Expression of human hsp70 in rat fibroblasts enhances cell survival and facilitates recovery from translational and transcriptional inhibition following heat shock

Abstract

We report here our studies on the inhibitional effect of 45 degrees C heat shock on transcriptional and translational activity and their subsequent recovery at 37 degrees C in Rat-1 cells, thermotolerant Rat-1 cells (TT Rat-1), and Rat-1 cells transfected with human hsp70 gene (HR24, M21). Specifically, we ask whether overexpression of hsp70 protects 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 hsp70, by itself, confers thermal resistance as expressed in enhanced survival and translational tolerance, but not transcriptional tolerance. In addition, the expression of human hsp70 in Rat-1 cells facilitates cells' ability to recover from heat-induced inhibition in protein and RNA synthesis. After healing at 45 degrees C for 25 min, the time required for RNA and protein synthesis to recover is considerably shorter in HR24, M21, and TT 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' translational tolerance, as well as their ability to recover from translational and transcriptional inhibition after heat shock.