Garcia-Bermejo L, Vilaboa N E, Perez C, Galan A, De Blas E, Aller P
Centro de Investigaciones Biológicas, CSIC, Madrid, Spain.
Exp Cell Res. 1997 Oct 10;236(1):268-74. doi: 10.1006/excr.1997.3725.
The administration of sodium butyrate at 0.75 mM induced the functional differentiation of U-937 human promonocytic leukemia cells with negligible cell mortality. However, the drug rapidly caused cell death with characteristics of apoptosis when used at concentrations of 5 mM and above. In addition, butyrate stimulated the expression of the stress-responsive heat-shock protein 70 (HSP70) gene when applied at both differentiation-inducing and apoptosis-inducing concentrations. The induction of HSP70 by butyrate was inhibited by the simultaneous addition of cAMP-increasing agents (dibutyryl cAMP or the combination of forskolin plus theophylline). However, these agents did not prevent differentiation and only partially reduced apoptosis. Moreover, the DNA topoisomerase II inhibitor etoposide, which provoked U-937 cell differentiation and apoptosis with the same or greater efficiency than butyrate, failed to stimulate HSP70 expression. Finally, it was observed that cAMP-increasing agents also abrogated the induction of HSP70 and reduced the apoptosis caused by cadmium chloride, a typical inducer of the stress response. Taken together, these results indicate that HSP70 expression is not required for differentiation of promonocytic cells, as earlier proposed, and that butyrate probably triggers the stress response in these cells.
以0.75 mM的浓度施用丁酸钠可诱导U - 937人原单核细胞白血病细胞发生功能分化，细胞死亡率可忽略不计。然而，当使用浓度为5 mM及以上时，该药物会迅速导致具有凋亡特征的细胞死亡。此外，丁酸盐在诱导分化和诱导凋亡的浓度下施用时，都会刺激应激反应热休克蛋白70（HSP70）基因的表达。同时添加增加cAMP的试剂（二丁酰cAMP或福斯可林加茶碱的组合）可抑制丁酸盐对HSP70的诱导。然而，这些试剂并不能阻止分化，只是部分降低了凋亡。此外，DNA拓扑异构酶II抑制剂依托泊苷，其诱导U - 937细胞分化和凋亡的效率与丁酸盐相同或更高，但未能刺激HSP70表达。最后，观察到增加cAMP的试剂也消除了HSP70的诱导，并减少了由应激反应的典型诱导剂氯化镉引起的凋亡。综上所述，这些结果表明，如先前提出的那样，HSP70表达并非原单核细胞分化所必需，并且丁酸盐可能触发了这些细胞中的应激反应。
