{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:03:27Z","timestamp":1791263007251,"version":"4.1.0"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[1998,9,21]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014Remodeling of the distribution of gap junctions is an important feature of anatomic substrates of arrhythmias in patients with healed myocardial infarcts. Mechanisms underlying this process are poorly understood but probably involve changes in gap junction protein (connexin) synthesis, assembly into channels, and degradation. The half-life of the principal cardiac gap junction protein, connexin43 (Cx43), is only 1.5 to 2 hours in primary cultures of neonatal myocytes, but it is unknown whether rapid turnover of Cx43 occurs in the adult heart or is unique to disaggregated neonatal myocytes that are actively reestablishing connections in vitro. To characterize connexin turnover dynamics in the adult heart and to elucidate its potential role in remodeling of gap junctions, we measured Cx43 turnover kinetics and characterized the proteolytic pathways involved in Cx43 degradation in isolated perfused adult rat hearts. Hearts were labeled for 40 minutes with Krebs-Henseleit buffer containing [\n            <jats:sup>35<\/jats:sup>\n            S]methionine, and then chase perfusions were performed with nonradioactive buffer for 0, 60, 120, and 240 minutes. Quantitative immunoprecipitation assays of Cx43 radioactivity in 4 hearts at each time point yielded a monoexponential decay curve indicating a Cx43 half-life of 1.3 hours. Proteolytic pathways responsible for Cx43 degradation were elucidated by perfusing isolated rat hearts for 4 hours with specific inhibitors of either lysosomal or proteasomal proteolysis. Immunoblot analysis demonstrated significant increases (\u224830%) in Cx43 content in hearts perfused with either lysosomal or proteasomal pathway inhibitors. Most of the Cx43 in hearts perfused with lysosomal inhibitors consisted of phosphorylated isoforms, whereas nonphosphorylated Cx43 accumulated selectively in hearts perfused with a specific proteasomal inhibitor. These results indicate that Cx43 turns over rapidly in the adult heart and is degraded by multiple proteolytic pathways. Regulation of Cx43 degradation could play an important role in gap junction remodeling in response to cardiac injury.\n          <\/jats:p>","DOI":"10.1161\/01.res.83.6.629","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:47:05Z","timestamp":1339462025000},"page":"629-635","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":352,"title":["Rapid Turnover of Connexin43 in the Adult Rat Heart"],"prefix":"10.1161","volume":"83","author":[{"given":"Michael A.","family":"Beardslee","sequence":"first","affiliation":[{"name":"From the Departments of Medicine and Pathology (M.A.B., J.G.L., J.E.S.), Washington University School of Medicine, St Louis, Mo, and the Department of Pediatrics (E.C.B.), University of Chicago, Chicago, Ill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James G.","family":"Laing","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Pathology (M.A.B., J.G.L., J.E.S.), Washington University School of Medicine, St Louis, Mo, and the Department of Pediatrics (E.C.B.), University of Chicago, Chicago, Ill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C.","family":"Beyer","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Pathology (M.A.B., J.G.L., J.E.S.), Washington University School of Medicine, St Louis, Mo, and the Department of Pediatrics (E.C.B.), University of Chicago, Chicago, Ill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey E.","family":"Saffitz","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Pathology (M.A.B., J.G.L., J.E.S.), Washington University School of Medicine, St Louis, Mo, and the Department of Pediatrics (E.C.B.), University of Chicago, Chicago, Ill."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.63.1.182"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115173"},{"key":"e_1_3_2_3_2","first-page":"801","volume":"139","year":"1991","unstructured":"Smith JH, Green CR, Peters NS, Rothery S, Severs NJ. 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Proteolysis of connexin43 containing gap junctions in normal and heat-stressed cardiac myocytes. Cardiovasc Res. 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