Hughes F M, Cidlowski J A
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
J Steroid Biochem Mol Biol. 1998 Apr;65(1-6):207-17. doi: 10.1016/s0960-0760(97)00188-x.
Glucocorticoids are well known to stimulate apoptosis in immature thymocytes. Apoptosis in this and other cells is characterized by cell shrinkage, DNA fragmentation and activation of a class of proteases named caspases. We have utilized the flow cytometer to evaluate the coordinate regulation of cell shrinkage and DNA fragmentation in glucocorticoid-treated rat thymocytes and explore the role of caspases upstream of both changes. The results indicate that the activation of apoptosis by glucocorticoids in a cell population is an asynchronous event with only a percentage of the cells displaying apoptotic characteristics at any given time. Both cell shrinkage and chromatin degradation are tightly coupled with similar proportions of the cells displaying each characteristic. The coordinate appearance of these characteristics may suggest a similar mechanism of regulation. Incubation of thymocytes with the general caspase inhibitor Z-VAD-FMK completely blocked both cell shrinkage and DNA fragmentation in spontaneous and glucocorticoid-induced thymocyte apoptosis, implicating an early upstream role for proteases in the activation of thymocyte apoptosis.
众所周知，糖皮质激素可刺激未成熟胸腺细胞发生凋亡。这种细胞及其他细胞的凋亡特征为细胞萎缩、DNA片段化以及一类名为半胱天冬酶的蛋白酶的激活。我们利用流式细胞仪评估糖皮质激素处理的大鼠胸腺细胞中细胞萎缩和DNA片段化的协同调控，并探究半胱天冬酶在这两种变化上游的作用。结果表明，糖皮质激素在细胞群体中激活凋亡是一个异步事件，在任何给定时间只有一定比例的细胞表现出凋亡特征。细胞萎缩和染色质降解紧密相关，表现出每种特征的细胞比例相似。这些特征的协同出现可能暗示存在相似的调控机制。用通用的半胱天冬酶抑制剂Z-VAD-FMK孵育胸腺细胞，可完全阻断自发和糖皮质激素诱导的胸腺细胞凋亡中的细胞萎缩和DNA片段化，这表明蛋白酶在胸腺细胞凋亡激活过程中起早期上游作用。
