Melatonin: A Versatile Protector against Oxidative DNA Damage

Galano, Annia; Tan, Dun Xian; Reíter, Russel J.

doi:10.3390/molecules23030530

Cited by 216 publications

(144 citation statements)

References 338 publications

(439 reference statements)

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“…SIRT1 knockout also blocked the inhibitory effect of melatonin on oxidative stress in diabetic hearts, while it has been reported that melatonin has direct anti-oxidative protection including directly scavenging free radicals and enhancing the activity of the antioxidant enzyme and indirect anti-oxidative protection dependent on its interaction with RORα. 16,49 Interestingly, recent study has found that melatonin increases SIRT1-dependent NF-kB deacetylation through a RORα-dependent mechanism, 50 suggesting the existence of a melatonin-RORα-SIRT1 connection may be involved in the inhibition of ROS. Moreover, melatonin and SIRT1 have a long evolutionary history and exert cooperative biological effects in some conditions.…”

Section: Discussionmentioning

confidence: 99%

Melatonin prevents Drp1‐mediated mitochondrial fission in diabetic hearts through SIRT1‐PGC1α pathway

Ding

Feng

Tang

et al. 2018

Journal of Pineal Research

267

190

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Myocardial contractile dysfunction is associated with an increase in mitochondrial fission in patients with diabetes. However, whether mitochondrial fission directly promotes diabetes‐induced cardiac dysfunction is still unknown. Melatonin exerts a substantial influence on the regulation of mitochondrial fission/fusion. This study investigated whether melatonin protects against diabetes‐induced cardiac dysfunction via regulation of mitochondrial fission/fusion and explored its underlying mechanisms. Here, we show that melatonin prevented diabetes‐induced cardiac dysfunction by inhibiting dynamin‐related protein 1 (Drp1)‐mediated mitochondrial fission. Melatonin treatment decreased Drp1 expression, inhibited mitochondrial fragmentation, suppressed oxidative stress, reduced cardiomyocyte apoptosis, improved mitochondrial function and cardiac function in streptozotocin (STZ)‐induced diabetic mice, but not in SIRT1−/− diabetic mice. In high glucose‐exposed H9c2 cells, melatonin treatment increased the expression of SIRT1 and PGC‐1α and inhibited Drp1‐mediated mitochondrial fission and mitochondria‐derived superoxide production. In contrast, SIRT1 or PGC‐1α siRNA knockdown blunted the inhibitory effects of melatonin on Drp1 expression and mitochondrial fission. These data indicated that melatonin exerted its cardioprotective effects by reducing Drp1‐mediated mitochondrial fission in a SIRT1/PGC‐1α‐dependent manner. Moreover, chromatin immunoprecipitation analysis revealed that PGC‐1α directly regulated the expression of Drp1 by binding to its promoter. Inhibition of mitochondrial fission with Drp1 inhibitor mdivi‐1 suppressed oxidative stress, alleviated mitochondrial dysfunction and cardiac dysfunction in diabetic mice. These findings show that melatonin attenuates the development of diabetes‐induced cardiac dysfunction by preventing mitochondrial fission through SIRT1‐PGC1α pathway, which negatively regulates the expression of Drp1 directly. Inhibition of mitochondrial fission may be a potential target for delaying cardiac complications in patients with diabetes.

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Section: Discussionmentioning

confidence: 99%

Melatonin prevents Drp1‐mediated mitochondrial fission in diabetic hearts through SIRT1‐PGC1α pathway

Ding

Feng

Tang

et al. 2018

Journal of Pineal Research

267

190

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“…59 Melatonin has been shown to inhibit the harmful effects of fructose on clock genes and protect against reactive oxygen species. 60 Melatonin has also been shown to regulate leptin and adiponectin secretion cycles, further underlying the reciprocal relationship of these hormonal cascades. 61 Addressing these hormonal changes in hunger signaling and food cravings may offer therapeutic benefit for the prevention of metabolic syndrome in shift workers.…”

Section: Melatoninmentioning

confidence: 99%

Shift Workers at Risk for Metabolic Syndrome

Kulkarni¹,

Schow²,

Shubrook³

2020

Journal of Osteopathic Medicine

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In this highly digitalized era, sleep disorders are becoming more common and are associated with an increased burden of chronic disease. Shift workers are at an increased risk for both sleep disorders and metabolic syndrome. In this article, the authors outline the connection between circadian discordance, hormonal imbalance, and the development of metabolic syndrome in shift workers. Based on a literature review of animal model studies, observational studies, and clinical trials conducted between August and October of 2018, the authors offer several clinical interventions, including work schedules, light therapy, medications, and dietary habits to improve the circadian synchronicity of shift workers and reduce their risk of morbidity and mortality. It is important for physicians to be familiar with the consequences of shift work and ways to mitigate the risks for this patient population. M any of the human body's neurohormonal cascades, including key metabolic cascades and the sleep-wake cycle, follow 24-hour rhythms. These circadian rhythms evolve in response to a light-dark cycle established by sunrise and sunset along with the daily rhythm of other external factors, such as temperature and noise.Today, people are exposed to synthetic light, heat, and other stimulating cues that do not follow a 24-hour cyclic pattern. These synthetic factors interfere with the carefully coordinated interplay between external regulators and the endogenous maintenance of circadian rhythms. 1 Shift workers are increasingly affected by this phenomenon. 2 This discordance among shift workers has been linked to disruption in the sleep-wake cycle and metabolic pathways, leading to sleep deprivation and an increased risk of metabolic syndrome. 3In this review, we discuss the relationship between metabolic syndrome and shift work. We completed PubMed searches in August and October 2018 using the following keywords: "shift worker demographics," "metabolic syndrome and shift workers," "risk factors associated with metabolic syndrome in shift work," "circadian rhythm and shift work," "cortisol release and shift work," "shift work and exercise habits," "shift work and nutrition habits," "circadian rhythm discordance and metabolic syndrome," "sleep hygiene and shift work disorder," "nutrition and sleep hygiene," "exercise and cortisol release," "sleep disorders and shift work," "sleep disorders and metabolic syndrome," "osteopathic manipulation and sleep latency," "shift work and heart rate variability," and "osteopathic manipulation and heart rate variability." Of the literature reviewed, 38 articles were experimental studies (animal model or clinical trials), 35 were review articles, and 17 were observational studies. Based on this literature

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“…On the other hand, there is abundant evidence supporting the protective effects of melatonin against oxidative damage to DNA . The data gathered so far indicate that such protection is mediated by different pathways including both direct, that is, free radical scavenging processes, and indirect means of action.…”

Section: Introductionmentioning

confidence: 99%

“…42,49,50 On the other hand, there is abundant evidence supporting the protective effects of melatonin against oxidative damage to DNA. 51 The data gathered so far indicate that such protection is mediated by different pathways including both direct, that is, free radical scavenging processes, 52,53 and indirect means of action. The latter may involve inhibiting metal-induced oxidation, 67,68 activating antioxidative enzymes, 77,78 inhibiting pro-oxidative enzymes, 80 and/or enhancing the DNA repair machinery.…”

mentioning

confidence: 99%

Melatonin and its metabolites as chemical agents capable of directly repairing oxidized DNA

Pérez-González

Castañeda‐Arriaga

Álvarez-Idaboy

et al. 2018

Journal of Pineal Research

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Oxidative stress mediates chemical damage to DNA yielding a wide variety of products. In this work, the potential capability of melatonin and several of its metabolites to repair directly (chemically) oxidative lesions in DNA was explored. It was found that all the investigated molecules are capable of repairing guanine‐centered radical cations by electron transfer at very high rates, that is, diffusion‐limited. They are also capable of repairing C‐centered radicals in the sugar moiety of 2′‐deoxyguanosine (2dG) by hydrogen atom transfer. Although this was identified as a rather slow process, with rate constants ranging from 1.75 to 5.32 × 102 M−1 s−1, it is expected to be fast enough to prevent propagation of the DNA damage. Melatonin metabolites 6‐hydroxymelatonin (6OHM) and 4‐hydroxymelatonin (4OHM) are also predicted to repair OH adducts in the imidazole ring. In particular, the rate constants corresponding to the repair of 8‐OH‐G adducts were found to be in the order of 104 M−1 s−1 and are assisted by a water molecule. The results presented here strongly suggest that the role of melatonin in preventing DNA damage might be mediated by its capability, combined with that of its metabolites, to directly repair oxidized sites in DNA through different chemical routes.

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Melatonin: A Versatile Protector against Oxidative DNA Damage

Cited by 216 publications

References 338 publications

Melatonin prevents Drp1‐mediated mitochondrial fission in diabetic hearts through SIRT1‐PGC1α pathway

Melatonin prevents Drp1‐mediated mitochondrial fission in diabetic hearts through SIRT1‐PGC1α pathway

Shift Workers at Risk for Metabolic Syndrome

Melatonin and its metabolites as chemical agents capable of directly repairing oxidized DNA

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