Hsf1-mediated stress response can transiently enhance cellular radioresistance.
To elucidate how the heat-shock transcription factor 1 (Hsf1)-mediated stress response affects cellular radioresistance, mouse embryo fibroblasts with Hsf1-gene knockout (Hsf1(-/-) cells) or with normal wild-type Hsf1 expression (Hsf1 wild-type cells) were preconditioned by heating (43 degrees C, 30 min) without or with quercetin (an inhibitor of Hsf1) and then exposed to gamma radiation (4 or 6 Gy). Some cell samples were infected with virus-based vectors to overexpress the constitutively active (mutant) form of Hsf1 or individual heat-shock proteins (Hsps). The heat preconditioning transiently up-regulated the Hsp levels in Hsf1 wild-type cells and significantly improved their postirradiation survival; these effects could be abolished by quercetin or simulated (without preheating) by the Hsf1 overexpression. In contrast, no enhanced radioresistance was found in heat-preconditioned Hsf1(-/-) cells that were unable to trigger Hsf1-mediated Hsp induction after heating. However, when the constitutively active Hsf1 was overexpressed in Hsf1(-/-) cells, the latter accumulated stress-inducible Hsps and became more radioresistant like heat-preconditioned Hsf1 wild-type cells. The overexpression of Hsp70 or/ and Hsp27 also enhanced radioresistance of both cell cultures. Thus the preirradiation stress response resulting in the intracellular Hsp accumulation can improve survival of severely irradiated mammalian cells.
Medical Radiology Research Center, Obninsk 249036, Russia. aekabakov@hotmail.com
Alexander E
AE
Kabakov
Yana V
YV
Malyutina
David S
DS
Latchman
D000818:Animals; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response / Q000502:physiology* / Q000528:radiation effects*; D051379:Mice; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D014157:Transcription Factors