Studies of Heat and PGA 1 -Induced Cold Tolerance Show That HSP27 May Help Preserve Actin Morphology During Hypothermia

Abstract

Preservation of organs and tissue prior to transplantation is highly limited by hypothermic storage times. One potential method to increase preservation times is to condition tissue and/or cells for hypothermia by administering prior physiological stress. In a prior study, we have demonstrated that mammalian cells in culture can be conditioned to better withstand 4°C hypothermia if they are exposed to prior 42.5° C heat shock. However, the mechanisms by which heat confers tolerance to hypothermia are not known. Since it is likely that heat shock proteins (HSPs) are playing a role in this phenomenon, and since antiproliferative prostaglandins (PGs) often induce a different spectrum of HSPs than induced by heat shock, the effect of prostaglandin A₁ (PGA₁) on HSP synthesis and induction of cold tolerance in IMR-90 human diploid fibroblasts was examined and compared to the effect of heat shock. Both heat shock and PGA₁ induced the same concentration of HSP70, but only heat induced HSP27 above basal levels. Furthermore, the degree of cold tolerance conferred by PGA₁ with respect to cell membrane integrity, cell morphology, and actin structure was suboptimal as compared to the degree of cold tolerance conferred by heat shock. One mechanism by which heat may induce a greater degree of cold tolerance than does PGA₁ is through the induction of HSP27, a known stabilizer of actin. An additive effect of sub-optimal heat shock, which induces the maximum level of HSP27, and PGA₁ exposure supports this finding since this combination gives better cold tolerance than either treatment alone.