التفاصيل البيبلوغرافية
| العنوان: |
Activation function 2 (AF2) of estrogen receptor-α is required for the atheroprotective action of estradiol but not to accelerate endothelial healing. |
| المؤلفون: |
Billon-Galés, Audrey, Krust, Andrée, Fontaine, Coralie, Abot, Anne, Flouriot, Gilles, Toutain, Céline, Berges, Hortense, Gadeau, Alain-Pierre, Lenfant, Françoise, Gourdy, Pierre, Chambon, Pierre, Arnal, Jean-François |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 8/9/2011, Vol. 108 Issue 32, p13311-13316, 6p |
| مصطلحات موضوعية: |
SELECTIVE estrogen receptor modulators, ESTROGEN antagonists, PHYSIOLOGICAL effects of estradiol, STEROLS, ENDOTHELINS, ENDOTHELIAL growth factors, THERAPEUTICS |
| مستخلص: |
17β-Estradiol (E2) regulates estrogen receptor-α (ERα) target gene transcription through the two independent activation functions (AFs), AF1 and AF2, located in the N-terminal and ligand binding domain of ERα, respectively. We previously reported that ERα is required for the E2 atheroprotective action as well as for its accelerative action on endothelial healing, but its AF1 function is dispensable. Here, we investigated the role of ERαAF2 in these two major beneficial actions of E2 by electively targeting ERαAF2 (named ERαAF20 ). Our results prove four points. (i) Compared with WT ERα, the ability of ERαAF20 to stimulate the C3 complement or the estrogen response element-thymidine kinase promoter in two cell lines was dramatically decreased, confirming the importance of AF2 in the E2-induced transcriptional activity of ERα. (ii) The uterotrophic action of E2 was totally absent in ERαAF20 mice, showing the crucial role of ERαAF2 in E2-induced uterus hyperplasia. (iii) ERαAF2 was dispensable for the accelerative action of E2 on endothelial healing, underlining the functionality of ERαAF20 in vivo. (iv) Finally, the atheroprotective effect of E2 was abrogated in ERαAF20 LDL-r-/- mice. Thus, whereas ERαAF1 and ERαAF2 are both required for the uterotrophic action of E2, we show that only ERαAF2 is necessary for its atheroprotective effect. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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