Protective effect of sulforaphane against dopaminergic cell death.
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.
Han
Ji Man
JM
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-ku, Seoul, 138-736, Korea.
Lee
Yong Jin
YJ
Lee
So Yeon
SY
Kim
Eun Mee
EM
Moon
Younghye
Y
Kim
Ha Won
HW
Hwang
Onyou
O
D001708:Biopterins / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D002875:Chromosomes / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D017879:Isothiocyanates; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
D017879:Isothiocyanates; D011809:Quinones; D017382:Reactive Oxygen Species; D013454:Sulfoxides; D013861:Thiocyanates; D001708:Biopterins; D016627:Oxidopamine; D007770:L-Lactate Dehydrogenase; C003402:sapropterin; C016766:sulforaphane; D004298:Dopamine