title: 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.
authors.affiliation: Clinical Neurocardiology Section, CNP/DIR/NINDS/NIH, 9000 Rockville Pike, Bldg. 10 Rm. 5N220, Bethesda, MD, 20892-1620, USA. goldsteind@ninds.nih.gov.
authors.forename: David S
authors.initials: DS
authors.lastname: Goldstein
authors.affiliation: Clinical Neurocardiology Section, CNP/DIR/NINDS/NIH, 9000 Rockville Pike, Bldg. 10 Rm. 5N220, Bethesda, MD, 20892-1620, USA.
authors.forename: Yunden
authors.initials: Y
authors.lastname: Jinsmaa
authors.affiliation: Clinical Neurocardiology Section, CNP/DIR/NINDS/NIH, 9000 Rockville Pike, Bldg. 10 Rm. 5N220, Bethesda, MD, 20892-1620, USA.
authors.forename: Patti
authors.initials: P
authors.lastname: Sullivan
authors.affiliation: Clinical Neurocardiology Section, CNP/DIR/NINDS/NIH, 9000 Rockville Pike, Bldg. 10 Rm. 5N220, Bethesda, MD, 20892-1620, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Holmes
authors.affiliation: Clinical Neurocardiology Section, CNP/DIR/NINDS/NIH, 9000 Rockville Pike, Bldg. 10 Rm. 5N220, Bethesda, MD, 20892-1620, USA.
authors.forename: Irwin J
authors.initials: IJ
authors.lastname: Kopin
authors.affiliation: Clinical Neurocardiology Section, CNP/DIR/NINDS/NIH, 9000 Rockville Pike, Bldg. 10 Rm. 5N220, Bethesda, MD, 20892-1620, USA.|Sackler Faculty of Medicine, Chaim Sheba Medical Center and Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yehonatan
authors.initials: Y
authors.lastname: Sharabi
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D016716:PC12 Cells; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats
chemical_list: D015259:Dopamine Agents; D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; C005975:3,4-dihydroxyphenylethanol; C007430:3,4-dihydroxyphenylacetaldehyde; D008995:Monoamine Oxidase; D010626:Phenylethyl Alcohol; D004298:Dopamine
keywords: Cysteinyl-dopamine; DOPAL; DOPET; Hydroxytyrosol; Monoamine oxidase; Parkinson’s disease