title: Hydroxytyrosol induces phase II detoxifying enzyme expression and effectively protects dopaminergic cells against dopamine- and 6-hydroxydopamine induced cytotoxicity.
abstract: Parkinson's disease (PD) is the second most common late-age onset neurodegenerative disease. Except for the symptomatic alleviating treatment, no disease modifying therapy is currently available. In this study, we investigated the potential neuroprotective role of hydroxytyrosol (HT), a major phenolic compound present in olive oil, against dopaminergic cell death. We found that HT effectively protected dopaminergic SH-SY5Y cells against dopamine (DA) and 6-hydroxydopamine (6-OHDA) induced cell death, but had no apparent effect on 1-methyl-4-phenylpyridinium (MPP(+))-induced cytotoxicity. Furthermore, we have shown that HT efficiently induced the expression of phase II detoxifying enzymes, including NAD(P)H quinone oxidoreductase 1 (NQO1). Using an NQO1 inhibitor, we revealed that increased NQO1 expression contributed to the protective effect of HT against dopaminergic cell death. Together, our findings suggest that HT has a protective effect against DA- and 6-OHDA-induced dopaminergic cell death, supporting the beneficial effect of olive oil in preventing DA-metabolism related dopaminergic neuron dysfunction.
authors.affiliation: Key Laboratory of Brain Functional Genomics (East China Normal University), Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics (East China Normal University), School of Life Sciences, East China Normal University, Shanghai, China. Electronic address: xiaoqsh2003@163.com.
authors.forename: Guohua
authors.initials: G
authors.lastname: Yu
authors.affiliation: Key Laboratory of Brain Functional Genomics (East China Normal University), Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics (East China Normal University), School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Ajun
authors.initials: A
authors.lastname: Deng
authors.affiliation: Key Laboratory of Brain Functional Genomics (East China Normal University), Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics (East China Normal University), School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Wanbin
authors.initials: W
authors.lastname: Tang
authors.affiliation: Key Laboratory of Brain Functional Genomics (East China Normal University), Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics (East China Normal University), School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Junzhi
authors.initials: J
authors.lastname: Ma
authors.affiliation: Key Laboratory of Brain Functional Genomics (East China Normal University), Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics (East China Normal University), School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Chonggang
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Brain Functional Genomics (East China Normal University), Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics (East China Normal University), School of Life Sciences, East China Normal University, Shanghai, China; Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA.
authors.forename: Jiyan
authors.initials: J
authors.lastname: Ma
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003603:Cytotoxins; D004298:Dopamine / Q000633:toxicity*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D006801:Humans; D050217:Metabolic Detoxication, Phase II / Q000502:physiology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D018696:Neuroprotective Agents / Q000494:pharmacology; D016627:Oxidopamine / Q000633:toxicity*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D003603:Cytotoxins; D018696:Neuroprotective Agents; C005975:3,4-dihydroxyphenylethanol; D016627:Oxidopamine; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D010626:Phenylethyl Alcohol; D004298:Dopamine
keywords: Dopamine; Hydroxytyrosol; Oxidative stress; Parkinson's disease