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However, in most studies, melatonin was administered before MI\/R, thus, the results lack clinical significance in patients with acute myocardial infarction. We hypothesize that melatonin posttreatment at different times has different curative effects. Administered of Melatonin (150\u2009\u03bcM) at different times after the onset of reoxygenation (<jats:italic>t<\/jats:italic>\u2009=\u2009\u221215, 0, 5, 10, 15, and 30\u2009min). Cellular apoptosis, oxidative stress, and mitochondrial function were assessed. Mitophagy\u2010related protein levels,\u00a0mitochondrial membrane potential (MMP), and mitochondrial permeability transition pore (mPTP) activity were also measured. A\/R injury upregulated mitophagy, which was associated with increased cellular apoptosis, oxidative stress, and mitochondrial dysfunction. Melatonin posttreatment (<jats:italic>t<\/jats:italic>\u2009=\u2009\u221215, 0, 5, 10, 15, and 30\u2009min) significantly inhibited excessive mitophagy after A\/R injury, reduced cellular apoptosis and oxidative stress, restored mitochondrial function and MMP, and restrained mPTP opening. The therapeutic time window in which melatonin posttreatment protected H9c2 cells against A\/R injury was large (from \u221215 to 30\u2009min after the onset of reperfusion), but the earlier the melatonin administration was, the better its protective effect was. This mechanism is likely due to a reduction in mPTP activity and MMP collapse, which lead to the inhibition of mitophagy.<\/jats:p>","DOI":"10.1002\/cbin.11759","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T12:15:13Z","timestamp":1641471313000},"page":"637-648","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Temporal effect of melatonin posttreatment on anoxia\/reoxygenation injury in H9c2 cells"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7494-8799","authenticated-orcid":false,"given":"Yang","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Beijing Anzhen Hospital Capital Medical University\u2010Beijing Institute of Heart Lung and Blood Vessel Diseases  Beijing People's Republic of 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