The nuclear melatonin receptor RORα is a novel endogenous defender against myocardial ischemia/reperfusion injury

Journal of Pineal Research
Ben HeJun Pu

Abstract

Circadian rhythm disruption or decrease in levels of circadian hormones such as melatonin increases ischemic heart disease risk. The nuclear melatonin receptors RORs are pivotally involved in circadian rhythm regulation and melatonin effects mediation. However, the functional roles of RORs in the heart have never been investigated and were therefore the subject of this study on myocardial ischemia/reperfusion (MI/R) injury pathogenesis. RORα and RORγ subtypes were detected in the adult mouse heart, and RORα but not RORγ was downregulated after MI/R. To determine the pathological consequence of MI/R-induced reduction of RORα, we subjected RORα-deficient staggerer mice and wild-type (WT) littermates to MI/R injury, resulting in significantly increased myocardial infarct size, myocardial apoptosis and exacerbated contractile dysfunction in the former. Mechanistically, RORα deficiency promoted MI/R-induced endoplasmic reticulum stress, mitochondrial impairments, and autophagy dysfunction. Moreover, RORα deficiency augmented MI/R-induced oxidative/nitrative stress. Given the emerging evidence of RORα as an essential melatonin effects mediator, we further investigated the RORα roles in melatonin-exerted cardioprotection, in particula...Continue Reading

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Citations

Jun 7, 2016·Journal of Pineal Research·Fedor SimkoRussel J Reiter
Jul 29, 2016·Journal of Pineal Research·Carlos QuintanaJosé Quintana
Oct 26, 2016·Journal of Pineal Research·Jianqiang HuDongdong Sun
Nov 28, 2016·Journal of Pineal Research·Hiroshi TamuraNorihiro Sugino
Feb 6, 2017·Journal of Pineal Research·Wenkai RenYulong Yin
Apr 26, 2017·Journal of Pineal Research·Maryam MajidiniaBahman Yousefi
Feb 1, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Fedor SimkoLudovit Paulis
Mar 24, 2018·Journal of Pineal Research·Amanda LochnerBarbara Huisamen
Jul 28, 2016·Journal of Cardiovascular Pharmacology and Therapeutics·Seithikurippu R Pandi-PerumalDaniel P Cardinali
Jun 12, 2018·Journal of Pineal Research·Annia Galano, Russel J Reiter
Jun 1, 2018·Journal of Pineal Research·Natalia Jorgelina PradoWalter Manucha
Nov 6, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Ju Youn BeakBrian C Jensen
Jan 24, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jieru CaiXiaoqiang Ding
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Feb 19, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hui CheLihong Wang
Aug 9, 2016·Journal of Pineal Research·Russel J ReiterLilian Qin

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