An anti-Parkinson's disease drug, N-propargyl-1(R)-aminoindan (rasagiline), enhances expression of anti-apoptotic Bcl-2 in human dopaminergic SH-SY5Y cells

被引:115
作者
Akao, Y
Maruyama, W
Yi, H
Shamoto-Nagai, M
Youdim, MBH
Naoi, M [1 ]
机构
[1] Inst Appl Biochem, Dept Brain Sci, Gifu, Japan
[2] Gifu Int Inst Biotechnol, Gifu, Japan
[3] Natl Inst Longev Sci, Dept Basic Gerontol, Aichi, Japan
[4] Technion Israel Inst Technol, Fac Med, Eve Topf & NPF Ctr, Haifa, Israel
基金
日本学术振兴会;
关键词
rasagiline; anti-apoptosis; bcl-2; family; gene expression; Parkinson's disease; neuroprotection; mitochondria; monoamine oxidase-B inhibitor;
D O I
10.1016/S0304-3940(02)00332-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
N-Propargyl-1(R)-aminoindan (rasagiline) is now under phase III clinical trials for Parkinson's disease (PD), and it rescues dopamine neurons from cell death in animal and cellular models of PD. Recently, we proved that rasagiline protected dopaminergic SH-SY5Y cells against apoptosis induced by a dopaminergic neurotoxin, N-methyl(R)salsolinol, and the mechanism was clarified to be due to suppression of death signal transduction in mitochondria. In this paper, the effects of rasagiline on the levels of anti-apoptotic bcl-2 gene family were studied. Rasagiline increased the levels of bcl-2 and bcl-x(1) mRNA at 100-10 nM and 100-10 pM, but not the level of pro-apoptotic bax mRNA. Enhanced expression of bcl-2 family indicates the ability of rasagiline to adjust the apoptotic threshold and protect degenerating neurons in PD. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:105 / 108
页数:4
相关论文
共 15 条
[1]   Apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol, is mediated by activation of caspase 3 [J].
Akao, Y ;
Nakagawa, Y ;
Maruyama, W ;
Takahashi, T ;
Naoi, M .
NEUROSCIENCE LETTERS, 1999, 267 (03) :153-156
[2]  
Finberg JPM, 1998, NEUROREPORT, V9, P703
[3]   Neuroprotective action of cycloheximide involves induction of bcl-2 and antioxidant pathways [J].
Furukawa, K ;
Estus, S ;
Fu, WM ;
Mark, RJ ;
Mattson, MP .
JOURNAL OF CELL BIOLOGY, 1997, 136 (05) :1137-1149
[4]   Neuroprotective effect of rasagiline, a selective monoamine oxidase-B inhibitor, against closed head injury in the mouse [J].
Huang, W ;
Chen, Y ;
Shohami, E ;
Weinstock, M .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1999, 366 (2-3) :127-135
[5]   The proto-oncogene Bcl-2 and its role in regulating apoptosis [J].
Kroemer, G .
NATURE MEDICINE, 1997, 3 (06) :614-620
[6]  
Maruyama W, 2000, ADV RES NEURODEGENER, V8, P171
[7]   Enantio-specific induction of apoptosis by an endogenous neurotoxin, N-methyl(R)salsolinol, in dopaminergic SH-SY5Y cells:: suppression of apoptosis by N-(2-heptyl)-N-methylpropargylamine [J].
Maruyama, W ;
Boulton, AA ;
Davis, BA ;
Dostert, P ;
Naoi, M .
JOURNAL OF NEURAL TRANSMISSION, 2001, 108 (01) :11-24
[8]   Transfection-enforced Bcl-2 overexpression and an anti-Parkinson drug, rasagiline, prevent nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase induced by an endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol [J].
Maruyama, W ;
Akao, Y ;
Youdim, MBH ;
Davis, BA ;
Naoi, M .
JOURNAL OF NEUROCHEMISTRY, 2001, 78 (04) :727-735
[9]   Future of neuroprotection in Parkinson's disease [J].
Naoi, M ;
Maruyama, W .
PARKINSONISM & RELATED DISORDERS, 2001, 8 (02) :139-145
[10]  
*PARK STUD GROUP, 2001, RELAT DISORD, V7, pS60