Comparison of the apoptosis-inducing abilities of various protein synthesis inhibitors in U937 cells
Comparison of the apoptosis-inducing abilities of various protein synthesis inhibitors in U937 cells
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DOI：
10.1271/bbb.66.835
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发表时间：
2002-04-01
影响因子：
1.6
通讯作者：
Muramatsu, T
中科院分区：
文献类型：
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作者：
Kageyama, A;Kusano, I;Muramatsu, T
我们比较了蓖麻毒素、白喉毒素、放线菌亚胺和茴香素对人髓系白血病U937细胞的诱导凋亡作用，发现它们在3h内几乎完全抑制蛋白质的合成，其中以茴香霉素的诱导作用最强。6h后，分别有53%、30%和10%的细胞出现细胞凋亡性改变。此外，还观察到在茴香霉素处理的细胞中caspase-3样活性迅速增加。在蓖麻毒素处理的细胞中，也观察到类似于caspase-3活性的增加，但时间较慢。而白喉毒素或放线菌酮处理6h后，该酶活力仅略有升高。由于蓖麻毒素和茴香霉素都能作用于28S核糖体RNA，我们的结果提示这一作用机制可能是它们有效诱导细胞凋亡的原因，仅抑制蛋白质合成是不足以诱导细胞凋亡的。
We compared the abilities of ricin, diphtheria toxin, cycloheximide, and anisomycin to induce apoptosis, using human myeloid leukemia U937 cells at the concentration of each toxin at which almost complete protein synthesis inhibition was attained within 3 h. Among these toxins, anisomycin was found to be the most potent apoptosis inducer. After a 6-h exposure to anisomycin (1 mug/ml), nearly 95% of the cells had apoptotic nuclear morphological changes, while 53%, 30%, and 10% of the cells showed apoptotic changes after exposure to ricin (0.1 mug/ml), diphtheria toxin (10 mug/ml), and cycloheximide (10 mug/ml), respectively. Furthermore, a rapid increase in caspase-3-like activity was observed in anisomycin-treated cells. A similar increase in caspase-3-like activity was also observed in ricin-treated cells on a slower time schedule. However, only a slight increase in the protease activity was induced by diphtheria toxin or cycloheximide even after 6 h of incubation. Since both ricin and anisomycin are known to act on 28S ribosomal RNA, our results suggest that this action mechanism may be responsible for their potent apoptosis induction, and protein synthesis inhibition alone is not sufficient to induce apoptosis.