Advertisement

Neurochemical Research

, Volume 41, Issue 9, pp 2173–2178 | Cite as

3,4-Dihydroxyphenylethanol (Hydroxytyrosol) Mitigates the Increase in Spontaneous Oxidation of Dopamine During Monoamine Oxidase Inhibition in PC12 Cells

  • David S. Goldstein
  • Yunden Jinsmaa
  • Patti Sullivan
  • Courtney Holmes
  • Irwin J. Kopin
  • Yehonatan Sharabi
Short Communication

Abstract

The catecholaldehyde hypothesis predicts that monoamine oxidase (MAO) inhibition should slow the progression of Parkinson’s disease, by decreasing production of the autotoxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL). Inhibiting MAO, however, diverts the fate of cytoplasmic dopamine toward potentially harmful spontaneous oxidation products, indicated by increased 5-S-cysteinyl-dopamine (Cys-DA) levels. 3,4-Dihydroxyphenylethanol (hydroxytyrosol) is an abundant anti-oxidant phenol in constituents of the Mediterranean diet. Whether hydroxytyrosol alters enzymatic or spontaneous oxidation of dopamine has been unknown. Rat pheochromocytoma PC12 cells were incubated with hydroxytyrosol (10 µM, 180 min) alone or with the MAO-A inhibitor clorgyline (1 nM) or the MAO-B inhibitors rasagiline or selegiline (0.5 µM). Hydroxytyrosol decreased levels of DOPAL by 30 % and Cys-DA by 49 % (p < 0.0001 each). Co-incubation with hydroxytyrosol prevented the increases in Cys-DA seen with all 3 MAO inhibitors. Hydroxytyrosol therefore inhibits both enzymatic and spontaneous oxidation of endogenous dopamine and mitigates the increase in spontaneous oxidation during MAO inhibition.

Keywords

Hydroxytyrosol DOPET DOPAL Cysteinyl-dopamine Monoamine oxidase Parkinson’s disease 

Abbreviations

ALDH

Aldehyde dehydrogenase

DA

Dopamine

DHPG

3,4-dihydroxyphenylglycol

DOPAC

3,4-dihydroxyphenylacetic acid

DOPAL

3,4-dihydroxyphenylacetaldehyde

DOPET

3,4-dihydroxyphenylethanol

NE

Norepinephrine

PD

Parkinson disease

VMAT

Vesicular monoamine transporter

Notes

Acknowledgments

The research reported here was supported by the intramural research program of the National Institute of Neurological Disorders and Stroke.

Authors Contribution

David S. Goldstein: Conception and design, data analysis, data interpretation, drafting the article, final approval. Patti Sullivan: Data acquisition, data analysis. Yunden Jinsmaa: Data acquisition, data analysis, conception and design, drafting the article, revising the article. Courtney Holmes: Methods development, new reagents or analytic tools. Irwin J. Kopin: Conception and design, drafting the article, revising the article critically for important intellectual content. Yehonatan Sharabi: Conception and design, data analysis, drafting the article, revising the article critically for important intellectual content.

Compliance with Ethical Standards

Conflict of interest

None of the authors has a conflict of interest to report. Dr. Goldstein is Chair of the Education Committee and sits on the Board of Directors of the American Autonomic Society, under an approved Outside Activity. For these services he receives no payment in cash or kind.

References

  1. 1.
    Burke WJ (2003) 3,4-dihydroxyphenylacetaldehyde: a potential target for neuroprotective therapy in Parkinson’s disease. Curr Drug Targets CNS Neurol Disord 2:143–148CrossRefPubMedGoogle Scholar
  2. 2.
    Stokes AH, Hastings TG, Vrana KE (1999) Cytotoxic and genotoxic potential of dopamine. J Neurosci Res 55:659–665CrossRefPubMedGoogle Scholar
  3. 3.
    Jana S, Sinha M, Chanda D, Roy T, Banerjee K, Munshi S, Patro BS, Chakrabarti S (2011) Mitochondrial dysfunction mediated by quinone oxidation products of dopamine: implications in dopamine cytotoxicity and pathogenesis of Parkinson’s disease. Biochim Biophys Acta 1812:663–673CrossRefPubMedGoogle Scholar
  4. 4.
    Cavalieri EL, Li KM, Balu N, Saeed M, Devanesan P, Higginbotham S, Zhao J, Gross ML, Rogan EG (2002) Catechol ortho-quinones: the electrophilic compounds that form depurinating DNA adducts and could initiate cancer and other diseases. Carcinogenesis 23:1071–1077CrossRefPubMedGoogle Scholar
  5. 5.
    De Marco F, Perluigi M, Marcante ML, Coccia R, Foppoli C, Blarzino C, Rosei MA (2002) Cytotoxicity of dopamine-derived tetrahydroisoquinolines on melanoma cells. Biochem Pharmacol 64:1503–1512CrossRefPubMedGoogle Scholar
  6. 6.
    Bisaglia M, Mammi S, Bubacco L (2007) Kinetic and structural analysis of the early oxidation products of dopamine: analysis of the interactions with alpha-synuclein. J Biol Chem 282:15597–15605CrossRefPubMedGoogle Scholar
  7. 7.
    Linsenbardt AJ, Wilken GH, Westfall TC, Macarthur H (2009) Cytotoxicity of dopaminochrome in the mesencephalic cell line, MN9D, is dependent upon oxidative stress. Neurotoxicology 30:1030–1035CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Fornstedt B, Carlsson A (1991) Effects of inhibition of monoamine oxidase on the levels of 5-S-cysteinyl adducts of catechols in dopaminergic regions of the brain of the guinea pig. Neuropharmacology 30:463–468CrossRefPubMedGoogle Scholar
  9. 9.
    Montine TJ, Picklo MJ, Amarnath V, Whetsell WO Jr, Graham DG (1997) Neurotoxicity of endogenous cysteinylcatechols. Exp Neurol 148:26–33CrossRefPubMedGoogle Scholar
  10. 10.
    Spencer JP, Whiteman M, Jenner P, Halliwell B (2002) 5-s-Cysteinyl-conjugates of catecholamines induce cell damage, extensive DNA base modification and increases in caspase-3 activity in neurons. J Neurochem 81:122–129CrossRefPubMedGoogle Scholar
  11. 11.
    Goldstein DS, Jinsmaa Y, Sullivan P, Holmes C, Kopin IJ, Sharabi Y (2016) Comparison of monoamine oxidase inhibitors in decreasing production of the autotoxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde in PC12 cells. J Pharmacol Exp Ther 356:484–493CrossRefGoogle Scholar
  12. 12.
    Rodriguez-Morato J, Xicota L, Fito M, Farre M, Dierssen M, de la Torre R (2015) Potential role of olive oil phenolic compounds in the prevention of neurodegenerative diseases. Molecules 20:4655–4680CrossRefPubMedGoogle Scholar
  13. 13.
    de la Torre R, Covas MI, Pujadas MA, Fito M, Farre M (2006) Is dopamine behind the health benefits of red wine? Eur J Nutr 45:307–310CrossRefPubMedGoogle Scholar
  14. 14.
    Carluccio MA, Siculella L, Ancora MA, Massaro M, Scoditti E, Storelli C, Visioli F, Distante A, De Caterina R (2003) Olive oil and red wine antioxidant polyphenols inhibit endothelial activation: antiatherogenic properties of Mediterranean diet phytochemicals. Arterioscler Thromb Vasc Biol 23:622–629CrossRefPubMedGoogle Scholar
  15. 15.
    Lopez de las Hazas MC, Rubio L, Kotronoulas A, de la Torre R, Sola R, Motilva MJ (2015) Dose effect on the uptake and accumulation of hydroxytyrosol and its metabolites in target tissues in rats. Mol Nutr Food Res 59:1395–1399CrossRefPubMedGoogle Scholar
  16. 16.
    Gallardo E, Palma-Valdes R, Espartero JL, Santiago M (2014) In vivo striatal measurement of hydroxytyrosol, and its metabolite (homovanillic alcohol), compared with its derivative nitrohydroxytyrosol. Neurosci Lett 579:173–176CrossRefPubMedGoogle Scholar
  17. 17.
    Tasset I, Pontes AJ, Hinojosa AJ, de la Torre R, Tunez I (2011) Olive oil reduces oxidative damage in a 3-nitropropionic acid-induced Huntington’s disease-like rat model. Nutr Neurosci 14:106–111CrossRefPubMedGoogle Scholar
  18. 18.
    Laschinski G, Kittner B, Brautigam M (1986) Direct inhibition of tyrosine hydroxylase from PC-12 cells by catechol derivatives. Naunyn Schmiedebergs Arch Pharmacol 332:346–350CrossRefPubMedGoogle Scholar
  19. 19.
    Goldstein DS, Sullivan P, Cooney A, Jinsmaa Y, Kopin IJ, Sharabi Y (2015) Rotenone decreases intracellular aldehyde dehydrogenase activity: implications for the pathogenesis of Parkinson’s disease. J Neurochem 133:14–25CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Goldstein DS, Jinsmaa Y, Sullivan P, Holmes C, Kopin IJ, Sharabi Y (2015) Comparison of monoamine oxidase inhibitors in decreasing production of the autotoxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) in PC12 cells. J Pharmacol Exp Ther 356:484–493CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York (outside the USA)  2016

Authors and Affiliations

  • David S. Goldstein
    • 1
  • Yunden Jinsmaa
    • 1
  • Patti Sullivan
    • 1
  • Courtney Holmes
    • 1
  • Irwin J. Kopin
    • 1
  • Yehonatan Sharabi
    • 1
    • 2
  1. 1.Clinical Neurocardiology SectionCNP/DIR/NINDS/NIHBethesdaUSA
  2. 2.Sackler Faculty of MedicineChaim Sheba Medical Center and Tel Aviv UniversityTel AvivIsrael

Personalised recommendations