Hydroxytyrosol induces phase II detoxifying enzyme expression and effectively protects dopaminergic cells against dopamine- and 6-hydroxydopamine induced cytotoxicity

Neurochem Int. 2016 Jun:96:113-20. doi: 10.1016/j.neuint.2016.03.005. Epub 2016 Mar 9.

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.

Keywords: Dopamine; Hydroxytyrosol; Oxidative stress; Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cytotoxins
  • Dopamine / toxicity*
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism*
  • Dose-Response Relationship, Drug
  • Enzyme Induction / drug effects
  • Enzyme Induction / physiology
  • Humans
  • Metabolic Detoxication, Phase II / physiology*
  • NAD(P)H Dehydrogenase (Quinone) / antagonists & inhibitors
  • NAD(P)H Dehydrogenase (Quinone) / biosynthesis*
  • Neuroprotective Agents / pharmacology
  • Oxidopamine / toxicity*
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / pharmacology

Substances

  • Antioxidants
  • Cytotoxins
  • Neuroprotective Agents
  • 3,4-dihydroxyphenylethanol
  • Oxidopamine
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human
  • Phenylethyl Alcohol
  • Dopamine