DOPAMINE-INDUCED NEUROTOXICITY IN A CATECHOLAMINERGIC CELL LINE
DOPAMINE-INDUCED NEUROTOXICITY IN A CATECHOLAMINERGIC CELL LINE
批准号:
5203799
负责人:
J M MASSERANO
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
大脑中过度活跃的多巴胺能神经元被认为是
在精神分裂症病因学中的重要作用。 已经
假设,长期暴露于儿茶酚胺神经元,
过量的多巴胺或多巴胺的氧化代谢物可
产生神经元损伤,细胞死亡,并部分负责
精神分裂症的一些负面症状 儿茶酚胺已经被
显示对原发性肾上腺素和多巴胺神经元具有神经毒性
培养(J Neurosci Res 26:428,1990; J Pharmacol Exp Ther 262:1274,
1992年)。 我们正在评估多巴胺的神经毒性作用,
Chikaraishi及其同事开发的克隆细胞系(J Neurosci
13:1280,1993)。 该细胞系来源于酪氨酸羟化酶
从携带SV的转基因小鼠的CNS获得的阳性肿瘤
大鼠转录控制下的40 T抗原癌基因
酪氨酸羟化酶基因 我们发现,将CATH. a细胞与
多巴胺产生剂量依赖性细胞死亡,
浓度的多巴胺(500 mM)杀死80%的细胞,相对于
未经处理的细胞 发现这种细胞死亡是由于细胞凋亡,
使用凝胶电泳技术通过DNA片段化进行评价,
流式细胞术分析。 细胞凋亡似乎是由多巴胺引起的
自氧化,因为多巴胺后细胞内过氧化物增加
处理,过氧化氢酶抑制细胞死亡。 Bcl-2水平
以剂量依赖性方式减少,以响应多巴胺。这些
研究结果表明,多巴胺的氧化产物导致
神经毒性,并可调节bcl-2水平。bcl-2的调节可能
在阻止多巴胺神经元的神经变性方面很重要,
帕金森氏症。
英文摘要
Overactive dopaminergic neurons in the brain are thought to play an
important role in the etiology of schizophrenia. It has been
hypothesized that prolonged exposure of catecholamine neurons to
excessive levels of dopamine or the oxidative metabolites of dopamine may
produce neuronal damage, cell death, and be partially responsible for
some of the negative symptoms of schizophrenia. Catecholamines have been
shown to be neurotoxic to norepinephrine and dopamine neurons in primary
culture (J Neurosci Res 26:428, 1990; J Pharmacol Exp Ther 262:1274,
1992). We are evaluating the neurotoxic effects of dopamine by using a
clonal cell line developed by Chikaraishi and co-workers (J Neurosci
13:1280, 1993). This cell line was derived from a tyrosine hydroxylase
positive tumor obtained from the CNS of transgenic mice carrying the SV
40 T antigen oncogene under the transcriptional control of the rat
tyrosine hydroxylase gene. We found that incubation of CATH.a cells with
dopamine produced dose-dependent cell death, with the highest
concentration of dopamine (500 mM) killing 80% of the cells relative to
untreated cells. This cell death was found to be due to apoptosis as
evaluated by DNA fragmentation using gel-electrophoresis techniques and
flow cytometry analysis. Apoptosis appeared to be produced by dopamine
autoxidation, since intracellular peroxides increase after dopamine
treatment, and cell death was inhibited by catalase. Bcl-2 levels
decrease in a dose dependent manner in response to dopamine. These
findings suggest that the oxidative products of dopamine cause
neurotoxicity and can regulate bcl-2 levels. The regulation of bcl-2 may
be important in deterring the neurodegeneration of dopamine neurons in
Parkinson's disease.
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THE EFFECTS OF COCAINE ON DOPAMINE UPTAKE IN THE RAT BRAIN
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批准号:3781476
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J M MASSERANO
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依托单位:
REGULATION OF SECOND MESSENGER SYSTEMS IN EBV-TRANSFORMED B-CELL LINES
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批准号:3781514
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J M MASSERANO
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依托单位:
THE EFFECTS OF COCAINE ON TYROSINE HYDROXYLASE ACTIVITY IN THE RAT BRAIN
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批准号:3759485
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J M MASSERANO
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依托单位:
DOPAMINE INDUCED NEUROTOXICITY IN A CATECHOLAMINERGIC CELL LINE
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批准号:6162909
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J M MASSERANO
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依托单位:
DOPAMINE INDUCED NEUROTOXICITY IN A CATECHOLAMINERGIC CELL LINE
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批准号:6111174
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J M MASSERANO
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依托单位:
DOPAMINE-INDUCED NEUROTOXICITY IN A CATECHOLAMINERGIC CELL LINE
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批准号:2578795
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J M MASSERANO
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依托单位:
DOPAMINE-INDUCED NEUROTOXICITY IN A CATECHOLAMINERGIC CELL LINE
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批准号:3781515
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J M MASSERANO
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依托单位:
DOPAMINE-INDUCED NEUROTOXICITY IN A CATECHOLAMINERGIC CELL LINE
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批准号:3759521
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J M MASSERANO
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依托单位:
THE EFFECTS OF COCAINE ON TYROSINE HYDROXYLASE ACTIVITY IN THE RAT BRAIN
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批准号:5203770
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J M MASSERANO
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依托单位:
REGULATION OF SECOND MESSENGER SYSTEMS IN EBV-TRANSFORMED B-CELL LINES
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批准号:2578794
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J M MASSERANO
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依托单位:
THE EFFECTS OF COCAINE ON DOPAMINE UPTAKE IN THE RAT BRAIN
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批准号:5203769
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财政年份:--
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负责人:J M MASSERANO
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依托单位:
THE EFFECTS OF COCAINE ON DOPAMINE UPTAKE IN THE RAT BRAIN
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批准号:3845376
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J M MASSERANO
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依托单位:
THE EFFECTS OF COCAINE ON DOPAMINE UPTAKE IN THE RAT BRAIN
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批准号:3759484
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J M MASSERANO
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依托单位:
REGULATION OF SECOND MESSENGER SYSTEMS IN EBV-TRANSFORMED B-CELL LINES
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批准号:3759520
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J M MASSERANO
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依托单位:
THE EFFECTS OF COCAINE ON TYROSINE HYDROXYLASE ACTIVITY IN THE RAT BRAIN
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批准号:3781477
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J M MASSERANO
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依托单位:
THE EFFECTS OF COCAINE ON TYROSINE HYDROXYLASE ACTIVITY IN THE RAT BRAIN
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批准号:3845377
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J M MASSERANO
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依托单位:
REGULATION OF SECOND MESSENGER SYSTEMS IN EBV-TRANSFORMED B-CELL LINES
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批准号:5203798
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J M MASSERANO
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依托单位:
THE EFFECTS OF COCAINE ON TYROSINE HYDROXYLASE ACTIVITY IN THE RAT BRAIN
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批准号:2578770
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项目类别:
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资助金额:$0.0万
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负责人:J M MASSERANO
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