Beaver J P, Waring P
Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra/Australia.
Eur J Cell Biol. 1995 Sep;68(1):47-54.
Free radical damage has been implicated in the induction of apoptosis in some cells. We investigated whether the status of a cell's oxidant defence system is involved in the signalling pathways triggering apoptosis. We used three unrelated agents, dexamethasone, thapsigargin and gliotoxin to induce apoptosis in thymocytes from 10-day-old BALB/c mice. With all stimuli there was a correlation between the percentage of cells undergoing apoptosis (as measured with propidium iodide DNA staining) and the percentage of cells with lowered [GSH]i. Treatment with either 1 mM reduced glutathione or 10 nM thapsigargin inhibited dexamethasone-induced apoptosis in thymocytes at 6 h, as well as the rise in the percentage of cells with lowered [GSH]i that normally accompanied the onset of apoptosis. Furthermore, following treatment of thymocytes with oxidized glutathione, a normal product of the action of the cell's oxidant defence system, high levels of apoptosis were observed. This suggested that the onset of apoptosis was not simply the result of a loss of GSH from the cytosol. From our evidence we suggest that a decrease in [GSH]i, or an increase in [GSSG]i or perhaps a change in the ratio of [GSH]i to [GSSG]i constitutes a trigger for apoptosis.
自由基损伤已被认为与某些细胞凋亡的诱导有关。我们研究了细胞氧化防御系统的状态是否参与触发细胞凋亡的信号通路。我们使用了三种不相关的试剂，地塞米松、毒胡萝卜素和gliotoxin来诱导10日龄BALB/c小鼠胸腺细胞凋亡。在所有刺激下，发生凋亡的细胞百分比（用碘化丙啶DNA染色测量）与细胞内谷胱甘肽（[GSH]i）降低的细胞百分比之间存在相关性。用1 mM还原型谷胱甘肽或10 nM毒胡萝卜素处理可在6小时时抑制地塞米松诱导的胸腺细胞凋亡，以及抑制通常伴随凋亡开始时细胞内[GSH]i降低的细胞百分比的升高。此外，在用氧化型谷胱甘肽（细胞氧化防御系统作用的正常产物）处理胸腺细胞后，观察到高水平的细胞凋亡。这表明细胞凋亡的开始不仅仅是细胞质中谷胱甘肽丢失的结果。根据我们的证据，我们认为细胞内[GSH]i的降低、[GSSG]i的增加或[GSH]i与[GSSG]i比值的变化可能构成细胞凋亡的触发因素。
