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Role of arachdonate cascade in apoptosis of neronal cells

花生四烯酸级联在神经元细胞凋亡中的作用

基本信息

批准号：
10680580
负责人：
HIGUCHI Yoshihiro
金额：
$ 0.77万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

Glutamate caused GSH depletion inducing apoptosis through endogenously produced active oxygen species and thereby 1-2 Mbp giant DNA and high molecular weight DNA fragmentation prior to the internucleosomal DNA fragmentation seen in C6 rat glioma cells. During apoptosis induced by GSH-depletion, reactive oxygen species (ROS) caused lipid peroxidation associated with PK-C activation. AA promoted cell death by changing the apoptosis to necrosis through lipid peroxidation initiated by lipid hydroperoxides produced by 12-lipoxygenase under the GSH depletion in C6 cells. Some ROS such as hydroperoxide produced by unknown pathway make hydroxy radicals and induce 8-OH-dG formation in the cells. The conversion of apoptosis to necrosis may be a possible event under GSH depleted conditions and a model of glial cell death. GSH depletion caused by glutamate induces 8-OH-dG formation. Polyunsaturated fatty acids enhanced lipid peroxidation associated with 8-OH-dG formation through a chain reaction. BSO, an inhibitor for GSH synthesis, also induced lipid peroxidation and consequently leads to 1-2 Mbp giant DNA fragmentation. Polyunsaturated fatty acids enhanced the giant DNA fragmentation and 3'-OH temini in chromosomal DNA promoting lipid peroxidation by a chain reaction under the GSH depletion induced by both glutamate and BSO. Ultraviolet (UV) radiation activated caspase-3 associated with cleavage of poly (ADP-ribose) polymerase in T-24 carcinoma cells,. UV induced apoptosis through no producing ROS, at least DCFH reactive ROS, activation of caspase-3 and internucleosomal DNA fragmentation. It is suggested that mechanism of cell death on GSH depletion -induced apoptosis is different from that of UV-induced apoptosis.

谷氨酸导致GSH耗竭，通过内源性产生的活性氧物质诱导细胞凋亡，从而在C6大鼠胶质瘤细胞中观察到核小体间DNA片段化之前产生1-2 Mbp的巨型DNA和高分子量DNA片段化。在GSH耗竭诱导的细胞凋亡过程中，活性氧（ROS）引起与PK-C激活相关的脂质过氧化反应。AA促进细胞死亡，通过改变细胞凋亡坏死，通过脂质过氧化作用引发的脂质过氧化作用下产生的12-脂氧合酶在GSH耗竭C6细胞。某些活性氧（如氢过氧化物）通过未知途径产生羟自由基，诱导细胞内8-OH-dG的形成。细胞凋亡向坏死的转化可能是GSH耗竭条件下和胶质细胞死亡模型下的一个可能事件。谷氨酸引起的GSH耗竭诱导8-OH-dG形成。多不饱和脂肪酸通过链式反应增强与8-OH-dG形成相关的脂质过氧化。GSH合成的抑制剂BSO也可诱导脂质过氧化反应，导致1-2 Mbp的DNA大片段化。多不饱和脂肪酸增强了染色体DNA的大片段化和3 '-OH末端，在谷氨酸和BSO诱导的GSH耗竭下通过连锁反应促进脂质过氧化。紫外线（UV）辐射激活T-24癌细胞中与聚（ADP-核糖）聚合酶切割相关的caspase-3。紫外线通过不产生活性氧、至少DCFH活性氧、激活caspase-3和核小体间DNA断裂等途径诱导细胞凋亡。提示GSH耗竭诱导的细胞凋亡与紫外线诱导的细胞凋亡的死亡机制不同。