Industrial chemicals induced neural apoptosis with its relation to active oxygen species
Industrial chemicals induced neural apoptosis with its relation to active oxygen species
批准号:
07807041
负责人:
OGAWA Yasutaka
金额:
$1.09万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
1995
资助国家:
日本
项目状态:
已结题
起止时间:
1995 至 1996
中文摘要
本研究的目的是探讨工业化学品神经毒性伴随神经细胞凋亡的过程。本实验假设在化学物质的作用下,活性氧能诱导神经元凋亡,所用的化学物质为2,5-己二酮和顺铂。2,5-己二酮是已知的神经毒性物质,它是正己烷和甲基正丁基酮的代谢产物。它影响轴突,其病理学是众所周知的轴突肿胀充满神经丝。顺铂被用作抗癌药物,其神经毒性是特异性的感觉神经。所用材料为原代培养的神经元,其被认为具有更多的体内特性。结果表明:(1)2,5-己二酮可引起小鼠背根神经节细胞DNA的断裂。(2)顺铂诱导小鼠背根神经节神经元DNA断裂。(3)2,5-己二酮不直接作用于DNA链,也不诱发活性氧自由基。(4)顺铂不直接作用于DNA链,也不诱发活性氧自由基。2,5-己二酮诱导的细胞凋亡可得到梯状条带,但水平较弱,有待进一步放大。抗氧化物质保护顺铂引起的神经细胞死亡,但不能检测到活性氧。
英文摘要
Aim of our study is to investigate the process relating to neurotoxicity of industrial chemicals accompanied by neuronal apoptosis. The hypothesis we are based on is that under the chemical assault apoptosis of neurons will be induced by active oxygen species.Chemical substances we used were 2,5-hexanedione and cisplatin. 2,5-Hexanedione is well known neurotoxic substance which is a metabolite of n-hexane and methyl n-butyle ketone. It affects axons and its pathology is well-known by axonal swelling filled with neurofilaments. Cisplatin is used as anti-cancer drug and its neurotoxicity is specific to sensory nerves. Material used were Primary culture neurons were used as materials which is believed to have more in vivo characters. Also single strand DNA was used to measure the direct effect of the chemicals to DNA.The results were as follows ;(1) 2,5-Hexanedione induced fragmentation of DNA in mouse dorsal root ganglion neurons.(2) Cisplatin induced fragmentation of DNA in mouse dorsal root ganglion neurons.(3) 2,5-Hexanedione did not directly affect DNA strands nor induced active oxygen radicals(4) Cisplatine did not directly affect DNA strands nor induced active oxygen radicalsTo study further, we tried to detect DNA ladder in cultured cell. We got the ladder from 2,5-hexanedione induced apoptosis but the level was very week and needs further amplification. Antioxidant substances protected neuronal cell death by cisplatin but could not detect active oxygen species itself.
期刊论文(10)
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Ogawa,Y.: "2,5-Hexanedione induced apoptosis in cultured mouse DRG neurons" International Archives of Occupational and Environmental Health. 68. 495-497 (1996)
小川,Y.:“2,5-己二酮诱导培养的小鼠 DRG 神经元细胞凋亡”国际职业和环境健康档案。
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通讯作者:
Ogawa, Y., Shimizu, H., Kim, S.U: "2,5-Hexanedione induced apoptosis in cultured mouse DRG neurons" International Archives of Occupational and Environmental Health. 68 (6). 495-497 (1996)
Okawa, Y.、Shimizu, H.、Kim, S.U:“2,5-己二酮诱导培养的小鼠 DRG 神经元细胞凋亡”国际职业与环境健康档案。
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Endo-Ichikawa, Y., Kohno, H., Furukawa, T., Ueda, T., Ogawa, Y., Tokunaga, R., Taketani, S: "Requirement of multiple DNA-protein interactions for inducible expression of RNR3 gene in Saccharomyces cerevisiae in response to DNA damage" Biochemical and Biop
Endo-Ichikawa, Y.、Kohno, H.、Furukawa, T.、Ueda, T.、Okawa, Y.、Tokunaga, R.、Taketani, S:“RNR3 基因诱导表达需要多种 DNA-蛋白质相互作用
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Y. Ogawa: "2,5-Hexanedione induced apoptosis in cultured mouse DRG neurons" The proceedings for the 1995 Medichem Congress.
Y. Okawa:“2,5-己二酮诱导培养的小鼠 DRG 神经元细胞凋亡”1995 年 Medichem 大会的会议记录。
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Endo-Ichikawa,Y.: "Requirement of multiple DNA-protein interactions for inducible expression of RNA3 gene in Saccharomyces cerevisiae in response to DNA damage" Biomedical and Biophysical Research Communications. 222. 280-286 (1996)
Endo-Ichikawa,Y.:“酿酒酵母中 RNA3 基因诱导表达对 DNA 损伤的反应需要多种 DNA-蛋白质相互作用”生物医学和生物物理研究通讯。
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