Homocysteine is toxic for dopaminergic neurons in primary mesencephalic culture
Homocysteine is toxic for dopaminergic neurons in primary mesencephalic culture
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DOI：
10.1097/wnr.0b013e3282aaa0b4
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发表时间：
2007-08-27
期刊：
影响因子：
1.7
通讯作者：
Nakashima, Kenji
中科院分区：
文献类型：
--
作者：
Imamura, Keiko;Takeshima, Takao;Nakashima, Kenji
在帕金森病患者中观察到与L-3，4-二羟基苯丙氨酸（L-多巴）治疗相关的高同型半胱氨酸血症。我们研究了同型半胱氨酸（Hcy）对E14大鼠原代中脑培养的毒性。暴露于0-5 mM Hcy以剂量依赖性方式减少酪氨酸羟化酶（TH）阳性多巴胺能神经元和微管相关蛋白2（MAP 2）阳性神经元的数量。TH阳性神经元较其他MAP 2阳性神经元更易受Hcy损伤。在多巴胺能神经元中，5 μ M利血平增强了Hcy的毒性，而50 μ M α-甲基酪氨酸减弱了毒性作用，表明细胞内多巴胺增加了Hcy的细胞毒性。Hcy可增强MPP +对多巴胺能神经元的毒性。提示同型半胱氨酸的毒性作用与氧化应激有关。同型半胱氨酸对多巴胺能神经元有毒性，高同型半胱氨酸血症可能改变帕金森病的临床病程。
Hyperhomocysteinemia associated with L-3,4-dihydroxyphenylalanine (L-dopa) treatment has been observed in patients with Parkinson's disease. We investigated the toxicity of homocysteine (Hcy) on El4-rat-primary mesencephalic culture. Exposure to 0-5 mM Hcy decreased number of tyrosine hydroxylase (TH)-positive dopaminergic neurons and microtubule associated protein 2 (MAP2)-positive neurons in a dose-dependent manner. TH-positive neurons had vulnerability to the insult of Hcy compared with the other MAP2-positive neurons. In dopaminergic neurons, 5 mu M reserpine enhanced the Hcy toxicity, whereas 50 mu M alpha-methyltyrosine attenuated the toxic effect, showing that the intracellular dopamine increased the cytotoxicity of Hcy. Hcy enhanced the toxicity of 1-methyl-4-phenylpyridinium (MPP +) for dopaminergic neurons. It was suggested that the Hcy toxicity was associated with the oxidative stress. Hcy is toxic for dopaminergic neurons, and hyperhomocysteinemia may modify the clinical course of Parkinson's disease.