Lee Y J, Kim D, Corry P M
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073.
J Cell Physiol. 1990 Sep;144(3):401-7. doi: 10.1002/jcp.1041440306.
The possible mechanism for heat protection by the protein synthesis inhibitor histidinol was investigated in CHO cells. Histidinol (HST, 5 mM), an analogue of the essential amino acid L-histidine, added for 2 hr before and during heating at 43 degrees C, protected cells from killing at 43 degrees C. Treatment with HST produced a 600-fold increase in survival from 3 x 10(-4) to 1.8 x 10(-1) after 2.5 hr at 43 degrees C. Although the cells were washed after HST treatment, substantial protective effect was still observed during heating at 43 degrees C. This protective effect gradually decreased with increased incubation time after the drug treatment. However, the protective effect was immediately reduced by treatment with histidine (HIS, 0.25-5 mM) during heating. The amount of reduction was dependent upon HIS concentration: five millimolar HIS completely inhibited HST-induced heat protection. Furthermore, protein synthesis which was inhibited by 95% by 5 mM HST, resumed immediately with 5 mM HIS treatment. In addition, when cells were labeled during or after HST treatment, neither preferential accumulation of heat shock protein families nor phosphorylation of 28 kDa protein was observed. Therefore, these results suggest that the cessation of protein synthesis itself is one of the events involved in protection.
在CHO细胞中研究了蛋白质合成抑制剂组氨醇的热保护可能机制。组氨醇（HST，5 mM）是必需氨基酸L-组氨酸的类似物，在43℃加热前和加热期间添加2小时，可保护细胞免受43℃的杀伤。用HST处理后，在43℃处理2.5小时后，存活率从3×10⁻⁴提高到1.8×10⁻¹，增加了600倍。尽管在HST处理后细胞被洗涤，但在43℃加热期间仍观察到显著的保护作用。这种保护作用随着药物处理后孵育时间的增加而逐渐降低。然而，在加热期间用组氨酸（HIS，0.25 - 5 mM）处理可立即降低保护作用。降低的程度取决于HIS的浓度：5 mM HIS完全抑制了HST诱导的热保护。此外，5 mM HST抑制95%的蛋白质合成在用5 mM HIS处理后立即恢复。另外，当细胞在HST处理期间或之后进行标记时，未观察到热休克蛋白家族的优先积累或28 kDa蛋白的磷酸化。因此，这些结果表明蛋白质合成的停止本身是参与保护的事件之一。
