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Succinobucol, a Lipid-Lowering Drug, Protects Against 3-Nitropropionic Acid-Induced Mitochondrial Dysfunction and Oxidative Stress in SH-SY5Y Cells via Upregulation of Glutathione Levels and Glutamate Cysteine Ligase Activity

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Abstract

Succinobucol (succinyl ester of probucol) is a lipid-lowering compound with anti-inflammatory and antioxidant properties. Recent experimental evidence has highlighted the potential neuroprotective effects of succinobucol. In the present study, cultured neuroblastoma (SH-SY5Y) cells were used to investigate mechanisms mediating the potential protective effect of succinobucol against mitochondrial metabolic impairment and oxidative stress induced by 3-nitropropionic acid (3-NP), a succinate dehydrogenase inhibitor that has been used in experimental models of the Huntington disease (HD). 3-NP decreased cellular viability after 24 h of incubation. This decline in cellular viability was preceded by (i) reduced mitochondrial complex II activity, (ii) increased reactive species generation, (iii) decreased mitochondrial membrane potential (ΔΨm), and (iv) diminished glutathione (GSH) levels. Succinobucol pretreatment (6 days) significantly prevented 3-NP-induced loss of cellular viability, generation of reactive oxygen species, and decrease of ΔΨm. However, succinobucol pretreatment did not protect against 3-NP-induced inhibition of mitochondrial complex II activity, pointing to the mitigation of secondary events resultant from mitochondrial complex II inhibition. Succinobucol pretreatment (6 days) significantly increased (50 %) the levels of GSH in SH-SY5Y cells, and this event was paralleled by significant increases in glutamate cysteine ligase messenger RNA (mRNA) expression and activity (GCL; the first enzyme in the GSH biosynthesis). The present findings are the first to show that succinobucol increases GSH levels via upregulation of GCL activity (possibly through the activation of the nuclear (erythroid-derived 2)-related factor (Nrf2)/antioxidant response element (ARE) pathway), displaying protective effects against mitochondrial dysfunction-derived oxidative stress.

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References

  1. Roos RA (2010) Huntington’s disease: a clinical review. Orphanet J Rare Dis 5:40. doi:10.1186/1750-1172-5-40

    Article  PubMed Central  PubMed  Google Scholar 

  2. Southwell AL, Patterson PH (2011) Gene therapy in mouse models of huntington disease. Neuroscientist 17:153–162. doi:10.1177/1073858410386236

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  3. Reiner A, Albin RL, Anderson KD, D’Amato CJ, Penney JB, Young AB (1988) Differential loss of striatal projection neurons in Huntington disease. Proc Natl Acad Sci U S A 85:5733–5737

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Vonsattel JP, DiFiglia M (1998) Huntington disease. J Neuropathol Exp Neurol 57:369–384

    Article  PubMed  CAS  Google Scholar 

  5. Heinsen H, Strik M, Bauer M, Luther K, Ulmar G, Gangnus D, Jungkunz G, Eisenmenger W, Gotz M (1994) Cortical and striatal neurone number in Huntington’s disease. Acta Neuropathol 88:320–333

    Article  PubMed  CAS  Google Scholar 

  6. Mann DM, Oliver R, Snowden JS (1993) The topographic distribution of brain atrophy in Huntington’s disease and progressive supranuclear palsy. Acta Neuropathol 85:553–559

    PubMed  CAS  Google Scholar 

  7. Damiano M, Galvan L, Deglon N, Brouillet E (2010) Mitochondria in Huntington’s disease. Biochim Biophys Acta 1802:52–61. doi:10.1016/j.bbadis.2009.07.012

    Article  PubMed  CAS  Google Scholar 

  8. Mochel F, Haller RG (2011) Energy deficit in Huntington disease: why it matters. J Clin Invest 121:493–499. doi:10.1172/JCI45691

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  9. Oliveira JM (2010) Nature and cause of mitochondrial dysfunction in Huntington’s disease: focusing on huntingtin and the striatum. J Neurochem 114:1–12. doi:10.1111/j.1471-4159.2010.06741.x

    PubMed  CAS  Google Scholar 

  10. Ramaswamy S, McBride JL, Kordower JH (2007) Animal models of Huntington’s disease. ILAR J 48:356–373

    Article  PubMed  CAS  Google Scholar 

  11. Beal MF, Brouillet E, Jenkins BG, Ferrante RJ, Kowall NW, Miller JM, Storey E, Srivastava R, Rosen BR, Hyman BT (1993) Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J Neurosci 13:4181–4192

    PubMed  CAS  Google Scholar 

  12. Tunez I, Tasset I, Perez-De La Cruz V, Santamaria A (2010) 3-Nitropropionic acid as a tool to study the mechanisms involved in Huntington’s disease: past, present and future. Molecules 15:878–916. doi:10.3390/molecules15020878

    Article  PubMed  CAS  Google Scholar 

  13. Kumar P, Kumar A (2009) Possible role of sertraline against 3-nitropropionic acid induced behavioral, oxidative stress and mitochondrial dysfunctions in rat brain. Prog Neuropsychopharmacol Biol Psychiatry 33:100–108. doi:10.1016/j.pnpbp.2008.10.013

    Article  PubMed  CAS  Google Scholar 

  14. Bizat N, Hermel JM, Humbert S, Jacquard C, Creminon C, Escartin C, Saudou F, Krajewski S, Hantraye P, Brouillet E (2003) In vivo calpain/caspase cross-talk during 3-nitropropionic acid-induced striatal degeneration: implication of a calpain-mediated cleavage of active caspase-3. J Biol Chem 278:43245–43253. doi:10.1074/jbc.M305057200

    Article  PubMed  CAS  Google Scholar 

  15. Kumar P, Kalonia H, Kumar A (2010) Huntington’s disease: pathogenesis to animal models. Pharmacol Rep 62:1–14

    Article  PubMed  CAS  Google Scholar 

  16. Lee WT, Itoh T, Pleasure D (2002) Acute and chronic alterations in calcium homeostasis in 3-nitropropionic acid-treated human NT2-N neurons. Neuroscience 113:699–708

    Article  PubMed  CAS  Google Scholar 

  17. Lee WT, Yin HS, Shen YZ (2002) The mechanisms of neuronal death produced by mitochondrial toxin 3-nitropropionic acid: the roles of N-methyl-D-aspartate glutamate receptors and mitochondrial calcium overload. Neuroscience 112:707–716

    Article  PubMed  CAS  Google Scholar 

  18. Montilla P, Espejo I, Munoz MC, Bujalance I, Munoz-Castaneda JR, Tunez I (2004) Effect of red wine on oxidative stress and hypercholesterolemia induced by feeding a high-cholesterol diet in rat. J Physiol Biochem 60:259–264

    Article  PubMed  CAS  Google Scholar 

  19. Perez-De La Cruz V, Gonzalez-Cortes C, Pedraza-Chaverri J, Maldonado PD, Andres-Martinez L, Santamaria A (2006) Protective effect of S-allylcysteine on 3-nitropropionic acid-induced lipid peroxidation and mitochondrial dysfunction in rat brain synaptosomes. Brain Res Bull 68:379–383. doi:10.1016/j.brainresbull.2005.09.013

    Article  PubMed  CAS  Google Scholar 

  20. Perez-De La Cruz V, Elinos-Calderon D, Carrillo-Mora P, Silva-Adaya D, Konigsberg M, Moran J, Ali SF, Chanez-Cardenas ME, Perez-De La Cruz G, Santamaria A (2010) Time-course correlation of early toxic events in three models of striatal damage: modulation by proteases inhibition. Neurochem Int 56:834–842. doi:10.1016/j.neuint.2010.03.008

    Article  PubMed  CAS  Google Scholar 

  21. Elinos-Calderon D, Robledo-Arratia Y, Perez-De La Cruz V, Maldonado PD, Galvan-Arzate S, Pedraza-Chaverri J, Santamaria A (2010) Antioxidant strategy to rescue synaptosomes from oxidative damage and energy failure in neurotoxic models in rats: protective role of S-allylcysteine. J Neural Transm 117:35–44. doi:10.1007/s00702-009-0299-5

    Article  PubMed  CAS  Google Scholar 

  22. Ayala-Pena S (2013) Role of oxidative DNA damage in mitochondrial dysfunction and Huntington’s disease pathogenesis. Free Radic Biol Med 62:102–110. doi:10.1016/j.freeradbiomed.2013.04.017

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Chaturvedi RK, Flint Beal M (2013) Mitochondrial diseases of the brain. Free Radic Biol Med 63:1–29. doi:10.1016/j.freeradbiomed.2013.03.018

    Article  PubMed  CAS  Google Scholar 

  24. Liu J, Wang LN (2014) Mitochondrial enhancement for neurodegenerative movement disorders: a systematic review of trials involving creatine, coenzyme Q10, idebenone and mitoquinone. CNS Drugs 28:63–68. doi:10.1007/s40263-013-0124-4

    Article  PubMed  CAS  Google Scholar 

  25. Cusin C, Franco FB, Fernandez-Robles C, DuBois CM, Welch CA (2013) Rapid improvement of depression and psychotic symptoms in Huntington’s disease: a retrospective chart review of seven patients treated with electroconvulsive therapy. Gen Hosp Psychiatry 35(678):e3–e5. doi:10.1016/j.genhosppsych.2013.01.015

    PubMed  Google Scholar 

  26. Gallina P, Paganini M, Lombardini L, Giordano G, Mascalchi M, Romoli AM, Ghelli E, Porfirio B, Vannelli GB, Di Lorenzo N (2011) Progress in restorative neurosurgery: human fetal striatal transplantation in Huntington’s disease. Review. J Neurosurg Sci 55:371–381

    PubMed  CAS  Google Scholar 

  27. Colle D, Santos DB, Moreira EL, Hartwig JM, dos Santos AA, Zimmermann LT, Hort MA, Farina M (2013) Probucol increases striatal glutathione peroxidase activity and protects against 3-nitropropionic acid-induced pro-oxidative damage in rats. PLoS One 8:e67658. doi:10.1371/journal.pone.0067658

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Colle D, Hartwig JM, Soares FA, Farina M (2012) Probucol modulates oxidative stress and excitotoxicity in Huntington’s disease models in vitro. Brain Res Bull 87:397–405. doi:10.1016/j.brainresbull.2012.01.003

    Article  PubMed  CAS  Google Scholar 

  29. Colle D, Santos DB, Hartwig JM, Godoi M, Braga AL, Farina M (2013) Succinobucol versus probucol: higher efficiency of succinobucol in mitigating 3-NP-induced brain mitochondrial dysfunction and oxidative stress in vitro. Mitochondrion. doi:10.1016/j.mito.2013.01.005

    PubMed  Google Scholar 

  30. Yamashita S, Matsuzawa Y (2009) Where are we with probucol: a new life for an old drug? Atherosclerosis 207:16–23. doi:10.1016/j.atherosclerosis.2009.04.002

    Article  PubMed  CAS  Google Scholar 

  31. Buckley MM, Goa KL, Price AH, Brogden RN (1989) Probucol. A reappraisal of its pharmacological properties and therapeutic use in hypercholesterolaemia. Drugs 37:761–800

    Article  PubMed  CAS  Google Scholar 

  32. Yamashita S, Hbujo H, Arai H, Harada-Shiba M, Matsui S, Fukushima M, Saito Y, Kita T, Matsuzawa Y (2008) Long-term probucol treatment prevents secondary cardiovascular events: a cohort study of patients with heterozygous familial hypercholesterolemia in Japan. J Atheroscler Thromb 15:292–303

    Article  PubMed  Google Scholar 

  33. Browne KF, Prystowsky EN, Heger JJ, Cerimele BJ, Fineberg N, Zipes DP (1984) Prolongation of the QT interval induced by probucol: demonstration of a method for determining QT interval change induced by a drug. Am Heart J 107:680–684

    Article  PubMed  CAS  Google Scholar 

  34. Tardif JC, Gregoire J, L’Allier PL (2002) Prevention of restenosis with antioxidants: mechanisms and implications. Am J Cardiovasc Drugs 2:323–334

    Article  PubMed  CAS  Google Scholar 

  35. Stocker R (2009) Molecular mechanisms underlying the antiatherosclerotic and antidiabetic effects of probucol, succinobucol, and other probucol analogues. Curr Opin Lipidol 20:227–235. doi:10.1097/MOL.0b013e32832aee68

    Article  PubMed  CAS  Google Scholar 

  36. Kunsch C, Luchoomun J, Grey JY, Olliff LK, Saint LB, Arrendale RF, Wasserman MA, Saxena U, Medford RM (2004) Selective inhibition of endothelial and monocyte redox-sensitive genes by AGI-1067: a novel antioxidant and anti-inflammatory agent. J Pharmacol Exp Ther 308:820–829. doi:10.1124/jpet.103.059733

    Article  PubMed  CAS  Google Scholar 

  37. Midwinter RG, Maghzal GJ, Dennis JM, Wu BJ, Cai H, Kapralov AA, Belikova NA, Tyurina YY, Dong LF, Khachigian L, Neuzil J, Kagan VE, Stocker R (2012) Succinobucol induces apoptosis in vascular smooth muscle cells. Free Radic Biol Med 52:871–879. doi:10.1016/j.freeradbiomed.2011.11.029

    Article  PubMed  CAS  Google Scholar 

  38. Weingarten DM (2004) Process of preparing esters and ethers of probucol and derivatives thereof. Patent WO2004062622

  39. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  PubMed  CAS  Google Scholar 

  40. Petegnief V, Friguls B, Sanfeliu C, Sunol C, Planas AM (2003) Transforming growth factor-alpha attenuates N-methyl-D-aspartic acid toxicity in cortical cultures by preventing protein synthesis inhibition through an Erk1/2-dependent mechanism. J Biol Chem 278:29552–29559. doi:10.1074/jbc.M300661200

    Article  PubMed  CAS  Google Scholar 

  41. Ali SF, LeBel CP, Bondy SC (1992) Reactive oxygen species formation as a biomarker of methylmercury and trimethyltin neurotoxicity. Neurotoxicology 13:637–648

    PubMed  CAS  Google Scholar 

  42. Fischer JC, Ruitenbeek W, Berden JA, Trijbels JM, Veerkamp JH, Stadhouders AM, Sengers RC, Janssen AJ (1985) Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin Chim Acta 153:23–36

    Article  PubMed  CAS  Google Scholar 

  43. Reers M, Smith TW, Chen LB (1991) J-aggregate formation of a carbocyanine as a quantitative fluorescent indicator of membrane potential. Biochemistry 30:4480–4486

    Article  PubMed  CAS  Google Scholar 

  44. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    Article  PubMed  CAS  Google Scholar 

  45. Cooper AJL (1998) Role of astrocytes in maintaining cerebral glutathione homeostasis and in protecting the brain against xenobiotics and oxidative stress. In: Francis Ta (ed) The role of glutathione in the nervous system, Washington, pp 91–115

  46. Wendel A (1981) Glutathione peroxidase. Methods Enzymol 77:325–333

    Article  PubMed  CAS  Google Scholar 

  47. Seelig GF, Meister A (1985) Glutathione biosynthesis; gamma-glutamylcysteine synthetase from rat kidney. Methods Enzymol 113:379–390

    Article  PubMed  CAS  Google Scholar 

  48. Engel D, Zomkowski AD, Lieberknecht V, Rodrigues AL, Gabilan NH (2013) Chronic administration of duloxetine and mirtazapine downregulates proapoptotic proteins and upregulates neurotrophin gene expression in the hippocampus and cerebral cortex of mice. J Psychiatr Res 47:802–808. doi:10.1016/j.jpsychires.2013.02.013

    Article  PubMed  Google Scholar 

  49. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  50. Liot G, Bossy B, Lubitz S, Kushnareva Y, Sejbuk N, Bossy-Wetzel E (2009) Complex II inhibition by 3-NP causes mitochondrial fragmentation and neuronal cell death via an NMDA- and ROS-dependent pathway. Cell Death Differ 16:899–909. doi:10.1038/cdd.2009.22

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  51. Lubos E, Loscalzo J, Handy DE (2011) Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 15:1957–1997. doi:10.1089/ars.2010.3586

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  52. Dringen R, Hirrlinger J (2003) Glutathione pathways in the brain. Biol Chem 384:505–516. doi:10.1515/BC.2003.059

    Article  PubMed  CAS  Google Scholar 

  53. Farina M, Campos F, Vendrell I, Berenguer J, Barzi M, Pons S, Sunol C (2009) Probucol increases glutathione peroxidase-1 activity and displays long-lasting protection against methylmercury toxicity in cerebellar granule cells. Toxicol Sci 112:416–426. doi:10.1093/toxsci/kfp219

    Article  PubMed  CAS  Google Scholar 

  54. Lu SC (2013) Glutathione synthesis. Biochim Biophys Acta 1830:3143–3153. doi:10.1016/j.bbagen.2012.09.008

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  55. Satoh T, McKercher SR, Lipton SA (2013) Nrf2/ARE-mediated antioxidant actions of pro-electrophilic drugs. Free Radic Biol Med 65:645–657. doi:10.1016/j.freeradbiomed.2013.07.022

    Article  PubMed  CAS  Google Scholar 

  56. Jung KA, Kwak MK (2010) The Nrf2 system as a potential target for the development of indirect antioxidants. Molecules 15:7266–7291. doi:10.3390/molecules15107266

    Article  PubMed  CAS  Google Scholar 

  57. Cao Z, Hallur S, Qiu HZ, Peng X, Li Y (2004) Induction of endogenous glutathione by the chemoprotective agent, 3H-1,2-dithiole-3-thione, in human neuroblastoma SH-SY5Y cells affords protection against peroxynitrite-induced cytotoxicity. Biochem Biophys Res Commun 316:1043–1049. doi:10.1016/j.bbrc.2004.02.156

    Article  PubMed  CAS  Google Scholar 

  58. Muldrew KM, Franks AM (2009) Succinobucol: review of the metabolic, antiplatelet and cardiovascular effects. Expert Opin Investig Drugs 18:531–539. doi:10.1517/13543780902849244

    Article  PubMed  CAS  Google Scholar 

  59. Santos DB, Peres KC, Ribeiro RP, Colle D, dos Santos AA, Moreira EL, Souza DO, Figueiredo CP, Farina M (2012) Probucol, a lipid-lowering drug, prevents cognitive and hippocampal synaptic impairments induced by amyloid beta peptide in mice. Exp Neurol 233:767–775. doi:10.1016/j.expneurol.2011.11.036

    Article  PubMed  CAS  Google Scholar 

  60. Ribeiro RP, Moreira EL, Santos DB, Colle D, Dos Santos AA, Peres KC, Figueiredo CP, Farina M (2013) Probucol affords neuroprotection in a 6-OHDA mouse model of Parkinson’s disease. Neurochem Res. doi:10.1007/s11064-012-0965-0

    PubMed  Google Scholar 

  61. Solesio ME, Saez-Atienzar S, Jordan J, Galindo MF (2013) 3-Nitropropionic acid induces autophagy by forming mitochondrial permeability transition pores rather than activating the mitochondrial fission pathway. Br J Pharmacol 168:63–75. doi:10.1111/j.1476-5381.2012.01994.x

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  62. Uo T, Veenstra TD, Morrison RS (2009) Histone deacetylase inhibitors prevent p53-dependent and p53-independent Bax-mediated neuronal apoptosis through two distinct mechanisms. J Neurosci 29:2824–2832. doi:10.1523/JNEUROSCI. 6186-08.2009

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  63. Tabrizi SJ, Cleeter MW, Xuereb J, Taanman JW, Cooper JM, Schapira AH (1999) Biochemical abnormalities and excitotoxicity in Huntington’s disease brain. Ann Neurol 45:25–32

    Article  PubMed  CAS  Google Scholar 

  64. Procaccio V, Bris C, Chao de la Barca JM, Oca F, Chevrollier A, Amati-Bonneau P, Bonneau D, Reynier P (2014) Perspectives of drug-based neuroprotection targeting mitochondria. Rev Neurol (Paris) 170:390–400. doi:10.1016/j.neurol.2014.03.005

    Article  CAS  Google Scholar 

  65. Lambert AJ, Brand MD (2004) Superoxide production by NADH:ubiquinone oxidoreductase (complex I) depends on the pH gradient across the mitochondrial inner membrane. Biochem J 382:511–517. doi:10.1042/BJ20040485

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  66. Adam-Vizi V (2005) Production of reactive oxygen species in brain mitochondria: contribution by electron transport chain and non-electron transport chain sources. Antioxid Redox Signal 7:1140–1149. doi:10.1089/ars.2005.7.1140

    Article  PubMed  CAS  Google Scholar 

  67. Witting PK, Wu BJ, Raftery M, Southwell-Keely P, Stocker R (2005) Probucol protects against hypochlorite-induced endothelial dysfunction: identification of a novel pathway of probucol oxidation to a biologically active intermediate. J Biol Chem 280:15612–15618. doi:10.1074/jbc.M414256200

    Article  PubMed  CAS  Google Scholar 

  68. Franklin CC, Backos DS, Mohar I, White CC, Forman HJ, Kavanagh TJ (2009) Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate cysteine ligase. Mol Aspects Med 30:86–98. doi:10.1016/j.mam.2008.08.009

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  69. Forman HJ, Zhang H, Rinna A (2009) Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med 30:1–12. doi:10.1016/j.mam.2008.08.006

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  70. Lu SC (2009) Regulation of glutathione synthesis. Mol Aspects Med 30:42–59. doi:10.1016/j.mam.2008.05.005

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  71. Liu RM, Gao L, Choi J, Forman HJ (1998) Gamma-glutamylcysteine synthetase: mRNA stabilization and independent subunit transcription by 4-hydroxy-2-nonenal. Am J Physiol 275:L861–L869

    PubMed  CAS  Google Scholar 

  72. McMahon M, Itoh K, Yamamoto M, Hayes JD (2003) Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression. J Biol Chem 278:21592–21600. doi:10.1074/jbc.M300931200

    Article  PubMed  CAS  Google Scholar 

  73. Anderson ME (1998) Glutathione: an overview of biosynthesis and modulation. Chem Biol Interact 111–112:1–14

    Article  PubMed  Google Scholar 

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Acknowledgments

The financial supports by (i) the FINEP Research Grant “Rede Instituto Brasileiro de Neurociência (IBN-Net)” no. 01.06.0842-00, (ii) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), (iii) Fundação de Apoio à Pesquisa do Estado de Santa Catarina (FAPESC-TO 1346/2010-3), (iv) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and (v) INCT-CNPq-Excitotoxicity and Neuroprotection are gratefully acknowledged. M.F. is a recipient of the CNPq fellowship.

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  1. Departamento de Bioquímica, Centro de Ciências Biológicas, Campus Universitário, Trindade, Bloco C, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, 88040-900, Brazil

    Dirleise Colle, Danúbia Bonfanti Santos, Juliana Montagna Hartwig, Daiane Fátima Engel, Andreza Fabro de Bem & Marcelo Farina

  2. Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil

    Antonio L. Braga

  3. Escola de Química e Alimentos, Universidade Federal do Rio Grande, Campus Santo Antônio da Patrulha, Rio Grande, RS, Brazil

    Marcelo Godoi

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Figure S1

Effects of succinobucol treatment on Nrf-2 nuclear translocation in SH-SY5Y cells. Cells were treated with succinobucol (3 μM) or vehicle (DMSO 0.05 %) for 6 hours or 6 days. Tert-butylhydroquinone (TBQ) (10 μM) for 6 hours was used as a positive control. The nuclear translocation of Nrf-2 was evaluated by immunofluorescence (green). Nuclear counterstaining was made with Hoechst 33258 (blue). A representative merge of the two fluorescence images (green and blue) is shown (Magnification 100 ×). (GIF 126 kb)

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Colle, D., Santos, D.B., Hartwig, J.M. et al. Succinobucol, a Lipid-Lowering Drug, Protects Against 3-Nitropropionic Acid-Induced Mitochondrial Dysfunction and Oxidative Stress in SH-SY5Y Cells via Upregulation of Glutathione Levels and Glutamate Cysteine Ligase Activity. Mol Neurobiol 53, 1280–1295 (2016). https://doi.org/10.1007/s12035-014-9086-x

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