Thermotolerance and Heat Shock Proteins in Mammalian Cells

Abstract

One of the more intriguing aspects of thermal biology is the response of heated cells to subsequent exposures at elevated temperatures. It has been clearly demonstrated by Gerner and Schneider (1) and Henle and Leeper (2) that an initial heat dose can induce a temporary state of heat resistance. This state has been termed thermotolerance. If the initial heat dose is at temperatures greater than about 43?C, the transient resistance manifests itself only if an intervening period at 37?C is permitted. Maximum thermotolerance is reached around 6 hr after transfer to 37?C; tolerance maintains itself for some time, decays slowly, and disappears by perhaps 100 hr. Alternatively, if the initial heating is at temperatures lower than 43?C, thermotolerance can develop during the heating period. The crucial role of protein synthesis in the development of thermotolerance has been recognized for some time (3). Protein synthesis is inhibited at temperatures of 43?C or higher, but goes on at lower temperatures. Thermotolerance also cannot develop if protein synthesis is inhibited by means other than heat itself, as, for example, during incubation in medium in which water has been replaced by deuterium oxide (4) or if cells are at low temperature (1, 2). It has been known for a considerable time that heat induces synthesis of a family of proteins, usually referred to as heat shock proteins (hsp) (5). These proteins, perhaps as many as 20 or more, range in molecular weight from less than 20,000 to more than 100,000. Because of the important role that protein synthesis appears to play in the development of thermotolerance, as discussed in the previous paragraph, it is not surprising that experiments were performed to determine whether or not hsp may play a role in conferring heat resistance on cells. Indeed, several studies have now shown that in mammalian cells there is a good temporal correlation between the induction of heat shock proteins and the development of thermotolerance (6, 7). Furthermore, it has been demonstrated that thermotolerance can be