Paradoxical increase of heat-shock response with age in a substrain of F344 rats: comparison between F344/DuCrj and F344/Jcl.

The ability of hepatocytes isolated from young (7-10 months) and old (31 months) male F344/Jcl and F344/DuCrj rats to express heat shock protein (hsp) 27, hsp70 and hsp90 was determined after a mild heat shock (42.5 degrees C for 30 min). The induction of these three mRNA levels by the heat shock was 50-80% lower in hepatocytes isolated from old F344/Jcl rats than in those from young rats. However, the hepatocytes from old F344/DuCrj showed a marked increase (200-250%) in the induction of hsp mRNAs by heat shock when compared to cells from young rats. Because heat shock transcription factor (HSF) plays a critical role in regulating the transcription of hsp genes, the effect of age on the binding activity HSF to heat shock element (HSE) was also studied. Again, the induction of binding activity of HSF to HSE was significantly increased with age in hepatocytes from F344/DuCrj rats while the reverse was true for the cells from F344/Jcl. The induced levels of hsp mRNAs were positively correlated with the binding activity of HSF to HSE in hepatocyte extracts from both F344 substrains, suggesting that the diverse age-related changes of heat-shock response in F344 substrains occurs in HSF activity. The contradictory age-related change in the heat-shock response is discussed with the differences in biochemical and genetic properties of substrains of F344 rats.