Role of arachdonate cascade in apoptosis of neronal cells

谷氨酸导致GSH耗竭，通过内源性产生的活性氧物种诱导细胞凋亡，从而在C6大鼠胶质瘤细胞出现核小体间DNA碎裂之前1-2 MBP的巨型DNA和高分子量DNA碎裂。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。AA通过12-脂氧合酶在GSH耗竭作用下产生的脂质过氧化作用，使C6细胞发生脂质过氧化，使细胞死亡，从而促进细胞死亡。一些ROS，如未知途径产生的过氧化氢，在细胞内产生羟基自由基，诱导8-OH-DG的形成。细胞凋亡转化为坏死可能是GSH耗竭条件下的一种可能事件，也是神经胶质细胞死亡的一种模型。谷氨酸引起的GSH耗竭导致8-OH-DG的形成。多不饱和脂肪酸通过连锁反应增强与8-OH-DG形成相关的脂质过氧化。GSH合成的抑制剂BSO也会引起脂质过氧化，从而导致1-2 MBP的DNA大片段。在谷氨酸和BSO共同诱导的GSH耗竭下，多不饱和脂肪酸增加了染色体DNA中的大片段DNA和3‘-OH模板蛋白，通过连锁反应促进了脂质过氧化。紫外线(UV)辐射激活caspase-3与T-24癌细胞中聚(ADP-核糖)聚合酶的裂解相关。紫外线通过产生NO、ROS、至少DCFH反应性ROS、激活caspase-3和核小体DNA断裂等途径诱导细胞凋亡。提示GSH耗竭诱导细胞凋亡的细胞死亡机制与紫外线诱导的细胞死亡机制不同。

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.