naa a22 4500 510746233 CHVBK 20180411083047.0 cr unu---uuuuu 180411e20130701xx s 000 0 eng 10.1007/s12192-012-0400-0 doi (NATIONALLICENCE)springer-10.1007/s12192-012-0400-0 A delayed antioxidant response in heat-stressed cells expressing a non-DNA binding HSF1 mutant [Elektronische Daten] [Sanne Hensen, Lonneke Heldens, Siebe van Genesen, Ger Pruijn, Nicolette Lubsen] 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 24h after heat shock. The primary response to heat shock (6h recovery), of which 30% was HSF1-dependent, had decayed 24h 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 24h 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 6h after heat shock; in HSF1 K80Q cells this response was delayed to 24h 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. Cell Stress Society International, 2013 Heat shock factor 1 nationallicence NRF2 nationallicence Stress response nationallicence HSPA1A nationallicence HSPA6 nationallicence HSP : Heat shock protein nationallicence HSF1 : Heat shock factor 1 nationallicence HSE : Heat shock element nationallicence MEF : Mouse embryonic fibroblast nationallicence NRF2 : Nuclear factor (erythroid-derived 2)-related factor 2 nationallicence ARE : Antioxidant response element nationallicence ATF : Activating transcription factor nationallicence KEAP1 : Kelch-like ECH associated protein 1 nationallicence Hensen Sanne 271 Department of Biomolecular Chemistry, Radboud University Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands aut Heldens Lonneke 271 Department of Biomolecular Chemistry, Radboud University Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands aut van Genesen Siebe 271 Department of Biomolecular Chemistry, Radboud University Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands aut Pruijn Ger 271 Department of Biomolecular Chemistry, Radboud University Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands aut Lubsen Nicolette 271 Department of Biomolecular Chemistry, Radboud University Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands aut Cell Stress and Chaperones Springer Netherlands 18/4(2013-07-01), 455-473 1355-8145 18:4<455 2013 18 12192 https://doi.org/10.1007/s12192-012-0400-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12192-012-0400-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hensen Sanne 271 Department of Biomolecular Chemistry, Radboud University Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- Heldens Lonneke 271 Department of Biomolecular Chemistry, Radboud University Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- van Genesen Siebe 271 Department of Biomolecular Chemistry, Radboud University Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- Pruijn Ger 271 Department of Biomolecular Chemistry, Radboud University Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- Lubsen Nicolette 271 Department of Biomolecular Chemistry, Radboud University Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands aut NATIONALLICENCE 773 0- Cell Stress and Chaperones Springer Netherlands 18/4(2013-07-01), 455-473 1355-8145 18:4<455 2013 18 12192 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer