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We examined by Western blots the effect of variations of the heating sessions, such as duration and intensity on the following aspects: 70-kDa heat shock protein (HSP70) and HSP72 induction. Protein ubiquitination PLCgamma , PKCepsilon and PKCalpha levels in murine liver and brain were also studied. Results demonstrated that maximal induction of HSP72 was obtained after heat shock at 43.5 degrees C in both organs. Preconditioning at lower temperatures (either acclimation to 39 degrees C or induction of thermotolerance to 43.5 degrees C with a single exposure to 39 degrees C) attenuated the heat shock response. Hepatic HSP72 induction was elicited only as a consequence of hyperthermia since either fasting or restraint were unable to trigger its synthesis. On the contrary, a ubiquitination decrease of a 31 kDa protein was obtained both after hyperthermia and fasting This indicates that the latter is a more generic response of hepatic cells to noxious stimuli. Analysis of the above mentioned enzymes showed that in liver of naive mice PKCalpha is barely present while PKCepsilon is quite abundant. All hyperthermic treatments caused a general decrease of the latter, except for the heat shock at 43.5 degrees C that caused an increase. PLCgamma decreased after all heating sessions. It is known that hyperthermia in the range of 41-45 degrees C induces apoptotic death in many cell types. Therefore we analyzed the presence of the typical apoptotic DNA ladder. Our data strongly suggest that both hyperthermia and restraint induce necrosis in liver while apoptosis and necrosis become evident in brain. All these effects are still present 24 h from the last heating session: This indicates that in vivo, hyperthermia produces long term modifications of the hepatic cell.