Nuclear Factor-κB Regulates Estrogen Receptor-α Transcription in the Human Heart

Mahmoodzadeh S, Fritschka S, Dworatzek E, Pham TH, Becher E, Kuehne A, Davidson MM, Regitz-Zagrosek V (2009)
Journal of Biological Chemistry 284(37): 24705-24714.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Mahmoodzadeh, Shokoufeh; Fritschka, Stephan; Dworatzek, Elke; Pham, Thi H.; Becher, EvaUniBi ; Kuehne, Arne; Davidson, Mercy M.; Regitz-Zagrosek, Vera
Abstract / Bemerkung
strogen receptor (ER)-mediated effects have been associated with the modulation of myocardial hypertrophy in animal models and in humans, but the regulation of ER expression in the human heart has not yet been analyzed. In various cell lines and tissues, multiple human estrogen receptor α (hERα) mRNA isoforms are transcribed from distinct promoters and differ in their 5′-untranslated regions. Using PCR-based strategies, we show that in the human heart the ERα mRNA is transcribed from multiple promoters, namely, A, B, C, and F, of which the F-promoter is most frequently used variant. Transient transfection reporter assays in a human cardiac myocyte cell line (AC16) with F-promoter deletion constructs demonstrated a negative regulatory region within this promoter. Site-directed mutagenesis and electrophoretic mobility shift assays indicated that NF-κB binds to this region. An inhibition of NF-κB activity by parthenolide significantly increased the transcriptional activity of the F-promoter. Increasing NF-κB expression by tumor necrosis factor-α reduced the expression of ERα, indicating that the NF-κB pathway inhibits expression of ERα in human cardiomyocytes. Finally, 17β-estradiol induced the transcriptional activity of hERα promoters A, B, C, and F. In conclusion, inflammatory stimuli suppress hERα expression via activation and subsequent binding of NF-κB to the ERα F-promoter, and 17β-estradiol/hERα may antagonize the inhibitory effect of NF-κB. This suggests interplay between estrogen/estrogen receptors and the pro-hypertrophic and inflammatory responses to NF-κB.
Erscheinungsjahr
2009
Zeitschriftentitel
Journal of Biological Chemistry
Band
284
Ausgabe
37
Seite(n)
24705-24714
ISSN
0021-9258
Page URI
https://pub.uni-bielefeld.de/record/2964904

Zitieren

Mahmoodzadeh S, Fritschka S, Dworatzek E, et al. Nuclear Factor-κB Regulates Estrogen Receptor-α Transcription in the Human Heart. Journal of Biological Chemistry. 2009;284(37):24705-24714.
Mahmoodzadeh, S., Fritschka, S., Dworatzek, E., Pham, T. H., Becher, E., Kuehne, A., Davidson, M. M., et al. (2009). Nuclear Factor-κB Regulates Estrogen Receptor-α Transcription in the Human Heart. Journal of Biological Chemistry, 284(37), 24705-24714. https://doi.org/10.1074/jbc.M109.000463
Mahmoodzadeh, S., Fritschka, S., Dworatzek, E., Pham, T. H., Becher, E., Kuehne, A., Davidson, M. M., and Regitz-Zagrosek, V. (2009). Nuclear Factor-κB Regulates Estrogen Receptor-α Transcription in the Human Heart. Journal of Biological Chemistry 284, 24705-24714.
Mahmoodzadeh, S., et al., 2009. Nuclear Factor-κB Regulates Estrogen Receptor-α Transcription in the Human Heart. Journal of Biological Chemistry, 284(37), p 24705-24714.
S. Mahmoodzadeh, et al., “Nuclear Factor-κB Regulates Estrogen Receptor-α Transcription in the Human Heart”, Journal of Biological Chemistry, vol. 284, 2009, pp. 24705-24714.
Mahmoodzadeh, S., Fritschka, S., Dworatzek, E., Pham, T.H., Becher, E., Kuehne, A., Davidson, M.M., Regitz-Zagrosek, V.: Nuclear Factor-κB Regulates Estrogen Receptor-α Transcription in the Human Heart. Journal of Biological Chemistry. 284, 24705-24714 (2009).
Mahmoodzadeh, Shokoufeh, Fritschka, Stephan, Dworatzek, Elke, Pham, Thi H., Becher, Eva, Kuehne, Arne, Davidson, Mercy M., and Regitz-Zagrosek, Vera. “Nuclear Factor-κB Regulates Estrogen Receptor-α Transcription in the Human Heart”. Journal of Biological Chemistry 284.37 (2009): 24705-24714.

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