Advanced search
1 file | 6.16 MB Add to list

Compound A, a selective glucocorticoid receptor modulator, enhances heat shock protein Hsp70 gene promoter activation

Ilse Beck (UGent) , Zuzanna Drebert (UGent) , Ruben Hoya-Arias, Ali A Bahar, Michael Devos (UGent) , Dorien Clarisse (UGent) , Sofie Desmet (UGent) , Nadia Bougarne (UGent) , Bart Ruttens (UGent) , Valerie Gossye, et al.
(2013) PLOS ONE. 8(7).
Author
Organization
Abstract
Compound A possesses glucocorticoid receptor (GR)-dependent anti-inflammatory properties. Just like classical GR ligands, Compound A can repress NF-kappa B-mediated gene expression. However, the monomeric Compound A-activated GR is unable to trigger glucocorticoid response element-regulated gene expression. The heat shock response potently activates heat shock factor 1 (HSF1), upregulates Hsp70, a known GR chaperone, and also modulates various aspects of inflammation. We found that the selective GR modulator Compound A and heat shock trigger similar cellular effects in A549 lung epithelial cells. With regard to their anti-inflammatory mechanism, heat shock and Compound A are both able to reduce TNF-stimulated I kappa B alpha degradation and NF-kappa B p65 nuclear translocation. We established an interaction between Compound A-activated GR and Hsp70, but remarkably, although the presence of the Hsp70 chaperone as such appears pivotal for the Compound A-mediated inflammatory gene repression, subsequent novel Hsp70 protein synthesis is uncoupled from an observed CpdA-induced Hsp70 mRNA upregulation and hence obsolete in mediating CpdA's anti-inflammatory effect. The lack of a Compound A-induced increase in Hsp70 protein levels in A549 cells is not mediated by a rapid proteasomal degradation of Hsp70 or by a Compound A-induced general block on translation. Similar to heat shock, Compound A can upregulate transcription of Hsp70 genes in various cell lines and BALB/c mice. Interestingly, whereas Compound A-dependent Hsp70 promoter activation is GR-dependent but HSF1-independent, heat shock-induced Hsp70 expression alternatively occurs in a GR-independent and HSF1-dependent manner in A549 lung epithelial cells.
Keywords
EXPRESSION, BINDING, TRANSCRIPTION, RNA ACTIVATOR, MOLECULAR CHAPERONES, CANCER CELLS, BETA-CATENIN, KAPPA-B INHIBITION, TUMOR-NECROSIS-FACTOR, PROTEASOME INHIBITION LEADS

Downloads

  • fetchObject.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 6.16 MB

Citation

Please use this url to cite or link to this publication:

MLA
Beck, Ilse, Zuzanna Drebert, Ruben Hoya-Arias, et al. “Compound A, a Selective Glucocorticoid Receptor Modulator, Enhances Heat Shock Protein Hsp70 Gene Promoter Activation.” PLOS ONE 8.7 (2013): n. pag. Print.
APA
Beck, I., Drebert, Z., Hoya-Arias, R., Bahar, A. A., Devos, M., Clarisse, D., Desmet, S., et al. (2013). Compound A, a selective glucocorticoid receptor modulator, enhances heat shock protein Hsp70 gene promoter activation. PLOS ONE, 8(7).
Chicago author-date
Beck, Ilse, Zuzanna Drebert, Ruben Hoya-Arias, Ali A Bahar, Michael Devos, Dorien Clarisse, Sofie Desmet, et al. 2013. “Compound A, a Selective Glucocorticoid Receptor Modulator, Enhances Heat Shock Protein Hsp70 Gene Promoter Activation.” Plos One 8 (7).
Chicago author-date (all authors)
Beck, Ilse, Zuzanna Drebert, Ruben Hoya-Arias, Ali A Bahar, Michael Devos, Dorien Clarisse, Sofie Desmet, Nadia Bougarne, Bart Ruttens, Valerie Gossye, Geertrui Denecker, Sam Lievens, Marc Bracke, Jan Tavernier, Wim Declercq, Kris Gevaert, Wim Vanden Berghe, Guy Haegeman, and Karolien De Bosscher. 2013. “Compound A, a Selective Glucocorticoid Receptor Modulator, Enhances Heat Shock Protein Hsp70 Gene Promoter Activation.” Plos One 8 (7).
Vancouver
1.
Beck I, Drebert Z, Hoya-Arias R, Bahar AA, Devos M, Clarisse D, et al. Compound A, a selective glucocorticoid receptor modulator, enhances heat shock protein Hsp70 gene promoter activation. PLOS ONE. 2013;8(7).
IEEE
[1]
I. Beck et al., “Compound A, a selective glucocorticoid receptor modulator, enhances heat shock protein Hsp70 gene promoter activation,” PLOS ONE, vol. 8, no. 7, 2013.
@article{4223768,
  abstract     = {Compound A possesses glucocorticoid receptor (GR)-dependent anti-inflammatory properties. Just like classical GR ligands, Compound A can repress NF-kappa B-mediated gene expression. However, the monomeric Compound A-activated GR is unable to trigger glucocorticoid response element-regulated gene expression. The heat shock response potently activates heat shock factor 1 (HSF1), upregulates Hsp70, a known GR chaperone, and also modulates various aspects of inflammation. We found that the selective GR modulator Compound A and heat shock trigger similar cellular effects in A549 lung epithelial cells. With regard to their anti-inflammatory mechanism, heat shock and Compound A are both able to reduce TNF-stimulated I kappa B alpha degradation and NF-kappa B p65 nuclear translocation. We established an interaction between Compound A-activated GR and Hsp70, but remarkably, although the presence of the Hsp70 chaperone as such appears pivotal for the Compound A-mediated inflammatory gene repression, subsequent novel Hsp70 protein synthesis is uncoupled from an observed CpdA-induced Hsp70 mRNA upregulation and hence obsolete in mediating CpdA's anti-inflammatory effect. The lack of a Compound A-induced increase in Hsp70 protein levels in A549 cells is not mediated by a rapid proteasomal degradation of Hsp70 or by a Compound A-induced general block on translation. Similar to heat shock, Compound A can upregulate transcription of Hsp70 genes in various cell lines and BALB/c mice. Interestingly, whereas Compound A-dependent Hsp70 promoter activation is GR-dependent but HSF1-independent, heat shock-induced Hsp70 expression alternatively occurs in a GR-independent and HSF1-dependent manner in A549 lung epithelial cells.},
  articleno    = {e69115},
  author       = {Beck, Ilse and Drebert, Zuzanna and Hoya-Arias, Ruben and Bahar, Ali A and Devos, Michael and Clarisse, Dorien and Desmet, Sofie and Bougarne, Nadia and Ruttens, Bart and Gossye, Valerie and Denecker, Geertrui and Lievens, Sam and Bracke, Marc and Tavernier, Jan and Declercq, Wim and Gevaert, Kris and Vanden Berghe, Wim and Haegeman, Guy and De Bosscher, Karolien},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keywords     = {EXPRESSION,BINDING,TRANSCRIPTION,RNA ACTIVATOR,MOLECULAR CHAPERONES,CANCER CELLS,BETA-CATENIN,KAPPA-B INHIBITION,TUMOR-NECROSIS-FACTOR,PROTEASOME INHIBITION LEADS},
  language     = {eng},
  number       = {7},
  pages        = {18},
  title        = {Compound A, a selective glucocorticoid receptor modulator, enhances heat shock protein Hsp70 gene promoter activation},
  url          = {http://dx.doi.org/10.1371/journal.pone.0069115},
  volume       = {8},
  year         = {2013},
}

Altmetric
View in Altmetric
Web of Science
Times cited: