Protective effect of sulforaphane against dopaminergic cell death

Auteur(s) :
Lee SY., Lee YJ., Tschann JM., Hwang O.
Date :
Avr, 2007
Source(s) :
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. #321-1 p249-256
Adresse :
Hwang O (reprint author), Univ Ulsan, Coll Med, Dept Biochem & Mol Biol, 3880-1 Pungnap Dong, Seoul 138736, South Korea Univ Ulsan, Coll Med, Dept Biochem & Mol Biol, Seoul 138736, South Korea Univ Seoul, Dept Life Sci, Seoul, South Korea E-mail Addresses: oyhwang@amc.seoul.kr Publisher: AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA, http://www.aspetjournals.org Discipline: PHARMACOLOGY & TOXICOLOGY CC Editions/Collections: Life Sciences (LS)

Sommaire de l'article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder with a selective loss of dopaminergic neurons in the substantia nigra. Evidence suggests oxidation of dopamine (DA) to DA quinone and consequent oxidative stress as a major factor contributing to this vulnerability. We have previously observed that exposure to or induction of NAD(P)H:quinone reductase (QR1), the enzyme that catalyzes the reduction of quinone, effectively protects DA cells. Sulforaphane (SF) is a drug identified as a potent inducer of QR1 in various nonneuronal cells. In the present study, we show that SF protects against compounds known to induce DA quinone production (6-hydroxydopamine and tetrahydrobiopterin) in DAergic cell lines CATH. a and SK-N-BE(2)C as well as in mesencephalic DAergic neurons. SF leads to attenuation of the increase in protein-bound quinone in tetrahydrobiopterin-treated cells, but this does not occur in cells that have been depleted of DA, suggesting involvement of DA quinone. SF pretreatment prevents membrane damage, DNA fragmentation, and accumulation of reactive oxygen species. SF causes increases in mRNA levels and enzymatic activity of QR1 in a dose-dependent manner. Taken together, these results indicate that SF causes induction of QR1 gene expression, removal of intracellular DA quinone, and protection against toxicity in DAergic cells. Thus, this major isothiocyanate found in cruciferous vegetables may serve as a potential candidate for development of treatment and/or prevention of PD.

Source : Pubmed
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