Human hydroxyindole-O-methyltransferase in pineal gland, retina and Y79 retinoblastoma cells

Bernard, Marianne; Donohue, Susan J.; Klein, David C.

doi:10.1016/0006-8993(95)00651-6

Cited by 61 publications

(55 citation statements)

References 31 publications

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“…The functional role played by AANAT-2 in these locations, is of great interest and several possibilities, apart from the MEL synthesis, can be suggested, as the reduction of the oxidative formation of aldehydes of serotonin and other arylalkylamines (Bernard et al, 1995;Coon et al, 2002) and/or a detoxification role, as it is considered the original function of this enzyme Klein, 2007). Nevertheless, in addition to the expected Hiomt expression in goldfish pineal and retina, where MEL synthesis is well documented in vivo and in vitro (Iigo et al, 1991;1997), we found positive signals for HIOMT transcripts in gonads and, to a lesser extent, in liver and gut.…”

Section: Distribution Of Aanat-2 and Hiomt-2 Mrna In Goldfishmentioning

confidence: 99%

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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(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: Distribution Of Aanat-2 and Hiomt-2 Mrna In Goldfishmentioning

confidence: 99%

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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“…Conversely, it is thought that AANAT may also act to detoxify arylalkylamines; and, that this was selected for in the retinal photoreceptors. In some mammals, including human, rhesus monkey and cow, the retina has essentially no capacity to make melatonin, but expresses high levels of AANAT activity (Wiechmann, 1993;Rodriquez et al, 1994;Bernard et al, 1995;Coon et al, 1996;Craft et al, 1999;Coon et al, 2002).…”

Section: A Third Aanat Gene In Percomorph Fishesmentioning

confidence: 99%

Evolution of arylalkylamine N-acetyltransferase: Emergence and divergence

Coon

Klein

2006

Molecular and Cellular Endocrinology

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106

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The melatonin rhythm-generating enzyme, arylalkylamine N-acetyltransferase (AANAT) is known to have recognizable ancient homologs in bacteria and fungi, but not in other eukaryotes. Analysis of new cDNA and genomic sequences has identified several additional homologs in other groupings. First, an AANAT homolog has been found in the genome of the cephalochordate amphioxus, representing the oldest homolog in chordates. Second, two AANAT homologs have been identified in unicellular green algae. The homologs in amphioxus, unicellular green algae, fungi and bacteria are similarly primitive in that they lack sequences found in vertebrate AANATs that are involved in regulation and that facilitate binding and catalysis. In addition, all these sequences are intronless. These features are consistent with horizontal transfer of the AANAT ancestor from bacteria to green algae, fungi and chordates. Lastly, a third AANAT gene has been found in teleost fish, suggesting that AANAT genes serve multiple functions in addition to melatonin synthesis.

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“…In some nonmammalian organisms, it is also released to the blood in certain quantities [19,30,35,77,145,153,155]. However, primates and ungulates so-far investigated exhibited high nocturnal expression levels of AA-NAT, but are reported to not form melatonin at substantial rates, because the NASconverting enzyme, hydroxyindole O-methyltransferase (HIOMT) is poorly expressed [13,65,66]. However, recent data show HIOMT expression in cultured human retinal pigment cells (ARPE-19 cells) [162].…”

Section: Introductionmentioning

confidence: 99%

Melatonin Metabolism in the Central Nervous System

Hardeland¹

2010

112

110

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Abstract:The metabolism of melatonin in the central nervous system is of interest for several reasons. Melatonin enters the brain either via the pineal recess or by uptake from the blood. It has been assumed to be also formed in some brain areas. Neuroprotection by melatonin has been demonstrated in numerous model systems, and various attempts have been undertaken to counteract neurodegeneration by melatonin treatment. Several concurrent pathways lead to different products. Cytochrome P 450 subforms have been demonstrated in the brain. They either demethylate melatonin to Nacetylserotonin, or produce 6-hydroxymelatonin, which is mostly sulfated already in the CNS. Melatonin is deacetylated, at least in pineal gland and retina, to 5-methoxytryptamine. N 1 -acetyl-N 2 -formyl-5-methoxykynuramine is formed by pyrrole-ring cleavage, by myeloperoxidase, indoleamine 2,3-dioxygenase and various non-enzymatic oxidants. Its product, N 1 -acetyl-5-methoxykynuramine, is of interest as a scavenger of reactive oxygen and nitrogen species, mitochondrial modulator, downregulator of cyclooxygenase-2, inhibitor of cyclooxygenase, neuronal and inducible NO synthases. Contrary to other nitrosated aromates, the nitrosated kynuramine metabolite, 3-acetamidomethyl-6-methoxycinnolinone, does not re-donate NO. Various other products are formed from melatonin and its metabolites by interaction with reactive oxygen and nitrogen species. The relative contribution of the various pathways to melatonin catabolism seems to be influenced by microglia activation, oxidative stress and brain levels of melatonin, which may be strongly changed in experiments on neuroprotection. Many of the melatonin metabolites, which may appear in elevated concentrations after melatonin administration, possess biological or pharmacological properties, including N-acetylserotonin, 5-methoxytryptamine and some of its derivatives, and especially the 5-methoxylated kynuramines.

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Human hydroxyindole-O-methyltransferase in pineal gland, retina and Y79 retinoblastoma cells

Cited by 61 publications

References 31 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

Evolution of arylalkylamine N-acetyltransferase: Emergence and divergence

Melatonin Metabolism in the Central Nervous System

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