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

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.

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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

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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.

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Correspondence to David S. Goldstein.

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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.

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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

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Keywords

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