Antioxidant compounds protect dopamine neurons from death due to oxidative stress in vitro

被引:42
作者
Stull, ND [1 ]
Polan, DP [1 ]
Iacovitti, L [1 ]
机构
[1] Thomas Jefferson Univ, Coll Med, Dept Neurol, Philadelphia, PA 19107 USA
关键词
neuroprotection; antioxidant; caspase inhibitor; dopamine neurons; MPTP; oxidative stress; Parkinson's disease;
D O I
10.1016/S0006-8993(02)02269-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Using tissue culture models of oxidative stress caused by serum deprivation or MPTP/MPP+ toxicity, the present study establishes that the antioxidants epigallocatechin gallate, lazaroids U74389G and U83836E. reservatrol, MnTBAP, MCI 186, trolox, and melatonin protect 68-100% of dopamine (DA) neurons from cell death. In contrast. the nitric oxide inhibitor LY83583, the caspase inhibitors Z-VAD-FMK, Ac-DQMD-CHO and Z-DEVD-FMK, and the CDK-5 inhibitor, roscovotine were not neuroprotective, although death was often delayed by 1 day in vitro. We conclude that antioxidants are more effective at preventing cell death in vitro than are inhibitors at later stages in the death cascade. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:181 / 185
页数:5
相关论文
共 25 条
[11]   α-synuclein promotes mitochondrial deficit and oxidative stress [J].
Hsu, LJ ;
Sagara, Y ;
Arroyo, A ;
Rockenstein, E ;
Sisk, A ;
Mallory, M ;
Wong, J ;
Takenouchi, T ;
Hashimoto, M ;
Masliah, E .
AMERICAN JOURNAL OF PATHOLOGY, 2000, 157 (02) :401-410
[12]   Melatonin rescues dopamine neurons from cell death in tissue culture models of oxidative stress [J].
Iacovitti, L ;
Stull, ND ;
Johnston, K .
BRAIN RESEARCH, 1997, 768 (1-2) :317-326
[13]   Neurotransmitters, KCl and antioxidants rescue striatal neurons from apoptotic cell death in culture [J].
Iacovitti, L ;
Stull, ND ;
Mishizen, A .
BRAIN RESEARCH, 1999, 816 (02) :276-285
[14]   Activation of caspase-3 in developmental models of programmed cell death in neurons of the substantia nigra [J].
Jeon, BS ;
Kholodilov, NG ;
Oo, TF ;
Kim, SY ;
Tomaselli, KJ ;
Srinivasan, A ;
Stefanis, L ;
Burke, RE .
JOURNAL OF NEUROCHEMISTRY, 1999, 73 (01) :322-333
[15]   Melatonin protects nigral dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPP+) neurotoxicity in rats [J].
Jin, BK ;
Shin, DY ;
Jeong, MY ;
Gwag, MR ;
Baik, HW ;
Yoon, KS ;
Cho, YH ;
Joo, WS ;
Kim, YS ;
Baik, HH .
NEUROSCIENCE LETTERS, 1998, 245 (02) :61-64
[16]   Melatonin increases striatal dopaminergic function in 6-OHDA-lesioned rats [J].
Joo, WS ;
Jin, BK ;
Park, CW ;
Maeng, SH ;
Kim, YS .
NEUROREPORT, 1998, 9 (18) :4123-4126
[17]   Melatonin protects 6-OHDA-induced neuronal death of nigrostriatal dopaminergic system [J].
Kim, YS ;
Joo, WS ;
Jin, BK ;
Cho, YH ;
Baik, HH ;
Park, CW .
NEUROREPORT, 1998, 9 (10) :2387-2390
[18]  
LEW J, 1995, NEUROBIOL AGING, V16, P263, DOI 10.1016/0197-4580(95)00014-6
[19]   Apoptosis in neurodegenerative disorders [J].
Mattson, MP .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2000, 1 (02) :120-129
[20]   Expression of cyclin-dependent kinase 5 and its activator p35 in models of induced apoptotic death in neurons of the substantia nigra in vivo [J].
Neystat, M ;
Rzhetskaya, M ;
Oo, TF ;
Kholodilov, N ;
Yarygina, O ;
Wilson, A ;
El-Khodor, BF ;
Burke, RE .
JOURNAL OF NEUROCHEMISTRY, 2001, 77 (06) :1611-1625