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

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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 17β-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 17β-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 17β-estradiol (while 17β-estradiol was unable to modify the response, the action of prednisolone in both the stress response and the cell cycle was equivocal).

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Abbreviations

AAG:

17-allylamino-17-demethoxygeldanamycin

CFU:

colony-forming units

Cxm:

cycloheximide

GA:

geldanamycin

HS:

heat shock

Hsp90:

heat-shock protein 90

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Correspondence to E. Tiligada.

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This work was financially supported by theUniversity of Athens, Greece.

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Papamichael, K., Vovou, I., Miligkos, V. et al. Effect of the Hsp90 modulators on the heat-shock response in eukaryotic cells. Folia Microbiol 51, 33–37 (2006). https://doi.org/10.1007/BF02931447

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