ArticleDrug design, development and therapy2020
Melatonin Attenuates Anoxia/Reoxygenation Injury by Inhibiting Excessive Mitophagy Through the MT2/SIRT3/FoxO3a Signaling Pathway in H9c2 Cells.
Article in Drug design, development and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 80 citations in OpenAlex.
- Fumarate Hydratase Lactylation Exacerbates Traumatic Brain Injury Pathology via Mitochondrial Dysfunction and Neuroinflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Melatonin alleviates mitochondrial damage by regulating SIRT3‑mediated mitochondrial dynamics in granulosa cells under PCOS‑like conditions.Molecular medicine reports · 2026Article
- Mitophagy in Metabolic Dysfunction-Associated Fatty Liver Disease: Mechanisms, Regulatory Networks, and Therapeutic Perspectives.Inflammation · 2026Review
- Cardamonin activates AMPK/FOXO3a/Nrf-2 axis to ameliorate oxidative stress in hyperlipidemia induced cardiac injury in mice.Molecular biology reports · 2026Article
- Melatonin and mitochondrial protection in cardiac ischemia-reperfusion injury: mechanisms, evidence and translational perspectives.Basic research in cardiology · 2026Review
- Apigenin Protects H9c2 Cells Against Oxygen-Glucose Deprivation/Reperfusion Injury by Regulating Autophagy via the HIF-1α/miR-20a Axis.Pharmacology research & perspectives · 2026Article
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Melatonin at the Crossroads of Oxidative Stress, Immunity, and Cancer Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- Dysregulated Redox Signaling and Its Impact on Inflammatory Pathways, Mitochondrial Dysfunction, Autophagy and Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- The G-allele of rs10830963 inInternational journal of molecular sciences · 2025Article
- The role of mitochondrial dysfunction in ovarian granulosa cells in polycystic ovary syndrome.Endocrine connections · 2025Review
- Melatonin as a shield against skeletal muscle damage: A study on ischemia-reperfusion injury.Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES · 2025Article
- The Protective Effect of Melatonin on LPS-Induced Myocardial InjuryCombinatorial chemistry & high throughput screening · 2025Article
- The study on the role of O-GlcNAcylation of SIRT3 in regulating mitochondrial oxidative stress during simulate myocardial ischemia-reperfusion.Scientific reports · 2024Article
- Melatonin regulates mitochondrial dynamics and mitophagy: Cardiovascular protection.Journal of cellular and molecular medicine · 2024Review
- Activation of Sirtuin3 by honokiol ameliorates alveolar epithelial cell senescence in experimental silicosis via the cGAS-STING pathway.Redox biology · 2024Article
- SIRT3 and RORα are two prospective targets against mitophagy during simulated ischemia/reperfusion injury in H9c2 cells.Heliyon · 2024Article
- Mitochondrial quality control in human health and disease.Military Medical Research · 2024Review
- SIRT1 restores mitochondrial structure and function in rats by activating SIRT3 after cerebral ischemia/reperfusion injury.Cell biology and toxicology · 2024Article
- Exploring the therapeutic potential of Sirt6-enriched adipose stem cell-derived exosomes in myocardial ischemia-reperfusion injury: unfolding new epigenetic frontiers.Clinical epigenetics · 2024Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAutophagy caused by ischemia/reperfusion (I/R) increases the extent of cardiomyocyte damage. Melatonin (Mel) diminishes cardiac injury through regulating autophagy and mitochondrial dynamics. However, illustrating the specific role of mitophagy in the cardioprotective effects of melatonin remains a challenge. The aim of our research was to investigate the impact and underlying mechanisms of melatonin in connection with mitophagy during anoxia/reoxygenation (A/R) injury in H9c2 cells.
methodsH9c2 cells were pretreated with melatonin with or without the melatonin membrane receptor 2 (MT2) antagonist 4-P-PDOT, the MT2 agonist IIK7 and the sirtuin 3 (SIRT3) inhibitor 3-TYP for 4 hours and then subjected to A/R injury. Cell viability, cellular apoptosis, necrosis levels and oxidative markers were assessed. The expression of SIRT3 and forkhead box O3a (FoxO3a), mitochondrial function and the levels of mitophagy-related proteins were also evaluated.
resultsA/R injury provoked enhanced mitophagy in H9c2 myocytes. In addition, increased mitophagy was correlated with decreased cellular viability, increased oxidative stress and mitochondrial dysfunction in H9c2 cells. However, melatonin pretreatment notably increased cell survival and decreased cell apoptosis and oxidative response after A/R injury, accompanied by restored mitochondrial function. The inhibition of excessive mitophagy is involved in the cardioprotective effects of melatonin, as shown by the decreased expression of the mitophagy-related molecules Parkin, Beclin1, and BCL2-interacting protein 3-like (BNIP3L, best known as NIX) and decreased light chain 3 II/light chain 3 I (LC3 II/LC3 I) ratio and upregulation of p62 expression. Moreover, the decreased expression of SIRT3 and FoxO3a in A/R-injured H9c2 cells was abrogated by melatonin, but these beneficial effects were attenuated by the MT2 antagonist 4-P-PDOT or the SIRT3 inhibitor 3-TYP and enhanced by the MT2 agonist IIK7.
conclusionThese results indicate that melatonin protects H9c2 cells during A/R injury through suppressing excessive mitophagy by activating the MT2/SIRT3/FoxO3a pathway. Melatonin may be a useful candidate for alleviating myocardial ischemia/reperfusion (MI/R) injury in the future, and the MT2 receptor might become a therapeutic target.
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