No abstract

Application of a mild heat pretreatment, performed by shifting cells from 27 °C to 37 °C led to the protection of yeast cells from death due to a subsequent extreme heat shock at 53 °C. The presence of cycloheximide inhibited this induction of thermotolerance, indicating the involvement of de novo protein. The phosphatase inhibitor sodium molybdate induced thermotolerance to the non‐pretreated yeast cells. This induction of thermotolerance did not seem to depend upon de novo protein synthesis. Thus, acquisition of thermotolerance in yeast may involve a number of cellular mechanisms depending on the conditions the organism encounters at any particular time.

Environmental conditions such as temperature, radiation, hypoxia, nutrients and drugs stimulate the adaptive sensory and signaling machinery of the cell. This stress response may influence cell cycle regulation, cellular differentiation, oncogenic transforma-tion, cell survival and apoptosis. The impact of the cytoprotective reprogramming in cancer pharmacology is presented by the recent extensive literature regarding the interplay between stress tolerance and anticancer drug effectiveness and resistance, relying on the dominating intrinsic pathways, which are simultaneously activated and regulate the death process either positively or negatively. This review presents the data that argue for the emergence of either common or specific mechanisms depending on the type, duration and severity of stress in all eukaryotic organisms from yeast to mammals. The understanding of the complexity and the balance between noxious and protective signal transduction pathways would contribute to a more explicit evaluation of the current therapeutic regiments and to the development of new leads targeting malignancy.

No abstract

The possible role of the heat-shock protein 90 (Hsp90) complex on the heat-shock (HS) response in yeast using the Hsp90 inhibitors geldanamycin (GA) and 17-allylamino-17-demethoxygeldanamycin (AAG), and prednisolone and 17beta-estradiol as modulators was investigated. Following long- or short-term administration of the drugs, either alone or in combination, the response was determined as cell viability and growth after exposure to HS. Upon short-term preconditioning, both Hsp90 inhibitors conferred cycloheximide-dependent thermal resistance to the yeast cultures, while upon long-term treatment the induction of thermotolerance was confined only to AAG. Co-administration of prednisolone or 17beta-estradiol failed to significantly alter the response to Hsp90 inhibitors. However, since short-term incubation with prednisolone alone induced thermotolerance, increased the budding cell fraction and tended to reduce the adaptive response to GA, its effect on GA-induced thermotolerance is not yet explained. Generally, GA and AAG showed a comparable short-term action but a different long-term effect on the HS response in yeast; this response was not related to any regulation by prednisolone or 17beta-estradiol (while 17beta-estradiol was unable to modify the response, the action of prednisolone in both the stress response and the cell cycle was equivocal).