{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:43:59Z","timestamp":1792622639890,"version":"4.5.0"},"reference-count":34,"publisher":"The Endocrine Society","issue":"2","funder":[{"name":"Department of Veterans Affairs Biomedical Laboratory Research and Development Service"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Estrogen acting through estrogen receptor \u03b2 (ER\u03b2) 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 ER\u03b2 as being important to the function of estrogen in this regard. Here we address whether membrane ER\u03b2 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 ER\u03b2 that are necessary for membrane or nuclear localization in cells. We previously determined that cysteine 418 is the site of palmitoylation of ER\u03b2 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 ER\u03b2. To test the importance of the nuclear receptor, we determined a 4\u2013amino acid deletion in the E domain of ER\u03b2 that strongly blocked nuclear localization. Using these tools, we expressed WT and mutant ER\u03b2 constructs into cardiomyocytes and cardiac fibroblasts from ER\u03b2-deleted mice. We determined the ability of estrogen to mitigate cell pathology stimulated by AngII and whether the membrane ER\u03b2 is necessary and sufficient.<\/jats:p>","DOI":"10.1210\/endocr\/bqac200","type":"journal-article","created":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T07:23:34Z","timestamp":1670052214000},"source":"Crossref","is-referenced-by-count":6,"title":["Membrane Estrogen Receptor \u03b2 Is Sufficient to Mitigate Cardiac Cell Pathology"],"prefix":"10.1210","volume":"164","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2064-5725","authenticated-orcid":false,"given":"Amrita","family":"Ahluwalia","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Department of Veterans Affairs, Medical Center, Long Beach , Long Beach, California 90822 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Hoa","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Veterans Affairs, Medical Center, Long Beach , Long Beach, California 90822 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie","family":"Moreira","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Veterans Affairs, Medical Center, Long Beach , Long Beach, California 90822 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Aziz","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Veterans Affairs, Medical Center, Long Beach , Long Beach, California 90822 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karanvir","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Veterans Affairs, Medical Center, Long Beach , Long Beach, California 90822 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khushin N","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Veterans Affairs, Medical Center, Long Beach , Long Beach, California 90822 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3015-4177","authenticated-orcid":false,"given":"Ellis R","family":"Levin","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Veterans Affairs, Medical Center, Long Beach , Long Beach, California 90822 , USA"},{"name":"Department of Medicine, University of California, Irvine , Irvine, California 92717 , USA"},{"name":"Department of Biochemistry, University of California, Irvine , Irvine, California 92717 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2022,12,3]]},"reference":[{"issue":"4","key":"2022122309005174600_bqac200-B1","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1093\/cvr\/cvm081","article-title":"Ligand-dependent activation of ER{beta} lowers blood pressure and attenuates cardiac hypertrophy in ovariectomized spontaneously hypertensive rats","volume":"77","author":"Jazbutyte","year":"2008","journal-title":"Cardiovasc Res"},{"issue":"5554","key":"2022122309005174600_bqac200-B2","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1126\/science.1065250","article-title":"Abnormal vascular function and hypertension in mice deficient in estrogen receptor beta","volume":"295","author":"Zhu","year":"2002","journal-title":"Science"},{"issue":"11","key":"2022122309005174600_bqac200-B3","doi-asserted-by":"crossref","first-page":"4352","DOI":"10.1210\/en.2013-1358","article-title":"ER\u03b2 selective agonist inhibits angiotensin-induced cardiovascular pathology in female mice","volume":"154","author":"Pedram","year":"2013","journal-title":"Endocrinology"},{"issue":"2","key":"2022122309005174600_bqac200-B4","doi-asserted-by":"crossref","first-page":"H469","DOI":"10.1152\/ajpheart.00723.2004","article-title":"Estrogen receptor-beta mediates male-female differences in the development of pressure overload hypertrophy","volume":"288","author":"Skavdahl","year":"2005","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"7","key":"2022122309005174600_bqac200-B5","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1161\/01.ATV.0000223344.11128.23","article-title":"Estrogen receptor beta protects the murine heart against left ventricular hypertrophy","volume":"26","author":"Babiker","year":"2006","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"11","key":"2022122309005174600_bqac200-B6","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1210\/me.2010-0154","article-title":"Estrogen receptor-beta prevents cardiac fibrosis","volume":"24","author":"Pedram","year":"2010","journal-title":"Mol Endocrinol"},{"issue":"28","key":"2022122309005174600_bqac200-B7","doi-asserted-by":"crossref","first-page":"26339","DOI":"10.1074\/jbc.M414409200","article-title":"Estrogen inhibits cardiomyocyte hypertrophy in vitro. Antagonism of calcineurin-related hypertrophy through induction of MCIP1","volume":"280","author":"Pedram","year":"2005","journal-title":"J Biol Chem"},{"issue":"24","key":"2022122309005174600_bqac200-B8","doi-asserted-by":"crossref","first-page":"3805","DOI":"10.1091\/mbc.e13-08-0444","article-title":"Estrogen regulates histone deacetylases to prevent cardiac hypertrophy","volume":"24","author":"Pedram","year":"2013","journal-title":"Mol Biol Cell"},{"key":"2022122309005174600_bqac200-B9","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.mce.2016.06.018","article-title":"Estrogen receptor beta signals to inhibition of cardiac fibrosis","volume":"434","author":"Pedram","year":"2016","journal-title":"Mol Cell Endocrinol"},{"issue":"276","key":"2022122309005174600_bqac200-B10","doi-asserted-by":"crossref","first-page":"ra36","DOI":"10.1126\/scisignal.2004013","article-title":"Estrogen reduces lipid content in the liver exclusively from membrane receptor 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