Expression of Human hsp70 in Rat Fibroblasts Enhances Cell Survival and Facilitates Recovery from Translational and Transcriptional Inhibition following Heat Shock1

We report here our studies on the ¡nhibitionaleffect of 45°Cheat shock on transcriptions! and translational activity and their subsequent recovery at 37°Cin Rat-1 cells, thermotolerant Rat-1 cells ('IT Rat-1), and Rat-1 cells transfected with human hsp70 gene (IIR24, M21). Specifically, we ask whether overexpression of hspTOprotects cells from heat-induced inhibition in RNA and protein synthesis, and/or facilitates cells' ability to recover from translational or transcriptional inhibition after heat shock treatment. Our data demonstrate that the constitutive expression of human hspTO, by itself, confers thermal resistance as expressed in enhanced survival and translational tolerance, but not tran scriptional tolerance. In addition, the expression of human hsp70 in Rat1 cells facilitates cells' ability to recover from heat-induced inhibition in protein and RNA synthesis. After heating at 45°Cfor 25 min, the time required for RNA and protein synthesis to recover is considerably shorter in IIR24, M21, and II Rat-1 cells than that in control Rat-1 cells. These results provide strong evidence for a direct link between the expression of a functional form of mammalian hsp70, and cells' transla tional tolerance, as well as their ability to recover from translational and transcriptional inhibition after heat shock.