银杏平颤方对PD鼠中脑多巴胺神经元凋亡的影响及机制探讨
|
摘要
帕金森病是一种神经系统退行性疾病,目前该病已成为老年致残和病死的主要疾病
之一,它的主要病理变化是投射至纹状体的黑质致密部多巴胺神经元和轴突丢失。黑质
内多巴胺神经元的减少,使纹状体内多巴胺含量降低,引起中枢多巴胺和乙酰胆碱比例
失调,在临床上出现震颤、肌肉僵直、运动弛缓等一系列症状。随着研究的深入,已发
现 PD 中中脑黑质多巴胺神经元丢失的主要方式之一是细胞凋亡,但由于 PD 病因及病机
的复杂性,至今尚无理想的治疗方法,中医药用于防治帕金森病已取得了可喜的苗头,
本实验根据中医理论和临床实践,组成了银杏平颤方, 从细胞凋亡的诱因、调控分子等
多个方面研究并比较了银杏平颤方及拆方对 MPTP 诱导 PD 鼠的防治作用,揭示了中药的
作用和机制。
本实验分为四个部分:(1)观察 PD 鼠中脑黑质致密部多巴胺神经元的丢失和凋亡
以及银杏平颤全方和拆方的作用;(2)观察 PD 鼠脑内线粒体酶复合体的活性变化以及
银杏平颤全方和拆方的影响;(3)应用免疫组化技术观察 PD 鼠脑内不同部位钙结合蛋
白 Calbindin D28k 的表达和中药的影响;(4)应用免疫组化和原位杂交技术观察 PD 鼠
黑质致密部凋亡的主要调控分子 Caspase-9、Caspase-3、Bcl-2、Caspase-3mRNA 和
Bcl-2mRNA 的表达以及中药的作用。
实验选用 C57BL/6J 小鼠,应用 0.3%MPTP(生理盐水配制)按 30mg/kg/天腹腔注射,
连续 5 天,复制 PD 模型。动物随机分为六组:(1)正常对照组(NC);(2)模型对照组
(MC);(3)银杏平颤全方治疗组(简称全方组, GBPR);(4)中药清热解毒方治疗组(简
称解毒组, JDR); (5) 中药平肝熄风方治疗组(简称平肝组, PGR);(6)中药化瘀通络
方治疗组(简称化瘀组, HYR)。动物的存活期分别是 14 天和 28 天。
主要实验结果如下:
1. 中药银杏平颤全方和拆方可抑制 PD 鼠中脑黑质致密部 TH 阳性神经元的丢失和
凋亡
实验研究表明:造模后 PD 鼠中脑黑质致密部酪氨酸羟化酶(TH)阳性神经元的数
目比正常组明显减少,14 天,减少了 52.14%,28 天,减少了 60.78%;黑质致密部 TH
阳性神和纤维的光密度也明显降低,两个时间段分别降低了 90.42%和 93.20%。14 天,
各中药治疗组可部分减少黑质致密部 TH 阳性神经元的丢失,其丢失程度较模型组明显
减低,其中解毒组和化瘀组分别减少了16.60%和17.55%,效果较好;全方组和平肝组分别
减少了 22.72%和 20.61%。28 天,全方组 TH 阳性神经元的数量减少的程度最低,其丢失
率为 33.2%, 其它三个拆方组减少的程度较大,解毒组为 49.23%、平肝组为 44.9%和化瘀
组为43.94%; 中药各组也可不同程度的增加PD鼠黑质致密部TH阳性神经元和纤维的光
密度。
造模后,Tunel 方法显示 PD 鼠中脑黑质致密部凋亡细胞的数量明显增多,阳性细胞
2 银杏平颤方对 PD 鼠中脑多巴胺神经元凋亡的影响及机制探讨
核的着色强度也明显增加,14 天更明显;各中药治疗组可抑制该部位细胞的凋亡,14
天,解毒组效果最好,28 天,全方组和平肝组效果较显著。
2. 中药银杏平颤全方和拆方可调节 PD 鼠脑内线粒体酶复合体的活性
通过常规比色法和测氧法检测了不同组别动物脑内线粒体酶复合体 I、II 和 IV 的
活性,结果表明MPTP可导致 PD 鼠脑内线粒体(包括中脑黑质)酶复合体 I、IV 的活
性下降,对酶复合体 II 的活性无明显影响。银杏平颤全方中药在早期可以部分拮抗 MPTP
引起的线粒体酶复合体 I、IV 的活性下降;拆方各组中药中,解毒中药在早期(14 天)
一般都能抑制线粒体酶复合体活性的下降,甚至提高线粒体酶复合体Ⅱ的活性,但在后
期(28 天)无此作用;而平肝中药在早期抑制 MPTP 引起的线粒体酶复合体活性的下降
的效果不明显,后期效果显著;化瘀中药则在两个时段均能抑制 MPTP 引起的线粒体酶
复合体Ⅳ活性的下降,提高线粒体酶复合体Ⅱ的活性,但对线粒体酶复合体 I 的下降在
后期无明显抑制作用。提示银杏平颤全方及其拆方中药可能通过部分阻止线粒体酶复合
体活性的下降,保护线粒体的功能,防止多巴胺神经元的凋亡。
3. 中药银杏平颤全方和拆方可调节 PD 鼠脑内 Calbindin D28k 的表达
Calbindin D28k(CB)是脑内神经元内存在着一个重要的钙结合蛋白,它可以通过结
合细胞内的钙离子,调节细胞内的钙平衡,对神经元损伤起到部分保护作用。我们的实
验显示 PD 鼠脑内多巴胺神经元丢失的敏感区内(黑质和 VTA)Calbindin D28k 的表达可
反射性的增高,在海马 CA1 区和 CA2 区 Calbindin D28k 的表达也升高,而在脑皮质
Calbindin D28k 的表达降低。提示不同脑区神经元对 MPTP 的毒性反应不同,神经元内
Calbindin D28k 的表达增高,可能是细胞内钙超载导致神经元启动自我保护机制的结
果。一般来说,全方和化瘀中药可上调中脑、皮质和海马 CB 表达,早期(14 天)较后
期(28 天)更明显,提示中药可能通过增加钙结合蛋白 CB 的表达,调节细胞内的钙平
衡,达到保护神经元的目的。另外我们同样观察到解毒组中药在早期上调 CB 的作用明
显,后期效果不显著;而平肝中药在后期上调 CB 的效果明显,这提示在 PD 早期多巴
胺神经元内各种自由基的产生加速、细胞
Parkinson’s disease(PD) is a neurodegenerative disease. It is one of the
main diseases with high incidence and disable rate , also many sequelae. A
major pathological hallmark of Parkinson’s disease is a progressive loss of
dopaminergic neurons in the substantia nigra pars compacta(SNpc) and their axons,
which project to the striatum. The loss of dopaminergic neurons results in
decrease of dopamine in the striatum and imbalance in dopamine and acetylcholine.
So Parkinson’s disease is characterized by resting tremor ,rigidity and akinesia .
Recent studies have suggested that main causes of neuronal death in PD are
apoptosis. Despite extensive research, the disease remains poorly understood
and there is still no effective treatment. Chinese herbal medicine have efficacy
at treating PD. According to the theory of traditional Chinese medicine and based
on clinical practices, Ginkgo Biloba Pingchan Recipe(GBPR) is consisted. To
elucidate the effect and mechanism of GBPR and its three separated
prescriptions, we observed the changes of apoptosis-related molecules and
factors in SNpc in Parkinsonian mice model with MPTP-treated.
This study is consisted of four parts:(1)To observe the loss and apoptosis
of dopaminergic neurons in SNpc in Parkinsonian mice and the roles of GBPR and
its three separated prescriptions;(2) To observe the activity of the
mitochondrial complex in brain in Parkinsonian mice and influence of GBPR and
its three separated prescriptions;(3) To observe the expression of the
calcium-binding protein calbindin D28k in brain in Parkinsonian mice and
influence of GBPR and its three separated prescriptions by ABC
immunohistochemistry technique;(4) To observe the expression of the apoptotic
regulated factors Caspase-9、Caspase-3、Bcl-2、Caspase-3mRNA and Bcl-2mRNA in
SNpc in Parkinsonian mice and the effect of GBPR and its three separated
prescriptions by ABC immunohistochemistry and in situ hybridization technique.
In experimental research, male C57BL/6J mice are injected intraperitoneally
with a total cumulative dose of 150mg/kg MPTP ,30mg /kg daily to induce
Parkinson’s disease model. The modeled mice are called Parkinsonian mice. The
英文摘要 5
experimental animals is divided randomly into six groups:(1)The normal control
group( NC); (2) The model control group( MC);(3) Ginkgo Biloba Pingchan Recipe
group( GBPR); (4) Jiedu Recipe group (JDR); (5) Pinggan Recipe group(PGR); (6)
Huayu Recipe group;(HYR) .The animals were killed respectively on the 14th and
the 28th day after first injecting with MPTP.
The main results are displayed as follow:
1.Chinese herbal medicine Ginkgo Biloba Pingchan Recipe and its separated
Recipe may inhibit the loss and apoptosis of TH+ dopaminergic neurons
In the experimental studying, ABC immunohistochemistry technique is
used.The TH+ dopaminergic neurons were counted in every group . The number of
TH+ neurons in SNpc in MC is decreased by 52.14% on the 14th day and 60.78%
on the 28th day.The option density for TH+ neurons and fibers also obviously
reduced by 90.42% on the 14th day and 93.20% on the 28th day.The loss of TH+
neurons are partly inhibited in SNpc of Chinese herbal medicine. The number
of TH+ neurons in SNpc of JDR and HYR is decreased by 16.6% and 17.55% on the
14th day; The number of TH+neuronsin SNpc of GBPR and PGR is decreased by 22.72%
and 20.61% on the 14th day. On 28th Day, The degree of loss of TH+ neurons in SNpc
of GBPR is lightest ,for 33.2%; HYR,PGR and JDR are respectively for 43.94%,44.9%
and 49.23%. The option density for TH+ neurons and fibers in SNpc of Chinese
herbal medicine is also increased.The trend is similar to the changes of number
of TH+ neurons.
The apoptotic cells in SNpc is found by Tunel tethnique. The number and
density of apoptotic cells in SNpc in MC are increased,on 14th day is more
obvious. Chinese he
之一,它的主要病理变化是投射至纹状体的黑质致密部多巴胺神经元和轴突丢失。黑质
内多巴胺神经元的减少,使纹状体内多巴胺含量降低,引起中枢多巴胺和乙酰胆碱比例
失调,在临床上出现震颤、肌肉僵直、运动弛缓等一系列症状。随着研究的深入,已发
现 PD 中中脑黑质多巴胺神经元丢失的主要方式之一是细胞凋亡,但由于 PD 病因及病机
的复杂性,至今尚无理想的治疗方法,中医药用于防治帕金森病已取得了可喜的苗头,
本实验根据中医理论和临床实践,组成了银杏平颤方, 从细胞凋亡的诱因、调控分子等
多个方面研究并比较了银杏平颤方及拆方对 MPTP 诱导 PD 鼠的防治作用,揭示了中药的
作用和机制。
本实验分为四个部分:(1)观察 PD 鼠中脑黑质致密部多巴胺神经元的丢失和凋亡
以及银杏平颤全方和拆方的作用;(2)观察 PD 鼠脑内线粒体酶复合体的活性变化以及
银杏平颤全方和拆方的影响;(3)应用免疫组化技术观察 PD 鼠脑内不同部位钙结合蛋
白 Calbindin D28k 的表达和中药的影响;(4)应用免疫组化和原位杂交技术观察 PD 鼠
黑质致密部凋亡的主要调控分子 Caspase-9、Caspase-3、Bcl-2、Caspase-3mRNA 和
Bcl-2mRNA 的表达以及中药的作用。
实验选用 C57BL/6J 小鼠,应用 0.3%MPTP(生理盐水配制)按 30mg/kg/天腹腔注射,
连续 5 天,复制 PD 模型。动物随机分为六组:(1)正常对照组(NC);(2)模型对照组
(MC);(3)银杏平颤全方治疗组(简称全方组, GBPR);(4)中药清热解毒方治疗组(简
称解毒组, JDR); (5) 中药平肝熄风方治疗组(简称平肝组, PGR);(6)中药化瘀通络
方治疗组(简称化瘀组, HYR)。动物的存活期分别是 14 天和 28 天。
主要实验结果如下:
1. 中药银杏平颤全方和拆方可抑制 PD 鼠中脑黑质致密部 TH 阳性神经元的丢失和
凋亡
实验研究表明:造模后 PD 鼠中脑黑质致密部酪氨酸羟化酶(TH)阳性神经元的数
目比正常组明显减少,14 天,减少了 52.14%,28 天,减少了 60.78%;黑质致密部 TH
阳性神和纤维的光密度也明显降低,两个时间段分别降低了 90.42%和 93.20%。14 天,
各中药治疗组可部分减少黑质致密部 TH 阳性神经元的丢失,其丢失程度较模型组明显
减低,其中解毒组和化瘀组分别减少了16.60%和17.55%,效果较好;全方组和平肝组分别
减少了 22.72%和 20.61%。28 天,全方组 TH 阳性神经元的数量减少的程度最低,其丢失
率为 33.2%, 其它三个拆方组减少的程度较大,解毒组为 49.23%、平肝组为 44.9%和化瘀
组为43.94%; 中药各组也可不同程度的增加PD鼠黑质致密部TH阳性神经元和纤维的光
密度。
造模后,Tunel 方法显示 PD 鼠中脑黑质致密部凋亡细胞的数量明显增多,阳性细胞
2 银杏平颤方对 PD 鼠中脑多巴胺神经元凋亡的影响及机制探讨
核的着色强度也明显增加,14 天更明显;各中药治疗组可抑制该部位细胞的凋亡,14
天,解毒组效果最好,28 天,全方组和平肝组效果较显著。
2. 中药银杏平颤全方和拆方可调节 PD 鼠脑内线粒体酶复合体的活性
通过常规比色法和测氧法检测了不同组别动物脑内线粒体酶复合体 I、II 和 IV 的
活性,结果表明MPTP可导致 PD 鼠脑内线粒体(包括中脑黑质)酶复合体 I、IV 的活
性下降,对酶复合体 II 的活性无明显影响。银杏平颤全方中药在早期可以部分拮抗 MPTP
引起的线粒体酶复合体 I、IV 的活性下降;拆方各组中药中,解毒中药在早期(14 天)
一般都能抑制线粒体酶复合体活性的下降,甚至提高线粒体酶复合体Ⅱ的活性,但在后
期(28 天)无此作用;而平肝中药在早期抑制 MPTP 引起的线粒体酶复合体活性的下降
的效果不明显,后期效果显著;化瘀中药则在两个时段均能抑制 MPTP 引起的线粒体酶
复合体Ⅳ活性的下降,提高线粒体酶复合体Ⅱ的活性,但对线粒体酶复合体 I 的下降在
后期无明显抑制作用。提示银杏平颤全方及其拆方中药可能通过部分阻止线粒体酶复合
体活性的下降,保护线粒体的功能,防止多巴胺神经元的凋亡。
3. 中药银杏平颤全方和拆方可调节 PD 鼠脑内 Calbindin D28k 的表达
Calbindin D28k(CB)是脑内神经元内存在着一个重要的钙结合蛋白,它可以通过结
合细胞内的钙离子,调节细胞内的钙平衡,对神经元损伤起到部分保护作用。我们的实
验显示 PD 鼠脑内多巴胺神经元丢失的敏感区内(黑质和 VTA)Calbindin D28k 的表达可
反射性的增高,在海马 CA1 区和 CA2 区 Calbindin D28k 的表达也升高,而在脑皮质
Calbindin D28k 的表达降低。提示不同脑区神经元对 MPTP 的毒性反应不同,神经元内
Calbindin D28k 的表达增高,可能是细胞内钙超载导致神经元启动自我保护机制的结
果。一般来说,全方和化瘀中药可上调中脑、皮质和海马 CB 表达,早期(14 天)较后
期(28 天)更明显,提示中药可能通过增加钙结合蛋白 CB 的表达,调节细胞内的钙平
衡,达到保护神经元的目的。另外我们同样观察到解毒组中药在早期上调 CB 的作用明
显,后期效果不显著;而平肝中药在后期上调 CB 的效果明显,这提示在 PD 早期多巴
胺神经元内各种自由基的产生加速、细胞
Parkinson’s disease(PD) is a neurodegenerative disease. It is one of the
main diseases with high incidence and disable rate , also many sequelae. A
major pathological hallmark of Parkinson’s disease is a progressive loss of
dopaminergic neurons in the substantia nigra pars compacta(SNpc) and their axons,
which project to the striatum. The loss of dopaminergic neurons results in
decrease of dopamine in the striatum and imbalance in dopamine and acetylcholine.
So Parkinson’s disease is characterized by resting tremor ,rigidity and akinesia .
Recent studies have suggested that main causes of neuronal death in PD are
apoptosis. Despite extensive research, the disease remains poorly understood
and there is still no effective treatment. Chinese herbal medicine have efficacy
at treating PD. According to the theory of traditional Chinese medicine and based
on clinical practices, Ginkgo Biloba Pingchan Recipe(GBPR) is consisted. To
elucidate the effect and mechanism of GBPR and its three separated
prescriptions, we observed the changes of apoptosis-related molecules and
factors in SNpc in Parkinsonian mice model with MPTP-treated.
This study is consisted of four parts:(1)To observe the loss and apoptosis
of dopaminergic neurons in SNpc in Parkinsonian mice and the roles of GBPR and
its three separated prescriptions;(2) To observe the activity of the
mitochondrial complex in brain in Parkinsonian mice and influence of GBPR and
its three separated prescriptions;(3) To observe the expression of the
calcium-binding protein calbindin D28k in brain in Parkinsonian mice and
influence of GBPR and its three separated prescriptions by ABC
immunohistochemistry technique;(4) To observe the expression of the apoptotic
regulated factors Caspase-9、Caspase-3、Bcl-2、Caspase-3mRNA and Bcl-2mRNA in
SNpc in Parkinsonian mice and the effect of GBPR and its three separated
prescriptions by ABC immunohistochemistry and in situ hybridization technique.
In experimental research, male C57BL/6J mice are injected intraperitoneally
with a total cumulative dose of 150mg/kg MPTP ,30mg /kg daily to induce
Parkinson’s disease model. The modeled mice are called Parkinsonian mice. The
英文摘要 5
experimental animals is divided randomly into six groups:(1)The normal control
group( NC); (2) The model control group( MC);(3) Ginkgo Biloba Pingchan Recipe
group( GBPR); (4) Jiedu Recipe group (JDR); (5) Pinggan Recipe group(PGR); (6)
Huayu Recipe group;(HYR) .The animals were killed respectively on the 14th and
the 28th day after first injecting with MPTP.
The main results are displayed as follow:
1.Chinese herbal medicine Ginkgo Biloba Pingchan Recipe and its separated
Recipe may inhibit the loss and apoptosis of TH+ dopaminergic neurons
In the experimental studying, ABC immunohistochemistry technique is
used.The TH+ dopaminergic neurons were counted in every group . The number of
TH+ neurons in SNpc in MC is decreased by 52.14% on the 14th day and 60.78%
on the 28th day.The option density for TH+ neurons and fibers also obviously
reduced by 90.42% on the 14th day and 93.20% on the 28th day.The loss of TH+
neurons are partly inhibited in SNpc of Chinese herbal medicine. The number
of TH+ neurons in SNpc of JDR and HYR is decreased by 16.6% and 17.55% on the
14th day; The number of TH+neuronsin SNpc of GBPR and PGR is decreased by 22.72%
and 20.61% on the 14th day. On 28th Day, The degree of loss of TH+ neurons in SNpc
of GBPR is lightest ,for 33.2%; HYR,PGR and JDR are respectively for 43.94%,44.9%
and 49.23%. The option density for TH+ neurons and fibers in SNpc of Chinese
herbal medicine is also increased.The trend is similar to the changes of number
of TH+ neurons.
The apoptotic cells in SNpc is found by Tunel tethnique. The number and
density of apoptotic cells in SNpc in MC are increased,on 14th day is more
obvious. Chinese he
引文
1.Prochiantz A,di Porzio U,Kato A,Berger B,Glowinski J. In vitro maturation
of mesencephalic dopaminergic neurons from mouse embryos is enhanced in presence
of their strital target cells. Proc Natl Acad Sci USA, 1979;76: 5387-5391
2.Hoffmann PC,Hemmendinger LM,Kotake C,Heller A. Enhanced dopamine cell
survival in reaggregates containing target cell. Brain Res, 1983;274: 275-281
3. Macaya A,Burke RE. Effect of striatal lesion with quinolinate on the
development of substantia nigra dopamiergic neurons: a quantitative
morphological analysis. Dev Neurosci, 1992;14:362-368
4.Neystat, M., M.Rzhetskaya, T. F.Oo, et al. expression of cyclin-dependent
kinase 5 and its activator p35 in models of induced apoptotic death in neurons
32 银杏平颤方对 PD 鼠中脑多巴胺神经元凋亡的影响及机制探讨
of the substantia nigra in vivo. J Neurochem, 2001;77:1611-1625
5.Macaya A,Munell F,Gubits RM,et al. Apoptosis in substantia nigra following
developmental stratal excitotoxic injury. Proc Natl Acad Sci USA, 1994;91:
8117-8121
6.Marti MJ,James CJ,Oo TF,et al 。Early developmental destruction of terminals
in the striatal target induces apoptosis in dopamine neurons of the substantia
nigra.J Neurosci, 1997;17:2030-2039
7. Oo TF, Burker RE. The time course of developmental cell death in phenotypically
defined dopaminergic neurons of the substantia nigra. Dev Brain Res, 1997;98:
191-196
8.Jackson-Lewia,V.,M.Vila, R.Djaldetti, et al. Developmental cell death in
dopaminergic neurons of the substantia nigra of mice. J Comp Neurol, 2000; 424:
476-488
9.Takahashi T, Deng Y,Maruyaama W,et al. Uptake of a
neurotox-in-candidate,(R),1,2-dimenthyl-6,7-dihydroxy-1,2,3,4-tetra-hydrois
oquinoline into human dopaminergic neuroblastoma SH-SY5Y cells by dopamine
transport system. J Neural Transm Gen Sect, 1994; 98: 107-118
10.Dipasquale B, Marini AM,Youle RJ. Apoptosis and DNA degradation induced by
1-methyl-4-phenylpyridinium in neurons. Biochem Biophys Res Commum,
1991;181:1442-1448
11.Jason P. Sheehan, Patricia E.Palmer, Gregory A. Helm, et al. MPP+ induced
apoptotic cell death in SH-SY5Y neuroblastoma cells: an electron microscope
study. J. Neurosci. Res, 1997;48(3):226-237
12.Christopher P.Fall and James P. Bennett, Jr. Characterization and time course
of MPP+-induced apoptosis in human SH-SY5Yneuroblastoma cells. J. Neurosci.
Res, 1999;55:620-628
13.方芳,陈晓春,朱元贵等. MPP+对 SH-SY5Y 细胞凋亡的诱导作用.福建医科大学学
报,2001;35(3):211-216
14.方芳,陈晓春,朱元贵等. MPP+诱导 SH-SY5Y 细胞凋亡的可能机制. 中国神经科学
杂志, 2002; 18(2):522-526
15.Walkinshaw G,and Waters CM. Neurotoxin-induced cell death in neuronal PC12
cells is mediated by indution of apoptosis. Neurosci,1994;63(4):975-987
16.Woodgate A, Macgibbon G, Walton M, et al . The toxicity of 6-OHDA on PC12
d PC19 cells. Brain ResMol Brain Res,1999;69(1):84-92
17.Hartley A,Stone JM,Heron C,et al. Complex I inhibitors induce dose-dependent
apoptosis in PC12 cells: relevance to Parkinson’s disease. J. Neurochem,
1994;63(4):1987-1990
18.Walkinshaw G,and Waters CM. Induction of apoptosis in catecholaminergic PC12
cells by L-dopa. J Clin Invest, 1995;95: 2458-2464
19.韩燕 陈俊抛 田时雨等. 左旋多巴诱导PC12细胞凋亡的实验研究. 中华神经科杂志,
1999;32(5):284-286
20.韩燕 陈俊抛 田时雨等. L-dopa 诱导 PC12 细胞凋亡及 Bcl-2、Bax 表达的改变. 中
国神经免疫学和神经病学杂志, 2001;8(2):88-91
21.Zeevalk GD,Bemard LP, Nicklas WJ. Role of oxidative stress and the glutathione
system in loss of dopamine neurons due to impairment of energy metabolism . J
综述一 帕金森病中细胞凋亡的研究进展 33
Neurochem,1998;70: 1421-1430
22.Del Rio MJ,Velez-pardo C.17β-Estrdiol protects lymphocytes against dopamine
and iron-induced apoptosis by a genomic-independent mechanism: implication in
Parkinson’s disease. Gen Pharmacol ,2001;35:1-9
23.陈晓春 朱元贵 朱理安等,Bcl-2 和 Bax 在多巴胺诱导 PC12 凋亡中的作用.中华老
年医学杂志, 2001;20(2):124-127
24.陈晓春 朱元贵 王小众等,一氧化氮和 caspase-3 在多巴胺诱导 PC12 凋亡中的作
用。 中国病理生理杂志 2001;17(10):971-975
25.李立宏 高国栋 王学廉 等.多巴胺诱导 PC12 细胞凋亡的免疫组织化学及超微结构
分析. 第四军医大学学报, 2001;22(4):326-329
26.Mitchell IJ,Lawson S,Moser B,et al。Glutamate-induced apoptosis results
in a loss of striatal neurons in the parkinsonian rat.Neuroscience,1994;63
(1):1
27. Wang ZH,Ji Y, Shan W, et al. Therapeutic effects of astrocytes expressing
both tyrosine hydroxylase and brain-derived neurotrophic factor on a rat model
of Parkinson’s disease. Neuroscience, 2002;113(3): 629-640
28.He,Y., T.Lee,and S.K.Leong. 6-Hydroxydopamine induced apoptosis of
dopaminergic cells in the rat substantia nigra. Brain Res, 2000;858:163-166
29.Ichitani Y,Okamura H,Matsumoto Y,et al;Degeneration of the nigral dopamine
neurons after 6-hydroxydopamine injection into the rat striatum.Brain Res, 1991;
549:350-353
30.Ichitani Y,Okamura H,Nakahara D;et al ;Biochemiacal and immunocytochemical
changes induced by intrastriatal 6- hydroxydopamine injection in the rat
nigrostriatal dopamine neuron system:evidence for cell death in the substantia
nigra.Exp Neurol, 1994;130:269-278
31.Jeon BS,Jackson-Lewis V,Burke RE.6-Hydroxydopamine lesion of the rat
substanta nigra:time course and morphology of cell death。Neurodegeneration,
1995;4:131-137
32.Jackson-Lewis V,Jakowec M,Burke RE,et al 。Time course and morphology of
dopaminergic neuronal death caused by the neurotoxin
1-methyl-4-phenyl-1236-tetrahydropyridine.Neurodegeneration, 1995;4:257-269
33.Tatton NA,Kish SJ。In situ detection of apoptotic nuclei in the substantia
nigra compacta of 1-methyl-4-phenyl-1236-tetrahydropyridine-treated mice using
terminal deoxynucleotidyl transferse labeling and acridine
orange.Neuroscience ,1997;77:1037-1048
34.郭明、陈生弟、刘振国、陈红专.帕金森病小鼠黑质细胞凋亡的实验研究. 中华神经
科杂志, 1998;31(4):216-219
35.郭明、陈生弟、刘振国、陈红专.MPTP 诱发 C57-BL 小鼠黑质细胞凋亡.上海第二医科
大学学报,1999;19(1):28-31
36.匡国锋 童启进 王德新 赵伟秦. MPTP 小鼠黑质神经元细胞凋亡及 Deprenyl 抗凋
亡作用的研究. 脑与神经疾病杂志, 1999;7(3):133-135
37.Richter C, Gogvadze V, Laffranchi R et al. Oxidants in mitochondrial :from
physiology to disease. Biochim.biophys.Acta, 1995;1271:67-74
38.Mahalik TJ,Hahn WF,Clayton GH, et al . Programmed cell death in developing
grafts of fetal substantia nigra. Exp Neurol, 1994;129: 27-36
34 银杏平颤方对 PD 鼠中脑多巴胺神经元凋亡的影响及机制探讨
39.Zawada WM, Zastrow DJ,Clarkson ED, et al . Growth factors improve immediate
survival of embrymic dopamine neurons after transplantation into rats. Brain
Res ,1998; 786: 96-103
40. Ko..sel S, Egensperger R , v. Eitzen U, et al. On the question of apoptosis
in the parkinsonian substantia nigra. Acta Neuropathol, 1997; 93:105-108
41.Banati RB,Blunt SB,Graeber MB. What does apoptosis have to do with Parkinson’
s disease?Mov Disord, 1999;14:384-385
42.Jellinger AK Cell death mechanisms in Parkinson ’ s disease. J Neural
Transm ,2000;107:1-29
43.Anglade P,Vyas S,Javoy-Agid F,et al .Apoptotic degeneration of nigral
dopaminergic neurons in Parkinson’s disease. Neurology ,1996 ;46-2: A467
44.Anglade P,Vyas S,Javoy-Agid F,et al .Apoptosis and autophagy in nigral
neurons of patients with Parkinson’s disease. Histol histopathol 1997a,12:25-31
45.Mochizuki H,Goto K,Mori H ,et al.Histochemical detection of apoptosis in
Parkinsin’disease .J neurol sci, 1996;137:120-123
46.Mochizuki H,Mori H,Mizuno Y.Apoptosis in neurodegenerative disorders。 J
Neural Transm Suppl,1997;50:25-40
47.Kingsbury AE,Marsden CD ,Foster OJF. DNA fragmentation in human substantia
nigra: apoptosis or perimortem effect? Mov Disord, 1998,13: 877-884
48.Wullner U,Kornhuber J, Weller M, et al. Cell death and apoptosis regulating
proteins in Parkinson ’ s disease-a cautionary note. Acta Neuropathol,
1999,97:408—412
49.Majno G, Joris I。 Apoptosis ,oncosis and necrosis :an overview of cell
death. Am J Pathol ,1995,146:3—14
50.Fujikawa DG,Shinmei SS, Cai B, et al 。 Neuronal death induced by
Lithium-Pilocarpine-induced seizures is morphologically necrotic despite
“apoptotic ”biochemical features.Ann Neurol, 1998;44:463
51.Tompkins MM, Basgall EJ, Zamrini E, et al Apoptotic-like changes in Lewy
body-associated disorders and normal aging in substantia nigral neurons. Am J
pathol, 1997;150: 119-131.
52. Tatton NA ,Maclean-Fraser A,Tatton WG,et al ,A fluorescent double-labeling
method to detect and confirm apoptotic nuclei in Parkinson’s disease.Ann Neurol,
1998;44(suppl 1):s142-s148
53.Olanow, W. An introduction to the free radical hypothesis in Parkinson’s
disease. Ann. Neurol, 1992;32:S2-S9
54.Ziv. I.,Melamed,E.,Nardi,N., et al. dopamiNeinduce apoptosis-like
cell death in cultured chick sympathetic neurons — a possible pathogenic
mechanism in Parkinson’s disease. Neurosci Lett, 1994; 170: 136-140
55.Offen,D.,Ziv,I., Gorodin, S., et al . Dopamine-induced programmed cell death
in mouse thymocytes. Biochim. Biophys.Acta, 1995; 1268:171—177
56.Offen D., Ziv,I., Panet, HL., et al. Dopamine-induced apoptosis is inhibited
in PC12 cells expressing Bcl-2. Cellular and Molecular Neurobiology,
1997;17(3):289-304
57.Maruyama W,Akao Y,Carrillo MC,et al. Neuroprotection by propargylamines
in Parkinson’s disease :suppression of apoptosis and induction of prosurvival
综述一 帕金森病中细胞凋亡的研究进展 35
genes. Neurotoxicol Teratol, 2002;24(5):675-682
58.周国庆 周孝达 王桂松等. 多巴胺和谷胱甘肽对 PC12 细胞凋亡的影响.上海第二医
科大学学报, 1999;19(1):44-46
59. Choi HJ, Kim SW, Lee SY,et al. Involvement of apoptosis and calcium
mobilization in tetrahydrobiopterin-induced dopaminergic cell death. Exp Neurol,
2003;181(2):281-90.
60.Naoi M,Maruyama W. Cell death of dopamine neurons in aging and Parkinson’
s disease. Mech Aging Dev,1999;111(2-3):175-188
61.Junn E, Mouradian MM. Apoptotic signaling in dopamine-induced cell death:
the role of oxidative stress, p38 mitogen-activated protein kinase, cytochrome
c and caspases. J Neurochem. 2001 ;78(2):374-83.
62.梁立平 左旋多巴诱发羟自由基增高的机制与防治. 中华神经科杂志, 1998;31
(4):223-225
63.Ali SF, David SN,Newport GD, et al. MPTP-induced oxidative stress and
neurotoxicity are age-dependent:evidence from measures of reactive oxygen
speces and striatal dopamine levels. Synapse, 1994;18:27-34
64. Kalivendi SV, Kotamraju S, Cunningham S,et al. 1-Methyl-4-phenylpyridinium
(MPP+)-induced apoptosis and mitochondrial oxidant generation: role of
transferrin-receptor-dependent iron and hydrogen peroxide. Biochem J,
2003 ;371(Pt 1):151-64.
65.Chuang JI, Chen TH. Effect of melatonin on temporal changes of reactive oxygen
species and glutathione after MPP(+) treatment in human astrocytoma U373MG
cells. : J Pineal Res, 2004 ;36(2):117-25.
66.Chun HS,Gibson GE, Degiorgio LA et al. Dopaminergic cell death induced by
MPP+,oxidant and specific neurotoxicants shares the common molecular mechanism.
J Neurochem, 2001; 76(4):1010-21
67.Kumar R,Agarwal AK, Seth PK.Free radical-generated neurotoxicity of
6-hydroxydopamine. J Neurochem ,1995;64:1703—7
68.Glinka Y,Youdim MBH. Inhibition of mitochondrial complexes I and IV by
6-hydroxydopamine. Eur J Pharmacol, 1995;292:329-32
69.Marlene Jimenez Del Rio,Carlos Velez-Pardo. Monoamine neurotoxins-induced
apoptosis in lymphocytes by a common oxidative stress mechanism: involvement
of hydrogen peroxide(H2O2),caspase-3,and nuclear factor kappa-B(NF-κ
B),P53,c-Jun transcription factors. Bioche Pharmacology ,2002;63: 677-688
70.Dipietrantonio AM,Hsieh T,Wu JM. Activation of caspase-3 in HL-60cells
exposed to hydrogen peroxide. Biophys Res Commun, 1999;255:477-82
71.张宝,莫永炎,周玫,陈瑗. 锰超氧化物歧化酶过表达对 H2O2诱导 PC12 细胞凋亡的
影响. 第一军医大学学报 , 2000;20(6):510-512
72.Kitazawa M,Anantharam V,Kanthasamy AG. Dieldrin-induced oxidative stress
and neurochemical changes contribute to apoptopic cell death in dopaminergic
cells. Free Radic Biol Med ,2001;31(11)1473-85
73.Sian J,Dexter DT,Less AJ,et al。Alteration in glutathion levels in Parkinson’
s disease and other neurogenerative disorders affecting basal ganglia. Ann
Neurol,1994;36:348
36 银杏平颤方对 PD 鼠中脑多巴胺神经元凋亡的影响及机制探讨
74.Perry TL, Hansen S, Jones K. Brain amino acids and glutathione in progressive
supranuclear palsy. Neurology,1998;38:943-946
75.Jenner P,Fahn S,Cohen G,et al. Oxidative stress as a course of nigra cell
death in Parkinson’s disease and incidental Lewy body disease. Ann Neurol,
1992;32: S116-123
76.Merad-Boudia M,Nicole A,Santiard-Baron D et al . Mitochondrial impairment
as an early event in the process of apoptosis induced glutathione depletion in
neuronal cell : relevance to Parkinson’s disease. Biochem Pharmacol,
1998;56(5):645-655
77.Schapira AHV,Cooper JM,Dexter D,et al. Anatomic and disease specificity
of NADH CoQ reductase 78.deficiency in Parkinson ’ s diseases. J
Neurochem,1990;55:2142-2145
Janetzky B,Hauck S,Youdim MBH, et al. Unaltered aconitase activity, but
decreased complex I activity in substantia nigra pars compact of patient with
Parkinson’s disease. Neurosci Lett,1994;169:126-128
79.Haas RH,Nasirian F, Nakano K, et al. Low platelet mitochondrial complex I
and complex II/III activity in early untreated Parkinson ’ s disease. Ann
Neurol ,1995;37:714-722
80.Swerdlow RH, Parks JK,Miller SW,et al.Origin and functional consequences of
the complex I defect in Parkinson’s disease. Ann Neurol ,1996;40:663-671
81.高枫, 陈清棠. 原发性帕金森病线粒体复合物 I 功能缺陷. 北京医科大学学报,
1999;31(3):268
82.高枫, 陈清棠, 李险峰. 帕金森病患者线粒体功能缺陷的研究. 中华神经科杂
志,1999;32(4):199-201
83.William G.Tatton andRuth M.E.Chalmers-Redman. Mitochondria in
neurodegenerative apoptosis: An opportunity for therapy? Ann
Neurol,1998;44(suppl 1):s134-s141
84.Adams JD,Jr, Klaidman LK, Leung AC. MPP+and MPDP+ induced oxygen radical
formation with mitochondrial enzymes. Free Rad Biol Med, 1993;15:181-186
85.Zoratti M,Szabo I. The mitochondrial permeability transition. Biochim
Biophys Acta, 1995;1241;139-176
86.Greenlund LJ,Deckwerth TL,Johnson EM,Jr. Superoxide dismutase delays
neuronal apoptosis: a role for reactive oxygen species in programmed neuronal
death. Neuron, 1995;14;303-315
87.Marchetti P, Susin SA,Decaudin D, et al .Apoptosis associated derangement
of mitochondrial function in cells lacking mitochondrial DNA. Cancer
Res ,1996;56:2033-2038
88.Zamzami N,Marchetti P, Castedo M, et al. Sequential reduction of
mitochondrial transmembrane potential and generation of reactive oxygen species
in early programmed cell death. J Exp Med, 1995a;182:367-377
89.Maruyama W,Akao Y,Carrillo MC,et al. Neuroprotection by propargylamines
in Parkinson’s disease :suppression of apoptosis and induction of prosurvival
genes. Neurotoxicol Teratol, 2002;24(5):675-682
90.Christopher P.Fall and James P. Bennett, Jr. Characterization and time course
of MPP+-induced apoptosis in human SH-SY5Yneuroblastoma cells. J. Neurosci.
综述一 帕金森病中细胞凋亡的研究进展 37
Res, 1999;55:620-628
91.Kroemer G,Zamzami N,Susin SA.Mitochondrial control of apoptosis. Immunol
Today, 1997;18:44-51
92.Halestrup AP,Woodfield KY,Connern CP,et al.Oxidative stress,thoil reagents,
and membrane potential modulate the mitochondrial permeability transition by
affecting nucleotide binding to the adenine nucleotide. J Biol Chem,
1997;272(6):3346-3354
93.Green DR , Reed JC. Mitochondria and apoptosis. Science,
1998;281(5381):1309-1312
94.Rego AC, Oliveira CR. Mitochondrial dysfunction and reactive oxygen species
in excitotoxicity and apoptosis: implications for the pathogenesis of
neurodegenerative diseases. Neurochem Res, 2003 ;28(10):1563-74.
95.Antonsson B. Mitochondria and the Bcl-2 family proteins in apoptosis
signaling pathways. Mol Cell Biochem, 2004;256-257(1-2):141-55.
96. Liston P, Fong WG, Korneluk RG. The inhibitors of apoptosis: there is more
to life than Bcl-2. Oncogene, 2003 ;22(53):8568-80.
97.Tatton WG,Olanow CW. Apoptosis in neurodegenerative disease: the role of
mitochondria. Biochim Biophysi Acta, 1999;1410:195-213
98.Fiskum G, Starkov A, Polster BM,et al. Mitochondrial mechanisms of neural
cell death and neuroprotective interventions in Parkinson's disease. Ann N Y
Acad Sci, 2003;991:111-9.
99.Park TH, Kwon OS, Park SY,et al. N-methylated beta-carbolines protect PC12
cells from cytotoxic effect of MPP+ by attenuation of mitochondrial membrane
permeability change.Neurosci Res, 2003 ;46(3):349-58.
100.Chalmers-Redman RM, Fraser AD, Carlile GW, et al.Glucose protection from
MPP+-induced apoptosis depends on mitochondrial membrane potential and ATP
synthase. Biochem Biophys Res Commun, 1999 ;257(2):440-7.
101.Nagatsu T,Mogi M,Ichinose H, et al. Changes in cytokines and neurotrophins
in Parkinson’s disease. J Neural Transm Suppl, 2000;(60):277-290
102.Burke RE,Antonelli M,Sulzer D.Glial cell line-derived neurotrophic growth
factor inhibits apoptotic death of postnatal substantia nigra dopamine neurons
in primary culture. J Neurochem, 1998;71(2):517-525
103.Schatz DS,Kuafmann WA,Saria A,Humpel C. Dopamine neurons in a simple
GDNF-treated meso-striatal organotypic co-culture model. Exp Brain Res,
1999;127(2):270-278.
104.Clarkson ED,Zawada WM,Freed CR. GDNF reduces apoptosis in dopamineergic
neurons in vitro. Neuroreport, 1995;7(1):145-149
105.Clarkson ED,Zawada WM,Freed CR. GDNF improves survival and reduces apoptosis
in human embryonic dopamineergic neurons in vitro. Cell Tissue Res,
1997;289(2):207-210
106.Thajeb P,Ling ZD, Potter ED,et al. The effects of storage conditions and
trophic supplementation on the survival of fetal mesencephalic cells. Cell
Transplant, 1997;6(3):297-307
107.Kaddis FG,Zawada WM, Schaack J, Freed CR. Conditioned medium from aged monkey
fibroblasts stably expressing GDNF and BDNF improveds survival of embryonic
38 银杏平颤方对 PD 鼠中脑多巴胺神经元凋亡的影响及机制探讨
dopamine neurons in vitro. Cell Tissue Res, 1996;286(2):241-247
108.Zawada WM, Zastrow DJ,Clarkson ED, et al. Growth factors improve immediate
survival of embryonic dopamine neurons after transplantation into rats. Brain
Res, 1988; 786(1-2):96-103
109.Wang ZH,Ji Y, Shan W, et al. Therapeutic effects of astrocytes expressing
both tyrosine hydroxylase and brain-derived neurotrophic factor on a rat model
of Parkinson’s disease. Neuroscience, 2002;113(3): 629-640
110.Brundin P, Karlsson J, Emgard M,et al. Improving the survival of grafed
dopaminergic neurons : a review over current approaches. Cell Transplant,
2000;9(2):179-195
111.Sawada H,Ibi M,Kihara T, et al. Neuroprotective mechanism of glial cell
line-derived neurotrophic factor in mesencephalic neurons. J Neurochem, 2000;
74(3):1175-1184
112.Lingor P,Unsicker K, Krieglstein K. GDNF and NT-4 protect midbrain
dopaminergic neurons from toxic damage by iron and nitric oxide . Exp Neurol,
2000;163(1):55-62
113.Petersen AA,Larsen KE, Behr GG, et al. Brain-derived neurotrophic factor
inhibits apoptosis and dopamine-induced free radical production in striatal
neurons but does not prevent cell death. Brain Res Bull, 2001;56(3-4): 331-335.
114.Toth G,Yang H, Anguelov RA, et al. Gene transfer of glial cell dedrived
neurotrophic factor and cardiotrophin-1 protects PC12 cells from
injury:involvement of thephosphatidylinositol3-kinase and mitogen-activated
protein kinase kinase pathways. J Neurosci Res, 2002; 69(5):622-632
115.徐仁,孙圣刚,刘煜敏,等.实验性帕金森病纹状体、大脑皮质和海马组织 MCa、CaM、
MDA含量的变化. 中华神经科杂志,2000;33(1):27
116.Greenamyre JT, MacKenzie G, Peng TI,et al. Mitochondrial dysfunction in
Parkinson's disease.Biochem Soc Symp, 1999;66:85-97.
117.Lacopino AM,Christakos S. Specific reduction of calcium-binding protein
(28-kilodalton calbindin-D)gene expression in aging and neurodegenerative
diseases. Proc Natl Acad Sci USA, 1990 ;87(11):4078-82
118.WANG Lian-Gang, WU Sheng-Xi, WUYi-Jun, et al.Calbindin-D28kmRNA expression
in substanti anigra in mice Parkinson's disease 第 四 军 医 大 学 学
报,2001;22(1):33-36
119.McMahon A, Wong BS, Iacopino AM,et al. Calbindin-D28k buffers intracellular
calcium and promotes resistance to degeneration in PC12 cells.Brain Res Mol Brain
Res, 1998;54(1):56-63
120.Ray SK, Fidan M, Nowak MW,et al.Oxidative stress and Ca2+ influx upregulate
calpain and induce apoptosis in PC12 cells. Brain Res, 2000 ;852(2):326-34
121. Rodnitzky RL. Can calcium antagonists provide a neuroprotective effect in
Parkinson’s disease? Drugs, 1999; 57(6): 845-9
122.Choi HJ, Kim SW, Lee SY,et al. Involvement of apoptosis and calcium
mobilization in tetrahydrobiopterin-induced dopaminergic cell death.Exp Neurol,
2003 ;181(2):281-90.
123.Mcconkey DJ,Mutt LK. Calcium flux measurements in apoptosis.Methods
CellBiol, 2001;66:229-246
综述一 帕金森病中细胞凋亡的研究进展 39
124.Schild L,Keilhoff G,Augustin W, et al. Distinct Ca2+ thresholds determine
cytochrome c release or permeability transition pore opening in brain
mitochondria. FASEB J,2001; 15(3):565-7
125. Brustovetsky N,Brustovestsky T,Jemmerson R, et al. Cakcium-induced
cytochrome c release from CNS mitochondria is associated with the permeability
transition and rupture of the outer membrane. J Neurochem 2002; 80(2):207-218
126.Kruidering M,Schouten T, Evan GL,et al. Caspase-mediated cleavage of the
Ca2+/cakmodulin dependent protein kinase-like kinase facilitates neuronal
apoptosis. J Biol Chem, 2001; 276(42):38417-25 .
127.Blandini F,Porter RH, Greenamyre JT. Glutamate and Parkinson’s disease.
Mol Neurobiol, 1996; 12 73-94
128.Weihmuller FB, Ulas J, Nguyen L, et al. Elevated NMDA receptors in
parkinsonian stritum. Neuroreport, 1992; 3(11): 977-980
129.马坚林,范凯,张万琴等. 偏侧帕金森病大鼠模型丘脑底核谷氨酸能神经元的免疫
组化研究. 神经解剖学杂志, 2000; 16(4): 376-378
130.王传功, 徐霞,库宝善 NMDA 受体和 GABA 受体拮抗剂对小鼠帕金森模型的行为学药
理学影响. 中国行为医学科学, 1998; 7(1):19-21
131.Dargusch R, Piaseck D, Tan S, et al. The role of Bax in glutamate-induced
nerve cell death. J Neurochem, 2001; 76(1):295-301
132.Tan S, Schubert D,Maher P. Oxytosis:A novel form of programmed cell death.
Curr Top Med Chem, 2001;1(6): 497-506
133.Almeida A,Bolanos JP. A transient inhibition of mitochondrial ATP synthesis
by nitric oxide synthase activation triggered apoptosis in primary cortical
neurons. J Neurochem, 2001 ;77(2): 676-690
134.Zipfel GJ, Babcock DJ, Lee JM, et al. neuronal apoptosis after CNS injury :
the roles of glutamate and calcium. J Neurotrauma 2000;17(10):857-869
135.Greenamyre JT, Mackenzie G, Peng TI, et al. Mitochondrial dysfunction in
Parkinson’s disease. Biochem Soc Symp, 1999; 66:85-97
136.Itzhak Y, Gandia C, Huang PL,et al. Resistance of neuronal nitric oxide
synthase deficient mice to methamphetamine-induced dopaminergic
neurotoxicity. J Pharmacol. Exp. Ther, 1998; 284: 1040-1047
137.周国庆 周孝达 王桂松. 一氧化氮合成酶抑制剂对 MPTP 神经毒性的影响. 中国神
经精神杂志, 1998; 24(6):374-375
138.周国庆 周孝达 金永清等. 一氧化氮与帕金森病大鼠模型神经损伤的研究. 中风
与神经疾病杂志, 2000; 17(5): 288-289
139.Ebadi M, Sharma SK. Peroxynitrite and mitochondrial dysfunction in the
pathogenesis of Parkinson's disease.Antioxid Redox,. 2003 ;5(3):319-35.
140.Brown GC,Borutaite V. Nitric oxide, cytochrome c and mitochondria. Biochem
Soc Symp, 1999; 66: 17-25
141.Bal-Price A, Brown GC. Nitric-oxide-induced necrosis and apoptosis in P C12
ccells midiated by mitochrodria. J Neurochem, 2000; 75(4): 1455-1464
142.Dennis J, Bennett JP Jr. Interactions among nitric oxide and Bcl-family
proteins after MPP+ exposure of SH-SY5Y neural cells I: MPP+ increases
mitochondrial NO and Bax protein. J Neurosci Res, 2003 ;72(1):76-88.
40 银杏平颤方对 PD 鼠中脑多巴胺神经元凋亡的影响及机制探讨
143.Emerit J, Edeas M, Bricaire F. Neurodegenerative diseases and oxidative
stress.Biomed Pharmacother, 2004 ;58(1):39-46.
144.陈晓春 朱元贵 王小众等. 一氧化氮和 caspase-3 在多巴胺诱导 PC12 细胞凋亡中
的作用. 中国病理生理杂志, 2001;17(10):971-975
145.Lipton SA, Choi YB, Pan ZH et al. A redox-based mechanism for neuroprotective
and neurodestractive effects of nitric oxide and related nitroso-compounds.
Nature ,1993; 364: 626-632
146.Matthew J. LaVois and Teresa G. Hastings, Peroxynitric- and nitrite-induced
oxidation of dopamine: implications for nitric oxide in dopaminergic cell loss.
J Neuroche, 1999;73(6):2546-2553
147.Uehara T, Kikuchi Y, Nomura Y.Caspase activation accompanying cytochrome
c release from mitochondria is possibly involved in nitric oxide-induced
neuronal apoptosis in SH-SY5Y cells. J Neurochem, 1999 ;72(1):196-205.
148.Jellinger KA. Cell death mechanisms in Parkinson’s disease. J Neural
Trans ,2000;107(1):21-29
149.Itano Y, Nomura Y. 1-methyl-4-phenyl-pyridinium ion (MPP+) causes DNA
fragmentation and increases the Bcl-2 expression in human neuroblastoma, SH-SY5Y
cells, hrough different mechanisms. Brain Res, 1995 ;704(2):240-45.
150.Veech GA, Dennis J, Keeney PM,et al.Disrupted mitochondrial electron
transport function increases expression of anti-apoptotic bcl-2 and bcl-X(L)
proteins in SH-SY5Y neuroblastoma and in Parkinson disease cybrid cells through
oxidative stress. J Neurosci Res, 2000 ;61(6):693-700.
151.Kuwana T, Newmeyer DD. Bcl-2-family proteins and the role of mitochondria
in apoptosis.Curr Opin Cell Biol, 2003 ;15(6):691-9.
152.Cheng EH, Kirsch DG, Clem RT,et al.Conversion of bcl-2 to bax-like death
factor by caspases . Science, 1997;278(12):1966-1969
153.Reed JC. Double identity for proteins of the bcl-2 family. Nature,
1997;387(6635): 773-776
154.Kirsch DG,Doseff A,Chau BN et al. Caspase-3 dependent cleavage of bcl-2
promotes release of cytochrome C. J Biol Chem, 1999; 274(30): 21155-21161
155.Zhou P,Chou J,Olea RS,et al. Solution structure of Apaf-1 CARD and its
interaction with caspase-9 CARD: A structural basis for specific adaptor/caspase
interaction. Proc Natl Acad Sci USA,1999;96:11265-11270
156.Ashkenazi A,Dixit VM. Death receptors:signaling and modulation. Science,
1998;281:1305-1308
157.Rao RV,Hermel E, Castro-Obregon S, et al. Coupling endoplasmic reticulum
luminal enviroment affect cell sensitivity to apoptosis. J Cell Biol, 2000;
150:731-740
158.Wolf BB,Green DR. Suicidal tendencies: apoptotic cell death by caspase
family proteinases . J Biol Chem ,1999; 274:20049-20052
159.Change HY, Yang X. Protease for cell suicide:functions and regulation of
caspases. Micro Mol Biol Rev, 2000; 64: 821-846
160.Hartmmann A,Hunot S, Michel PP, et al. Caspase-3: a vulnerability factor
and final effector in apoptosis death of dopaminergic neurons in Parkinson’
s disease. Proc Natl Acad Sci USA, 2000, 97(6): 2875-2880
综述一 帕金森病中细胞凋亡的研究进展 41
161.Turmel H, Hartmenn A, Parain K. Caspase-3 activation in
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treaded mice. J Mov Disord,
2001;16(2):185-189
162.James Bilsland,Sophie Roy,Steve Xanthoudakis, et al. Caspase inhibitors
attenuate 1-methyl-4-phenylpyridinium toxicity in primary cultures of
mesencephalic dopaminergic neurons.J Neurosci, 2002 ;22(7):2637-49
163.Schierle GS,Hansson O,Leist M, et al.Caspase inhibition reduces apoptosis
and increase survival of nigral transplants. Nal Med, 1999;5:97-100
164.Dodel RC, Du Y, Bales R,et al.Peptide inhibitors of caspase-3-like proteases
attenuate 1-methyl-4-phenylpyridinum-induced toxicity of cultured fetal rat
mesencephalic dopamine neurons. Neuroscience, 1998 ;86(3):701-7.
165. Viswanath V, Wu Y, Boonplueang R, Chen S,et al Caspase-9 activation results
in downstream caspase-8 activation and bid cleavage in
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease.J
Neurosci, 2001;21(24):9519-28
166.Kaul S, Kanthasamy A, Kitazawa M, et all. Caspase-3 dependent proteolytic
activation of protein kinase C delta mediates and regulates
1-methyl-4-phenylpyridinium (MPP+)-induced apoptotic cell death in
dopaminergic cells: relevance to oxidative stress in dopaminergic
degeneration.Eur J Neurosci, 2003 ;18(6):1387-401.
167 .Amoroso S, D'Alessio A, Sirabella R, et al.Ca(2+)-independent caspase-3
but not Ca(2+)-dependent caspase-2 activation induced by oxidative stress leads
to SH-SY5Y human neuroblastoma cell apoptosis. Neurosci Res,
2002;68(4):454-62.
168. Waldmeier PC, Tatton WG. Interrupting apoptosis in neurodegenerative
disease: potential for effective therapy? Drug Discov Today,
2004 ;9(5):210-8.
169.Thomas M, Le WD. Minocycline: neuroprotective mechanisms in Parkinson's
disease.Curr Pharm Des, 2004;10(6):679-86.
170.O'Brien T, Lee D. Prospectsfor caspase inhibitors.Mini Rev Med Chem;
2004 ;4(2):153-65.
171. Voncoelln R, Kugler S, Bahr M. Rescue from death but not from functional
impairment: caspase inhibition protects dopaminergic cells against
6-hydroxydopamine-induced apoptosis but not against the loss of their terminals.
J Neurochem, 2001;77: 263-273
172.Jackson-Lewis V,M Vila, R Djaldetti,et al. Developmental cell death in
dopaminergic neurons of the substantia nigra of mice. J Comp Neurol, 2000;
424:476-488
173.Jeon BS,NG kholodilov, Tinmarla F.Oo,et al.Activation of caspase-3 in
developmental models of progammed cell death in neurons of the substantia nigra.J
Neurochem, 1999; 73:322-333
174.Tinmarla F.Oo, Robert Siman,and Robert E. Burke. Distinct nuclear and
cytoplasmic in two models of induced apoptotic death in dopamine neurons of the
substantia nigra. Exper Neurol, 2002; 175:1-9
175.Eberhardt O.,RV Coelln, S.Kugler,et al. Protection by synergistic effects
42 银杏平颤方对 PD 鼠中脑多巴胺神经元凋亡的影响及机制探讨
of adenovirus-mediated Xchromosome-linked inhibitor of apoptosis and glial cell
line-derived neurotrophic factor gene transfer in the
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease. J
Neurosci, 2000; 20: 9126-9134
176.Deveraux QL,Reed JC. IAP family proteins suppressors of apoptosis. Genes
Dev,1999;13:239-542
177.Kasof GM,Gomes BC. Livin, a novel inhibitor of apoptosis protein family
member . J Biol Chem,2001;276:3238-465
178.Crocker SJ, Liston P, Anisman H, et al. Attenuation of MPTP-induced
neurotoxicity and behavioural impairment in NSE-XIAP transgenic mice. Neurobiol
Dis, 2003 ;12(2):150-61.
179.Eberhardt O, Coelln RV, Kugler S,et al. Protection by synergistic effects
of adenovirus-mediated X-chromosome-linked inhibitor of apoptosis and glial
cell line-derived neurotrophic factor gene transfer in the
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. J
Neurosci, 2000 ;20(24):9126-34.
180.Suzuki Y,Nkabayashi Y, Takahashi R.Ubiquitin protein ligase activity of
X-linked inhibitor of apoptosis protein promotes proteasomal degradation of
caspase 3 and enhances its antiapoptotic effect in Fas induced cell death.Proc
Natl Acad Sci USA,2001;98(15):8662 8667.
181.Wang CY,MaYo MW,Korneluk RG,et al.NF-κB antiapoptosis:induction of TRAF1
and TRAF2 and cIAP1 and cIAP2 to suppress caspase 8 activation.
Science,1999;281:1680-1683
182.Du C,Fang M,Li Y,et al. Smac,a mitochondrial protein that promotes
cytochromecdependent caspase activation by eliminating IAP in
hibition .Cell,2000;102(1):33-42.
183.Verhagen AM,Ekert PG,Pakusch M,et al.Identification of DIABLO,a mammalian
protein that promotes apoptosis by binding to and antagonizing IAP
protieins.Cell,2000;102(1):43-53.
184.Roberts DL,Merrison W,Macfarlane M,et al.The inhibitor of apoptosis
proteinbinding domain of Smac is not essential for its proapoptotic activity.J
Cell Biol,2001,153(1):221 228.
185.Yang QH, Du C. Smac/DIABLO selectively reduces the levels of c-IAP1 and
c-IAP2 but not that of XIAP and livin in HeLa cells. J Biol Chem, 2004; [Epub
ahead of print]
186.Suzuki Y, Takahashi-Niki K, Akagi T,et al. Mitochondrial protease Omi/HtrA2
enhances caspase activation through multiple pathways. Cell Death Differ,
2004;11(2):208-16.
187.Cande C, Cecconi F, Dessen P, Kroemer G. Apoptosis-inducing factor (AIF):
key to the conserved caspase-independent pathways of cell death?J Cell Sci,
2002;115(Pt 24):4727-34.
188.Susin SA,Lorenzo HK,Zamzami N,et al.Molecular characterization of
mitochondrial apoptosis inducing factor.Nature,1999;397(6718):441-446.
189.Yu SW, Wang H, Dawson TM,et al. Poly(ADP-ribose) polymerase-1 and apoptosis
inducing factor in neurotoxicity.Neurobiol Dis, 2003 ;14(3):303-17.
综述一 帕金森病中细胞凋亡的研究进展 43
190.Wang H, Shimoji M, Yu SW,et al. Apoptosis inducing factor and PARP-mediated
injury in the MPTP mouse model of Parkinson's disease. Ann N Y Acad Sci,
2003 ;991:132-9.
191.Lewis TS,Shapiro PS,Ahn NG.Signal transduction through MAP kinase
cascades.Adv Cancer Res,1998;74(1):49-139.
192.Luo Y,Umegaki H,Wang X,et aL.Dopamine induces apoptosis through an
oxidation-involved SAPK/JNK activation pathway.J BC,1998;273(6):3756-3764.
193.Kang CD,Jang JH,Kim KW,et al.Activation of c-jun N-terminal
kinase/stress-activated protein kinase and the dicreased ratio of Bcl-2 toBax
are associated with the auto-oxidized dopamine-induced apoptosis in PC12 cells.
Neuroscience Letters, 1998;256(1):37-40.
194.Saporito MS,Brown EM,Miller MS,et al.CEP-1347/KT-7515,an inhibitor of
C-jun N-terminal kinase/stress-activated protein kinase,attenuates the
1-methyl-4-phenyl tetrahydropyridine-mediate loss of nigro striatal dopaminer
gic neurons in vivo.J Pharmacol Exp Ther,1999;288(2):421-427.
195.Saporito MS,Thomas BA,Scott RW.MPTP activates c-jun NH2-Terminal kinase
(JNK) and its upstream regulatory kinase MKK4 in nigro striatal neuron s in
vivo.J Neuro Chem,2000;75(3):1200-1208.
196.Oo TF,Henchcliffe C,James D,et al.Expression of c-fos,c-jun,and
c-jun-N-terminal Kinase(JNK) in a developmental model of induced apoptotic death
in neurons of the substantian nigra.J Neurochem,1999;72(2):557
197.Wang W,ShiL,Xie Y,et al.SP600125,a new JNK inhibitor,protects dopaminergic
neurons in the MPTP mpdel of Parkinson ’ s disease. Neurosci Res,
2004;48(2):195-202
198. Xu GX,Thomas H,Michael W,et al. Genetransfer of the JNK interacting protein
-1 protects dopaminergic neurons in the MPTP model of Parkinson’s desease. Proc
Natl Acad Sci USA, 2001;98(18):10433-10438.
199.Gearan T,Gastillo OA,Schwarzschild MA. The parkinsonian neurotoxin ,MPP+
induces phosphorylated c-jun in dopaminergric neurons of mesencephalic
cultures. Parkinsonism Relat Disord, 2001;8(1):19-22
200.Hirata Y,Adachi K,Kiuchi K.Activation of JNK pathway and induction of
apoptosisby manganese in PC12 cells.JNurrochem,1998;71(4):1607-1615.
201.Chun HS,Gibson GE,De Giorgio LA,et al.Dopaminergic celldeath induced by
MPP+,oxidant and specific neurotoxicants shares the common molecular
mechanism.J Neurochem,2001;76(4):1010-1021.
202.Evan G,Littlewood T. A matter of life and cell
death .Science,1998;281(5381):1317
203.Daily D,Barzilai A,Offen D,et al.The involvement of p53 in dopamine
inducedapoptosis of cerebellar granule neurons leukemic cells overexpressing
P53.Cell Mol Neurobiol,1999;19(2):261
204.Duan W, Zhu X, Ladenheim B,et al. p53 inhibitors preserve dopamine neurons
and motor function in experimental parkinsonism.Ann Neurol,
2002;52(5):597-606.
44 银杏平颤方对 PD 鼠中脑多巴胺神经元凋亡的影响及机制探讨
205.Nakaso K, Yoshimoto Y, Yano H,et al. p53-mediated mitochondrial dysfunction
by proteasome inhibition in dopaminergic SH-SY5Y cells. Neurosci Lett,
2004;354(3):213-6.
of mesencephalic dopaminergic neurons from mouse embryos is enhanced in presence
of their strital target cells. Proc Natl Acad Sci USA, 1979;76: 5387-5391
2.Hoffmann PC,Hemmendinger LM,Kotake C,Heller A. Enhanced dopamine cell
survival in reaggregates containing target cell. Brain Res, 1983;274: 275-281
3. Macaya A,Burke RE. Effect of striatal lesion with quinolinate on the
development of substantia nigra dopamiergic neurons: a quantitative
morphological analysis. Dev Neurosci, 1992;14:362-368
4.Neystat, M., M.Rzhetskaya, T. F.Oo, et al. expression of cyclin-dependent
kinase 5 and its activator p35 in models of induced apoptotic death in neurons
32 银杏平颤方对 PD 鼠中脑多巴胺神经元凋亡的影响及机制探讨
of the substantia nigra in vivo. J Neurochem, 2001;77:1611-1625
5.Macaya A,Munell F,Gubits RM,et al. Apoptosis in substantia nigra following
developmental stratal excitotoxic injury. Proc Natl Acad Sci USA, 1994;91:
8117-8121
6.Marti MJ,James CJ,Oo TF,et al 。Early developmental destruction of terminals
in the striatal target induces apoptosis in dopamine neurons of the substantia
nigra.J Neurosci, 1997;17:2030-2039
7. Oo TF, Burker RE. The time course of developmental cell death in phenotypically
defined dopaminergic neurons of the substantia nigra. Dev Brain Res, 1997;98:
191-196
8.Jackson-Lewia,V.,M.Vila, R.Djaldetti, et al. Developmental cell death in
dopaminergic neurons of the substantia nigra of mice. J Comp Neurol, 2000; 424:
476-488
9.Takahashi T, Deng Y,Maruyaama W,et al. Uptake of a
neurotox-in-candidate,(R),1,2-dimenthyl-6,7-dihydroxy-1,2,3,4-tetra-hydrois
oquinoline into human dopaminergic neuroblastoma SH-SY5Y cells by dopamine
transport system. J Neural Transm Gen Sect, 1994; 98: 107-118
10.Dipasquale B, Marini AM,Youle RJ. Apoptosis and DNA degradation induced by
1-methyl-4-phenylpyridinium in neurons. Biochem Biophys Res Commum,
1991;181:1442-1448
11.Jason P. Sheehan, Patricia E.Palmer, Gregory A. Helm, et al. MPP+ induced
apoptotic cell death in SH-SY5Y neuroblastoma cells: an electron microscope
study. J. Neurosci. Res, 1997;48(3):226-237
12.Christopher P.Fall and James P. Bennett, Jr. Characterization and time course
of MPP+-induced apoptosis in human SH-SY5Yneuroblastoma cells. J. Neurosci.
Res, 1999;55:620-628
13.方芳,陈晓春,朱元贵等. MPP+对 SH-SY5Y 细胞凋亡的诱导作用.福建医科大学学
报,2001;35(3):211-216
14.方芳,陈晓春,朱元贵等. MPP+诱导 SH-SY5Y 细胞凋亡的可能机制. 中国神经科学
杂志, 2002; 18(2):522-526
15.Walkinshaw G,and Waters CM. Neurotoxin-induced cell death in neuronal PC12
cells is mediated by indution of apoptosis. Neurosci,1994;63(4):975-987
16.Woodgate A, Macgibbon G, Walton M, et al . The toxicity of 6-OHDA on PC12
d PC19 cells. Brain ResMol Brain Res,1999;69(1):84-92
17.Hartley A,Stone JM,Heron C,et al. Complex I inhibitors induce dose-dependent
apoptosis in PC12 cells: relevance to Parkinson’s disease. J. Neurochem,
1994;63(4):1987-1990
18.Walkinshaw G,and Waters CM. Induction of apoptosis in catecholaminergic PC12
cells by L-dopa. J Clin Invest, 1995;95: 2458-2464
19.韩燕 陈俊抛 田时雨等. 左旋多巴诱导PC12细胞凋亡的实验研究. 中华神经科杂志,
1999;32(5):284-286
20.韩燕 陈俊抛 田时雨等. L-dopa 诱导 PC12 细胞凋亡及 Bcl-2、Bax 表达的改变. 中
国神经免疫学和神经病学杂志, 2001;8(2):88-91
21.Zeevalk GD,Bemard LP, Nicklas WJ. Role of oxidative stress and the glutathione
system in loss of dopamine neurons due to impairment of energy metabolism . J
综述一 帕金森病中细胞凋亡的研究进展 33
Neurochem,1998;70: 1421-1430
22.Del Rio MJ,Velez-pardo C.17β-Estrdiol protects lymphocytes against dopamine
and iron-induced apoptosis by a genomic-independent mechanism: implication in
Parkinson’s disease. Gen Pharmacol ,2001;35:1-9
23.陈晓春 朱元贵 朱理安等,Bcl-2 和 Bax 在多巴胺诱导 PC12 凋亡中的作用.中华老
年医学杂志, 2001;20(2):124-127
24.陈晓春 朱元贵 王小众等,一氧化氮和 caspase-3 在多巴胺诱导 PC12 凋亡中的作
用。 中国病理生理杂志 2001;17(10):971-975
25.李立宏 高国栋 王学廉 等.多巴胺诱导 PC12 细胞凋亡的免疫组织化学及超微结构
分析. 第四军医大学学报, 2001;22(4):326-329
26.Mitchell IJ,Lawson S,Moser B,et al。Glutamate-induced apoptosis results
in a loss of striatal neurons in the parkinsonian rat.Neuroscience,1994;63
(1):1
27. Wang ZH,Ji Y, Shan W, et al. Therapeutic effects of astrocytes expressing
both tyrosine hydroxylase and brain-derived neurotrophic factor on a rat model
of Parkinson’s disease. Neuroscience, 2002;113(3): 629-640
28.He,Y., T.Lee,and S.K.Leong. 6-Hydroxydopamine induced apoptosis of
dopaminergic cells in the rat substantia nigra. Brain Res, 2000;858:163-166
29.Ichitani Y,Okamura H,Matsumoto Y,et al;Degeneration of the nigral dopamine
neurons after 6-hydroxydopamine injection into the rat striatum.Brain Res, 1991;
549:350-353
30.Ichitani Y,Okamura H,Nakahara D;et al ;Biochemiacal and immunocytochemical
changes induced by intrastriatal 6- hydroxydopamine injection in the rat
nigrostriatal dopamine neuron system:evidence for cell death in the substantia
nigra.Exp Neurol, 1994;130:269-278
31.Jeon BS,Jackson-Lewis V,Burke RE.6-Hydroxydopamine lesion of the rat
substanta nigra:time course and morphology of cell death。Neurodegeneration,
1995;4:131-137
32.Jackson-Lewis V,Jakowec M,Burke RE,et al 。Time course and morphology of
dopaminergic neuronal death caused by the neurotoxin
1-methyl-4-phenyl-1236-tetrahydropyridine.Neurodegeneration, 1995;4:257-269
33.Tatton NA,Kish SJ。In situ detection of apoptotic nuclei in the substantia
nigra compacta of 1-methyl-4-phenyl-1236-tetrahydropyridine-treated mice using
terminal deoxynucleotidyl transferse labeling and acridine
orange.Neuroscience ,1997;77:1037-1048
34.郭明、陈生弟、刘振国、陈红专.帕金森病小鼠黑质细胞凋亡的实验研究. 中华神经
科杂志, 1998;31(4):216-219
35.郭明、陈生弟、刘振国、陈红专.MPTP 诱发 C57-BL 小鼠黑质细胞凋亡.上海第二医科
大学学报,1999;19(1):28-31
36.匡国锋 童启进 王德新 赵伟秦. MPTP 小鼠黑质神经元细胞凋亡及 Deprenyl 抗凋
亡作用的研究. 脑与神经疾病杂志, 1999;7(3):133-135
37.Richter C, Gogvadze V, Laffranchi R et al. Oxidants in mitochondrial :from
physiology to disease. Biochim.biophys.Acta, 1995;1271:67-74
38.Mahalik TJ,Hahn WF,Clayton GH, et al . Programmed cell death in developing
grafts of fetal substantia nigra. Exp Neurol, 1994;129: 27-36
34 银杏平颤方对 PD 鼠中脑多巴胺神经元凋亡的影响及机制探讨
39.Zawada WM, Zastrow DJ,Clarkson ED, et al . Growth factors improve immediate
survival of embrymic dopamine neurons after transplantation into rats. Brain
Res ,1998; 786: 96-103
40. Ko..sel S, Egensperger R , v. Eitzen U, et al. On the question of apoptosis
in the parkinsonian substantia nigra. Acta Neuropathol, 1997; 93:105-108
41.Banati RB,Blunt SB,Graeber MB. What does apoptosis have to do with Parkinson’
s disease?Mov Disord, 1999;14:384-385
42.Jellinger AK Cell death mechanisms in Parkinson ’ s disease. J Neural
Transm ,2000;107:1-29
43.Anglade P,Vyas S,Javoy-Agid F,et al .Apoptotic degeneration of nigral
dopaminergic neurons in Parkinson’s disease. Neurology ,1996 ;46-2: A467
44.Anglade P,Vyas S,Javoy-Agid F,et al .Apoptosis and autophagy in nigral
neurons of patients with Parkinson’s disease. Histol histopathol 1997a,12:25-31
45.Mochizuki H,Goto K,Mori H ,et al.Histochemical detection of apoptosis in
Parkinsin’disease .J neurol sci, 1996;137:120-123
46.Mochizuki H,Mori H,Mizuno Y.Apoptosis in neurodegenerative disorders。 J
Neural Transm Suppl,1997;50:25-40
47.Kingsbury AE,Marsden CD ,Foster OJF. DNA fragmentation in human substantia
nigra: apoptosis or perimortem effect? Mov Disord, 1998,13: 877-884
48.Wullner U,Kornhuber J, Weller M, et al. Cell death and apoptosis regulating
proteins in Parkinson ’ s disease-a cautionary note. Acta Neuropathol,
1999,97:408—412
49.Majno G, Joris I。 Apoptosis ,oncosis and necrosis :an overview of cell
death. Am J Pathol ,1995,146:3—14
50.Fujikawa DG,Shinmei SS, Cai B, et al 。 Neuronal death induced by
Lithium-Pilocarpine-induced seizures is morphologically necrotic despite
“apoptotic ”biochemical features.Ann Neurol, 1998;44:463
51.Tompkins MM, Basgall EJ, Zamrini E, et al Apoptotic-like changes in Lewy
body-associated disorders and normal aging in substantia nigral neurons. Am J
pathol, 1997;150: 119-131.
52. Tatton NA ,Maclean-Fraser A,Tatton WG,et al ,A fluorescent double-labeling
method to detect and confirm apoptotic nuclei in Parkinson’s disease.Ann Neurol,
1998;44(suppl 1):s142-s148
53.Olanow, W. An introduction to the free radical hypothesis in Parkinson’s
disease. Ann. Neurol, 1992;32:S2-S9
54.Ziv. I.,Melamed,E.,Nardi,N., et al. dopamiNeinduce apoptosis-like
cell death in cultured chick sympathetic neurons — a possible pathogenic
mechanism in Parkinson’s disease. Neurosci Lett, 1994; 170: 136-140
55.Offen,D.,Ziv,I., Gorodin, S., et al . Dopamine-induced programmed cell death
in mouse thymocytes. Biochim. Biophys.Acta, 1995; 1268:171—177
56.Offen D., Ziv,I., Panet, HL., et al. Dopamine-induced apoptosis is inhibited
in PC12 cells expressing Bcl-2. Cellular and Molecular Neurobiology,
1997;17(3):289-304
57.Maruyama W,Akao Y,Carrillo MC,et al. Neuroprotection by propargylamines
in Parkinson’s disease :suppression of apoptosis and induction of prosurvival
综述一 帕金森病中细胞凋亡的研究进展 35
genes. Neurotoxicol Teratol, 2002;24(5):675-682
58.周国庆 周孝达 王桂松等. 多巴胺和谷胱甘肽对 PC12 细胞凋亡的影响.上海第二医
科大学学报, 1999;19(1):44-46
59. Choi HJ, Kim SW, Lee SY,et al. Involvement of apoptosis and calcium
mobilization in tetrahydrobiopterin-induced dopaminergic cell death. Exp Neurol,
2003;181(2):281-90.
60.Naoi M,Maruyama W. Cell death of dopamine neurons in aging and Parkinson’
s disease. Mech Aging Dev,1999;111(2-3):175-188
61.Junn E, Mouradian MM. Apoptotic signaling in dopamine-induced cell death:
the role of oxidative stress, p38 mitogen-activated protein kinase, cytochrome
c and caspases. J Neurochem. 2001 ;78(2):374-83.
62.梁立平 左旋多巴诱发羟自由基增高的机制与防治. 中华神经科杂志, 1998;31
(4):223-225
63.Ali SF, David SN,Newport GD, et al. MPTP-induced oxidative stress and
neurotoxicity are age-dependent:evidence from measures of reactive oxygen
speces and striatal dopamine levels. Synapse, 1994;18:27-34
64. Kalivendi SV, Kotamraju S, Cunningham S,et al. 1-Methyl-4-phenylpyridinium
(MPP+)-induced apoptosis and mitochondrial oxidant generation: role of
transferrin-receptor-dependent iron and hydrogen peroxide. Biochem J,
2003 ;371(Pt 1):151-64.
65.Chuang JI, Chen TH. Effect of melatonin on temporal changes of reactive oxygen
species and glutathione after MPP(+) treatment in human astrocytoma U373MG
cells. : J Pineal Res, 2004 ;36(2):117-25.
66.Chun HS,Gibson GE, Degiorgio LA et al. Dopaminergic cell death induced by
MPP+,oxidant and specific neurotoxicants shares the common molecular mechanism.
J Neurochem, 2001; 76(4):1010-21
67.Kumar R,Agarwal AK, Seth PK.Free radical-generated neurotoxicity of
6-hydroxydopamine. J Neurochem ,1995;64:1703—7
68.Glinka Y,Youdim MBH. Inhibition of mitochondrial complexes I and IV by
6-hydroxydopamine. Eur J Pharmacol, 1995;292:329-32
69.Marlene Jimenez Del Rio,Carlos Velez-Pardo. Monoamine neurotoxins-induced
apoptosis in lymphocytes by a common oxidative stress mechanism: involvement
of hydrogen peroxide(H2O2),caspase-3,and nuclear factor kappa-B(NF-κ
B),P53,c-Jun transcription factors. Bioche Pharmacology ,2002;63: 677-688
70.Dipietrantonio AM,Hsieh T,Wu JM. Activation of caspase-3 in HL-60cells
exposed to hydrogen peroxide. Biophys Res Commun, 1999;255:477-82
71.张宝,莫永炎,周玫,陈瑗. 锰超氧化物歧化酶过表达对 H2O2诱导 PC12 细胞凋亡的
影响. 第一军医大学学报 , 2000;20(6):510-512
72.Kitazawa M,Anantharam V,Kanthasamy AG. Dieldrin-induced oxidative stress
and neurochemical changes contribute to apoptopic cell death in dopaminergic
cells. Free Radic Biol Med ,2001;31(11)1473-85
73.Sian J,Dexter DT,Less AJ,et al。Alteration in glutathion levels in Parkinson’
s disease and other neurogenerative disorders affecting basal ganglia. Ann
Neurol,1994;36:348
36 银杏平颤方对 PD 鼠中脑多巴胺神经元凋亡的影响及机制探讨
74.Perry TL, Hansen S, Jones K. Brain amino acids and glutathione in progressive
supranuclear palsy. Neurology,1998;38:943-946
75.Jenner P,Fahn S,Cohen G,et al. Oxidative stress as a course of nigra cell
death in Parkinson’s disease and incidental Lewy body disease. Ann Neurol,
1992;32: S116-123
76.Merad-Boudia M,Nicole A,Santiard-Baron D et al . Mitochondrial impairment
as an early event in the process of apoptosis induced glutathione depletion in
neuronal cell : relevance to Parkinson’s disease. Biochem Pharmacol,
1998;56(5):645-655
77.Schapira AHV,Cooper JM,Dexter D,et al. Anatomic and disease specificity
of NADH CoQ reductase 78.deficiency in Parkinson ’ s diseases. J
Neurochem,1990;55:2142-2145
Janetzky B,Hauck S,Youdim MBH, et al. Unaltered aconitase activity, but
decreased complex I activity in substantia nigra pars compact of patient with
Parkinson’s disease. Neurosci Lett,1994;169:126-128
79.Haas RH,Nasirian F, Nakano K, et al. Low platelet mitochondrial complex I
and complex II/III activity in early untreated Parkinson ’ s disease. Ann
Neurol ,1995;37:714-722
80.Swerdlow RH, Parks JK,Miller SW,et al.Origin and functional consequences of
the complex I defect in Parkinson’s disease. Ann Neurol ,1996;40:663-671
81.高枫, 陈清棠. 原发性帕金森病线粒体复合物 I 功能缺陷. 北京医科大学学报,
1999;31(3):268
82.高枫, 陈清棠, 李险峰. 帕金森病患者线粒体功能缺陷的研究. 中华神经科杂
志,1999;32(4):199-201
83.William G.Tatton andRuth M.E.Chalmers-Redman. Mitochondria in
neurodegenerative apoptosis: An opportunity for therapy? Ann
Neurol,1998;44(suppl 1):s134-s141
84.Adams JD,Jr, Klaidman LK, Leung AC. MPP+and MPDP+ induced oxygen radical
formation with mitochondrial enzymes. Free Rad Biol Med, 1993;15:181-186
85.Zoratti M,Szabo I. The mitochondrial permeability transition. Biochim
Biophys Acta, 1995;1241;139-176
86.Greenlund LJ,Deckwerth TL,Johnson EM,Jr. Superoxide dismutase delays
neuronal apoptosis: a role for reactive oxygen species in programmed neuronal
death. Neuron, 1995;14;303-315
87.Marchetti P, Susin SA,Decaudin D, et al .Apoptosis associated derangement
of mitochondrial function in cells lacking mitochondrial DNA. Cancer
Res ,1996;56:2033-2038
88.Zamzami N,Marchetti P, Castedo M, et al. Sequential reduction of
mitochondrial transmembrane potential and generation of reactive oxygen species
in early programmed cell death. J Exp Med, 1995a;182:367-377
89.Maruyama W,Akao Y,Carrillo MC,et al. Neuroprotection by propargylamines
in Parkinson’s disease :suppression of apoptosis and induction of prosurvival
genes. Neurotoxicol Teratol, 2002;24(5):675-682
90.Christopher P.Fall and James P. Bennett, Jr. Characterization and time course
of MPP+-induced apoptosis in human SH-SY5Yneuroblastoma cells. J. Neurosci.
综述一 帕金森病中细胞凋亡的研究进展 37
Res, 1999;55:620-628
91.Kroemer G,Zamzami N,Susin SA.Mitochondrial control of apoptosis. Immunol
Today, 1997;18:44-51
92.Halestrup AP,Woodfield KY,Connern CP,et al.Oxidative stress,thoil reagents,
and membrane potential modulate the mitochondrial permeability transition by
affecting nucleotide binding to the adenine nucleotide. J Biol Chem,
1997;272(6):3346-3354
93.Green DR , Reed JC. Mitochondria and apoptosis. Science,
1998;281(5381):1309-1312
94.Rego AC, Oliveira CR. Mitochondrial dysfunction and reactive oxygen species
in excitotoxicity and apoptosis: implications for the pathogenesis of
neurodegenerative diseases. Neurochem Res, 2003 ;28(10):1563-74.
95.Antonsson B. Mitochondria and the Bcl-2 family proteins in apoptosis
signaling pathways. Mol Cell Biochem, 2004;256-257(1-2):141-55.
96. Liston P, Fong WG, Korneluk RG. The inhibitors of apoptosis: there is more
to life than Bcl-2. Oncogene, 2003 ;22(53):8568-80.
97.Tatton WG,Olanow CW. Apoptosis in neurodegenerative disease: the role of
mitochondria. Biochim Biophysi Acta, 1999;1410:195-213
98.Fiskum G, Starkov A, Polster BM,et al. Mitochondrial mechanisms of neural
cell death and neuroprotective interventions in Parkinson's disease. Ann N Y
Acad Sci, 2003;991:111-9.
99.Park TH, Kwon OS, Park SY,et al. N-methylated beta-carbolines protect PC12
cells from cytotoxic effect of MPP+ by attenuation of mitochondrial membrane
permeability change.Neurosci Res, 2003 ;46(3):349-58.
100.Chalmers-Redman RM, Fraser AD, Carlile GW, et al.Glucose protection from
MPP+-induced apoptosis depends on mitochondrial membrane potential and ATP
synthase. Biochem Biophys Res Commun, 1999 ;257(2):440-7.
101.Nagatsu T,Mogi M,Ichinose H, et al. Changes in cytokines and neurotrophins
in Parkinson’s disease. J Neural Transm Suppl, 2000;(60):277-290
102.Burke RE,Antonelli M,Sulzer D.Glial cell line-derived neurotrophic growth
factor inhibits apoptotic death of postnatal substantia nigra dopamine neurons
in primary culture. J Neurochem, 1998;71(2):517-525
103.Schatz DS,Kuafmann WA,Saria A,Humpel C. Dopamine neurons in a simple
GDNF-treated meso-striatal organotypic co-culture model. Exp Brain Res,
1999;127(2):270-278.
104.Clarkson ED,Zawada WM,Freed CR. GDNF reduces apoptosis in dopamineergic
neurons in vitro. Neuroreport, 1995;7(1):145-149
105.Clarkson ED,Zawada WM,Freed CR. GDNF improves survival and reduces apoptosis
in human embryonic dopamineergic neurons in vitro. Cell Tissue Res,
1997;289(2):207-210
106.Thajeb P,Ling ZD, Potter ED,et al. The effects of storage conditions and
trophic supplementation on the survival of fetal mesencephalic cells. Cell
Transplant, 1997;6(3):297-307
107.Kaddis FG,Zawada WM, Schaack J, Freed CR. Conditioned medium from aged monkey
fibroblasts stably expressing GDNF and BDNF improveds survival of embryonic
38 银杏平颤方对 PD 鼠中脑多巴胺神经元凋亡的影响及机制探讨
dopamine neurons in vitro. Cell Tissue Res, 1996;286(2):241-247
108.Zawada WM, Zastrow DJ,Clarkson ED, et al. Growth factors improve immediate
survival of embryonic dopamine neurons after transplantation into rats. Brain
Res, 1988; 786(1-2):96-103
109.Wang ZH,Ji Y, Shan W, et al. Therapeutic effects of astrocytes expressing
both tyrosine hydroxylase and brain-derived neurotrophic factor on a rat model
of Parkinson’s disease. Neuroscience, 2002;113(3): 629-640
110.Brundin P, Karlsson J, Emgard M,et al. Improving the survival of grafed
dopaminergic neurons : a review over current approaches. Cell Transplant,
2000;9(2):179-195
111.Sawada H,Ibi M,Kihara T, et al. Neuroprotective mechanism of glial cell
line-derived neurotrophic factor in mesencephalic neurons. J Neurochem, 2000;
74(3):1175-1184
112.Lingor P,Unsicker K, Krieglstein K. GDNF and NT-4 protect midbrain
dopaminergic neurons from toxic damage by iron and nitric oxide . Exp Neurol,
2000;163(1):55-62
113.Petersen AA,Larsen KE, Behr GG, et al. Brain-derived neurotrophic factor
inhibits apoptosis and dopamine-induced free radical production in striatal
neurons but does not prevent cell death. Brain Res Bull, 2001;56(3-4): 331-335.
114.Toth G,Yang H, Anguelov RA, et al. Gene transfer of glial cell dedrived
neurotrophic factor and cardiotrophin-1 protects PC12 cells from
injury:involvement of thephosphatidylinositol3-kinase and mitogen-activated
protein kinase kinase pathways. J Neurosci Res, 2002; 69(5):622-632
115.徐仁,孙圣刚,刘煜敏,等.实验性帕金森病纹状体、大脑皮质和海马组织 MCa、CaM、
MDA含量的变化. 中华神经科杂志,2000;33(1):27
116.Greenamyre JT, MacKenzie G, Peng TI,et al. Mitochondrial dysfunction in
Parkinson's disease.Biochem Soc Symp, 1999;66:85-97.
117.Lacopino AM,Christakos S. Specific reduction of calcium-binding protein
(28-kilodalton calbindin-D)gene expression in aging and neurodegenerative
diseases. Proc Natl Acad Sci USA, 1990 ;87(11):4078-82
118.WANG Lian-Gang, WU Sheng-Xi, WUYi-Jun, et al.Calbindin-D28kmRNA expression
in substanti anigra in mice Parkinson's disease 第 四 军 医 大 学 学
报,2001;22(1):33-36
119.McMahon A, Wong BS, Iacopino AM,et al. Calbindin-D28k buffers intracellular
calcium and promotes resistance to degeneration in PC12 cells.Brain Res Mol Brain
Res, 1998;54(1):56-63
120.Ray SK, Fidan M, Nowak MW,et al.Oxidative stress and Ca2+ influx upregulate
calpain and induce apoptosis in PC12 cells. Brain Res, 2000 ;852(2):326-34
121. Rodnitzky RL. Can calcium antagonists provide a neuroprotective effect in
Parkinson’s disease? Drugs, 1999; 57(6): 845-9
122.Choi HJ, Kim SW, Lee SY,et al. Involvement of apoptosis and calcium
mobilization in tetrahydrobiopterin-induced dopaminergic cell death.Exp Neurol,
2003 ;181(2):281-90.
123.Mcconkey DJ,Mutt LK. Calcium flux measurements in apoptosis.Methods
CellBiol, 2001;66:229-246
综述一 帕金森病中细胞凋亡的研究进展 39
124.Schild L,Keilhoff G,Augustin W, et al. Distinct Ca2+ thresholds determine
cytochrome c release or permeability transition pore opening in brain
mitochondria. FASEB J,2001; 15(3):565-7
125. Brustovetsky N,Brustovestsky T,Jemmerson R, et al. Cakcium-induced
cytochrome c release from CNS mitochondria is associated with the permeability
transition and rupture of the outer membrane. J Neurochem 2002; 80(2):207-218
126.Kruidering M,Schouten T, Evan GL,et al. Caspase-mediated cleavage of the
Ca2+/cakmodulin dependent protein kinase-like kinase facilitates neuronal
apoptosis. J Biol Chem, 2001; 276(42):38417-25 .
127.Blandini F,Porter RH, Greenamyre JT. Glutamate and Parkinson’s disease.
Mol Neurobiol, 1996; 12 73-94
128.Weihmuller FB, Ulas J, Nguyen L, et al. Elevated NMDA receptors in
parkinsonian stritum. Neuroreport, 1992; 3(11): 977-980
129.马坚林,范凯,张万琴等. 偏侧帕金森病大鼠模型丘脑底核谷氨酸能神经元的免疫
组化研究. 神经解剖学杂志, 2000; 16(4): 376-378
130.王传功, 徐霞,库宝善 NMDA 受体和 GABA 受体拮抗剂对小鼠帕金森模型的行为学药
理学影响. 中国行为医学科学, 1998; 7(1):19-21
131.Dargusch R, Piaseck D, Tan S, et al. The role of Bax in glutamate-induced
nerve cell death. J Neurochem, 2001; 76(1):295-301
132.Tan S, Schubert D,Maher P. Oxytosis:A novel form of programmed cell death.
Curr Top Med Chem, 2001;1(6): 497-506
133.Almeida A,Bolanos JP. A transient inhibition of mitochondrial ATP synthesis
by nitric oxide synthase activation triggered apoptosis in primary cortical
neurons. J Neurochem, 2001 ;77(2): 676-690
134.Zipfel GJ, Babcock DJ, Lee JM, et al. neuronal apoptosis after CNS injury :
the roles of glutamate and calcium. J Neurotrauma 2000;17(10):857-869
135.Greenamyre JT, Mackenzie G, Peng TI, et al. Mitochondrial dysfunction in
Parkinson’s disease. Biochem Soc Symp, 1999; 66:85-97
136.Itzhak Y, Gandia C, Huang PL,et al. Resistance of neuronal nitric oxide
synthase deficient mice to methamphetamine-induced dopaminergic
neurotoxicity. J Pharmacol. Exp. Ther, 1998; 284: 1040-1047
137.周国庆 周孝达 王桂松. 一氧化氮合成酶抑制剂对 MPTP 神经毒性的影响. 中国神
经精神杂志, 1998; 24(6):374-375
138.周国庆 周孝达 金永清等. 一氧化氮与帕金森病大鼠模型神经损伤的研究. 中风
与神经疾病杂志, 2000; 17(5): 288-289
139.Ebadi M, Sharma SK. Peroxynitrite and mitochondrial dysfunction in the
pathogenesis of Parkinson's disease.Antioxid Redox,. 2003 ;5(3):319-35.
140.Brown GC,Borutaite V. Nitric oxide, cytochrome c and mitochondria. Biochem
Soc Symp, 1999; 66: 17-25
141.Bal-Price A, Brown GC. Nitric-oxide-induced necrosis and apoptosis in P C12
ccells midiated by mitochrodria. J Neurochem, 2000; 75(4): 1455-1464
142.Dennis J, Bennett JP Jr. Interactions among nitric oxide and Bcl-family
proteins after MPP+ exposure of SH-SY5Y neural cells I: MPP+ increases
mitochondrial NO and Bax protein. J Neurosci Res, 2003 ;72(1):76-88.
40 银杏平颤方对 PD 鼠中脑多巴胺神经元凋亡的影响及机制探讨
143.Emerit J, Edeas M, Bricaire F. Neurodegenerative diseases and oxidative
stress.Biomed Pharmacother, 2004 ;58(1):39-46.
144.陈晓春 朱元贵 王小众等. 一氧化氮和 caspase-3 在多巴胺诱导 PC12 细胞凋亡中
的作用. 中国病理生理杂志, 2001;17(10):971-975
145.Lipton SA, Choi YB, Pan ZH et al. A redox-based mechanism for neuroprotective
and neurodestractive effects of nitric oxide and related nitroso-compounds.
Nature ,1993; 364: 626-632
146.Matthew J. LaVois and Teresa G. Hastings, Peroxynitric- and nitrite-induced
oxidation of dopamine: implications for nitric oxide in dopaminergic cell loss.
J Neuroche, 1999;73(6):2546-2553
147.Uehara T, Kikuchi Y, Nomura Y.Caspase activation accompanying cytochrome
c release from mitochondria is possibly involved in nitric oxide-induced
neuronal apoptosis in SH-SY5Y cells. J Neurochem, 1999 ;72(1):196-205.
148.Jellinger KA. Cell death mechanisms in Parkinson’s disease. J Neural
Trans ,2000;107(1):21-29
149.Itano Y, Nomura Y. 1-methyl-4-phenyl-pyridinium ion (MPP+) causes DNA
fragmentation and increases the Bcl-2 expression in human neuroblastoma, SH-SY5Y
cells, hrough different mechanisms. Brain Res, 1995 ;704(2):240-45.
150.Veech GA, Dennis J, Keeney PM,et al.Disrupted mitochondrial electron
transport function increases expression of anti-apoptotic bcl-2 and bcl-X(L)
proteins in SH-SY5Y neuroblastoma and in Parkinson disease cybrid cells through
oxidative stress. J Neurosci Res, 2000 ;61(6):693-700.
151.Kuwana T, Newmeyer DD. Bcl-2-family proteins and the role of mitochondria
in apoptosis.Curr Opin Cell Biol, 2003 ;15(6):691-9.
152.Cheng EH, Kirsch DG, Clem RT,et al.Conversion of bcl-2 to bax-like death
factor by caspases . Science, 1997;278(12):1966-1969
153.Reed JC. Double identity for proteins of the bcl-2 family. Nature,
1997;387(6635): 773-776
154.Kirsch DG,Doseff A,Chau BN et al. Caspase-3 dependent cleavage of bcl-2
promotes release of cytochrome C. J Biol Chem, 1999; 274(30): 21155-21161
155.Zhou P,Chou J,Olea RS,et al. Solution structure of Apaf-1 CARD and its
interaction with caspase-9 CARD: A structural basis for specific adaptor/caspase
interaction. Proc Natl Acad Sci USA,1999;96:11265-11270
156.Ashkenazi A,Dixit VM. Death receptors:signaling and modulation. Science,
1998;281:1305-1308
157.Rao RV,Hermel E, Castro-Obregon S, et al. Coupling endoplasmic reticulum
luminal enviroment affect cell sensitivity to apoptosis. J Cell Biol, 2000;
150:731-740
158.Wolf BB,Green DR. Suicidal tendencies: apoptotic cell death by caspase
family proteinases . J Biol Chem ,1999; 274:20049-20052
159.Change HY, Yang X. Protease for cell suicide:functions and regulation of
caspases. Micro Mol Biol Rev, 2000; 64: 821-846
160.Hartmmann A,Hunot S, Michel PP, et al. Caspase-3: a vulnerability factor
and final effector in apoptosis death of dopaminergic neurons in Parkinson’
s disease. Proc Natl Acad Sci USA, 2000, 97(6): 2875-2880
综述一 帕金森病中细胞凋亡的研究进展 41
161.Turmel H, Hartmenn A, Parain K. Caspase-3 activation in
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treaded mice. J Mov Disord,
2001;16(2):185-189
162.James Bilsland,Sophie Roy,Steve Xanthoudakis, et al. Caspase inhibitors
attenuate 1-methyl-4-phenylpyridinium toxicity in primary cultures of
mesencephalic dopaminergic neurons.J Neurosci, 2002 ;22(7):2637-49
163.Schierle GS,Hansson O,Leist M, et al.Caspase inhibition reduces apoptosis
and increase survival of nigral transplants. Nal Med, 1999;5:97-100
164.Dodel RC, Du Y, Bales R,et al.Peptide inhibitors of caspase-3-like proteases
attenuate 1-methyl-4-phenylpyridinum-induced toxicity of cultured fetal rat
mesencephalic dopamine neurons. Neuroscience, 1998 ;86(3):701-7.
165. Viswanath V, Wu Y, Boonplueang R, Chen S,et al Caspase-9 activation results
in downstream caspase-8 activation and bid cleavage in
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease.J
Neurosci, 2001;21(24):9519-28
166.Kaul S, Kanthasamy A, Kitazawa M, et all. Caspase-3 dependent proteolytic
activation of protein kinase C delta mediates and regulates
1-methyl-4-phenylpyridinium (MPP+)-induced apoptotic cell death in
dopaminergic cells: relevance to oxidative stress in dopaminergic
degeneration.Eur J Neurosci, 2003 ;18(6):1387-401.
167 .Amoroso S, D'Alessio A, Sirabella R, et al.Ca(2+)-independent caspase-3
but not Ca(2+)-dependent caspase-2 activation induced by oxidative stress leads
to SH-SY5Y human neuroblastoma cell apoptosis. Neurosci Res,
2002;68(4):454-62.
168. Waldmeier PC, Tatton WG. Interrupting apoptosis in neurodegenerative
disease: potential for effective therapy? Drug Discov Today,
2004 ;9(5):210-8.
169.Thomas M, Le WD. Minocycline: neuroprotective mechanisms in Parkinson's
disease.Curr Pharm Des, 2004;10(6):679-86.
170.O'Brien T, Lee D. Prospectsfor caspase inhibitors.Mini Rev Med Chem;
2004 ;4(2):153-65.
171. Voncoelln R, Kugler S, Bahr M. Rescue from death but not from functional
impairment: caspase inhibition protects dopaminergic cells against
6-hydroxydopamine-induced apoptosis but not against the loss of their terminals.
J Neurochem, 2001;77: 263-273
172.Jackson-Lewis V,M Vila, R Djaldetti,et al. Developmental cell death in
dopaminergic neurons of the substantia nigra of mice. J Comp Neurol, 2000;
424:476-488
173.Jeon BS,NG kholodilov, Tinmarla F.Oo,et al.Activation of caspase-3 in
developmental models of progammed cell death in neurons of the substantia nigra.J
Neurochem, 1999; 73:322-333
174.Tinmarla F.Oo, Robert Siman,and Robert E. Burke. Distinct nuclear and
cytoplasmic in two models of induced apoptotic death in dopamine neurons of the
substantia nigra. Exper Neurol, 2002; 175:1-9
175.Eberhardt O.,RV Coelln, S.Kugler,et al. Protection by synergistic effects
42 银杏平颤方对 PD 鼠中脑多巴胺神经元凋亡的影响及机制探讨
of adenovirus-mediated Xchromosome-linked inhibitor of apoptosis and glial cell
line-derived neurotrophic factor gene transfer in the
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease. J
Neurosci, 2000; 20: 9126-9134
176.Deveraux QL,Reed JC. IAP family proteins suppressors of apoptosis. Genes
Dev,1999;13:239-542
177.Kasof GM,Gomes BC. Livin, a novel inhibitor of apoptosis protein family
member . J Biol Chem,2001;276:3238-465
178.Crocker SJ, Liston P, Anisman H, et al. Attenuation of MPTP-induced
neurotoxicity and behavioural impairment in NSE-XIAP transgenic mice. Neurobiol
Dis, 2003 ;12(2):150-61.
179.Eberhardt O, Coelln RV, Kugler S,et al. Protection by synergistic effects
of adenovirus-mediated X-chromosome-linked inhibitor of apoptosis and glial
cell line-derived neurotrophic factor gene transfer in the
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. J
Neurosci, 2000 ;20(24):9126-34.
180.Suzuki Y,Nkabayashi Y, Takahashi R.Ubiquitin protein ligase activity of
X-linked inhibitor of apoptosis protein promotes proteasomal degradation of
caspase 3 and enhances its antiapoptotic effect in Fas induced cell death.Proc
Natl Acad Sci USA,2001;98(15):8662 8667.
181.Wang CY,MaYo MW,Korneluk RG,et al.NF-κB antiapoptosis:induction of TRAF1
and TRAF2 and cIAP1 and cIAP2 to suppress caspase 8 activation.
Science,1999;281:1680-1683
182.Du C,Fang M,Li Y,et al. Smac,a mitochondrial protein that promotes
cytochromecdependent caspase activation by eliminating IAP in
hibition .Cell,2000;102(1):33-42.
183.Verhagen AM,Ekert PG,Pakusch M,et al.Identification of DIABLO,a mammalian
protein that promotes apoptosis by binding to and antagonizing IAP
protieins.Cell,2000;102(1):43-53.
184.Roberts DL,Merrison W,Macfarlane M,et al.The inhibitor of apoptosis
proteinbinding domain of Smac is not essential for its proapoptotic activity.J
Cell Biol,2001,153(1):221 228.
185.Yang QH, Du C. Smac/DIABLO selectively reduces the levels of c-IAP1 and
c-IAP2 but not that of XIAP and livin in HeLa cells. J Biol Chem, 2004; [Epub
ahead of print]
186.Suzuki Y, Takahashi-Niki K, Akagi T,et al. Mitochondrial protease Omi/HtrA2
enhances caspase activation through multiple pathways. Cell Death Differ,
2004;11(2):208-16.
187.Cande C, Cecconi F, Dessen P, Kroemer G. Apoptosis-inducing factor (AIF):
key to the conserved caspase-independent pathways of cell death?J Cell Sci,
2002;115(Pt 24):4727-34.
188.Susin SA,Lorenzo HK,Zamzami N,et al.Molecular characterization of
mitochondrial apoptosis inducing factor.Nature,1999;397(6718):441-446.
189.Yu SW, Wang H, Dawson TM,et al. Poly(ADP-ribose) polymerase-1 and apoptosis
inducing factor in neurotoxicity.Neurobiol Dis, 2003 ;14(3):303-17.
综述一 帕金森病中细胞凋亡的研究进展 43
190.Wang H, Shimoji M, Yu SW,et al. Apoptosis inducing factor and PARP-mediated
injury in the MPTP mouse model of Parkinson's disease. Ann N Y Acad Sci,
2003 ;991:132-9.
191.Lewis TS,Shapiro PS,Ahn NG.Signal transduction through MAP kinase
cascades.Adv Cancer Res,1998;74(1):49-139.
192.Luo Y,Umegaki H,Wang X,et aL.Dopamine induces apoptosis through an
oxidation-involved SAPK/JNK activation pathway.J BC,1998;273(6):3756-3764.
193.Kang CD,Jang JH,Kim KW,et al.Activation of c-jun N-terminal
kinase/stress-activated protein kinase and the dicreased ratio of Bcl-2 toBax
are associated with the auto-oxidized dopamine-induced apoptosis in PC12 cells.
Neuroscience Letters, 1998;256(1):37-40.
194.Saporito MS,Brown EM,Miller MS,et al.CEP-1347/KT-7515,an inhibitor of
C-jun N-terminal kinase/stress-activated protein kinase,attenuates the
1-methyl-4-phenyl tetrahydropyridine-mediate loss of nigro striatal dopaminer
gic neurons in vivo.J Pharmacol Exp Ther,1999;288(2):421-427.
195.Saporito MS,Thomas BA,Scott RW.MPTP activates c-jun NH2-Terminal kinase
(JNK) and its upstream regulatory kinase MKK4 in nigro striatal neuron s in
vivo.J Neuro Chem,2000;75(3):1200-1208.
196.Oo TF,Henchcliffe C,James D,et al.Expression of c-fos,c-jun,and
c-jun-N-terminal Kinase(JNK) in a developmental model of induced apoptotic death
in neurons of the substantian nigra.J Neurochem,1999;72(2):557
197.Wang W,ShiL,Xie Y,et al.SP600125,a new JNK inhibitor,protects dopaminergic
neurons in the MPTP mpdel of Parkinson ’ s disease. Neurosci Res,
2004;48(2):195-202
198. Xu GX,Thomas H,Michael W,et al. Genetransfer of the JNK interacting protein
-1 protects dopaminergic neurons in the MPTP model of Parkinson’s desease. Proc
Natl Acad Sci USA, 2001;98(18):10433-10438.
199.Gearan T,Gastillo OA,Schwarzschild MA. The parkinsonian neurotoxin ,MPP+
induces phosphorylated c-jun in dopaminergric neurons of mesencephalic
cultures. Parkinsonism Relat Disord, 2001;8(1):19-22
200.Hirata Y,Adachi K,Kiuchi K.Activation of JNK pathway and induction of
apoptosisby manganese in PC12 cells.JNurrochem,1998;71(4):1607-1615.
201.Chun HS,Gibson GE,De Giorgio LA,et al.Dopaminergic celldeath induced by
MPP+,oxidant and specific neurotoxicants shares the common molecular
mechanism.J Neurochem,2001;76(4):1010-1021.
202.Evan G,Littlewood T. A matter of life and cell
death .Science,1998;281(5381):1317
203.Daily D,Barzilai A,Offen D,et al.The involvement of p53 in dopamine
inducedapoptosis of cerebellar granule neurons leukemic cells overexpressing
P53.Cell Mol Neurobiol,1999;19(2):261
204.Duan W, Zhu X, Ladenheim B,et al. p53 inhibitors preserve dopamine neurons
and motor function in experimental parkinsonism.Ann Neurol,
2002;52(5):597-606.
44 银杏平颤方对 PD 鼠中脑多巴胺神经元凋亡的影响及机制探讨
205.Nakaso K, Yoshimoto Y, Yano H,et al. p53-mediated mitochondrial dysfunction
by proteasome inhibition in dopaminergic SH-SY5Y cells. Neurosci Lett,
2004;354(3):213-6.