흰쥐 선조체에서 6-OHDA-유도 도파민 고갈 및 SH-SY5Y 세포주에서 6-OHDA-유도 산화적 스트레스에 대한 l-Deprenyl 의 신경 보호효과

• 영문명: Neuroprotective Effect of l-Deprenyl Against 6-OHDA-Induced Dopamine Deplection in Rat Striatum and 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells
• 발행기관: 대한약학회
• 저자명: 김은미(Eun Mi Kim) 최신규(Shinyu Choi) 이경림(Kyunglim Lee) 김화정(Hwa Jung Kim)
• 간행물 정보: 『약학회지』제49권 제4호 (2005년), 355~364쪽, 전체 10쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2005.08.31

영문 초록

A neurotoxin, 6-hydroxydopamine (6-OHDA) has long been used to form a Parkinson's disease (PD) model by inducing the lesion in catecholaminergic pathways, particularly the nigrostriatal dopamine (DA) pathway, Whereas l-depre- nyl, a selective inhibitor of monoamine oxidase (MAO) type B, is now widely used in the treatment of PD, the precise action mechanism of the drug remains elusive. In this study, we investigated whether l-deprenyl shows protective effect against the DA depletion induced by 6-OHDA in rat brain, and against 6-OHDA-induced neurotoxicity and oxidative stress in catecholaminergic neuroblastoma SH-SY5Y cells that are known to lack MAO-B activity, Pretreatment of l-deprenyl sig- nificantly enhanced the striatal DA, 3,4-dihydroxyphenylacetic acid, homovanilic acid, and 3-methoxytyramine levels compared to the untreated 6-OHDA-lesioned rat, indicating that l-deprenyl pretreatment prevents 6-OHDA-induced deple- tion of not only striatal dopamine but also its metabolites. Treatment of 6-OHDA for 24 hrs decreased the cell viability and increase the generation of ROS in dose-dependent manners. We further investigated whether caspase activity is involved in the action of l-deprenyl. Treatment of l-deprenyl (0.1~100μM) did not produce any changes in 6-OHDA-induced cleavage of poly (ADP-ridose) polymerase in SH-SY5Y cells. Our results suggest that the neuroprotective effect of l-deprenyl against 6-OHDA is due to its increased scavenger activity, but independent of inhibition of MAO-B or caspase-3 activation.

키워드

l-deprenyl 6-hydroxydopamine(6-OHDA) reactive oxygen species(ROS) caspase-3