(-)-Deprenyl protects human dopaminergic neuroblastoma SH-SY5Y cells from apoptosis induced by peroxynitrite and nitric oxide.
In Parkinson's disease the cell death of dopamine neurons has been proposed to be mediated by an apoptotic death process, in which nitric oxide may be involved. This article reports the induction of apoptosis by nitric oxide and peroxynitrite in human dopaminergic neuroblastoma SH-SY5Y cells and the antiapoptotic activity of (-)-deprenyl. After the cells were treated with a nitric oxide donor, NOR-4, or a peroxynitrite donor, SIN-1, DNA damage was quantitatively studied using a single-cell gel electrophoresis (comet) assay. NOR-4 and SIN-1 induced DNA damage dose-dependently. Cycloheximide and alkaline treatment of the cells prevented the DNA damage, indicating that the damage is apoptotic and that it depends on the intracellular signal transduction. Superoxide dismutase and the antioxidants reduced glutathione and alpha-tocopherol protected the cells from the DNA damage. (-)-Deprenyl protected the cells from the DNA damage induced by nitric oxide or peroxynitrite almost completely. The protection by (-)-deprenyl was significant even after it was washed from the cells, indicating that (-)-deprenyl may activate the intracellular system against apoptosis. These results suggest that (-)-deprenyl or related compounds may be neuroprotective to dopamine neurons through its antiapoptotic activity.
Maruyama
W
W
Department of Basic Gerontology, National Institute for Longevity Sciences, Aichi, Japan.
Takahashi
T
T
Naoi
M
M
D000978:Antiparkinson Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D006801:Humans; D008981:Molsidomine / Q000031:analogs & derivatives / Q000633:toxicity; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009566:Nitrates / Q000633:toxicity*; D009569:Nitric Oxide / Q000633:toxicity*; D016877:Oxidants / Q000633:toxicity; D011725:Pyridines / Q000633:toxicity; D012642:Selegiline / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000978:Antiparkinson Agents; D008996:Monoamine Oxidase Inhibitors; C102260:NOR 4; D009566:Nitrates; D016877:Oxidants; D011725:Pyridines; C039642:peroxynitric acid; D012642:Selegiline; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D004298:Dopamine