Molecular mechanim of cytotoxicity induced by dopamine and 6-hydroxydopamine

多巴胺和6-羟基多巴胺诱导细胞毒性的分子机制

基本信息

批准号：
08670708
负责人：
OGAWA Norio
金额：
$ 1.41万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670708/
关键词：
dopamine L-DOPA 6-OHDA free radical transition metal lipd peroxidation SOD glutathione (GSH)転写因子神経栄養因子鉄 NO DNA損傷

项目摘要

To promote possible neuroprotective strategies for Parkinson's disease, the present study was conducted to clarify differencies in biochemical mechanisms among cytotoxicites of dopamine (DA), levedopa (L-DOPA) and 6-hydroxydopamine (6-OHDA).1. DNA fragmentation induced by iron + hydrogen peroxide was extremely acclererated by DA and L-DOPA.Co-existence of 6-OHDA and zinc produed DNA fragmentation, although zinc alone did not produce DNA fragmentation. Aluminium-induced DNA fragmentation was differntly inhibited by DA-related compounds, indicating that action mechanism of alununium may be differant from those of the other transition metals.2. Production of hydroxyl radicals induced by iron was accelerated by 6-OHDA, although that was not affected by DA or L-DO PA.High production of hydroxyl radicals induced by cupper was suppressed by all DA-related compounds.3. Lipid peroxidation induced by iron was slightly inhibited by DA, but not affected by L-DOPA nor 6-OHDA.On the other hand, copper-induced lipid pereoxidation was extremely inhibited by DA, L-DOPA and 6-OHDA.4. Transition metals, especially copper, showed cytotoxicity against DAeregic neuronal cell line (B65). Among DA-related compounds, 6-OHDA showed cytotoxicity against B65 cells.5. Transition metals and 6-OHDA strongly increased superoxide dismutase (SOD) activities in B65 cells, but L-DOPA increased slightly SOD activities in those cells. Although iron and copper decreased slightly glutathione (GSH) activities, DA and 6-OHDA increased strongly GSH levels in B56 cells.Thus, DA, L-DOPA and 6-OHDA showed different cytotoxicities based on different interactions with transition metals, free radicals and redox states. The present results are useful information for establishing the neuroprotective strategies for Parkinson's disease.

为了促进帕金森氏病的神经保护策略，进行了本研究，以阐明多巴胺（DA），Levedopa（L-Dopa）和6-羟基羟基多巴胺（6-OHDA）的多巴胺（DA）的生化机制的差异。由DA和L-DOPA诱导的DNA片段化极度浓度。6-OHDA的Co存在，锌和锌产生DNA片段化，尽管单独锌并没有产生DNA片段化。铝诱导的DNA片段化被与DA相关的化合物抑制了不同，这表明弹霉的作用机理可能与其他过渡金属的作用机理不同。2。由6-OHDA加速了由铁诱导的羟基自由基的产生，尽管这不受DA或L-DO PA的影响。所有与DA相关的化合物抑制了由Cupper诱导的羟基自由基的产生。3。 DA诱导的铁诱导的脂质过氧化略微抑制，但另一方面不受L-DOPA或6-OHDA的影响，DA，L-DOPA和6-OHDA.4。过渡金属，尤其是铜，表现出针对辅助神经元细胞系的细胞毒性（B65）。在与DA相关的化合物中，6-OHDA对B65细胞显示细胞毒性5。过渡金属和6-OHDA在B65细胞中强烈增加了超氧化物歧化酶（SOD）活性，但是L-DOPA增加了这些细胞中略微SOD活性。尽管铁和铜的略微降低了谷胱甘肽（GSH）的活性，但DA和6-OHDA在B56细胞中的GSH水平强大升高。因此，基于与过渡金属，自由基和氧化还原状态的不同相互作用，DA，L，L-DOPA和6-OHDA显示出不同的细胞毒性。目前的结果是建立帕金森氏病神经保护策略的有用信息。