Thermotolerance and the heat shock proteins.

Mammalian cells can dramatically increase their tolerance to thermal damage after prior heat conditioning. The thermal history, the heat fractionation interval and the recovery conditions, all modify significantly the degree of thermotolerance exhibited. Several lines of evidence have suggested that perhaps that shock proteins (hsps) provide the protective mechanism. For example by following the synthesis and degradation of heat shock proteins during development and decay of thermotolerance, strong circumstantial evidence has been obtained in certain cases that hsps are involved in the acquisition, maintenance and decay of thermotolerance. The levels of certain heat shock proteins, particularly the class at 68-70 kDa, can also correlate with thermotolerance. On the other hand these correlations do not always hold. Moreover cycloheximide treatment during the heat shock does not appear to block the development of thermotolerance. In addition depletion of medium Ca2+ which also inhibits hsp induction can produce thermotolerance. However it should be emphasized that whilst hsp synthesis is elevated after heat shock, it is clear that there are low level of hsps, always present in unheated cells, which may be sufficient to confer tolerance. Other data now show that thermotolerance measured in terms of cells survival is closely parallel by thermal resistance of total protein synthesis. Moreover it is possible to demonstrate the development of thermotolerance in the total protein synthetic activity of Hela cells, either held continuously at 42 degrees C or treated briefly at 45 degrees C and returned to normal growth temperature. This development of tolerance in the total protein synthetic activity is nonetheless reduced by actinomycin D and a role for the nucleolus is suggested. The properties of hsps that might be of significance in the generation of thermotolerance are examined. For example there appears to be a specific role of hsp 70 in aiding repair of heat damaged nucleoli. Another heat shock protein appears to be ubiquitin which is likely to have a role in the degradation of the abnormal proteins which are postulated to be involved in the transcriptional activation of the hsp genes themselves.