of Tyr-Tyr (dityrosine) dimers through -C-C- bonds acting as covalent bridges, with a predominant involvement of residue Y39. The diverse oligomeric species exhibited a direct effect on the in vitro aggregation behavior of wild-type monomeric αS, decreasing the total yield of amyloid fibrils in aggregation assays monitored by thioflavin T (ThioT) fluorescence and light scattering, and by atomic force microscopy (AFM). Compared to the unmodified monomer, the photoinduced covalent oligomeric species demonstrated increased toxic effects on differentiated neuronal-like SH-SY5Y cells. The results highlight the importance of protein modification induced by oxidative stress in the initial molecular events leading to Parkinsons disease. © 2012 Elsevier Inc. All rights reserved.

Registro:

Documento: Artículo
Título:Biophysical properties and cellular toxicity of covalent crosslinked oligomers of α-synuclein formed by photoinduced side-chain tyrosyl radicals
Autor:Borsarelli, C.D.; Falomir-Lockhart, L.J.; Ostatná, V.; Fauerbach, J.A.; Hsiao, H.-H.; Urlaub, H.; Paleček, E.; Jares-Erijman, E.A.; Jovin, T.M.
Filiación:Laboratorio de Cinética y Fotoquímica, Centro de Investigaciones y Transferencia de Santiago Del Estero (CITSE-CONICET), Universidad Nacional de Santiago Del Estero, RN 9 Km 1125, 4206 Santiago del Estero, Argentina
Laboratory of Cellular Dynamics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Goettingen, Germany
Institute of Biophysics, Academy of Sciences of the Czech Republic, V.v.i., Královopolská 135, 612 65 Brno, Czech Republic
Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Laboratory of Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Goettingen, Germany
Bioanalytics, Department of Clinical Chemistry, University Medical Center Goettingen, Robert Koch Strasse 40, 37075 Goettingen, Germany
Palabras clave:Neurodegeneration; Oxidative stress; Parkinson's disease; Photocrosslinking; Protein aggregation; Protein photooxidation; SH-SY5Y; alpha synuclein; oligomer; tris(2,2' bipyridine)ruthenium; tyrosine; anion exchange chromatography; article; biophysics; controlled study; cytotoxicity; fluorescence; human; human cell; light absorption; light scattering; oligomerization; photosensitization; polyacrylamide gel electrophoresis; priority journal; steady state; Western blotting; alpha-Synuclein; Ammonium Sulfate; Amyloid; Cell Line; Cell Survival; Cross-Linking Reagents; Free Radicals; Humans; Kinetics; Organometallic Compounds; Oxidative Stress; Photochemical Processes; Photosensitizing Agents; Protein Stability; Tyrosine
Año:2012
Volumen:53
Número:4
Página de inicio:1004
Página de fin:1015
DOI: http://dx.doi.org/10.1016/j.freeradbiomed.2012.06.035
Título revista:Free Radical Biology and Medicine
Título revista abreviado:Free Radic. Biol. Med.
ISSN:08915849
CODEN:FRBME
CAS:alpha synuclein, 154040-18-3; tris(2,2' bipyridine)ruthenium, 14323-06-9; tyrosine, 16870-43-2, 55520-40-6, 60-18-4; Ammonium Sulfate, 7783-20-2; Amyloid; Cross-Linking Reagents; Free Radicals; Organometallic Compounds; Photosensitizing Agents; Tyrosine, 55520-40-6; alpha-Synuclein; ammonium peroxydisulfate, 22QF6L357F; tris(2,2'-bipyridyl)ruthenium(II)
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08915849_v53_n4_p1004_Borsarelli

Referencias:

  • Lees, A.J., Hardy, J., Revesz, T., Parkinson's disease (2009) Lancet, 373, pp. 2055-2066
  • Shults, C.W., Lewy bodies (2006) Proc. Natl. Acad. Sci. USA, 103, pp. 1661-1668
  • Uversky, V.N., Eliezer, D., Biophysics of Parkinson's disease: Structure and aggregation of α-synuclein (2009) Curr. Protein Pept. Sci., 10, pp. 483-499
  • Maguire-Zeiss, K.A., α-Synuclein: A therapeutic target for Parkinson's disease? (2008) Pharmacol. Res., 58, pp. 271-280
  • Bisaglia, M., Mammi, S., Bubacco, L., Structural insights on physiological functions and pathological effects of α-synuclein (2009) FASEB J, 23, pp. 329-340
  • Wang, W., Perovic, I., Chittuluru, J., Kaganovich, A., Nguyen, L.T.T., Liao, J.L., Auclair, J.R., Hoang, Q.Q., A soluble α-synuclein construct forms a dynamic tetramer (2011) Proc. Natl. Acad. Sci. USA, 108, pp. 17797-17802
  • Bartels, T., Choi, J.G., Selkoe, D.J., α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation (2011) Nature, 477, pp. 107-U123
  • Spillantini, M.G., Schmidt, M.L., Lee, V.M.Y., Trojanowski, J.Q., Jakes, R., Goedert, M., α-synuclein in Lewy bodies (1997) Nature, 388, pp. 839-840
  • Martinez, A., Portero-Otin, M., Pamplona, R., Ferrer, I., Protein targets of oxidative damage in human neurodegenerative diseases with abnormal protein aggregates (2010) Brain Pathol., 20, pp. 281-297
  • Torres-Bugeau, C.M., Borsarelli, C.D., Minahk, C.J., Chehin, R.N., The key role of membranes in amyloid formation from a biophysical perspective (2011) Curr. Protein Pept. Sci., 12, pp. 166-180
  • Olteanu, A., Pielak, G.J., Peroxidative aggregation of α-synuclein requires tyrosines (2004) Protein Sci., 13, pp. 2852-2856
  • Souza, J.M., Giasson, B.I., Chen, Q.P., Lee, V.M.Y., Ischiropoulos, H., Dityrosine cross-linking promotes formation of stable α-synuclein polymers - Implication of nitrative and oxidative stress in the pathogenesis of neurodegenerative synucleinopathies (2000) J. Biol. Chem., 275, pp. 18344-18349
  • Pennathur, S., Jackson-Lewis, V., Przedborski, S., Heinecke, J.W., Mass spectrometric quantification of 3-nitrotyrosine, ortho-tyrosine, and o,o '-dityrosine in brain tissue of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridien-treated mice, a model of oxidative stress in Parkinson's disease (1999) J. Biol. Chem, 274, pp. 34621-34628
  • Krishnan, S., Chi, E.Y., Wood, S.J., Kendrick, B.S., Li, C., Garzon-Rodriguez, W., Wypych, J., Carpenter, J.F., Oxidative dimer formation is the critical rate-limiting step for Parkinson's disease α-synuclein fibrillogenesis (2003) Biochemistry, 42, pp. 829-837
  • Ruf, R.A.S., Lutz, E.A., Zigoneanu, I.G., Pielak, G.J., α-Synuclein conformation affects its tyrosine-dependent oxidative aggregation (2008) Biochemistry, 47, pp. 13604-13609
  • Morris, A.M., Watzky, M.A., Finke, R.G., Protein aggregation kinetics, mechanism, and curve-fitting: A review of the literature (2009) BBA Proteins Proteomics, 1794, pp. 375-397
  • Roberti, M.J., Morgan, M., Menendez, G., Pietrasanta, L.I., Jovin, T.M., Jares-Erijman, E.A., Quantum Dots As Ultrasensitive nanoactuators and sensors of amyloid aggregation in live cells (2009) J. Am. Chem. Soc., 131, pp. 8102-8107
  • Lee, C.C., Nayak, A., Sethuraman, A., Belfort, G., McRae, G.J., A three-stage kinetic model of amyloid fibrillation (2007) Biophys. J., 92, pp. 3448-3458
  • Fink, A.L., The aggregation and fibrillation of α-synuclein (2006) Acc. Chem. Res., 39, p. 628. , - 634
  • Bertoncini, C.W., Soledad Celej, M., Small molecule fluorescent probes for the detection of amyloid self-assembly in vitro and in vivo (2011) Curr. Protein Pept. Sci, 12, pp. 206-220
  • Levine, H., Quantification of beta-sheet amyloid fibril structures with thioflavin T (1999) Amyloid, Prions, Other Protein Aggregates, pp. 274-284
  • Thirunavukkuarasu, S., Jares-Erijman, E.A., Jovin, T.M., Multiparametric fluorescence detection of early stages in the amyloid protein aggregation of pyrene-labeled α-synuclein (2008) J. Mol. Biol., 378, pp. 1064-1073
  • Celej, M.S., Caarls, W., Demchenko, A.P., Jovin, T.M., A triple-emission fluorescent probe reveals distinctive amyloid fibrillar polymorphism of wild-type α-synuclein and its familial Parkinson's disease mutants (2009) Biochemistry, 48, pp. 7465-7472
  • Yushchenko, D.A., Fauerbach, J.A., Thirunavukkuarasu, S., Jares-Erijman, E.A., Jovin, T.M., Fluorescent ratiometric MFC probe sensitive to early stages of α-synuclein aggregation (2010) Am. Chem. Soc., 132, pp. 7860-7861
  • Fauerbach, J.A., Yushchenko, D.A., Shahmoradian, S.H., Chiu, W., Jovin, T.M., Jares-Erijman, E.A., Supramolecular non-amyloid intermediates in the early stages of α-synuclein aggregation (2012) Biophys. J., , In press
  • Andrekopoulos, C., Zhang, H., Joseph, J., Kalivendi, S., Kalyanaraman, B., Bicarbonate enhances α-synuclein oligomerization and nitration: Intermediacy of carbonate radical anion and nitrogen dioxide radical (2004) Biochem. J., 378, pp. 435-447
  • Zhang, H., Andrekopoulos, C., Joseph, J., Crow, J., Kalyanaraman, B., The carbonate radical anion-induced covalent aggregation of human copper, zinc superoxide dismutase, and α-synuclein: Intermediacy of tryptophan- and tyrosine-derived oxidation products (2004) Free Radic. Biol. Med., 36, pp. 1355-1365
  • Norris, E.H., Giasson, B.I., Ischiropoulos, H., Lee, V.M.Y., Effects of oxidative and nitrative challenges on α-synuclein fibrillogenesis involve distinct mechanisms of protein modifications (2003) J. Biol. Chem., 278, pp. 27230-27240
  • Fancy, D.A., Kodadek, T., Chemistry for the analysis of protein-protein interactions: Rapid and efficient cross-linking triggered by long wavelength light (1999) Proc. Natl. Acad. Sci. USA, 96, pp. 6020-6024
  • Fancy, D.A., Denison, C., Kim, K., Xie, Y.Q., Holdeman, T., Amini, F., Kodadek, T., Scope, limitations and mechanistic aspects of the photo-induced cross-linking of proteins by water-soluble metal complexes (2000) Chem. Biol., 7, pp. 697-708
  • Nickel, U., Chen, Y.H., Schneider, S., Silva, M.I., Burrows, H.D., Formosinho, S.J., Mechanism and kinetics of photocatalyzed oxidation of p-phenylenediamines by peroxydisulfate in the presence of tris-2,2'-bipyridilruthenium(II) (1994) J. Phys. Chem., 98, pp. 2883-2888
  • Herman, L., Ghosh, S., Defrancq, E., Mesmaeker, A.K.D., Ru(II) complexes and light: Molecular tools for biomolecules (2008) J. Phys. Org. Chem, 21, pp. 670-681
  • Gau, B.C., Chen, H., Zhang, Y., Gross, M.L., Sulfate radical anion as a new reagent for fast photochemical oxidation of proteins (2010) Anal. Chem., 82, pp. 7821-7827
  • Bosio, G., Criado, S., Massad, W., Nieto, F.J.R., Gonzalez, M.C., Garcia, N.A., Martire, D.O., Kinetics of the interaction of sulfate and hydrogen phosphate radicals with small peptides of glycine, alanine, tyrosine and tryptophan (2005) Photochem. Photobiol. Sci., 4, pp. 840-846
  • Pattison, D.I., Rahmanto, A.S., Davies, M.J., Photo-oxidation of proteins (2012) Photochem. Photobiol. Sci., 11, pp. 38-53
  • Giulivi, C., Traaseth, N.J., Davies, K.J.A., Tyrosine oxidation products: Analysis and biological relevance (2003) Amino Acids, 25, pp. 227-232
  • Malencik, D.A., Sprouse, J.F., Swanson, C.A., Anderson, S.R., Dityrosine: Preparation, isolation, and analysis (1996) Anal. Biochem., 242, pp. 202-213
  • Bitan, G., Lomakin, A., Teplow, D.B., Amyloid beta-protein oligomerization - Prenucleation interactions revealed by photo-induced cross-linking of unmodified proteins (2001) J. Biol. Chem., 276, pp. 35176-35184
  • Bitan, G., Teplow, D.B., Rapid photochemical cross-linking - A new tool for studies of metastable, amyloidogenic protein assemblies (2004) Acc. Chem. Res., 37, pp. 357-364
  • Huang, C.J., Ren, G.P., Zhou, H., Wang, C.C., A new method for purification of recombinant human α-synuclein in Escherichia coli (2005) Protein Expr. Purif., 42, pp. 173-177
  • Weinreb, P.H., Zhen, W.G., Poon, A.W., Conway, K.A., Lansbury, P.T., NACP a protein implicated in Alzheimer's disease and learning, is natively unfolded (1996) Biochemistry, 35, pp. 13709-13715
  • Celej, M.S., Jares-Erijman, E.A., Jovin, T.M., Fluorescent N-arylaminonaphthalene sulfonate probes for amyloid aggregation of α-synuclein (2008) Biophys. J., 94, pp. 4867-4879
  • Tanielian, C., Wolff, C., Esch, M., Singlet oxygen production in water: Aggregation and charge-transfer effects (1996) J. Phys. Chem., 100, pp. 6555-6560
  • Davies, M.J., Singlet oxygen-mediated damage to proteins and its consequences (2003) Biochem. Biophys. Res. Commun., 305, pp. 761-770
  • Bayse, G.S., Morrison, M., Michaels, A.W., Lactoperoxidase-catalized iodination of tyrosine peptides (1972) Biochim. Biophys. Acta, 284, pp. 30-33
  • Palecek, E., Ostatna, V., Masarik, M., Bertoncini, C.W., Jovin, T.M., Changes in interfacial properties of α-synuclein preceding its aggregation (2008) Analyst, 132, pp. 76-84
  • Doneux, T., Dorcak, V., Palecek, E., Influence of the interfacial peptide organization on the catalysis of hydrogen evolution (2010) Langmuir, 26, pp. 1347-1353
  • Vetterl, V., Hason, S., Electrochemical properties of nucleic acid components (2005) Electrochemistry of Nucleic Acids and Proteins. Towards Electrochemical Sensors for Genomics and Proteomics, pp. 18-73. , E. Palecek, F. Scheller, J. Wang, Elsevier Amsterdam
  • Palecek, E., Ostatna, V., Electroactivity of nonconjugated proteins and peptides. Towards electroanalysis of all proteins (2007) Electroanalysis, 19, pp. 2383-2403
  • Zivanovic, M., Aleksic, M., Ostatna, V., Doneux, T., Palecek, E., Polylysine-catalyzed hydrogen evolution at mercury electrodes (2010) Electroanalysis, 22, pp. 2064-2070
  • Wood, S.J., Wypych, J., Steavenson, S., Louis, J.C., Citron, M., Biere, A.L., α-Synuclein fibrillogenesis is nucleation-dependent - Implications for the pathogenesis of Parkinson's disease (1999) J. Biol. Chem., 274, pp. 19509-19512
  • Cookson, M.R., The biochemistry of Parkinson's disease (2005) Annu. Rev. Biochem., 74, pp. 29-52
  • Winner, B., Jappelli, R., Maji, S.K., Desplats, P.A., Boyer, L., Aigner, S., Hetzer, C., Riek, R., In vivo demonstration that α-synuclein oligomers are toxic (2011) Proc. Natl. Acad. Sci. USA, 108, pp. 4194-4199
  • Jang, A., Lee, H.J., Suk, J.E., Jung, J.W., Kim, K.P., Lee, S.J., Non-classical exocytosis of α-synuclein is sensitive to folding states and promoted under stress conditions (2010) J. Neurochem., 113, pp. 1263-1274
  • Park, J.Y., Kim, K.S., Lee, S.B., Ryu, J.S., Chung, K.C., Choo, Y.K., Jou, I., Park, S.M., On the mechanism of internalization of α-synuclein into microglia: Roles of ganglioside GM1 and lipid raft (2009) J. Neurochem., 110, pp. 400-411
  • Hansen, C., Angot, E., Bergstrom, A.L., Steiner, J.A., Pieri, L., Paul, G., Outeiro, T.F., Brundin, P., α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells (2011) J. Clin. Invest., 121, pp. 715-725
  • Cushman, M., Johnson, B.S., King, O.D., Gitler, A.D., Shorter, J., Prion-like disorders: Blurring the divide between transmissibility and infectivity (2010) J. Cell Sci., 123, pp. 1191-1201
  • Alvarez-Erviti, L., Couch, Y., Richardson, J., Cooper, J.M., Wood, M.J.A., Alpha-synuclein release by neurons activates the inflammatory response in a microglial cell line (2011) Neurosci. Res., 69, pp. 337-342
  • Danzer, K.M., Krebs, S.K., Wolff, M., Birk, G., Hengerer, B., Seeding induced by α-synuclein oligomers provides evidence for spreading of α-synuclein pathology (2009) J. Neurochem., 111, pp. 192-203

Citas:

---------- APA ----------
Borsarelli, C.D., Falomir-Lockhart, L.J., Ostatná, V., Fauerbach, J.A., Hsiao, H.-H., Urlaub, H., Paleček, E.,..., Jovin, T.M. (2012) . Biophysical properties and cellular toxicity of covalent crosslinked oligomers of α-synuclein formed by photoinduced side-chain tyrosyl radicals. Free Radical Biology and Medicine, 53(4), 1004-1015.
http://dx.doi.org/10.1016/j.freeradbiomed.2012.06.035
---------- CHICAGO ----------
Borsarelli, C.D., Falomir-Lockhart, L.J., Ostatná, V., Fauerbach, J.A., Hsiao, H.-H., Urlaub, H., et al. "Biophysical properties and cellular toxicity of covalent crosslinked oligomers of α-synuclein formed by photoinduced side-chain tyrosyl radicals" . Free Radical Biology and Medicine 53, no. 4 (2012) : 1004-1015.
http://dx.doi.org/10.1016/j.freeradbiomed.2012.06.035
---------- MLA ----------
Borsarelli, C.D., Falomir-Lockhart, L.J., Ostatná, V., Fauerbach, J.A., Hsiao, H.-H., Urlaub, H., et al. "Biophysical properties and cellular toxicity of covalent crosslinked oligomers of α-synuclein formed by photoinduced side-chain tyrosyl radicals" . Free Radical Biology and Medicine, vol. 53, no. 4, 2012, pp. 1004-1015.
http://dx.doi.org/10.1016/j.freeradbiomed.2012.06.035
---------- VANCOUVER ----------
Borsarelli, C.D., Falomir-Lockhart, L.J., Ostatná, V., Fauerbach, J.A., Hsiao, H.-H., Urlaub, H., et al. Biophysical properties and cellular toxicity of covalent crosslinked oligomers of α-synuclein formed by photoinduced side-chain tyrosyl radicals. Free Radic. Biol. Med. 2012;53(4):1004-1015.
http://dx.doi.org/10.1016/j.freeradbiomed.2012.06.035