Deprenyl protects human dopaminergic neuroblastoma
SH-SY5Y cells from apoptosis
induced by peroxynitrite
and nitric oxide.
Maruyama W, Takahashi T, Naoi M
Dept of Basic Gerontology,
National Institute for Longevity Sciences, Aichi,
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.
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.