17β-Estradiol-induced interaction of estrogen receptor α and human atrial essential myosin light chain modulates cardiac contractile function.
In: Basic Research in Cardiology, Jg. 112 (2017), Heft 1, S. 1-15
Online
academicJournal
Zugriff:
Chronic increased workload of the human heart causes ventricular hypertrophy, re-expression of the atrial essential myosin light chain (hALC-1), and improved contractile function. Although hALC-1 is an important positive inotropic regulator of the human heart, little is known about its regulation. Therefore, we investigated the role of the sex hormone 17β-estradiol (E2) on hALC-1 gene expression, the underlying molecular mechanisms, and the impact of this regulatory process on cardiac contractile function. We showed that E2 attenuated hALC-1 expression in human atrial tissues of both sexes and in human ventricular AC16 cells. E2 induced the nuclear translocation of estrogen receptor alpha (ERα) and hALC-1 in AC16 cells, where they cooperatively regulate the transcriptional activity of hALC-1 gene promoter. E2-activated ERα required the estrogen response element (ERE) motif within the hALC-1 gene promoter to reduce its transcriptional activity (vehicle: 15.55 ± 4.80 vs. E2: 6.51 ± 3.69; ~2 fold). This inhibitory effect was potentiated in the presence of hALC-1 (vehicle: 11.13 ± 3.66 vs. E2: 2.18 ± 1.10; ~5 fold), and thus, hALC-1 acts as a co-repressor of ERα-mediated transcription. Yeast two-hybrid screening of a human heart cDNA library revealed that ERα interacts physically with hALC-1 in the presence of E2. This interaction was confirmed by Co-Immunoprecipitation and immunofluorescence in human atrium. As a further novel effect, we showed that chronic E2-treatment of adult mouse cardiomyocytes overexpressing hALC-1 resulted in reduced cell-shortening amplitude and twitching kinetics of these cells independent of Ca activation levels. Together, our data showed that the expression of hALC-1 gene is, at least partly, regulated by E2/ERα, while hALC-1 acts as a co-repressor. The inotropic effect of hALC-1 overexpression in cardiomyocytes can be significantly repressed by E2. [ABSTRACT FROM AUTHOR]
Titel: |
17β-Estradiol-induced interaction of estrogen receptor α and human atrial essential myosin light chain modulates cardiac contractile function.
|
---|---|
Autor/in / Beteiligte Person: | Duft, Karolin ; Schanz, Miriam ; Pham, Hang ; Abdelwahab, Ahmed ; Schriever, Cindy ; Kararigas, Georgios ; Dworatzek, Elke ; Davidson, Mercy ; Regitz-Zagrosek, Vera ; Morano, Ingo ; Mahmoodzadeh, Shokoufeh |
Link: | |
Zeitschrift: | Basic Research in Cardiology, Jg. 112 (2017), Heft 1, S. 1-15 |
Veröffentlichung: | 2017 |
Medientyp: | academicJournal |
ISSN: | 0300-8428 (print) |
DOI: | 10.1007/s00395-016-0590-1 |
Schlagwort: |
|
Sonstiges: |
|