Protein synthesis, thermotolerance and step down heating.

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.