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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Vesicular monoamine transporter
Burke WJ (2003) 3,4-dihydroxyphenylacetaldehyde: a potential target for neuroprotective therapy in Parkinson’s disease. Curr Drug Targets CNS Neurol Disord 2:143–148
Stokes AH, Hastings TG, Vrana KE (1999) Cytotoxic and genotoxic potential of dopamine. J Neurosci Res 55:659–665
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 1812:663–673
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 23:1071–1077
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 64:1503–1512
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 282:15597–15605
Linsenbardt AJ, Wilken GH, Westfall TC, Macarthur H (2009) Cytotoxicity of dopaminochrome in the mesencephalic cell line, MN9D, is dependent upon oxidative stress. Neurotoxicology 30:1030–1035
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 30:463–468
Montine TJ, Picklo MJ, Amarnath V, Whetsell WO Jr, Graham DG (1997) Neurotoxicity of endogenous cysteinylcatechols. Exp Neurol 148:26–33
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 81:122–129
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 356:484–493
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 20:4655–4680
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 45:307–310
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 23:622–629
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 59:1395–1399
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 579:173–176
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 14:106–111
Laschinski G, Kittner B, Brautigam M (1986) Direct inhibition of tyrosine hydroxylase from PC-12 cells by catechol derivatives. Naunyn Schmiedebergs Arch Pharmacol 332:346–350
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 133:14–25
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 356:484–493
The research reported here was supported by the intramural research program of the National Institute of Neurological Disorders and Stroke.
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.
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.
About this article
Cite this article
Goldstein, D.S., Jinsmaa, Y., Sullivan, P. et al. 3,4-Dihydroxyphenylethanol (Hydroxytyrosol) Mitigates the Increase in Spontaneous Oxidation of Dopamine During Monoamine Oxidase Inhibition in PC12 Cells. Neurochem Res 41, 2173–2178 (2016). https://doi.org/10.1007/s11064-016-1959-0
- Monoamine oxidase
- Parkinson’s disease