Anti-apoptotic function of L-(-)deprenyl (Selegiline) and related compounds.

Neurobiology (Budapest, Hungary) Pub Date : 2000-01-01
M Naoi, W Maruyama, K Yagi, M Youdim
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引用次数: 0

Abstract

(-)Deprenyl has been proposed to be neuroprotective to dopamine neurons in the parkinsonian brains. To clarify the mechanism, the effects of (-)deprenyl and structurally related compounds on apoptosis induced by a neurotoxin, N-methyl(R)-salsolinol, and reactive oxygen species, nitric oxide and peroxynitrite, were examined in dopaminergic SH-SY5Y cells. DNA damage was quantified by the single cell gel electrophoresis (comet) assay. (-)-Deprenyl protected the cells from apoptosis in a dose-dependent way, which required pre-treatment at least for 20 min. The effect was confirmed even after washing out of (-)deprenyl, indicating that (-)-deprenyl initiates the intracellular process to antagonize the apoptotic death program. The studies on the structure-activity relationship reveal that N-propargyl residue with hydrophobic structure is essential for the anti-apoptotic function. These results suggest that (-)deprenyl and related compounds may be applicable as neuroprotective agents in neurodegenerative diseases.

L-(-)去戊烯基(Selegiline)及其相关化合物的抗凋亡功能。
(-)去戊烯醇被认为对帕金森大脑中的多巴胺神经元具有神经保护作用。为了阐明其机制,我们在多巴胺能SH-SY5Y细胞中研究了(-)去戊烯基和结构相关化合物对神经毒素n -甲基(R)-沙索林醇、活性氧、一氧化氮和过氧亚硝酸盐诱导的细胞凋亡的影响。单细胞凝胶电泳(comet)法测定DNA损伤。(-)-去戊烯基以剂量依赖的方式保护细胞免于凋亡,这需要预处理至少20分钟。即使在洗去(-)去戊烯基后也证实了这种作用,这表明(-)-去戊烯基启动细胞内的过程来对抗凋亡死亡程序。构效关系的研究表明,具有疏水结构的n -丙炔残基对其抗凋亡功能至关重要。这些结果提示(-)去戊烯基及其相关化合物可作为神经退行性疾病的神经保护剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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