Effects on the expression of heat shock proteins by step-down heating and hypothermia in rat hepatoma cells with a different degree of heat sensitivity

Abstract

Thermosensitization induced by pretreatment at supra- and subnormal temperatures, rate of protein synthesis and expression of the major heat shock proteins under such conditions was investigated in relation to intrinsic heat sensitivity of rat hepatoma cells, i.e. Reuber H35 and HTC. The high degree of heat susceptibility of H35 cells was reflected by a high degree of thermosensitization after pretreatment by heat (step-down heating) at temperatures of 42-44 degrees C for 30 min or cold for 16 h at temperatures ranging from 0 to 25 degrees C. Sensitization under step-down heating conditions was found to be paralleled by a delayed recovery of protein synthesis. Despite an increased relative rate, enhancement of the absolute rate of synthesis of the major heat shock proteins, HSP28, HSP60, HSP68, HSP70, HSP84 and HSP100, was less pronounced during step-down exposure. Comparable results were obtained during recovery of sensitized H35 cells at 37 degrees C after exposure to heat following pretreatment at 0 degrees C. Furthermore, clear differences in the regulation of the specific HSP synthesis, depending on the particular treatment protocol, were observed.

Postconditioning Hormesis Put in Perspective: An Overview of Experimental and Clinical Studies

“…To study the effect of homologous heat postconditioning, cells were first exposed to a heat shock at 42°C or 43.5°C and subsequently incubated at mild 'fever-like' temperatures. An enhanced survival capacity and an enhanced synthesis of stress proteins were observed when the initial heat shock was followed by a post-exposure to a lower hyperthermic (fever-like) temperature (Schamhart et al 1992;Van Wijk et al 1994a). Similar observations were reported by Delpino et al (1992).…”

The similia principle: Results obtained in a cellular model system

“…They were not induced at 41 C and only to a small degree after the HS at 42 C. However, the combination (42 C followed by 41 C) caused a significant induction. 19 Similar observations were reported for mRNA levels of hsp68 and hsp84 when heat-shocked cells were post-exposed to 40 C and 41 C. 23 These observations were supported by the work of Delpino et al 24 who demonstrated enhanced synthesis of stress proteins and enhanced survival capacity due to step-down heating.…”

“…Schamhart et al 19 exposed cells initially for 30 min at either 42 C or 43.5 C and subsequently incubated them at mild (fever-like) temperatures (38-41 C) for 6 h. The survival capacity was then tested by exposing cells to a test treatment of 43.5 C for 1 h. 19,23 When cells were initially heat shocked at 42 C, a posttreatment of 40 C enhanced the survival capacity compared to cells that were exposed to 42 C and post-treated at 37 C. With this mild postconditioning, heat treatment appeared to be beneficial following the 42 C heat treatment, but it depressed the survival capacity of cells that had been exposed to 43.5 C pretreatment. Interestingly, the exposure of untreated cells to 40 C for 6 h was without effect on survival capacity.…”

“…Interestingly, the exposure of untreated cells to 40 C for 6 h was without effect on survival capacity. 23 Schamhart et al 19 were the first to study whether the synthesis of specific stress proteins (hsp28, hsp60, hsp68, hsp70, hsp84 and hsp100) induced by a 30 min HS at 42 C was influenced when the heat-shocked cells were subsequently exposed to a lower hyperthermic temperature for a period up to 8 h. In their analysis, they compared the expression of hsps in this postconditioning situation with the expression of the various stress proteins in cells after a HS at 42 C followed by incubation at 37 C. The production of these proteins was found to increase to a larger extent when cells heat shocked at 42 C were subsequently incubated at 41 C. Hsp28 and hsp68 demonstrated a particularly interesting behavior. They were not induced at 41 C and only to a small degree after the HS at 42 C. However, the combination (42 C followed by 41 C) caused a significant induction.…”

“…The state of enhanced sensitivity, reflecting the disturbed state of the living system, is an essential characteristic of our model. We observed it following exposure to a HS, 19 to arsenite 20 and to cadmium. 21 It offers the opportunity to study the stimulation of self-recovery by low doses of stressor since, due to this enhanced sensitivity, cells react to stimuli to which they normally would not react.…”