Apolipoprotein E influences melatonin biosynthesis by regulating NAT and MAOA expression in C6 cells

Liu, Ya‐Jing; Meng, Fantao; Wang, Lili; Zhang, Lifeng; Cheng, Xiaoguang; Zhou, Jiang‐Ning

doi:10.1111/j.1600-079x.2011.00954.x

Cited by 34 publications

(21 citation statements)

References 27 publications

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“…Melatonin (N‐acetyl‐5‐methoxytryptamine) is synthesized by the pineal gland or extra‐pineal tissues that exerts various biological effects, especially anti‐inflammatory and immunomodulatory functions . Melatonin is synthesized from tryptophan (Trp) by a highly conserved pathway involving the conversion of serotonin successively by two key enzymes such as N‐acetyltransferase (NAT) and HIOMT .…”

Section: Introductionmentioning

confidence: 99%

JNK–TLR9 signal pathway mediates allergic airway inflammation through suppressing melatonin biosynthesis

Shen

Fang

et al. 2016

Journal of Pineal Research

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Toll-like receptors (TLRs) play pivotal role in the pathogenesis of allergic airway diseases such as asthma. TLR9 is one of the most extensively studied TLRs as an approach to treat asthma. In this study, we investigated the role of TLR9 in the allergic airway inflammation and the underlying mechanism. Wild-type (WT) mice and TLR9(-/-) mice were sensitized and challenged with OVA to establish allergic airway disease model. We found that the expression of TLR9 was elevated concomitantly with airway inflammation post-OVA challenge, and TLR9 deficiency effectively inhibited airway inflammation, including serum OVA-specific immunoglobulin E (IgE), pulmonary inflammatory cell recruitment, mucus secretion, and bronchoalveolar lavage fluid (BALF) inflammatory cytokine production. Meanwhile, the protein expression of hydroxyindole-o-methyltransferase (HIOMT) in lung tissues, the level of melatonin in serum, and BALF were reduced in OVA-challenged WT mice, while these reductions were significantly restored by TLR9 deficiency. Additionally, we showed that although TLR9 deficiency had no effect on OVA-induced phosphorylation of JNK, inhibition of JNK by specific inhibitor SP600125 significantly decreased OVA-induced expression of TLR9, suggesting that JNK is the upstream signal molecular of TLR9. Furthermore, SP600125 treatment promoted resolution of allergic airway inflammation in OVA-challenged WT mice, but not further ameliorated allergic airway inflammation in OVA-challenged TLR9(-/-) mice. Similarly, SP600125 significantly restored the protein expression of HIOMT and the level of melatonin in OVA-challenged WT mice, while such effect was not further enhanced by TLR9 deficiency. Collectively, our results indicated that JNK-TLR9 signal pathway mediates allergic airway inflammation through suppressing melatonin biosynthesis.

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Section: Introductionmentioning

confidence: 99%

JNK–TLR9 signal pathway mediates allergic airway inflammation through suppressing melatonin biosynthesis

Shen

Fang

et al. 2016

Journal of Pineal Research

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“…A major breakthrough was the demonstration that the developing brain produces its own melatonin even in pinealectomized rats . Although an increasing number of publications have documented the expression of melatonin‐synthesizing enzymes as well as high levels of melatonin in the brain, melatonin production was only effectively demonstrated in cultured astrocytes and C6 rat glioma cells . Thus, concerns have been raised that question which other nonpineal cells could be responsible for melatonin synthesis.…”

Section: Discussionmentioning

confidence: 99%

Choroid plexus is an additional source of melatonin in the brain

Quintela

Gonçalves

Silva

et al. 2018

Journal of Pineal Research

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The cerebrospinal fluid melatonin is released from the pineal gland, directly into the third ventricle, or produced de novo in the brain from extrapineal melatonin sources leading to a melatonin concentration gradient in the cerebrospinal fluid. Despite the interest on this topic, the brain areas capable of producing melatonin are not yet clear. Bearing this in mind, we hypothesized that the choroid plexus (CP) could be one of these melatonin sources. We analyzed and confirmed the presence of the four enzymes required for melatonin synthesis in rat CP and demonstrated that arylalkylamine N‐acetyltransferase shows a circadian expression in female and male rat CP. Specifically, this enzyme colocalizes with mitochondria in rat CP epithelial cells, an organelle known to be involved in melatonin function and synthesis. Then, we demonstrated that melatonin is synthesized by porcine CP explants, although without a circadian pattern. In conclusion, our data show that the CP is a local source of melatonin to the central nervous system, probably contributing to its high levels in the cerebrospinal fluid. We believe that in the CP, melatonin might be regulated by its endogenous clock machinery and by the hormonal background.

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“…Cultured cortical astrocytes from neonatal rats were shown to synthesize melatonin (1) at rates attaining about one third of those of pinealocytes under same conditions [54]. Melatonin (1) formation was also demonstrated in C6 rat glioma cells [54,55]. The role of glial melatonin (1) deserves further attention.…”

Section: Synthesis Of N-acetylserotonin and Melatonin In The Central mentioning

confidence: 91%

Melatonin and Synthetic Melatonergic Agonists: Actions and Metabolism in the Central Nervous System

Hardeland¹,

Pöeggeler²

2012

CNSAMC

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The CNS is both source and target of melatonin. This methoxyindole formed in the pineal gland is also produced in other CNS regions and additionally enters the brain by uptake from the circulation as well as via the pineal recess. The mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN), not only controls the pineal, but also receives a feedback information on darkness. Two G protein-coupled melatonin receptors, MT1 and MT2, are responsible for the transduction of many melatonergic actions. High receptor densities are especially found in the SCN, but their presence at lower expression levels in other areas is functionally important. Various metabolites and analogs are formed in the CNS, such as N-acetylserotonin, 5-methoxytryptamine, 5-methoxytryptophol, 5-methoxylated kynuramines, and even 6-sulfatoxymelatonin. The chronobiological effects of melatonin go beyond the resetting of a single circadian oscillator. They contribute to phase relationships between oscillatory subsets and are required for robust rhythm amplitudes. CNS effects of melatonin comprise sleep initiation, antiexcitatory, antiepileptic, antinociceptive, anxiolytic, proneurotrophic, antiinflammatory, antioxidant and other neuroprotective actions. The role as a sleep-promoting compound, which is limited by its short half-life in the circulation, has led to the development of controlled-release formulations and of various synthetic agonists, such as ramelteon, agomelatine, tasimelteon, TIK-301, UCM765 and UCM924. Their differences concerning receptor affinities, preferences for receptor subtypes, and pharmacokinetics are discussed, as well as additional antidepressive actions of agomelatine and TIK-301 based on properties as antagonists of the serotonergic 5-HT2C receptor. Indirect antidepressive effects by melatonergic drugs are largely explained by circadian readjustments.

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Apolipoprotein E influences melatonin biosynthesis by regulating NAT and MAOA expression in C6 cells

Cited by 34 publications

References 27 publications

JNK–TLR9 signal pathway mediates allergic airway inflammation through suppressing melatonin biosynthesis

JNK–TLR9 signal pathway mediates allergic airway inflammation through suppressing melatonin biosynthesis

Choroid plexus is an additional source of melatonin in the brain

Melatonin and Synthetic Melatonergic Agonists: Actions and Metabolism in the Central Nervous System

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