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The nuclear melatonin receptors\n ROR<\/jats:styled-content>\n s are pivotally involved in circadian rhythm regulation and melatonin effects mediation. However, the functional roles of\n ROR<\/jats:styled-content>\n s in the heart have never been investigated and were therefore the subject of this study on myocardial ischemia\/reperfusion (\n MI<\/jats:styled-content>\n \/R) injury pathogenesis.\n ROR<\/jats:styled-content>\n \u03b1<\/jats:italic>\n and\n ROR<\/jats:styled-content>\n \u03b3<\/jats:italic>\n subtypes were detected in the adult mouse heart, and\n ROR<\/jats:styled-content>\n \u03b1<\/jats:italic>\n but not\n ROR<\/jats:styled-content>\n \u03b3<\/jats:italic>\n was downregulated after\n MI<\/jats:styled-content>\n \/R. To determine the pathological consequence of\n MI<\/jats:styled-content>\n \/R\u2010induced reduction of\n ROR<\/jats:styled-content>\n \u03b1<\/jats:italic>\n , we subjected\n ROR<\/jats:styled-content>\n \u03b1<\/jats:italic>\n \u2010deficient staggerer mice and wild\u2010type (\n WT<\/jats:styled-content>\n ) littermates to\n MI<\/jats:styled-content>\n \/R injury, resulting in significantly increased myocardial infarct size, myocardial apoptosis and exacerbated contractile dysfunction in the former. Mechanistically,\n ROR<\/jats:styled-content>\n \u03b1<\/jats:italic>\n deficiency promoted\n MI<\/jats:styled-content>\n \/R\u2010induced endoplasmic reticulum stress, mitochondrial impairments, and autophagy dysfunction. Moreover,\n ROR<\/jats:styled-content>\n \u03b1<\/jats:italic>\n deficiency augmented\n MI<\/jats:styled-content>\n \/R\u2010induced oxidative\/nitrative stress. Given the emerging evidence of\n ROR<\/jats:styled-content>\n \u03b1<\/jats:italic>\n as an essential melatonin effects mediator, we further investigated the\n ROR<\/jats:styled-content>\n \u03b1<\/jats:italic>\n roles in melatonin\u2010exerted cardioprotection, in particular against\n MI<\/jats:styled-content>\n \/R injury, which was significantly attenuated in\n ROR<\/jats:styled-content>\n \u03b1<\/jats:italic>\n \u2010deficient mice, but negligibly affected by cardiac\u2010specific silencing of\n ROR<\/jats:styled-content>\n \u03b3<\/jats:italic>\n . Finally, to determine cell type\u2010specific effects of\n ROR<\/jats:styled-content>\n \u03b1<\/jats:italic>\n , we generated mice with cardiomyocyte\u2010specific\n ROR<\/jats:styled-content>\n \u03b1<\/jats:italic>\n overexpression and they were less vulnerable to\n MI<\/jats:styled-content>\n \/R injury. In summary, our study provides the first direct evidence that the nuclear melatonin receptor\n ROR<\/jats:styled-content>\n \u03b1<\/jats:italic>\n is a novel endogenous protective receptor against\n MI<\/jats:styled-content>\n \/R injury and an important mediator of melatonin\u2010exerted cardioprotection; melatonin\u2010\n ROR<\/jats:styled-content>\n \u03b1<\/jats:italic>\n axis signaling thus appears important in protection against ischemic heart injury.\n <\/jats:p>","DOI":"10.1111\/jpi.12312","type":"journal-article","created":{"date-parts":[[2016,1,21]],"date-time":"2016-01-21T10:34:39Z","timestamp":1453372479000},"page":"313-326","source":"Crossref","is-referenced-by-count":146,"title":["The nuclear melatonin receptor\n ROR<\/scp>\n \u03b1<\/i>\n is a novel endogenous defender against myocardial ischemia\/reperfusion injury"],"prefix":"10.1111","volume":"60","author":[{"given":"Ben","family":"He","sequence":"first","affiliation":[{"name":"Department of Cardiology Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longwei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingchen","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cardiology Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Cardiology Ren Ji Hospital School of Medicine 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