Maruyama W, Takahashi T, Naoi M
Department of Basic Gerontology, National Institute for Longevity Sciences, Aichi, Japan.
J Neurochem. 1998 Jun;70(6):2510-5. doi: 10.1046/j.1471-4159.1998.70062510.x.
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.
在帕金森病中，多巴胺能神经元的细胞死亡被认为是由凋亡死亡过程介导的，一氧化氮可能参与其中。本文报道了一氧化氮和过氧亚硝酸盐在人多巴胺能神经母细胞瘤SH-SY5Y细胞中诱导凋亡的作用以及（-）-司来吉兰的抗凋亡活性。在用一氧化氮供体NOR-4或过氧亚硝酸盐供体SIN-1处理细胞后，使用单细胞凝胶电泳（彗星）试验对DNA损伤进行了定量研究。NOR-4和SIN-1剂量依赖性地诱导DNA损伤。用环己酰亚胺和碱性处理细胞可防止DNA损伤，表明这种损伤是凋亡性的，并且依赖于细胞内信号转导。超氧化物歧化酶以及抗氧化剂还原型谷胱甘肽和α-生育酚可保护细胞免受DNA损伤。（-）-司来吉兰几乎完全保护细胞免受一氧化氮或过氧亚硝酸盐诱导的DNA损伤。即使从细胞中洗去（-）-司来吉兰后，其保护作用仍然显著，这表明（-）-司来吉兰可能激活细胞内抗凋亡系统。这些结果表明，（-）-司来吉兰或相关化合物可能通过其抗凋亡活性对多巴胺能神经元具有神经保护作用。
