{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T06:50:40Z","timestamp":1794293440567,"version":"4.9.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Muscle-specific RING finger protein-1 (MuRF1) is an E3 ligase that inhibits cardiac hypertrophy. However, how MuRF1 regulates cardiac hypertrophy and function during pressure overload (PO) remains poorly understood. We investigated the role of endogenous MuRF1 in regulating cardiac hypertrophy in response to PO in vivo.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Transverse aortic constriction (TAC) for 4 weeks significantly reduced expression of MuRF1 in the mouse heart. After 2 and 4 weeks of TAC, MuRF1 knockout (\n              <jats:italic>Murf1<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              ) mice exhibited enhanced cardiac hypertrophy and left ventricular (LV) dysfunction compared with that of nontransgenic (NTg) mice. Histological analyses showed that\n              <jats:italic>Murf1<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice exhibited more severe fibrosis and apoptosis than NTg mice after TAC. TAC-induced increases in the activity of a nuclear factor of activated T cells (NFAT) luciferase reporter were significantly greater in\n              <jats:italic>Murf1<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              than in NTg mice. TAC-induced increases in calcineurin A (CnA) expression were also significantly enhanced in\n              <jats:italic>Murf1<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              compared with that in NTg mice. Coimmunoprecipitation assays showed that endogenous MuRF1 and CnA interact with one another. Polyubiquitination of CnA was attenuated in\n              <jats:italic>Murf1<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mouse hearts at baseline and in response to TAC, and the protein stability of CnA was enhanced in cardiomyocytes, in which MuRF1 was downregulated in vitro. Furthermore, MuRF1 directly ubiquitinated CnA in vitro. Cardiac-specific overexpression of ZAKI-4\u03b2, an endogenous inhibitor of CnA, significantly suppressed the enhancement of TAC-induced cardiac hypertrophy and dysfunction, as well as increases in cardiac fibrosis and apoptosis, in\n              <jats:italic>Murf1<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Endogenous MuRF1 negatively regulates cardiac hypertrophy and dysfunction in response to PO through inhibition of the calcineurin\u2013NFAT pathway.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.113.000713","type":"journal-article","created":{"date-parts":[[2014,2,14]],"date-time":"2014-02-14T03:39:17Z","timestamp":1392349157000},"page":"479-490","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":52,"title":["Muscle-Specific RING Finger 1 Negatively Regulates Pathological Cardiac Hypertrophy Through Downregulation of Calcineurin A"],"prefix":"10.1161","volume":"7","author":[{"given":"Yasuhiro","family":"Maejima","sequence":"first","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ (Y.M., S.U., P.Z., D.Z., J.S.); Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan (S.U., M.T., S.K.); Department of Genome Science, School of Dentistry, Aichi-Gakuin University, Nagoya, Aichi, Japan (M.Y.); and Department of Cardiovascular Medicine, Tokyo Medical and Dental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Usui","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ (Y.M., S.U., P.Z., D.Z., J.S.); Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan (S.U., M.T., S.K.); Department of Genome Science, School of Dentistry, Aichi-Gakuin University, Nagoya, Aichi, Japan (M.Y.); and Department of Cardiovascular Medicine, Tokyo Medical and Dental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyong","family":"Zhai","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ (Y.M., S.U., P.Z., D.Z., J.S.); Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan (S.U., M.T., S.K.); Department of Genome Science, School of Dentistry, Aichi-Gakuin University, Nagoya, Aichi, Japan (M.Y.); and Department of Cardiovascular Medicine, Tokyo Medical and Dental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Takamura","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ (Y.M., S.U., P.Z., D.Z., J.S.); Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan (S.U., M.T., S.K.); Department of Genome Science, School of Dentistry, Aichi-Gakuin University, Nagoya, Aichi, Japan (M.Y.); and Department of Cardiovascular Medicine, Tokyo Medical and Dental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Kaneko","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ (Y.M., S.U., P.Z., D.Z., J.S.); Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan (S.U., M.T., S.K.); Department of Genome Science, School of Dentistry, Aichi-Gakuin University, Nagoya, Aichi, Japan (M.Y.); and Department of Cardiovascular Medicine, Tokyo Medical and Dental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Zablocki","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ (Y.M., S.U., P.Z., D.Z., J.S.); Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan (S.U., M.T., S.K.); Department of Genome Science, School of Dentistry, Aichi-Gakuin University, Nagoya, Aichi, Japan (M.Y.); and Department of Cardiovascular Medicine, Tokyo Medical and Dental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Yokota","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ (Y.M., S.U., P.Z., D.Z., J.S.); Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan (S.U., M.T., S.K.); Department of Genome Science, School of Dentistry, Aichi-Gakuin University, Nagoya, Aichi, Japan (M.Y.); and Department of Cardiovascular Medicine, Tokyo Medical and Dental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuaki","family":"Isobe","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ (Y.M., S.U., P.Z., D.Z., J.S.); Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan (S.U., M.T., S.K.); Department of Genome Science, School of Dentistry, Aichi-Gakuin University, Nagoya, Aichi, Japan (M.Y.); and Department of Cardiovascular Medicine, Tokyo Medical and Dental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Sadoshima","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ (Y.M., S.U., P.Z., D.Z., J.S.); Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan (S.U., M.T., S.K.); Department of Genome Science, School of Dentistry, Aichi-Gakuin University, Nagoya, Aichi, Japan (M.Y.); and Department of Cardiovascular Medicine, Tokyo Medical and Dental..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra072139"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81573-1"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1983"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.15.6649-6659.2005"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.041614798"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2181"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4448"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065874"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.150.4.771"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000259559.48597.32"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.109.194928"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.112.270207"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00449.2009"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101968200"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-9639.2004.00136.x"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200402033"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.04.041"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.10.026"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.108.190397"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.09.027"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607795103"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31757"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000109415.17511.18"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.13.1595"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200422220"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.110.238717"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/81321"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2010.02.001"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200108089"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.09.009"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404341102"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp348"}],"container-title":["Circulation: Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCHEARTFAILURE.113.000713","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T01:50:19Z","timestamp":1715565019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCHEARTFAILURE.113.000713"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,5]]}},"alternative-id":["10.1161\/CIRCHEARTFAILURE.113.000713"],"URL":"https:\/\/doi.org\/10.1161\/circheartfailure.113.000713","relation":{},"ISSN":["1941-3289","1941-3297"],"issn-type":[{"value":"1941-3289","type":"print"},{"value":"1941-3297","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5]]},"assertion":[{"value":"2013-08-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-02-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-02-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}