Stable Expression of Human HSP70 Gene in Rodent Cells Confers Thermal Resistance

Abstract

When exposed to a non lethal heat shock, a variety of organisms and cell lines acquire a transient resistance to one or more subsequent exposures at elevated temperatures (Gener and Schneider, 1975; Henle and Leeper, 1976). This phenomenon has been termed thermotolerance (Henle and Dethlefsen, 1978). The mechanism for thermotolerance is not well understood. In mammalian systems, several studies suggest that heat shock proteins (HSPs) may be involved in the development of thermotolerance (Lindquist and Craig, 1988; Landry etal., 1982; Li and Werb, 1982; Subjeck etal., 1982). HSP70, a major heat shock protein, is synthesized by cells of many organisms in response to thermal or other environmental stresses (Lindquist and Craig, 1988; Landry etal., 1982; Li and Werb, 1982; Subjeck etal., 1982; Li, 1985;Lasglo and Li, 1985; Hahn and Li, 1990). It has been hypothesized that the transient induction of HSP70 may enable cells to recover from previous thermal stress, and/or to provide cells a transient degree of protection to subsequent heat challenge. A corollary of this hypothesis is that the overexpression of HSP70 in cells confers permanent heat resistance. We have initiated direct tests of the hypothesis that HSP70 protects cells from thermal stress by microinjecting human HSP70 into CHO cells or introducing a cloned human HSP70 gene into rat fibroblasts, and then evaluating the effect of human HSP70 gene expression on transient thermotolerance and permanent thermal resistance.