Skip to main content
Log in

Neuroprotective Effects of 3α-Acetoxyeudesma-1,4(15),11(13)-trien-12,6α-olide Against Dopamine-Induced Apoptosis in the Human Neuroblastoma SH-SY5Y Cell Line

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Dopamine (DA), as a neurotoxin, can elicit severe Parkinson’s disease-like syndrome by elevating intracellular reactive oxygen species (ROS) levels and apoptotic activity. We examined the inhibitory effects of 3α-acetoxyeudesma-1,4(15),11(13)-trien-12,6α-olide (AETO), purified from the leaves of Laurus nobilis L., on DA-induced apoptosis and α-synuclein (α-syn) formation in dopaminergic SH-SY5Y cells. AETO decreased the active form of caspase-3 and the levels of p53, which were accompanied by increased levels of Bcl-2 in a dose-dependent manner. Flow cytometric and Western blot analysis showed that AETO significantly inhibited DA-induced apoptosis along with suppression of intracellular tyrosinase activity, ROS generation, quinoprotein, and α-syn formation (P < 0.01). These results indicate that AETO inhibited DA-induced apoptosis, which is closely related to the suppression of intracellular tyrosinase activity and the formation of α-syn, ROS, and quinoprotein in SH-SY5Y cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Bonnet AM, Houeto JL (1999) Pathophysiology of Parkinson’s disease. Biomed Pharmacother 53:117–121

    Article  PubMed  CAS  Google Scholar 

  2. Olanow CW, Tatton WG (1999) Etiology and pathogenesis of Parkinson’s disease. Annu Rev Neurosci 22:123–144

    Article  PubMed  CAS  Google Scholar 

  3. Olanow CW (1993) A radical hypothesis for neurodegeneration. Trends Neurosci 16:439–444

    Article  PubMed  CAS  Google Scholar 

  4. Junn E, Mouradian MM (2001) Apoptotic signaling in dopamine-induced cell death: the role of oxidative stress, p38 mitogen-activated protein kinase, cytochrome c and caspases. J Neurochem 78:374–383

    Article  PubMed  CAS  Google Scholar 

  5. Graham DG (1978) Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 14:633–643

    PubMed  CAS  Google Scholar 

  6. Cohen G, Heikkila RE (1974) The generation of hydrogen peroxide, superoxide radical, and hydroxyl radical by 6-hydroxydopamine, dialuric acid, and related cytotoxic agents. J Biol Chem 249:2447–2452

    PubMed  CAS  Google Scholar 

  7. Hastings TG (1995) Enzymatic oxidation of dopamine: the role of prostaglandin H synthase. J Neurochem 64:919–924

    Article  PubMed  CAS  Google Scholar 

  8. Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59:1609–1623

    Article  PubMed  CAS  Google Scholar 

  9. Drukarch B, van Muiswinkel FL (2000) Drug treatment of Parkinson’s disease. Time for phase II. Biochem Pharmacol 59:1023–1031

    Article  PubMed  CAS  Google Scholar 

  10. Elsworth JD, Roth RH (1997) Dopamine synthesis, uptake, metabolism, and receptors: relevance to gene therapy of Parkinson’s disease. Exp Neurol 144:4–9

    Article  PubMed  CAS  Google Scholar 

  11. Karg E, Odh G, Wittbjer A et al (1993) Hydrogen peroxide as an inducer of elevated tyrosinase level in melanoma cells. J Invest Dermatol 100:209S–213S

    Article  PubMed  CAS  Google Scholar 

  12. Sulzer D, Zecca L (2000) Intraneuronal dopamine-quinone synthesis: a review. Neurotox Res 1:181–195

    Article  PubMed  CAS  Google Scholar 

  13. Tessari I, Bisaglia M, Valle F et al (2008) The reaction of alpha-synuclein with tyrosinase: possible implications for Parkinson disease. J Biol Chem 283:16808–16817

    Article  PubMed  CAS  Google Scholar 

  14. Masamoto Y, Ando H, Murata Y et al (2003) Mushrrom tyrosinase inhibitory activity of esculetin isolated from seeds of Euphorbia lathyris L. Biosci Biotechnol Biochem 67:631–634

    Article  PubMed  CAS  Google Scholar 

  15. Wada S, Ichikawa H, Tastsumi K (1995) Removal of phenols and aromatic amines from wastewater by a combination treatment with tyrosinase and a coagulant. Biotechnol Bioeng 45:304–309

    Article  PubMed  CAS  Google Scholar 

  16. Mun YJ, Lee SW, Jeong HW et al (2004) Inhibitory effect of miconazole on melanogenesis. Biol Pharm Bull 27:806–809

    Article  PubMed  CAS  Google Scholar 

  17. Huang D, Ou B, Hampsch-Woodill M, Flanagan JA et al (2002) Development and validation of oxygen radical absorbance capacity assay for lipophilic antioxidants using randomly methylated beta-cyclodextrin as the solubility enhancer. J Agric Food Chem 50:1815–1821

    Article  PubMed  CAS  Google Scholar 

  18. Bass DA, Parce JW, Dechatelet LR et al (1983) Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. J Immunol 130:1910–1917

    PubMed  CAS  Google Scholar 

  19. Ikeda Y, Tsuji S, Satoh A, Ishikura M, Shirasawa T, Shimizu T (2008) Protective effects of astaxanthin on 6-hydroxydopamine-induced apoptosis in human neuroblastoma SH-SY5Y cells. J Neurochem 107:1730–1740

    Article  PubMed  CAS  Google Scholar 

  20. Lee CS, Han ES, Song JH, Kim KY (2004) Inhibition of SIN-1-induced change in mitochondrial membrane permeability in PC12 cells by dopamine. Neurochem Res 29:1371–1379

    Article  PubMed  CAS  Google Scholar 

  21. Merchant SH, Gonchoroff NJ, Hutchison RE (2001) Apoptotic index by Annexin V flow cytometry: adjunct to morphologic and cytogenetic diagnosis of myelodysplastic syndromes. Cytometry 46:28–32

    Article  PubMed  CAS  Google Scholar 

  22. Paz MA, Fluckiger R, Boak A et al (1991) Specific detection of quinoproteins by redox-cycling staining. J Biol Chem 266:689–692

    PubMed  CAS  Google Scholar 

  23. Asanuma M, Miyazaki I, Ogawa N (2003) Dopamine- or L-DOPA-induced neurotoxicity: the role of dopamine quinone formation and tyrosinase in a model of Parkinson’s disease. Neurotox Res 5:165–176

    Article  PubMed  Google Scholar 

  24. Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA, Munday NA, Raju SM, Smulson ME, Yamin T–T, Yu VL, Miller DK (1995) Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 376:37–43

    Article  PubMed  CAS  Google Scholar 

  25. Hirsch EC (1993) Does oxidative stress participate in nerve cell death in Parkinson’s disease. Eur Neurol 33:52–59

    Article  PubMed  Google Scholar 

  26. Jenner P (1998) Oxidative mechanisms in nigral cell death in Parkinson’s disease. Mov Disord 13:24–34

    PubMed  Google Scholar 

  27. Gomez Sarosi LA, Rieber MS, Rieber M (2003) Hydrogen peroxide increases a 55-kDa tyrosinase concomitantly with induction of p53-dependent p21 waf1 expression and a greater Bax/Bcl-2 ratio in pigmented melanoma. Biochem Biophys Res Commun 312:355–359

    Article  PubMed  Google Scholar 

  28. Zhou ZD, Lim TM (2009) Dopamine (DA) induced irreversible proteasome inhibition via DA derived quinones. Free Radic Res 43:417–430

    Article  PubMed  CAS  Google Scholar 

  29. Baranyi M, Milusheva E, Vizi ES, Sperlagh B (2006) Chromatographic analysis of dopamine metabolism in a Parkinsonian model. J Chromatogr A 1120:13–20

    Article  PubMed  CAS  Google Scholar 

  30. Adams JD Jr, Odunze IN (1991) Oxygen free radicals and Parkinson’s disease. Free Radic Biol Med 10:161–169

    Article  PubMed  CAS  Google Scholar 

  31. Hsu LJ, Sagara Y, Arroyo A et al (2000) α-synuclein promotes mitochondrial deficit and oxidative stress. Am J Pathol 157:401–410

    Article  PubMed  CAS  Google Scholar 

  32. Gomez-Santos C, Ferrer I, Santidrian AF et al (2003) Dopamine induces autophagic cell death and alpha-synuclein increase in human neuroblastoma SH-SY5Y cells. J Neurosci Res 73:341–350

    Article  PubMed  CAS  Google Scholar 

  33. Xu Y, Stokes AH, Roskoski R et al (1998) Dopamine, in the presence of tyrosinase, covalently modifies and inactivates tyrosine hydroxylase. J Neurosci Res 54:691–697

    Article  PubMed  CAS  Google Scholar 

  34. Greggio E, Bergantino E, Carter D et al (2005) Tyrosinase exacerbates dopamine toxicity but is not genetically associated with Parkinson’s disease. J Neurochem 93:246–256

    Article  PubMed  CAS  Google Scholar 

  35. Hasegawa T, Treis A, Patenge N et al (2008) Parkin protects against tyrosinase-mediated dopamine neurotoxicity by suppressing stress-activated protein kinase pathways. J Neurochem 105:1700–1715

    Article  PubMed  CAS  Google Scholar 

  36. Miranda M, Botti D (1983) Harding-passey mouse-melanoma tyrosinase inactivation by reaction products and activation by L-epinephrine. Gen Pharmacol 14:231–237

    Article  PubMed  CAS  Google Scholar 

  37. Sulzer D (2007) Multiple hit hypotheses for dopamine neuron loss in Parkinson’s disease. Trends Neurosci 30:244–250

    Article  PubMed  CAS  Google Scholar 

  38. Burnard P, Berthon JY (2000) Resveratrol:an original mechanism on tyrosinase inhibition. Int J Cosmet Sci 22:219–226

    Article  Google Scholar 

  39. Ohguchi K, Tanaka T, Ito T, Iinuma M, Matsumoto K, Akao Y, Nozawa Y (2003) Inhibitory effects of resveratrol derivatives from dipterocarpaceae plants on tyrosinase activity. Biosci Biotechnol Biochem 67:1587–1589

    Article  PubMed  CAS  Google Scholar 

  40. Lee MK, Kang SJ, Poncz M, Song KJ, Park KS (2007) Resveratrol protects SH-SY5Y neuroblastoma cells from apoptosis induced by dopamine. Exp Mol Med 39:376–384

    PubMed  CAS  Google Scholar 

  41. Jin F, Wu Q, Lu YF, Gong QH, Shi JS (2008) Neuroprotective effect of resveratrol on 6-OHDA-induced Parkinson’s disease in rats. Eur J Parmacol 600:78–82

    Article  CAS  Google Scholar 

  42. Blanchet J, Longpre F, Bureau G, Morissette M, DiPaolo T, Bronchti G, Martinoli MG (2008) Resveratrol, a red wine polyphenol, protects dopaminergic neurons in MPTP-treated mice. Prog Neuropsychopharmacol Biol Psychiatry 32:1243–1250

    Article  PubMed  CAS  Google Scholar 

  43. Fornstedt B, Rosengren E, Carlsson A (1986) Occurrence and distribution of 5-S-cysteinyl derivatives of dopamine, dopa and dopac in the brains of eight mammalian species. Neuropharmacology 25:451–454

    Article  PubMed  CAS  Google Scholar 

  44. Kuhn DM, Arthur RE Jr, Thomas DM, Elferink LA (1999) Tyrosine hydroxylase is inactivated by catechol-quinones and converted to a redox-cycling quinoprotein: possible relevance to Parkinson’s disease. J Neurochem 73:1309–1317

    Article  PubMed  CAS  Google Scholar 

  45. LaVoie MJ, Ostaszewski BL, Weihofen A, Schlossmacher MG, Selkoe DJ (2005) Dopamine covalently modifies and functionally inactivates parkin. Nat Med 11:1214–1221

    Article  PubMed  CAS  Google Scholar 

  46. Whitehead RE, Ferrer JV, Javitch JA, Justice JB (2001) Reaction of oxidized dopamine with endogenous cysteine residues in the human dopamine transporter. J Neurochem 76:1242–1251

    Article  PubMed  CAS  Google Scholar 

  47. Xu J, Kao SY, Lee FJ, Song W, Jin LW, Yankner BA (2002) Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nat Med 8:600–606

    Article  PubMed  CAS  Google Scholar 

  48. Clayton DF, George JM (1998) The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease. Trends Neurosci 21:249–254

    Article  PubMed  CAS  Google Scholar 

  49. Hasegawa T, Matsuzaki-Kobayashi M, Takeda A et al (2006) Alpha-synuclein facilitates the toxicity of oxidized catechol metabolites: implications for selective neurodegeneration in Parkinson’s disease. FEBS Lett 580:2147–2152

    Article  PubMed  CAS  Google Scholar 

  50. Lee FJ, Liu F, Pristupa ZB et al (2001) Direct binding and functional coupling of alpha-synuclein to the dopamine transporters accelerate dopamine-induced apoptosis. FASEB J 15:916–926

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (Grant No. 2009-0086896).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Woongchon Mar or Jongheon Shin.

Additional information

The authors U. Koo and Kung-Woo Nam contributed equally to this article. Woongchon Mar and Jongheon Shin are senior co-authors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koo, U., Nam, KW., Ham, A. et al. Neuroprotective Effects of 3α-Acetoxyeudesma-1,4(15),11(13)-trien-12,6α-olide Against Dopamine-Induced Apoptosis in the Human Neuroblastoma SH-SY5Y Cell Line. Neurochem Res 36, 1991–2001 (2011). https://doi.org/10.1007/s11064-011-0523-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-011-0523-1

Keywords

Navigation