The multiple protective roles and molecular mechanisms of melatonin and its precursor N-acetylserotonin in targeting brain injury and liver damage and in maintaining bone health

Luo, Chengliang; Yang, Qiang; Liu, Yuancai; Zhou, Shuanhu; Jiang, Jiying; Reíter, Russel J.; Bhattacharya, Pallab; Cui, Yongchun; Yang, Hongwei; Ma, He; Yao, Jiemin; Lawler, Sean E.; Zhang, Xinmu; Fu, Jianfang; Rozental, Renato; Aly, Hany; Johnson, Mark D.; Chiocca, E. Antonio; Wang, Xin

doi:10.1016/j.freeradbiomed.2018.10.402

Cited by 62 publications

(72 citation statements)

References 210 publications

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“…Melatonin may prevent bone degradation and promote bone formation through mechanisms involving both melatonin receptor‐mediated and receptor‐independent actions. There are three principal mechanisms of melatonin's effects on bone metabolism: (a) promoting osteoblast differentiation and activity; (b) inhibiting osteoclast differentiation; (c) scavenging free radicals to resist osteoporosis (Figure ). Kim et al investigated whether combined fluid shear stress (FSS) and melatonin stimulate signal transduction in cilia‐less MC3T3‐E1 preosteoclasts.…”

Section: Mechanisms Underlying Melatonin's Action On Osteoporosismentioning

confidence: 99%

Melatonin: Another avenue for treating osteoporosis?

Tian

Jiang

et al. 2019

Journal of Pineal Research

109

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Melatonin is a signal molecule that modulates the biological circadian rhythms of vertebrates. Melatonin deficiency is thought to be associated with several disorders, including insomnia, cancer, and cardiovascular and neurodegenerative diseases. Accumulating evidence has also indicated that melatonin may be involved in the homeostasis of bone metabolism. Age‐related reductions in melatonin are considered to be critical factors in bone loss and osteoporosis with aging. Thus, serum melatonin levels might serve as a biomarker for the early detection and prevention of osteoporosis. Compared to conventional antiosteoporosis medicines, which primarily inhibit bone loss, melatonin both suppresses bone loss and promotes new bone formation. Mechanistically, by activating melatonin receptor 2 (MT2), melatonin upregulates the gene expression of alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP2), BMP6, osteocalcin, and osteoprotegerin to promote osteogenesis while inhibiting the receptor activator of NF‐kB ligand (RANKL) pathway to suppress osteolysis. In view of the distinct actions of melatonin on bone metabolism, we hypothesize that melatonin may be a novel remedy for the prevention and clinical treatment of osteoporosis.

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Section: Mechanisms Underlying Melatonin's Action On Osteoporosismentioning

confidence: 99%

Melatonin: Another avenue for treating osteoporosis?

Tian

Jiang

et al. 2019

Journal of Pineal Research

109

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“…Moreover, melatonin is also efficient in the prevention of apoptosis by acting through its MT2 membrane receptor [218] in bile duct-ligated young rats or inhibiting endoplasmic reticulum stress, a process that often induces apoptosis [53] in leptin-deficient mice. Similar mechanisms of protection are shown when melatonin reverses bone loss due to its antioxidant actions that prevent antiapoptotic events [147].…”

Section: Apoptosismentioning

confidence: 66%

“…The brain is highly sensitive to oxidative stress because it consumes a large amount of oxygen and generates more ROS than most other tissues. Moreover, it is rich in easily-oxidizable polyunsaturated fatty acids and endowed with relatively low levels of endogenous antioxidants [147,191]. This makes it a clear target in which to examine the role of antioxidants on apoptosis.…”

Section: Apoptosismentioning

confidence: 99%

Advances in Characterizing Recently-Identified Molecular Actions of Melatonin: Clinical Implications

Reíter¹,

Sharma²,

Rosales-Corral³

et al. 2020

Human Perspectives in Health Sciences and Technology

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IntroductionSome system-wide functions/aspects of melatonin were identified decades ago, e.g., regulation of seasonal reproduction [51,200,201], photoperiodic control of pineal melatonin synthesis [122,227], sleep initiation [31,117], antioxidant actions [67, 197], circadian rhythm modulation [208,279], cancer inhibition [27,86,163], etc. These aspects of melatonin are generally well known by the scientists working in the field, although the detailed mechanisms of these actions, in most cases, require further clarification. These functions are not discussed in detail in the current review, but they may be mentioned when they are germane to the discussion. Also, the functions of melatonin in plants [18,61,62,194] are not considered even though

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“…The difference between MT1 and MT2 receptor may be attributed in part to the sharp decrease in MT2 receptor expression observed in the later stages of thrombopoiesis (Figure ) or restricted binding site of MT2 receptor, preventing MT access . Another binding site, MT3 receptor, with low‐affinity for MT, is involved in the protection of cells from oxidative injuries by inhibition of electron transfer . Therefore, the effect of MT3 receptor on MK activities needs to be further evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…28 Another binding site, MT3 receptor, with low-affinity for MT, is involved in the protection of cells from oxidative injuries by inhibition of electron transfer. 29,30 Therefore, the effect of MT3 receptor on MK activities needs to be further evaluated. The influence of MT during thrombopoiesis described in this study is consistent with our previous works in which we showed that some neuroendocrine hormones mainly affect the later stages of thrombopoiesis, where they induce a quick elevation of circulating platelets.…”

Section: Discussionmentioning

confidence: 99%

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

Chen

Wang

et al. 2020

Journal of Pineal Research

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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 that MT has the capacity to promote the expansion of CD34+ and CD41+ cells, and accelerate proplatelet formation (PPF) and platelet production. Furthermore, in vivo experiments show that MT has a potential therapeutic effect on radiation‐induced thrombocytopenia. The underlying mechanism suggests that both extracellular signal‐regulated kinase 1/2 (ERK1/2) and Akt signaling are involved in the processes of thrombopoiesis facilitated by MT. Interestingly, in addition to the direct regulation of Akt signaling by its upstream phosphoinositide 3‐kinase (PI3K), ERK1/2 signaling is also regulated by PI3K via its effector, dual adaptor for phosphotyrosine and 3‐phosphoinositides (DAPP1), in megakaryocytes after MT treatment. Moreover, the expression level of DAPP1 during megakaryocyte differentiation is closely related to the activation of ERK1/2 and Akt at different stages of thrombopoiesis. In conclusion, our data suggest that MT treatment can promote thrombopoiesis, which is modulated by the DAPP1‐orchestrated activation of ERK1/2 and Akt signaling.

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The multiple protective roles and molecular mechanisms of melatonin and its precursor N-acetylserotonin in targeting brain injury and liver damage and in maintaining bone health

Cited by 62 publications

References 210 publications

Melatonin: Another avenue for treating osteoporosis?

Melatonin: Another avenue for treating osteoporosis?

Advances in Characterizing Recently-Identified Molecular Actions of Melatonin: Clinical Implications

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

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