| First Author | Ahluwalia A | Year | 2022 |
| Journal | Endocrinology | Volume | 164 |
| Issue | 2 | PubMed ID | 36461668 |
| Mgi Jnum | J:347578 | Mgi Id | MGI:7469733 |
| Doi | 10.1210/endocr/bqac200 | Citation | Ahluwalia A, et al. (2022) Membrane Estrogen Receptor beta Is Sufficient to Mitigate Cardiac Cell Pathology. Endocrinology 164(2) |
| abstractText | Estrogen acting through estrogen receptor beta (ERbeta) has been shown to oppose the stimulation of cardiac myocytes and cardiac fibroblasts that results in cardiac hypertrophy and fibrosis. Previous work has implicated signal transduction from ERbeta as being important to the function of estrogen in this regard. Here we address whether membrane ERbeta is sufficient to oppose key mechanisms by which angiotensin II (AngII) stimulates cardiac cell pathology. To do this we first defined essential structural elements within ERbeta that are necessary for membrane or nuclear localization in cells. We previously determined that cysteine 418 is the site of palmitoylation of ERbeta that is required and sufficient for cell membrane localization in mice and is the same site in humans. Here we determined in Chinese hamster ovarian (CHO) cells, and mouse and rat myocytes and cardiac fibroblasts, the effect on multiple aspects of signal transduction by expressing wild-type (WT ) or a C418A-mutant ERbeta. To test the importance of the nuclear receptor, we determined a 4-amino acid deletion in the E domain of ERbeta that strongly blocked nuclear localization. Using these tools, we expressed WT and mutant ERbeta constructs into cardiomyocytes and cardiac fibroblasts from ERbeta-deleted mice. We determined the ability of estrogen to mitigate cell pathology stimulated by AngII and whether the membrane ERbeta is necessary and sufficient. |
