YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Neuroprotective Effect of l-Deprenyl Against 6-OHDA-Induced Dopamine Depletion in Rat Striatum and 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells

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

  • Kim Eun-Mi (Research Institute of Pharmaceutical Sciences, College of Pharmacy Ewha Womans University, National Institute of Scientific Investigation) ;
  • Choi Sinkyu (Research Institute of Pharmaceutical Sciences, College of Pharmacy Ewha Womans University) ;
  • Lee Kyunglim (Research Institute of Pharmaceutical Sciences, College of Pharmacy Ewha Womans University) ;
  • Kim Hwa-Jung (Research Institute of Pharmaceutical Sciences, College of Pharmacy Ewha Womans University)
  • 김은미 (이화여자대학교 약학대학, 국립과학수사연구소) ;
  • 최신규 (이화여자대학교 약학대학) ;
  • 이경림 (이화여자대학교 약학대학) ;
  • 김화정 (이화여자대학교 약학대학)
  • Published : 2005.08.01
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Abstract

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-deprenyl, 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 significantly 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 depletion of not only striatal dopamine but also its metabolites. Treatment of 6-OHDA for 24hrs 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 $(0.1\~100{\mu}M)$ 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.

Keywords

References

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