Melatonin antagonizes ovarian aging via YTHDF2-MAPK-NF-κB pathway

Zhu, Ruigong; Ji, Xiuqing; Wu, Xuan; Chen, Jiajing; Li, Xuesong; Jiang, Hong; Fu, Haiping; Wang, Hui; Zhe, Liu; Tang, Xin; Sun, Shixiu; Li, Qingguo; Wang, Bingjian; Chen, Hongshan

doi:10.1016/j.gendis.2020.08.005

Cited by 16 publications

(19 citation statements)

References 63 publications

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“…In vitro mouse SSCs/progenitor cells treated with 10 μM chromium (VI) exhibited decreased METTL3 mRNA levels, but cells pretreated with 50 μM melatonin were able to attenuate the downregulation of METTL3 [ 1046 ]. An interesting observation was the significant elevation of METTL3 to levels above controls in the melatonin-only samples, whereas YTHDF2 levels were significantly elevated above the control samples in the melatonin + chromium (VI) cells after 4 h, which again supports the theory that the expression of YTHDF2 may be correlated with stress levels [ 1016 ], and can be increased by the presence of melatonin, and perhaps other antioxidants [ 1045 ].…”

Section: Melatonin May Attenuate the Stress-induced Aggregation Of Pathological Mlos Via Post-translational Modification And Rna Modificamentioning

confidence: 54%

“…Stimulation of oncogene Ras led to the suppression of YTHDF2 that stabilized the transcription of MAP2K4 and MAP4K4, upregulating the senescence-associated secretory phenotype (SASP) in human ovarian surface epithelial cells (HOSEpiC). Treating HOSEpiC cells with 1 μM of melatonin enhanced the expression of YTHDF2, reversed telomere shortening, and blocked Ras-induced growth arrest [ 1045 ]. The activation of cytoplasmic YTH domain “readers” [ 951 ] has been inversely correlated with oxidative stress.…”

Section: Melatonin May Attenuate the Stress-induced Aggregation Of Pathological Mlos Via Post-translational Modification And Rna Modificamentioning

confidence: 99%

“…Upon the induction of oxidative stress, YTHDF1 increases localization to SGs to lower the activation energy barrier and reduce the critical size for SG condensate formation [ 1016 ]. Substituting 1 μM melatonin with 10 mM N -acetyl-l-cysteine (NAC), an antioxidant, also augments YTHDF2 expression in oxidative-stress-induced senescent cells; therefore, it is believed that oxidative pathways may negatively regulate YTHDF2 expression [ 1045 ]. On the other hand, the mechanism(s) involved in the modulation of METTL3 by melatonin may not be as straightforward.…”

Section: Melatonin May Attenuate the Stress-induced Aggregation Of Pathological Mlos Via Post-translational Modification And Rna Modificamentioning

confidence: 99%

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Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders

Loh¹,

Reíter

2021

Antioxidants

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Biomolecular condensates are membraneless organelles (MLOs) that form dynamic, chemically distinct subcellular compartments organizing macromolecules such as proteins, RNA, and DNA in unicellular prokaryotic bacteria and complex eukaryotic cells. Separated from surrounding environments, MLOs in the nucleoplasm, cytoplasm, and mitochondria assemble by liquid–liquid phase separation (LLPS) into transient, non-static, liquid-like droplets that regulate essential molecular functions. LLPS is primarily controlled by post-translational modifications (PTMs) that fine-tune the balance between attractive and repulsive charge states and/or binding motifs of proteins. Aberrant phase separation due to dysregulated membrane lipid rafts and/or PTMs, as well as the absence of adequate hydrotropic small molecules such as ATP, or the presence of specific RNA proteins can cause pathological protein aggregation in neurodegenerative disorders. Melatonin may exert a dominant influence over phase separation in biomolecular condensates by optimizing membrane and MLO interdependent reactions through stabilizing lipid raft domains, reducing line tension, and maintaining negative membrane curvature and fluidity. As a potent antioxidant, melatonin protects cardiolipin and other membrane lipids from peroxidation cascades, supporting protein trafficking, signaling, ion channel activities, and ATPase functionality during condensate coacervation or dissolution. Melatonin may even control condensate LLPS through PTM and balance mRNA- and RNA-binding protein composition by regulating N6-methyladenosine (m6A) modifications. There is currently a lack of pharmaceuticals targeting neurodegenerative disorders via the regulation of phase separation. The potential of melatonin in the modulation of biomolecular condensate in the attenuation of aberrant condensate aggregation in neurodegenerative disorders is discussed in this review.

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Section: Melatonin May Attenuate the Stress-induced Aggregation Of Pathological Mlos Via Post-translational Modification And Rna Modificamentioning

confidence: 54%

Section: Melatonin May Attenuate the Stress-induced Aggregation Of Pathological Mlos Via Post-translational Modification And Rna Modificamentioning

confidence: 99%

Section: Melatonin May Attenuate the Stress-induced Aggregation Of Pathological Mlos Via Post-translational Modification And Rna Modificamentioning

confidence: 99%

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Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders

Loh¹,

Reíter

2021

Antioxidants

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“…The up-regulated mRNA expression of GDF9, BMP15, MOS, and CCNB1 suggested that IMP might be involved in regulating oocyte cytoplasmic maturation ( Su et al, 2004 ; De Castro et al, 2016 ; Liu et al, 2018 ), as well as promoting MPF activity ( Peter et al, 2002 ; Madgwick and Jones, 2007 ; Yang et al, 2017 ). Moreover, stable MOS and CCNB1 levels are essential for meiosis mediated by MAD1, MPS1, and APC/C Cdc 20 ( Alfonso-Pérez et al, 2019 ), as well as balancing the MAPK, NF-κB signal which affects the ROS and mitochondrial dysfunction-mediated oocyte aging ( Achache et al, 2020 ; Niu et al, 2020 ; Zhu et al, 2020 ). In addition, relatively high levels of GDF9 and BMP15 also help slow down the aging and reduce the apoptosis of oocytes by luteinizing hormone receptor, BCL2/BAX, connexin43-mediated regulating the steroidogenic acute regulatory protein expression, plasminogen activator, gap junctions ( Hussein et al, 2005 ; Chang et al, 2014 ; De Castro et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Imperatorin Ameliorates the Aging-Associated Porcine Oocyte Meiotic Spindle Defects by Reducing Oxidative Stress and Protecting Mitochondrial Function

Luo

Zhang

et al. 2020

Front. Cell Dev. Biol.

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Imperatorin (IMP) exhibits a variety of pharmacological properties, including antioxidant, anti-inflammatory, antibacterial, anti-cancer, and anti-hypertension activities. However, its effects on animal reproduction systems, especially oocyte development, maturation, and aging are not yet clear. In this study, the effects of IMP on oocyte development and aging as well as the underlying molecular mechanisms were explored. Oocytes were cultured for an additional 24 h for aging. Results revealed that the blastocyst formation and hatching rates of embryos, which were parthenogenetically activated aged oocytes, were significantly increased with IMP treatment (40 μM). Simultaneously, well-distributed cortical granules but no significant difference in zona pellucida hardness were observed after IMP treatment. During this stage, intracellular reactive oxygen species, apoptosis, and autophagy levels were decreased, while mitochondrial membrane potential, glutathione level, and activity of superoxide dismutase and catalase were increased. IMP-treated aged oocytes also showed significantly higher expression of MOS, CCNB1, BMP15, and GDF9 than non-IMP-treated aged oocytes although their levels were still lower than those in the fresh oocytes. These results suggest that IMP can effectively ameliorate the quality of aged porcine oocytes by reducing oxidative stress and protecting mitochondrial function.

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“…affects the ROS and mitochondrial dysfunction-mediated oocyte aging (Achache et al, 2020;Niu et al, 2020;Zhu et al, 2020). In addition, relatively high levels of GDF9 and BMP15 also help slow down the aging and reduce the apoptosis of oocytes by luteinizing hormone receptor, BCL2/BAX, connexin43-mediated regulating the steroidogenic acute regulatory protein expression, plasminogen activator, gap junctions (Hussein et al, 2005;Chang et al, 2014;De Castro et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

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Melatonin antagonizes ovarian aging via YTHDF2-MAPK-NF-κB pathway

Cited by 16 publications

References 63 publications

Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders

Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders

Imperatorin Ameliorates the Aging-Associated Porcine Oocyte Meiotic Spindle Defects by Reducing Oxidative Stress and Protecting Mitochondrial Function

Table_1.DOCX

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