Melatonin attenuates myocardial ischemia-reperfusion injury via improving mitochondrial fusion/mitophagy and activating the AMPK-OPA1 signaling pathways.


:Optic atrophy 1 (OPA1)-related mitochondrial fusion and mitophagy are vital to sustain mitochondrial homeostasis under stress conditions. However, no study has confirmed whether OPA1-related mitochondrial fusion/mitophagy is activated by melatonin and, consequently, attenuates cardiomyocyte death and mitochondrial stress in the setting of cardiac ischemia-reperfusion (I/R) injury. Our results indicated that OPA1, mitochondrial fusion, and mitophagy were significantly repressed by I/R injury, accompanied by infarction area expansion, heart dysfunction, myocardial inflammation, and cardiomyocyte oxidative stress. However, melatonin treatment maintained myocardial function and cardiomyocyte viability, and these effects were highly dependent on OPA1-related mitochondrial fusion/mitophagy. At the molecular level, OPA1-related mitochondrial fusion/mitophagy, which was normalized by melatonin, substantially rectified the excessive mitochondrial fission, promoted mitochondria energy metabolism, sustained mitochondrial function, and blocked cardiomyocyte caspase-9-involved mitochondrial apoptosis. However, genetic approaches with a cardiac-specific knockout of OPA1 abolished the beneficial effects of melatonin on cardiomyocyte survival and mitochondrial homeostasis in vivo and in vitro. Furthermore, we demonstrated that melatonin affected OPA1 stabilization via the AMPK signaling pathway and that blockade of AMPK repressed OPA1 expression and compromised the cardioprotective action of melatonin. Overall, our results confirm that OPA1-related mitochondrial fusion/mitophagy is actually modulated by melatonin in the setting of cardiac I/R injury. Moreover, manipulation of the AMPK-OPA1-mitochondrial fusion/mitophagy axis via melatonin may be a novel therapeutic approach to reduce cardiac I/R injury.


J Pineal Res


Zhang Y,Wang Y,Xu J,Tian F,Hu S,Chen Y,Fu Z




Has Abstract


2019-03-01 00:00:00












  • Effect of various cations on the activity of pineal gland N-acetyltransferase (EC and hydroxyindole-O-methyl transferase (EC in vitro.

    abstract::The effect of various cations on activity of hydroxyindole-O-methyltransferase (HIOMT) and N-acetyltransferase (NAT) from pineal gland was studied. Copper inhibited both enzymes while calcium and magnesium inhibited HIOMT; the mechanisms of these inhibitions are unknown at this stage. Calcium, magnesium, potassium, an...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Morton DJ

    更新日期:1987-01-01 00:00:00

  • Light suppression of melatonin in the squirrel monkey (Saimiri sciureus).

    abstract::This study examined plasma melatonin levels and the suppressant effect of light on melatonin production in the squirrel monkey. Monkeys were maintained on a 12:12 light-dark cycle (LD 12:12) with lights on from 07:00 to 19:00. Plasma levels of melatonin were determined by gas chromatography negative chemical ionizatio...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Hoban TM,Lewy AJ,Fuller CA

    更新日期:1990-01-01 00:00:00

  • Pineal melatonin concentrations during day and night in the adult hedgehog: effect of a light pulse at night and superior cervical ganglionectomy.

    abstract::The European hedgehog (Erinaceus europaeus L.) is a hibernating mammal and seasonal breeder in which numerous circadian and circannual rhythms are entrained and synchronized by photoperiod. The present study was undertaken in order to establish the involvement of the pineal gland in transducing the photoperiodic messa...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Saboureau M,Vivien-Roels B,Pevet P

    更新日期:1991-09-01 00:00:00

  • Attenuated nocturnal rise in pineal and serum melatonin in a genetically cardiomyopathic Syrian hamster with a deficient calcium pump.

    abstract::Day and nighttime melatonin production in the pineal gland was compared in normal and cardiomyopathic (polydystrophic) adult male Syrian hamsters. These strains of hamsters were selected for comparison because the cardiomyopathetic hamster displays a deficient transmembrane Ca(2+)-pump in a number of tissues, and intr...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Reiter RJ,White T,Lerchl A,Stokkan KA,Rodriguez C

    更新日期:1991-10-01 00:00:00

  • Melatonin prevents hypochlorous acid-mediated cyanocobalamin destruction and cyanogen chloride generation.

    abstract::Hypochlorous acid (HOCl) is a potent cytotoxic oxidant generated by the enzyme myeloperoxidase (MPO) in the presence of hydrogen peroxide (H2 O2 ) and chloride (Cl- ). Elevated levels of HOCl play an important role in various pathological conditions through oxidative modification of several biomolecules. Recently, we ...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Jeelani R,Maitra D,Chatzicharalampous C,Najeemuddin S,Morris RT,Abu-Soud HM

    更新日期:2018-04-01 00:00:00

  • Detection of recombinant and endogenous mouse melatonin receptors by monoclonal antibodies targeting the C-terminal domain.

    abstract::Melatonin receptors play important roles in the regulation of circadian and seasonal rhythms, sleep, retinal functions, the immune system, depression, and type 2 diabetes development. Melatonin receptors are approved drug targets for insomnia, non-24-hour sleep-wake disorders, and major depressive disorders. In mammal...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Cecon E,Ivanova A,Luka M,Gbahou F,Friederich A,Guillaume JL,Keller P,Knoch K,Ahmad R,Delagrange P,Solimena M,Jockers R

    更新日期:2019-03-01 00:00:00

  • The influence of melatonin on the content of vasopressin and oxytocin in the hypothalamus and neurohypophysis in euhydrated and dehydrated male rats.

    abstract::Melatonin injected in a single intraperitoneal dose of 100 micrograms/100 g b.w. to euhydrated rats resulted in a decrease of neurohypophysial oxytocin content but the hypothalamic oxytocin storage as well as the hypothalamo-neurohypophysial storage of vasopressin were not changed. Following 8 d of once-daily melatoni...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Juszczak M,Guzek JW,Lewy A

    更新日期:1986-01-01 00:00:00

  • Genome-wide profiling in melatonin-exposed human breast cancer cell lines identifies differentially methylated genes involved in the anticancer effect of melatonin.

    abstract::Epigenetic alterations have emerged as an important mechanism involved in tumorigenesis. The epigenetic impact of DNA methylation in various types of human cancer is not completely understood. Previously, we observed melatonin-induced differential expression of miRNA and miRNA-related genes in human breast cancer cell...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Lee SE,Kim SJ,Yoon HJ,Yu SY,Yang H,Jeong SI,Hwang SY,Park CS,Park YS

    更新日期:2013-01-01 00:00:00

  • Detection of the human GPR50 orphan seven transmembrane protein by polyclonal antibodies mapping different epitopes.

    abstract::GPR50 is an orphan seven transmembrane protein related to the melatonin receptor subfamily comprising MT(1) and MT(2) receptors. In the absence of any known ligand for GPR50, other tools are critical for the characterization of this protein. Here, we describe the generation, purification and characterization of the fi...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Hamouda HO,Chen P,Levoye A,Sözer-Topçular N,Daulat AM,Guillaume JL,Ravid R,Savaskan E,Ferry G,Boutin JA,Delagrange P,Jockers R,Maurice P

    更新日期:2007-08-01 00:00:00

  • Inhibitory effect of melatonin on diquat-induced lipid peroxidation in vivo as assessed by the measurement of F2-isoprostanes.

    abstract::Melatonin is a powerful antioxidant and free radical scavenger. A large body of in vivo and in vitro evidence shows that melatonin effectively inhibits membrane lipid peroxidation; this damage was based on the measurement of malondialdehyde and/or 4-hydroxynonenal levels. In the current study, for the first time using...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Zhang L,Wei W,Xu J,Min F,Wang L,Wang X,Cao S,Tan DX,Qi W,Reiter RJ

    更新日期:2006-05-01 00:00:00

  • Melatonin inhibits vasospastic action of hydrogen peroxide in human umbilical artery.

    abstract::We evaluated the antioxidant property of melatonin as it relates to the vasospastic effect of hydrogen peroxide (H2O2) on the human umbilical artery. Helical sections of umbilical arteries were obtained from healthy pregnant women who were delivered between weeks 37 and 39 of gestation. Changes in maximal potassium ch...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Okatani Y,Watanabe K,Hayashi K,Wakatsuki A,Sagara Y

    更新日期:1997-04-01 00:00:00

  • Correlation among cytokines, bronchopulmonary dysplasia and modality of ventilation in preterm newborns: improvement with melatonin treatment.

    abstract::Improved survival because of advances in neonatal care has resulted in an increased number of infants at risk for chronic lung disease. Even though the etiology of lung injury is multifactorial, recent animal and clinical data indicate that pulmonary damage depends in large part on the ventilatory strategies used. Ven...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Gitto E,Reiter RJ,Sabatino G,Buonocore G,Romeo C,Gitto P,Buggé C,Trimarchi G,Barberi I

    更新日期:2005-10-01 00:00:00

  • Neuroprotective effect of melatonin against hypoxia-induced retinal ganglion cell death in neonatal rats.

    abstract::The purpose of this study was to determine whether melatonin treatment would mitigate retinal ganglion cell (RGC) death in the developing retina following a hypoxic insult. Lipid peroxidation (LPO), glutathione (GSH), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) concentrations, expression of vascular end...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Kaur C,Sivakumar V,Robinson R,Foulds WS,Luu CD,Ling EA

    更新日期:2013-03-01 00:00:00

  • Melatonin enhances thrombopoiesis through ERK1/2 and Akt activation orchestrated by dual adaptor for phosphotyrosine and 3-phosphoinositides.

    abstract::Melatonin (MT), endogenously secreted by the pineal gland, is closely related to multiple biological processes; however, its effect on thrombopoiesis is still not well illustrated. Here, we demonstrate that MT administration can elevate peripheral platelet levels. Analysis of different stages in thrombopoiesis reveals...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Chen S,Qi Y,Wang S,Xu Y,Shen M,Hu M,Du C,Chen F,Chen M,Lu Y,Zhang Z,Quan Y,Wang C,Wang F,Wang J

    更新日期:2020-04-01 00:00:00

  • Melatonin reduces uranium-induced nephrotoxicity in rats.

    abstract::The protective role of exogenous melatonin on U-induced nephrotoxicity was investigated in rats. Animals were given single doses of uranyl acetate dihydrate (UAD) at 5 mg/kg (subcutaneous), melatonin at 10 or 20 mg/kg (intraperitoneal), and UAD (5 mg/kg) plus melatonin (10 or 20 mg/kg), or vehicle (control group). In ...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Bellés M,Linares V,Luisa Albina M,Sirvent J,Sánchez DJ,Domingo JL

    更新日期:2007-08-01 00:00:00

  • Systemic combined melatonin-mitochondria treatment improves acute respiratory distress syndrome in the rat.

    abstract::Despite high in-hospital mortality associated with acute respiratory distress syndrome (ARDS), there is no effective therapeutic strategy. We tested the hypothesis that combined melatonin-mitochondria treatment ameliorates 100% oxygen-induced ARDS in rats. Adult male Sprague-Dawley rats (n = 40) were equally categoriz...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Sun CK,Lee FY,Kao YH,Chiang HJ,Sung PH,Tsai TH,Lin YC,Leu S,Wu YC,Lu HI,Chen YL,Chung SY,Su HL,Yip HK

    更新日期:2015-03-01 00:00:00

  • Responsiveness of pineal N-acetyltransferase and melatonin in the cotton rat exposed to either artificial or natural light at night.

    abstract::In three separate experiments, the effect of acute exposure to either artificial or natural light during darkness of pineal N-acetyltransferase (NAT) activity and melatonin content was studied in the cotton rat (Sigmodon hispidus). The exposure of animals to an artificial-light irradiance of 160,000 microW/cm2 during ...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Nürnberger F,Joshi BN,Heinzeller T,Milin J,Reiter RJ

    更新日期:1985-01-01 00:00:00

  • Overexpression of rice serotonin N-acetyltransferase 1 in transgenic rice plants confers resistance to cadmium and senescence and increases grain yield.

    abstract::While ectopic overexpression of serotonin N-acetyltransferase (SNAT) in plants has been accomplished using animal SNAT genes, ectopic overexpression of plant SNAT genes in plants has not been investigated. Because the plant SNAT protein differs from that of animals in its subcellular localization and enzyme kinetics, ...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Lee K,Back K

    更新日期:2017-04-01 00:00:00

  • Characterization of melatonin high-affinity binding sites in purified cell nuclei of the hamster (Mesocricetus auratus) harderian gland.

    abstract::In the present paper, binding of melatonin to purified cell nuclei from harderian glands of male and female hamsters was assessed. Binding of 125I-melatonin to cell nuclei fulfills the criteria for binding to a receptor site. Binding kinetics exhibit properties such as dependence on time and temperature as well as rev...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Coto-Montes A,Tomás-Zapico C,Escames G,León J,Tolivia D,JosefaRodríguez-Colunga M,Acuña-Castroviejo D

    更新日期:2003-04-01 00:00:00

  • Exogenous melatonin modifies the circadian rhythm but does not increase the level of some immune parameters in the chicken.

    abstract::The effect of daily injection of the pineal hormone melatonin and naltrexone, an opioid antagonist, on the circadian rhythm and the level of immune parameters (plaque forming cell [PFC] number, serum agglutinin titer, lymphoid gland weight, total white blood cells (WBC) and their fraction number, and serum lysozyme [L...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Skwarło-Sońta K,Thaela MJ,Midura M,Lech B,Głuchowska B,Drela N,Kozłowska E,Kowalczyk R

    更新日期:1992-01-01 00:00:00

  • Melatonin enhances survival and preserves functional integrity of stem cells: A review.

    abstract::Despite state-of-the-art pharmaceutical regimens, continuous improvements in diagnostic techniques as well as refinements in equipment and interventional procedures, many diseases remain refractory to conventional therapies. Recent advances in stem cell (SC) biology have opened an avenue to exploring its therapeutic p...

    journal_title:Journal of pineal research

    pub_type: 杂志文章,评审


    authors: Lee MS,Yin TC,Sung PH,Chiang JY,Sun CK,Yip HK

    更新日期:2017-03-01 00:00:00

  • Melatonin identified in meats and other food stuffs: potentially nutritional impact.

    abstract::Melatonin has been identified in primitive photosynthetic bacteria, fungi, plants, and animals including humans. Vegetables, fruits, cereals, wine, and beers all contain melatonin. However, the melatonin content in meats has not been reported previously. Here, for the first time, we report melatonin in meats, eggs, co...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Tan DX,Zanghi BM,Manchester LC,Reiter RJ

    更新日期:2014-09-01 00:00:00

  • Melatonin and dehydroepiandrosterone combination: does this treatment exert a synergistic effect during experimental Trypanosoma cruzi infection?

    abstract::Previous studies showed that melatonin or dehydroepiandrosterone (DHEA) enhances the immune response against parasitic pathogens. The present study investigated the in vitro activity of melatonin combined with DHEA in a period of 24 hr during the course of in vivo T. cruzi infection. The in vitro activity of melatonin...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Kuehn CC,Rodrigues Oliveira LG,Santos CD,Ferreira DS,Alonso Toldo MP,de Albuquerque S,do Prado JC Jr

    更新日期:2009-10-01 00:00:00

  • Melatonin induces calcium release from CCK-8- and thapsigargin-sensitive cytosolic stores in pancreatic AR42J cells.

    abstract::Melatonin is produced following circadian rhythm with high levels being released at night and has been implicated in the regulation of physiological processes in major tissues, including the pancreas. The aim of our study was to examine the effects of melatonin on intracellular free Ca(2+) concentration ([Ca(2+) ](c))...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: del Castillo-Vaquero A,Salido GM,Gonzalez A

    更新日期:2010-10-01 00:00:00

  • Gene expression and functional characterization of melatonin receptors in the spinal cord of the rat: implications for pain modulation.

    abstract::Recently, a species-dependent distribution of melatonin binding sites have been found in lamina I-V and lamina X of the spinal cord. In order to learn more about the function of spinal melatonin receptors, we investigated (i) the gene expression for melatonin receptor subtypes in lumbar and thoracal spinal cord tissue...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Zahn PK,Lansmann T,Berger E,Speckmann EJ,Musshoff U

    更新日期:2003-08-01 00:00:00

  • Melatonin is involved in cholecystokinin-induced changes of ileal motility in rats.

    abstract::The aim of this study was to determine, in the rat, the interaction between melatonin and cholecystokinin in the regulation of the ileal interdigestive motility. This was analyzed by the chronic electromyography technique. Ileal motility was defined by the presence of intermittent spike bursts corresponding to the con...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Bonouali-Pellissier S

    更新日期:1994-09-01 00:00:00

  • Structure of the pineal gland in the adult cat.

    abstract::The ultrastructure of the pineal gland in the adult cat is described and compared with that of other mammals. Connective tissue spaces showed capillaries with nonfenestrated endothelia and numerous unmyelinated nerve fibers. In the proximal region of the gland, myelinated nerve fibers coming from the anterior commissu...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Boya J,Calvo JL,Rancaño D

    更新日期:1995-03-01 00:00:00

  • Anticonvulsant activity of melatonin against seizures induced by quinolinate, kainate, glutamate, NMDA, and pentylenetetrazole in mice.

    abstract::Melatonin was tested in an ongoing attempt to find the endogenous antagonists of quinolinic acid, an endogenous convulsant. Among a great number of metabolites that have been tried before, only a few were found (cerulein and quinaldic acid in mice and kynurenic acid in rats). In SHR (bred from Swiss) male mice, intrac...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Lapin IP,Mirzaev SM,Ryzov IV,Oxenkrug GF

    更新日期:1998-05-01 00:00:00

  • Malaria: therapeutic implications of melatonin.

    abstract::Malaria, which infects more than 300 million people annually, is a serious disease. Epidemiological surveys indicate that of those who are affected, malaria will claim the lives of more than one million individuals, mostly children. There is evidence that the synchronous maturation of Plasmodium falciparum, the parasi...

    journal_title:Journal of pineal research

    pub_type: 杂志文章,评审


    authors: Srinivasan V,Spence DW,Moscovitch A,Pandi-Perumal SR,Trakht I,Brown GM,Cardinali DP

    更新日期:2010-01-01 00:00:00

  • Effect of exogenous administration of melatonin and growth hormone on pro-antioxidant functions of the liver in aging male rats.

    abstract::Aging is accompanied by changes in the morphology and physiology of organs and tissues, such as the liver. This process might be due to the accumulation of oxidative damage induced by reactive oxygen (ROS) and reactive nitrogen species (RNS). Hepatocytes are very rich in mitochondria and have a high respiratory rate, ...

    journal_title:Journal of pineal research

    pub_type: 杂志文章


    authors: Kireev RA,Tresguerres AC,Castillo C,Salazar V,Ariznavarreta C,Vara E,Tresguerres JA

    更新日期:2007-01-01 00:00:00