{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:05:57Z","timestamp":1787580357177,"version":"build-2736575974"},"reference-count":33,"publisher":"American Physiological Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2014,12,1]]},"abstract":"<jats:p>\n                    We recently showed that progesterone treatment abolished arrhythmias and sudden cardiac death in a transgenic rabbit model of long QT syndrome type 2 (LQT2). Moreover, levels of cardiac sarco(endo)plasmic reticulum Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -ATPase type 2a (SERCA2a) were upregulated in LQT2 heart extracts. We hypothesized that progesterone treatment upregulated SERCA2a expression, thereby reducing Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependent arrhythmias in LQT2 rabbits. We therefore investigated the effect of progesterone on SERCA2a regulation in isolated cardiomyocytes. Cardiomyocytes from neonatal (3- to 5-day-old) rabbits were isolated, cultured, and treated with progesterone and other pharmacological agents. Immunoblotting was performed on total cell lysates and sarcoplasmic reticulum-enriched membrane fractions for protein abundance, and mRNA transcripts were quantified using real-time PCR. The effect of progesterone on baseline Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transients and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    clearance was determined using digital imaging. Progesterone treatment increased the total pool of SERCA2a protein by slowing its degradation. Using various pharmacological inhibitors of degradation pathways, we showed that progesterone-associated degradation of SERCA2a involves ubiquitination, and progesterone significantly decreases the levels of ubiquitin-tagged SERCA2a polypeptides. Our digital imaging data revealed that progesterone significantly shortened the decay and duration of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transients. Progesterone treatment increases protein levels and activity of SERCA2a. Progesterone stabilizes SERCA2a, in part, by decreasing the ubiquitination level of SERCA2a polypeptides.\n                  <\/jats:p>","DOI":"10.1152\/ajpcell.00127.2014","type":"journal-article","created":{"date-parts":[[2014,9,25]],"date-time":"2014-09-25T03:22:48Z","timestamp":1411615368000},"page":"C1050-C1057","source":"Crossref","is-referenced-by-count":21,"title":["Progesterone modulates SERCA2a expression and function in rabbit cardiomyocytes"],"prefix":"10.1152","volume":"307","author":[{"given":"Karni S.","family":"Moshal","sequence":"first","affiliation":[{"name":"Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Rhode Island Hospital, Alpert 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