Hahn G M, Shiu E C
Int J Radiat Oncol Biol Phys. 1985 Jan;11(1):159-64. doi: 10.1016/0360-3016(85)90375-x.
The heat sensitivity of mammalian cells is modified by the cells' previous thermal history. If CHO cells are exposed to 42 degrees C or lower, they show resistance to subsequent heating at higher temperatures ("thermotolerance," TT); if the sequence is reversed, then an increased sensitivity is seen ("step-down heating," SDH). There is considerable evidence that protein synthesis is required for the development of tolerance, but nothing is known about the molecular events leading to SDH. We now show that for HA1 cells, the rate of protein synthesis (rPS) is related to both TT and SDH. The rPS of TT cells is 30% higher than of unheated cells. There is only a transient reduction of rPS during the exposure of TT cells to temperatures up to 43 degrees C with recovery occurring during heating. At higher temperatures, the effect is more severe and no recovery is observed. No recovery is seen during heating at 43 degrees C in previously unheated cells. On the other hand, SDH sensitization occurs in unheated cells and only when there is a severe and prolonged inhibition of the rPS (less than 10% of the control value). TT cells do not show SDH and also only show transient rPS reductions. Our results indicate that proteins must be synthesized for the development of TT and that SDH develops primarily as a consequence of the inhibition of the development of TT.
哺乳动物细胞的热敏感性会因细胞之前的热经历而改变。如果中国仓鼠卵巢（CHO）细胞暴露于42摄氏度或更低温度，它们会对随后更高温度的加热表现出抗性（“热耐受”，TT）；如果顺序颠倒，就会出现敏感性增加的情况（“逐步降温加热”，SDH）。有大量证据表明，热耐受的形成需要蛋白质合成，但对于导致SDH的分子事件却一无所知。我们现在表明，对于HA1细胞，蛋白质合成速率（rPS）与TT和SDH都有关。TT细胞的rPS比未加热细胞高30%。在TT细胞暴露于高达43摄氏度的温度期间，rPS只是短暂降低，在加热过程中会恢复。在更高温度下，影响更严重，且未观察到恢复。在之前未加热的细胞中，43摄氏度加热期间未观察到恢复。另一方面，SDH致敏发生在未加热的细胞中，并且只有当rPS受到严重且长时间抑制（低于对照值的10%）时才会出现。TT细胞不会表现出SDH，并且也只表现出rPS的短暂降低。我们的结果表明，热耐受的形成必须合成蛋白质，并且SDH主要是由于热耐受形成受到抑制而产生的。
