Modifications of Stress Response in Mammalian Cells Incubated at Low Temperature, Thermotolerant Cells, and Neuronal Cells During Differentiation

Summary

The stress response is induced by a variety of environmental and physiological stresses, and it is modulated under various environmental and physiological conditions. In this study I demonstrated that the stress response in mammalian cells is modified by low-temperature incubation, the thermotolerant state, and the differentiation state of cells. First, the culture temperature of cells modifies induction of the stress response. Mouse FM3A cells maintained at low temperatures do not synthesize HSP70, although the cells maintained at 37°C do so. Low culture temperature also modulates the thermal sensitivity of cells. Because the thermosensitivity of mammalian cells is enhanced by transient incubation at low temperatures, cooling tumor tissues transiently before trials of clinical hyperthermia may be useful for cancer therapy. In addition, two kinds of stressor induce the stress response dependent on or independently of culture temperature. Second, the thermotolerant state of cells modulates induction of the stress response. Upon exposure to heat-shock and other stresses, nonthermotolerant HeLa cells transiently synthesize a large amount of HSP70, whereas thermotolerant cells synthesize only a small amount. The high HSP70 content in the thermotolerant cells seems to regulate the activity of heat shrek factor 1 negatively. Third, rat PC12 cells, which change into differentiated neuronal cells in response to nerve growth factor, reduce their stress response during neuronal differentiation. The diminished HSP70 expression in the differentiated neuronal cells may explain the high sensitivity of these cells to pathophysiological stressors. The significance of modulating the stress response is discussed.