Control of melatonin synthesis in the mammalian pineal gland: the critical role of serotonin acetylation

Ganguly, Shantanu; Coon, Steven L.; Klein, David C.

doi:10.1007/s00441-002-0579-y

Cited by 230 publications

(195 citation statements)

References 115 publications

(122 reference statements)

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“…This goldfish AANAT-2 deduced amino acid sequence shows more that 90% identity with Aanat-2 sequences from other fish species such as zebrafish, seabream, rainbow trout or pike. Moreover, characteristic binding motifs, phosphorylation sites and conserved regions of the AANAT family (Ganguly et al 2002;Klein, 2007) are identified in the goldfish sequence, supporting the homology of the encoded protein.…”

Section: Cloning Of Goldfish Aanat-2 and Hiomt-2 Genessupporting

confidence: 56%

MELATONIN-SYNTHESIZING ENZYMES IN PINEAL, RETINA, LIVER, AND GUT OF THE GOLDFISH (CARASSIUS): mRNA EXPRESSION PATTERN AND REGULATION OF DAILY RHYTHMS BY LIGHTING CONDITIONS

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Cerdá‐Reverter

Alonso-Gómez

et al. 2010

Chronobiology International

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(MAX 350 WORDS)Melatonin is currently proposed to be synthesized in non-photosensitive organs of vertebrates, besides its well-known sites of synthesis, the pineal gland and the retina.However, very few studies have demonstrated gene expression of MEL synthesizing enzymes in extrapineal and extraretinal locations. In the present study, present study focuses on the circadian expression of the two key enzymes of the melatoninergic pathway, the AANAT and the HIOMT in central and peripheral locations of the goldfish we give report of the full-length cloning of the two enzymes catalyzing the final steps of melatonin biosynthesis, the arylalkylamine N-acetyltransferase (AANAT) and the hydroxyindole-Omethyltransferase (HIOMT), in a teleosts fish, the goldfish (Carassius auratus). Both enzymes showed high similarity with other teleost sequences, corresponding to the goldfish AANAT-2 and HIOMT-2. Two forms of AANATs were widely known to exist in teleosts, but this is the first time that two isoforms of HIOMT are deduced from a phylogenetic analysis.Both enzymes were detected in several peripheral locations, including liver and gut, being present results the first to find HIOMT in non-photosensitive structures of a fish species. No studies exist on transcriptional regulation of the expression of MEL biosynthesis enzymes in non photosensitive structures in fish The daily expression pattern of both genes in pineal gland, retina, liver and gut was investigated using quantitative real time RT-PCR and cosinor analysis. This is the first time that a rhythmic expression of AANAT and HIOMT are found in digestive tissues of a vertebrate species, supporting a functional melatonin synthesis pathway in liver and gut of the goldfish. Besides, the transcriptional regulation of Aanat-2 in pineal and peripheral locations of goldfish maintained under different lighting conditions was investigated expression of gAANAT-2 is analyzed under different lighting conditions including continuous light and darkness, revealing, as expected, light-dependent rhythms in pineal gland and retina, but also in liver. Nevertheless, the persistence in hindgut of these Aanat-2 rhythms in constant conditions suggests that the expression of this transcript is under circadian clock and entrained by non-photic cues. Our results reinforce the existence of melatonin synthesis in gut and liver of the goldfish, while the rhythmic expression profiles reported point to a regulation of both genes in gut and liver by peripheral oscillators entrainable to non-photic cues.

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Section: Cloning Of Goldfish Aanat-2 and Hiomt-2 Genessupporting

confidence: 56%

MELATONIN-SYNTHESIZING ENZYMES IN PINEAL, RETINA, LIVER, AND GUT OF THE GOLDFISH (CARASSIUS): mRNA EXPRESSION PATTERN AND REGULATION OF DAILY RHYTHMS BY LIGHTING CONDITIONS

Velarde

Cerdá‐Reverter

Alonso-Gómez

et al. 2010

Chronobiology International

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“…Melatonin secretion involves a sympathetic stimulation of the cAMP second messenger system, a phosphorylation of the transcription factor CREB resulting in transcription of mRNA encoding the enzyme AANAT [29], which is a key enzyme in the melatonin synthesis [30]. The nighttime melatonin synthesis is a metabolic process consuming energy.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of day–night variations in protein levels in the rat pineal gland

et al. 2007

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The pineal gland secretes the hormone melatonin. This secretion exhibits a circadian rhythm with a zenith during night and a nadir during day. We have performed proteome analysis of the superficial pineal gland in rats during daytime and nighttime. The proteins were extracted and subjected to 2-DE. Of 1747 protein spots revealed by electrophoresis, densitometric analysis showed the up-regulation of 25 proteins during nighttime and of 35 proteins during daytime. Thirty-seven of the proteins were identified by MALDI-TOF MS. The proteins up-regulated during the night are involved in the Krebs cycle, energy transduction, calcium binding, and intracellular transport. During the daytime, enzymes involved in glycolysis, electron transport, and also the Krebs cycle were up-regulated as well as proteins taking part in RNA binding and RNA processing. Our data show a prominent day-night variation of the protein levels in the rat pineal gland. Some proteins are up-regulated during the night concomitant with the melatonin secretion of the gland. Other proteins are up-regulated during the day indicating a pineal metabolism not related to the melatonin synthesis.

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“…the O-methylation of N-acetyl 5-hydroxytryptamine by hydroxyindole-O-methyltransferase) (8 -10). Melatonin synthesis in the pineal increases at night by ϳ10-fold in response to stimulation by a neural pathway that includes the central oscillator in the hypothalamus, the suprachiasmatic nucleus (SCN) (11). Signals from the SCN are transmitted to the pineal gland by a pathway that passes through central and peripheral neural structures to a subset of cells in the superior cervical ganglia (SCG); the final link is made by projections from these cells that pervade the pineal perivascular space.…”

mentioning

confidence: 99%

“…Signals from the SCN are transmitted to the pineal gland by a pathway that passes through central and peripheral neural structures to a subset of cells in the superior cervical ganglia (SCG); the final link is made by projections from these cells that pervade the pineal perivascular space. Release of norepinephrine (NE) from these projections at night leads to an increase in melatonin production (11). Light acts on this system in mammals via the eyes to synchronize the SCN clock to environmental lighting cycles, which in turn synchronizes all circadian rhythms.…”

mentioning

confidence: 99%

“…Light acts on this system in mammals via the eyes to synchronize the SCN clock to environmental lighting cycles, which in turn synchronizes all circadian rhythms. In addition, light acts downstream of the clock to gate SCN stimulation of the pineal gland; as a result, prolonged light exposure or a pulse of light at night prevents NE release from SCG projections in the pineal perivascular space, thereby blocking adrenergic stimulation of pinealocytes (11).…”

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confidence: 99%

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Methionine Adenosyltransferase:Adrenergic-cAMP Mechanism Regulates a Daily Rhythm in Pineal Expression

Kim

Coon

Blackshaw

et al. 2005

Journal of Biological Chemistry

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(S)-Adenosylmethionine (SAM) is a critical element of melatonin synthesis as the methyl donor in the last step of the pathway, the O-methylation of N-acetyl 5-hydroxytryptamine by hydroxyindole-O-methyltransferase. The activity of the enzyme that synthesizes SAM, methionine adenosyltransferase (MAT), increases 2.5-fold at night in the pineal gland. In this study, we found that pineal MAT2A mRNA and the protein it encodes, MAT II, also increase at night, suggesting that the increase in MAT activity is caused by an increase in MAT II gene products. The night levels of MAT2A mRNA in the pineal gland were severalfold higher than in other neural and non-neural tissues examined, consistent with the requirement for SAM in melatonin synthesis. Related studies indicate that the nocturnal increase in MAT2A mRNA is caused by activation of a well described neural pathway that mediates photoneural-circadian regulation of the pineal gland. MAT2A mRNA and MAT II protein were increased in organ culture by treatment with norepinephrine (NE), the sympathetic neurotransmitter that stimulates the pineal gland at night. NE is known to markedly elevate pineal cAMP, and here it was found that cAMP agonists elevate MAT2A mRNA levels by increasing MAT2A mRNA synthesis and that drugs that block cAMP activation of cAMP dependent protein kinase block effects of NE. Therefore, the NE-cAMP dependent increase in pineal MAT activity seems to reflect an increase in MAT II protein, which occurs in response to cAMP3protein kinase-dependent increased MAT2A expression. The existence of this MAT regulatory system underscores the importance that MAT plays in melatonin biogenesis. These studies also point to the possibility that SAM production in other tissues might be regulated through cAMP .(S)-Adenosylmethionine (SAM), 1 the universal methyl donor, is synthesized by methionine adenosyltransferase (MAT; EC 2.5.1.6) (1-3). MAT exists in three forms, designated MAT I, MAT II, and MAT III. These three isoforms are the products of two genes (MAT1A and MAT2A) (4). MAT I and MAT III are expressed only in adult liver and are encoded by the MAT1A gene (5). MAT I is a tetramer and MAT III is a dimer of a single ␣1-subunit. In contrast to the restricted distribution of MAT I and III, MAT II is found in fetal hepatic tissue, adult extrahepatic tissues, and some transformed hepatocytes. Encoded by MAT2A, the ␣2 subunit plays the role of catalysis; the entire enzyme comprises only ␣2 or is constructed with regulatory ␤-subunits (6). The function of the ␤-subunit seems to be to down-regulate MAT II activity (7); however, the precise nature of the interaction between the ␣2-and ␤-subunits is still not clear.MAT in the pineal gland is of special interest because synthesis of the hormonal product of this tissue, melatonin, requires SAM at the last step (i.e. the O-methylation of N-acetyl 5-hydroxytryptamine by hydroxyindole-O-methyltransferase) (8 -10). Melatonin synthesis in the pineal increases at night by ϳ10-fold in response to stimulation by a neural pathway th...

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Control of melatonin synthesis in the mammalian pineal gland: the critical role of serotonin acetylation

Cited by 230 publications

References 115 publications

MELATONIN-SYNTHESIZING ENZYMES IN PINEAL, RETINA, LIVER, AND GUT OF THE GOLDFISH (CARASSIUS): mRNA EXPRESSION PATTERN AND REGULATION OF DAILY RHYTHMS BY LIGHTING CONDITIONS

MELATONIN-SYNTHESIZING ENZYMES IN PINEAL, RETINA, LIVER, AND GUT OF THE GOLDFISH (CARASSIUS): mRNA EXPRESSION PATTERN AND REGULATION OF DAILY RHYTHMS BY LIGHTING CONDITIONS

Proteomic analysis of day–night variations in protein levels in the rat pineal gland

Methionine Adenosyltransferase:Adrenergic-cAMP Mechanism Regulates a Daily Rhythm in Pineal Expression

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