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).
Papamichael
K
K
Department of Pharmacology, Medical School, University of Athens, Greece.
Vovou
I
I
Miligkos
V
V
Stavrinidis
E
E
Delitheos
A
A
Tiligada
E
E
D000222:Adaptation, Physiological / Q000187:drug effects; D016227:Benzoquinones / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D018869:Heat-Shock Response / Q000187:drug effects*; D006358:Hot Temperature; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D011239:Prednisolone / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors; D013997:Time Factors
D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D029701:Saccharomyces cerevisiae Proteins; C112765:tanespimycin; D004958:Estradiol; D011239:Prednisolone; C001277:geldanamycin