Document Detail

A delayed antioxidant response in heat-stressed cells expressing a non-DNA binding HSF1 mutant.
MedLine Citation:
PMID:  23321918     Owner:  NLM     Status:  MEDLINE    
To assess the consequences of inactivation of heat shock factor 1 (HSF1) during aging, we analyzed the effect of HSF1 K80Q, a mutant unable to bind DNA, and of dnHSF1, a mutant lacking the activation domain, on the transcriptome of cells 6 and 24 h after heat shock. The primary response to heat shock (6 h recovery), of which 30 % was HSF1-dependent, had decayed 24 h after heat shock in control cells but was extended in HSF1 K80Q and dnHSF1 cells. Comparison with literature data showed that even the HSF1 dependent primary stress response is largely cell specific. HSF1 K80Q, but not HSF1 siRNA-treated, cells showed a delayed stress response: an increase in transcript levels of HSF1 target genes 24 h after heat stress. Knockdown of NRF2, but not of ATF4, c-Fos or FosB, inhibited this delayed stress response. EEF1D_L siRNA inhibited both the delayed and the extended primary stress responses, but had off target effects. In control cells an antioxidant response (ARE binding, HMOX1 mRNA levels) was detected 6 h after heat shock; in HSF1 K80Q cells this response was delayed to 24 h and the ARE complex had a different mobility. Inactivation of HSF1 thus affects the timing and nature of the antioxidant response and NRF2 can activate at least some HSF1 target genes in the absence of HSF1 activity.
Sanne M M Hensen; Lonneke Heldens; Siebe T van Genesen; Ger J M Pruijn; Nicolette H Lubsen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-16
Journal Detail:
Title:  Cell stress & chaperones     Volume:  18     ISSN:  1466-1268     ISO Abbreviation:  Cell Stress Chaperones     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-14     Completed Date:  2013-12-30     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  9610925     Medline TA:  Cell Stress Chaperones     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  455-73     Citation Subset:  IM    
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MeSH Terms
DNA / metabolism
DNA-Binding Proteins / antagonists & inhibitors,  genetics,  metabolism*
HEK293 Cells
HSP70 Heat-Shock Proteins / genetics,  metabolism
Heme Oxygenase-1 / genetics,  metabolism
NF-E2-Related Factor 2 / antagonists & inhibitors,  genetics,  metabolism
RNA Interference
RNA, Messenger / metabolism
RNA, Small Interfering / metabolism
Stress, Physiological
Time Factors
Transcription Factors / antagonists & inhibitors,  genetics,  metabolism*
Reg. No./Substance:
0/DNA-Binding Proteins; 0/HSP70 Heat-Shock Proteins; 0/HSPA1A protein, human; 0/Hsp70B' protein, human; 0/NF-E2-Related Factor 2; 0/NFE2L2 protein, human; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Transcription Factors; 0/heat shock transcription factor; 9007-49-2/DNA; EC protein, human; EC Oxygenase-1

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