QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.110866v1 321/1/249    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Han, J. M. Articles by Hwang, O. Search for Related Content PubMed PubMed Citation Articles by Han, J. M. Articles by Hwang, O.

NEUROPHARMACOLOGY

Protective Effect of Sulforaphane against Dopaminergic Cell Death

Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea (J.M.H., Y.J.L., S.Y.L., E.M.K., Y.M., O.H.); and Department of Life Science, University of Seoul, Seoul, Korea (Y.J.L., H.W.K.)

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 non-neuronal 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.

Address correspondence to: Dr. Onyou Hwang, Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-ku, Seoul, 138-736, Korea. E-mail: oyhwang{at}amc.seoul.kr

This article has been cited by other articles:

				L. Mastrangelo, A. Cassidy, F. Mulholland, W. Wang, and Y. Bao Serotonin Receptors, Novel Targets of Sulforaphane Identified by Proteomic Analysis in Caco-2 Cells Cancer Res., July 1, 2008; 68(13): 5487 - 5491. [Abstract] [Full Text] [PDF]