Effect of the Hsp90 modulators on the heat-shock response in eukaryotic cells.

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).

The heat shock response is dependent on the external environment and on rapid ionic balancing by pharmacological agents in Saccharomyces cerevisiae.

AIMS: To investigate whether non-preconditioned yeast cells survive under heat shock, when placed in growth medium originated from protected cells and to provide insights into the ionic contribution in the response. METHODS AND RESULTS: The heat shock response was investigated by determining cell viability following exposure of yeast cells to 53 degrees C for 30 min, either in the absence or presence of drugs. Preconditioning was performed by incubating the cultures at 37 degrees C for 2 h. Under heat shock, non-preconditioned cell survival was significantly enhanced by the presence of the cell-free supernatant of resistant cultures. Addition of omeprazole or tetraethylammonium ions during the heat shock resulted in similar increases. Neither amiodarone nor mepivacaine showed any analogous effect. Omeprazole enhanced survival when added before the heat shock, while amiodarone exhibited a cytocidic action. CONCLUSIONS: Rapid balancing of ions may contribute to cell survival during heat shock, while survival under mild stress could probably be co-ordinated by additional events. SIGNIFICANCE AND IMPACT OF THE STUDY: Evidence is provided for the implication of the external environment and ionic homeostasis in the survival of yeast cells under unfavourable environmental conditions. This knowledge may be of importance in controlling both fermentation and therapeutic approaches.