Epigallocatechin-3-Gallate Protects and Prevents Paraquat-Induced Oxidative Stress and Neurodegeneration in Knockdown dj-1-β Drosophila melanogaster

ORIGINAL ARTICLE

Abstract

Epigallocatechin-3-gallate (EGCG) is a polyhydroxyphenol constituent of green tea (e.g., Camellia sinensis) with known antioxidant properties. Due to these properties, others have proposed it as a potential therapeutic agent for the treatment of Parkinson’s disease (PD). Previously, we demonstrated that EGCG prolonged the lifespan and locomotor activity in wild-type Canton-S flies exposed to the neurotoxicant paraquat (PQ), suggesting neuroprotective properties. Both gene mutations and environmental neurotoxicants (e.g., PQ) are factors involved in the development of PD. Thus, the first aim of this study was to create a suitable animal model of PD, which encompasses both of these factors. To create the model, we knocked down dj-1-β function specifically in the dopaminergic neurons to generate TH > dj-1-β-RNAi/+ Drosophila melanogaster flies. Next, we induced neurotoxicity in the transgenic flies with PQ. The second aim of this study was to validate the model by comparing the effects of vehicle, EGCG, and chemicals with known antioxidant and neuroprotective properties in vivo (e.g., propyl gallate and minocycline) on life-span, locomotor activity, lipid peroxidation, and neurodegeneration. The EGCG treatment provided protection and prevention from the PQ-induced reduction in the life-span and locomotor activity and from the PQ-induced increase in lipid peroxidation and neurodegeneration. These effects were augmented in the EGCG-treated flies when compared to the flies treated with either PG or MC. Altogether, these results suggest that the transgenic TH > dj-1-β-RNAi/+ flies treated with PQ serve as a suitable PD model for screening of potential therapeutic agents.

Keywords

Minocycline Parkinson’s disease DJ-1 Drosophila Epigallocatechin-3-gallate Propyl gallate 

Supplementary material

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References

  1. Ariga H, Takahashi-Niki K, Kato I, Maita H, Niki T, Iguchi-Ariga SM (2013) Neuroprotective function of DJ-1 in Parkinson’s disease. Oxidative Med Cell Longev 2013:683920CrossRefGoogle Scholar
  2. Blesa J, Trigo-Damas I, Quiroga-Varela A, Jackson-Lewis VR (2015) Oxidative stress and Parkinson’s disease. Front Neuroanat 9:91PubMedPubMedCentralGoogle Scholar
  3. Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P, Joosse M, van Dongen JW, Vanacore N, van Swieten JC, Brice A, Meco G, van Duijn CM, Oostra BA, Heutink P (2003) Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299:256–259CrossRefPubMedGoogle Scholar
  4. Bonilla E, Medina-Leendertz S, Villalobos V, Molero L, Bohórquez A (2006) Paraquat-induced oxidative stress in Drosophila melanogaster: effects of melatonin, glutathione, serotonin, minocycline, lipoic acid and ascorbic acid. Neurochem Res 31(12):1425–1432CrossRefPubMedGoogle Scholar
  5. Bonilla-Ramirez L, Jimenez-Del-Rio M, Velez-Pardo C (2011) Acute and chronic metal exposure impairs locomotion activity in Drosophila melanogaster: a model to study parkinsonism. Biometals 24(6):1045–1057CrossRefPubMedGoogle Scholar
  6. Bonilla-Ramirez L, Jimenez-Del-Rio M, Velez-Pardo C (2013) Low doses of paraquat and polyphenols prolong life span and locomotor activity in knock-down parkin Drosophila melanogaster exposed to oxidative stress stimuli: implication in autosomal recessive juvenile parkinsonism. Gene 512(2):355–363CrossRefPubMedGoogle Scholar
  7. Canet-Avilés RM, Wilson MA, Miller DW, Ahmad R, McLendon C, Bandyopadhyay S, Baptista MJ, Ringe D, Petsko GA, Cookson MR (2004) The Parkinson’s disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. Proc Natl Acad Sci U S A 101(24):9103–9108CrossRefPubMedPubMedCentralGoogle Scholar
  8. Caruana M, Vassallo N (2015) Tea polyphenols in Parkinson’s disease. Adv Exp Med Biol 863:117–137CrossRefPubMedGoogle Scholar
  9. Casani S, Gómez-Pastor R, Matallana E, Paricio N (2013) Antioxidant compound supplementation prevents oxidative damage in a Drosophila model of Parkinson’s disease. Free Radic Biol Med 61:151–160CrossRefPubMedGoogle Scholar
  10. Cassar M, Issa AR, Riemensperger T, Petitgas C, Rival T, Coulom H, Iché-Torres M, Han KA, Birman S (2015) A dopamine receptor contributes to paraquat-induced neurotoxicity in Drosophila. Hum Mol Genet 24(1):197–212CrossRefPubMedGoogle Scholar
  11. Cha GH, Kim S, Park J, Lee E, Kim M, Lee SB, Kim JM, Chung J, Cho KS (2005) Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila. Proc Natl Acad Sci U S A 102(29):10345–10350CrossRefPubMedPubMedCentralGoogle Scholar
  12. Chakrawarti L, Agrawal R, Dang S, Gupta S, Gabrani R (2016) Therapeutic effects of EGCG: a patent review. Expert Opin Ther Pat 26(8):907–916CrossRefPubMedGoogle Scholar
  13. Charan J, Biswas T (2013) How to calculate sample size for different study designs in medical research? Indian J Psychol Med 35(2):121–126CrossRefPubMedPubMedCentralGoogle Scholar
  14. Chen L, Cagniard B, Mathews T, Jones S, Koh HC, Ding Y, Carvey PM, Ling Z, Kang UJ, Zhuang X (2005) Age-dependent motor deficits and dopaminergic dysfunction in DJ-1 null mice. J Biol Chem 280(22):21418–21426CrossRefPubMedGoogle Scholar
  15. Choi JY, Park CS, Kim DJ, Cho MH, Jin BK, Pie JE, Chung WG (2002) Prevention of nitric oxide-mediated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridineinduced Parkinson’s disease in mice by tea phenolic epigallocatechin 3-gallate. Neurotoxicology 23:367–374CrossRefPubMedGoogle Scholar
  16. Cochemé HM, Murphy MP (2008) Complex I is the major site of mitochondrial superoxide production by paraquat. J Biol Chem 283(4):1786–1798CrossRefPubMedGoogle Scholar
  17. Cookson MR (2012) Parkinsonism due to mutations in PINK1, Parkin, and DJ-1 and oxidative stress and mitochondrial pathways. Cold Spring Harb Perspect Med 2(9):a009415CrossRefPubMedPubMedCentralGoogle Scholar
  18. Coulom H, Birman S (2004) Chronic exposure to rotenone models sporadic Parkinson’s disease in Drosophila melanogaster. J Neurosci 24(48):10993–10998CrossRefPubMedGoogle Scholar
  19. Dickson DW (2018) Neuropathology of Parkinson disease. Parkinsonism Relat Disord 46(Suppl 1):S30–S33CrossRefPubMedGoogle Scholar
  20. Dwivedi V, Lakhotia SC (2016) Ayurvedic Amalaki Rasayana promotes improved stress tolerance and thus has anti-aging effects in Drosophila melanogaster. J Biosci 41(4):697–711CrossRefPubMedGoogle Scholar
  21. Fernández-Hernández I, Scheenaard E, Pollarolo G, Gonzalez C (2016) The translational relevance of Drosophila in drug discovery. EMBO Rep 17(4):471–472CrossRefPubMedPubMedCentralGoogle Scholar
  22. Filograna R, Beltramini M, Bubacco L, Bisaglia M (2016) Anti-oxidants in Parkinson’s disease therapy: a critical point of view. Curr Neuropharmacol 14(3):260–271CrossRefPubMedPubMedCentralGoogle Scholar
  23. Forester SC, Lambert JD (2011) The role of antioxidant versus pro-oxidant effects of green tea polyphenols in cancer prevention. Mol Nutr Food Res 55(6):844–854CrossRefPubMedPubMedCentralGoogle Scholar
  24. Garrido-Mesa N, Zarzuelo A, Gálvez J (2013) What is behind the non-antibiotic properties of minocycline? Pharmacol Res 67(1):18–30CrossRefPubMedGoogle Scholar
  25. Goldberg MS, Pisani A, Haburcak M, Vortherms TA, Kitada T, Costa C, Tong Y, Martella G, Tscherter A, Martins A, Bernardi G, Roth BL, Pothos EN, Calabresi P, Shen J (2005) Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial parkinsonism-linked gene DJ-1. Neuron 45(4):489–496CrossRefPubMedGoogle Scholar
  26. Hijioka M, Inden M, Yanagisawa D, Kitamura Y (2017) DJ-1/PARK7: a new therapeutic target for neurodegenerative disorders. Biol Pharm Bull 40(5):548–552CrossRefPubMedGoogle Scholar
  27. Hosamani R, Muralidhara (2013) Acute exposure of Drosophila melanogaster to paraquat causes oxidative stress and mitochondrial dysfunction. Arch Insect Biochem Physiol 83(1):25–40CrossRefPubMedGoogle Scholar
  28. Hwang S, Song S, Hong YK, Choi G, Suh YS, Han SY, Lee M, Park SH, Lee JH, Lee S, Bang SM, Jeong Y, Chung WJ, Lee IS, Jeong G, Chung J, Cho KS (2013) Drosophila DJ-1 decreases neural sensitivity to stress by negatively regulating Daxx-like protein through dFOXO. PLoS Genet 9(4):e1003412CrossRefPubMedPubMedCentralGoogle Scholar
  29. Inamdar AA, Chaudhuri A, O'Donnell J (2012) The protective effect of minocycline in a paraquat-induced Parkinson’s disease model in Drosophila is modified in altered genetic backgrounds. Parkinson’s Dis 2012:938528Google Scholar
  30. Jimenez-Del-Rio M, Moreno S, Garcia-Ospina G, Buritica O, Uribe CS, Lopera F, Velez-Pardo C (2004) Autosomal recessive juvenile parkinsonism Cys212Tyr mutation in parkin renders lymphocytes susceptible to dopamine- and iron-mediated apoptosis. Mov Disord 19(3):324–330CrossRefPubMedGoogle Scholar
  31. Jimenez-Del-Rio M, Guzman-Martinez C, Velez-Pardo C (2010) The effects of polyphenols on survival and locomotor activity in Drosophila melanogaster exposed to iron and paraquat. Neurochem Res 35(2):227–238CrossRefPubMedGoogle Scholar
  32. Kim RH, Smith PD, Aleyasin H, Hayley S, Mount MP, Pownall S, Wakeham A, You-Ten AJ, Kalia SK, Horne P, Westaway D, Lozano AM, Anisman H, Park DS, Mak TW (2005) Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress. Proc Natl Acad Sci U S A 102(14):5215–5220CrossRefPubMedPubMedCentralGoogle Scholar
  33. Kinumi T, Kimata J, Taira T, Ariga H, Niki E (2004) Cysteine-106 of DJ-1 is the most sensitive cysteine residue to hydrogen peroxide-mediated oxidation in vivo in human umbilical vein endothelial cells. Biochem Biophys Res Commun 317(3):722–728CrossRefPubMedGoogle Scholar
  34. Kitada T, Tong Y, Gautier CA, Shen J (2009) Absence of nigral degeneration in aged parkin/DJ-1/PINK1 triple knockout mice. J Neurochem 111(3):696–702CrossRefPubMedPubMedCentralGoogle Scholar
  35. Kładna A, Michalska T, Berczyński P, Kruk I, Aboul-Enein HY (2012) Evaluation of the antioxidant activity of tetracycline antibiotics in vitro. Luminescence 27(4):249–255CrossRefPubMedGoogle Scholar
  36. Koros C, Simitsi A, Stefanis L (2017) Genetics of Parkinson’s disease: genotype-phenotype correlations. Int Rev Neurobiol 132:197–231CrossRefPubMedGoogle Scholar
  37. Kraus RL, Pasieczny R, Lariosa-Willingham K, Turner MS, Jiang A, Trauger JW (2005) Antioxidant properties of minocycline: neuroprotection in an oxidative stress assay and direct radical-scavenging activity. J Neurochem 94(3):819–827CrossRefPubMedGoogle Scholar
  38. Kwon HJ, Heo JY, Shim JH, Park JH, Seo KS, Ryu MJ, Han JS, Shong M, Son JH, Kweon GR (2011) DJ-1 mediates paraquat-induced dopaminergic neuronal cell death. Toxicol Lett 202(2):85–92CrossRefPubMedGoogle Scholar
  39. Langston JW (2017) The MPTP story. J Parkinson’s Dis 7(s1):S11–S22CrossRefGoogle Scholar
  40. Lavara-Culebras E, Paricio N (2007) Drosophila DJ-1 mutants are sensitive to oxidative stress and show reduced lifespan and motor deficits. Gene 400(1–2):158–165CrossRefPubMedGoogle Scholar
  41. Lavara-Culebras E, Muñoz-Soriano V, Gómez-Pastor R, Matallana E, Paricio N (2010) Effects of pharmacological agents on the lifespan phenotype of Drosophila DJ-1beta mutants. Gene 462(1–2):26–33CrossRefPubMedGoogle Scholar
  42. Lee LS, Kim SH, Kim YB, Kim YC (2014) Quantitative analysis of major constituents in green tea with different plucking periods and their antioxidant activity. Molecules 19(7):9173–9186CrossRefPubMedGoogle Scholar
  43. León-González AJ, Auger C, Schini-Kerth VB (2015) Pro-oxidant activity of polyphenols and its implication on cancer chemoprevention and chemotherapy. Biochem Pharmacol 98(3):371–380CrossRefPubMedGoogle Scholar
  44. Lin J, Prahlad J, Wilson MA (2012) Conservation of oxidative protein stabilization in an insect homologue of parkinsonism-associated protein DJ-1. Biochemistry 51(18):3799–3807CrossRefPubMedPubMedCentralGoogle Scholar
  45. Lucas JI, Marín I (2007) A new evolutionary paradigm for the Parkinson disease gene DJ-1. Mol Biol Evol 24(2):551–561CrossRefPubMedGoogle Scholar
  46. Macedo MG, Verbaan D, Fang Y, van Rooden SM, Visser M, Anar B, Uras A, Groen JL, Rizzu P, van Hilten JJ, Heutink P (2009) Genotypic and phenotypic characteristics of Dutch patients with early onset Parkinson’s disease. Mov Disord 24:196–203CrossRefPubMedGoogle Scholar
  47. Mahlknecht P, Seppi K, Poewe W (2015) The concept of prodromal Parkinson’s disease. J Parkinsons Dis 5(4):681–697CrossRefPubMedPubMedCentralGoogle Scholar
  48. Mathew S, Abraham TE, Zakaria ZA (2015) Reactivity of phenolic compounds towards free radicals under in vitro conditions. J Food Sci Technol 52(9):5790–5798CrossRefPubMedPubMedCentralGoogle Scholar
  49. Meulener M, Whitworth AJ, Armstrong-Gold CE, Rizzu P, Heutink P, Wes PD, Pallanck LJ, Bonini NM (2005) Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson’s disease. Curr Biol 15(17):1572–1577CrossRefPubMedGoogle Scholar
  50. Meulener MC, Xu K, Thomson L, Ischiropoulos H, Bonini NM (2006) Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging. Proc Natl Acad Sci U S A 103(33):12517–12522CrossRefPubMedPubMedCentralGoogle Scholar
  51. Mohr SE (2014) RNAi screening in Drosophila cells and in vivo. Methods 68(1):82–88CrossRefPubMedPubMedCentralGoogle Scholar
  52. Mora M, Medina-Leendertz SJ, Bonilla E, Terán RE, Paz MC, Arcaya JL (2013) Minocycline, but not ascorbic acid, increases motor activity and extends the life span of Drosophila melanogaster. Investig Clin 54(2):161–170Google Scholar
  53. Nanjo F, Goto K, Seto R, Suzuki M, Sakai M, Hara Y (1996) Scavenging effects of tea catechins and their derivatives on 1,1-diphenyl-2-picrylhydrazyl radical. Free Radic Biol Med 21(6):895–902CrossRefPubMedGoogle Scholar
  54. Navarro JA, Heßner S, Yenisetti SC, Bayersdorfer F, Zhang L, Voigt A, Schneuwly S, Botella JA (2014) Analysis of dopaminergic neuronal dysfunction in genetic and toxin-induced models of Parkinson’s disease in Drosophila. J Neurochem 131(3):369–382CrossRefPubMedGoogle Scholar
  55. Nelson ML, Levy SB (2011) The history of the tetracyclines. Ann N Y Acad Sci 1241:17–32CrossRefPubMedGoogle Scholar
  56. Niveditha S, Ramesh SR, Shivanandappa T (2017) Paraquat-induced movement disorder in relation to oxidative stress-mediated neurodegeneration in the brain of Drosophila melanogaster. Neurochem Res 42:3310–3320.  https://doi.org/10.1007/s11064-017-2373-y CrossRefPubMedGoogle Scholar
  57. Ortega-Arellano HF, Jimenez-Del-Rio M, Velez-Pardo C (2011) Life span and locomotor activity modification by glucose and polyphenols in Drosophila melanogaster chronically exposed to oxidative stress-stimuli: implications in Parkinson’s disease. Neurochem Res 36(6):1073–1086CrossRefPubMedGoogle Scholar
  58. Ortega-Arellano HF, Jimenez-Del-Rio M, Velez-Pardo C (2017) Minocycline protects, rescues and prevents knockdown transgenic parkin Drosophila against paraquat/iron toxicity: implications for autosomic recessive juvenile parkinsonism. Neurotoxicology 60:42–53CrossRefPubMedGoogle Scholar
  59. Oxenkrug G, Navrotskaya V, Vorobyova L, Summergrad P (2012) Minocycline effect on life and health span of Drosophila melanogaster. Aging Dis 3(5):352–359PubMedPubMedCentralGoogle Scholar
  60. Park J, Kim SY, Cha GH, Lee SB, Kim S, Chung J (2005) Drosophila DJ-1 mutants show oxidative stress-sensitive locomotive dysfunction. Gene 361:133–139CrossRefPubMedGoogle Scholar
  61. Pineda-Trujillo N, Carvajal-Carmona LG, Buriticá O, Moreno S, Uribe C, Pineda D, Toro M, García F, Arias W, Bedoya G, Lopera F, Ruiz-Linares A (2001) A novel Cys212Tyr founder mutation in parkin and allelic heterogeneity of juvenile parkinsonism in a population from North West Colombia. Neurosci Lett 298(2):87–90CrossRefPubMedGoogle Scholar
  62. Quintero-Espinosa D, Jimenez-Del-Rio M, Velez-Pardo C (2017) Knockdown transgenic Lrrk Drosophila resists paraquat-induced locomotor impairment and neurodegeneration: a therapeutic strategy for Parkinson’s disease. Brain Res 1657:253–261CrossRefPubMedGoogle Scholar
  63. Robb EL, Gawel JM, Aksentijević D, Cochemé HM, Stewart TS, Shchepinova MM, Qiang H, Prime TA, Bright TP, James AM, Shattock MJ, Senn HM, Hartley RC, Murphy MP (2015) Selective superoxide generation within mitochondria by the targeted redox cycler MitoParaquat. Free Radic Biol Med 89:883–894CrossRefPubMedGoogle Scholar
  64. Sanz FJ, Solana-Manrique C, Muñoz-Soriano V, Calap-Quintana P, Moltó MD, Paricio N (2017) Identification of potential therapeutic compounds for Parkinson’s disease using Drosophila and human cell models. Free Radic Biol Med 108:683–691CrossRefPubMedGoogle Scholar
  65. Sarkar S, Raymick J, Imam S (2016) Neuroprotective and therapeutic strategies against Parkinson’s disease: recent perspectives. Int J Mol Sci 17(6):904CrossRefPubMedCentralGoogle Scholar
  66. Severino JF, Goodman BA, Kay CW, Stolze K, Tunega D, Reichenauer TG, Pirker KF (2009) Free radicals generated during oxidation of green tea polyphenols: electron paramagnetic resonance spectroscopy combined with density functional theory calculations. Free Radic Biol Med 46(8):1076–1088CrossRefPubMedGoogle Scholar
  67. Singh NA, Mandal AK, Khan ZA (2016) Potential neuroprotective properties of epigallocatechin-3-gallate (EGCG). Nutr J 15(1):60CrossRefPubMedPubMedCentralGoogle Scholar
  68. Solanki I, Parihar P, Mansuri ML, Parihar MS (2015) Flavonoid-based therapies in the early management of neurodegenerative diseases. Adv Nutr 6(1):64–72CrossRefPubMedPubMedCentralGoogle Scholar
  69. Sun SY, An CN, Pu XP (2012) DJ-1 protein protects dopaminergic neurons against 6-OHDA/MG-132-induced neurotoxicity in rats. Brain Res Bull 88(6):609–616CrossRefPubMedGoogle Scholar
  70. Sveinbjornsdottir S (2016) The clinical symptoms of Parkinson’s disease. J Neurochem 139(Suppl 1):318–324CrossRefPubMedGoogle Scholar
  71. Taira T, Saito Y, Niki T, Iguchi-Ariga SMM, Takahashi K, Ariga H (2004) DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep 5(2):213–218CrossRefPubMedPubMedCentralGoogle Scholar
  72. Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, Marras C, Bhudhikanok GS, Kasten M, Chade AR, Comyns K, Richards MB, Meng C, Priestley B, Fernandez HH, Cambi F, Umbach DM, Blair A, Sandler DP, Langston JW (2011) Rotenone, paraquat, and Parkinson’s disease. Environ Health Perspect 119(6):866–872CrossRefPubMedPubMedCentralGoogle Scholar
  73. Wang X, Petrie TG, Liu Y, Liu J, Fujioka H, Zhu X (2012) Parkinson’s disease-associated DJ-1 mutations impair mitochondrial dynamics and cause mitochondrial dysfunction. J Neurochem 121(5):830–839CrossRefPubMedPubMedCentralGoogle Scholar
  74. Yamaguchi H, Shen J (2007) Absence of dopaminergic neuronal degeneration and oxidative damage in aged DJ-1-deficient mice. Mol Neurodegener 2:10CrossRefPubMedPubMedCentralGoogle Scholar
  75. Yoshida Y, Umeno A, Akazawa Y, Shichiri M, Murotomi K, Horie M (2015) Chemistry of lipid peroxidation products and their use as biomarkers in early detection of diseases. J Oleo Sci 64(4):347–356CrossRefPubMedGoogle Scholar

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Authors and Affiliations

  1. 1.Neuroscience Research Group, Medical Research Institute, Faculty of MedicineUniversity of Antioquia (UdeA)MedellinColombia

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