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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inducible-cAMP early repressor (ICER) is a potent inhibitor of CRE (cAMP-related element)-driven gene transcription. In the rat pineal gland, it has been proposed to be part of the mechanisms involved in the shutting down of the transcription of the gene coding for arylalkylamine N-acetyltransferase (AA-NAT, the melatonin rhythm-generating enzyme). In this study, we report that ICER is expressed in the pineal gland of the photoperiodic rodent Syrian hamster although with some difference compared to the rat. In the Syrian hamster pineal, Icer mRNA levels, low at daytime, displayed a 20-fold increase during the night. Nighttime administration of a beta-adrenergic antagonist, propranolol, significantly reduced Icer mRNA levels although daytime administration of a beta-adrenergic agonist, isoproterenol, was unable to raise the low amount of Icer mRNA. These observations indicate that Icer mRNA expression is induced by the clock-driven norepinephrine release and further suggest that this stimulation is restricted to nighttime, as already observed for Aa-nat gene transcription. Furthermore, we found that the daily profile of Icer mRNA displayed photoperiodic variation with a lengthening of the nocturnal peak in short versus long photoperiod. These data indicate that ICER may be involved in both daily and seasonal regulation of melatonin synthesis in the Syrian hamster.
Brain Res Mol Brain Res 2003 Apr 10
PMID:Expression and regulation of Icer mRNA in the Syrian hamster pineal gland. 1267 Jul 14

Somatostatin is a potent antiproliferative signal in both tumoral and normal mammalian cells, and altered somatostatin receptor (sst) expression is associated with carcinogenesis in human tissues. In this study, two normal and three tumoral human pineal glands were analyzed using the reverse transcriptase-polymerase chain reaction (RT-PCR) for the presence of mRNA coding for the five different somatostatin receptors (sst1-sst5). Pineal parenchymal tumor (PPT) differentiation was confirmed by immunohistochemical detection of neuroendocrine markers (synaptophysin, neurofilaments, and chromogranin A). The presence of mRNA coding for c-myc, a proto-oncogene, and for tryptophan hydroxylase (TPOH), serotonin N-acetyltransferase (NAT), and hydroxyindole-O-methyltransferase (HIOMT), enzymes of the melatonin pathway, was also analyzed by RT-PCR. Only the tumoral tissues contained c-myc mRNA. All five tissues contained TPOH, NAT, and HIOMT mRNA, the levels of HIOMT mRNA being lower in PPT than in the normal pineal gland, suggesting that PPT retain the ability to synthesize melatonin. All tissues contained sst1, sst2, and sst3 transcripts, but not sst4, while small amounts of sst5 mRNA were only found in normal pineal glands. Real-time PCR, performed only with the most abundant subtpe sst2, evidenced an about sixfold higher level in in normal pineal glands. These results demonstrate the presence of somatostatin receptors in the human pineal gland, as described in other species, and point to a differential expression of the sst2 and sst5 subtypes associated with carcinogenesis.
Cell Mol Neurobiol 2003 Feb
PMID:Differential somatostatin receptor subtype expression in human normal pineal gland and pineal parenchymal tumors. 1270 86

By RT-PCR two transcripts for arylalkylamine N-acetyltransferase (AA-NAT; serotonin N-acetyltransferase; EC 2.3.1.87), the key enzyme in melatonin synthesis, were found, for the first time, in the oocytes and blastoderms from freshly laid eggs (323- and 238-bp RT-PCR products), and one (238-bp product) in the pineal gland of Japanese quail (Coturnix coturnix japonica). The two products differed by an intron of 85-bp present in the 323-bp band and absent from the 238-bp band. The identity of the products was confirmed by restriction analysis and sequencing. The ratio of the 323:238-bp bands changed during oogenesis from approximately 17:1 in small 3-mm oocytes to approximately 4:1 in immature vitellogenic oocytes and approximately 1:1 in mature, preovulatory oocytes; it was reversed to approximately 0.2:1 in blastoderms from fertile freshly laid eggs, corresponding to embryo of approximately 40,000 cells. It is proposed that the longer 323-bp product, containing an intron, represents a translationally inactive form of the transcript, stored in maternal RNA. The shorter 238-bp product lacking an intron may represent the mature active AA-NAT mRNA found in the pineal gland and in early embryos, and-to a lower proportion-in older oocytes. These data constitute the first direct proof of an intron sequence in maternal RNA of avian oocyte. It is possible that differential processing of the immature mRNA is part of a transcriptional regulation mechanism of AA-NAT activity. A possible role of extrapineal melatonin in early avian development is discussed.
Mol Reprod Dev 2003 Jun
PMID:Presence and developmental regulation of serotonin N-acetyltransferase transcripts in oocytes and early quail embryos (Coturnix coturnix japonica). 1270 23

The study reports the change of transcription pattern of serotonin N-acetyltransferase gene and melatonin receptor genes during ontogenesis of the avian pineal gland. The RT-PCR technique was used to investigate the expression of the arylalkylamine N-acetyltransferase (AA-NAT) and melatonin receptor genes during development of the pineal glands isolated from Japanese quail (Coturnix coturnix japonica) embryos incubated from 3 days on until hatching (17 days), and in some organs (pineal, brain hemisphere, eye, leg, heart) of the 3-day-old quail embryo. It was shown that two phases of AA-NAT expression are observed during pineal gland development. The first, embryonic-type phase, lasts from the beginning until 7-10 days of incubation, and is marked by the presence of two RT-PCR products for AA-NAT: the shorter mature form without intron (238 bp), and the longer form (323 bp) containing an unprocessed intron of 85 bp. The second, adult-type phase is characterized by the presence of a single mature transcript, containing no intron; it starts from 7 to 10 days of incubation and lasts until hatching and in the adult pineal. The duration of this transition time from the embryonic to the adult transcription pattern in the quail pineal gland from 7 to 10 days of incubation we attribute to asynchronic embryo development, because quail chicks usually hatch between the 16th and 19th day of incubation. Analysis of the AA-NAT protein sequences for chick and quail (GeneBank accession no. U 46 502 and AF 007 068, respectively) revealed their perfect homology with the part of protein read from the sequence present in the adult-type phase of the pineal gland (the RT-PCR product of 238 bp). The presence of the intron (in the 323 bp RT-PCR product, accession no. AY 197 460) in the embryonic-phase of the pineal gland changes the reading frame of the mRNA sequence and the hypothetical resulting protein loses its homology with the chick and quail AA-NAT enzyme starting with 105th amino acid of the complete chick AA-NAT protein comprising 205 amino acids (accession no. U 46 502). In the whole embryos at stages 1-8 (according to the Hamburger-Hamilton classification) both RT-PCR products with and without intron were consistently found, and individual tissues from 3-day-old embryos also produced two AA-NAT products, i.e., the expression was of the embryonic-type. At the time of transition from the embryonic to the adult AA-NAT transcription pattern, in 7-11-day-old embryos, all three melatonin receptor transcripts (mel-1a, mel-1b, and mel-1c) were observed in the pineals, without consistent modifications of the band intensity. In the adult pineal, a single mature AA-NAT transcript was present as well as all three melatonin receptor transcripts, usually with preferential expression of the mel-1a band. The transition time from the embryonic to adult AA-NAT expression pattern coincides well with the acquisition of functional activity and the appearance of melatonin synthesis in the embryonic pineal reported for chicken, as related to quail. We suggest that the change in transcription pattern of the AA-NAT gene may reflect another, still unknown mechanism of regulating AA-NAT activity during ontogenesis, at the level of mRNA processing, whose specificity (or not) for embryonic development we wish to establish in the future.
Mol Reprod Dev 2004 Feb
PMID:Transition from embryonic to adult transcription pattern of serotonin N-acetyltransferase gene in avian pineal gland. 1469 29

Several lines of evidence show that the daily amount of melatonin produced differs greatly between individuals. Any polymorphism in the gene of arylalkylamine N-acetyltransferase (AA-NAT), a critical enzyme involved in melatonin biosynthesis, may contribute to the variability of melatonin production. The present study investigated the possible association between overnight melatonin excretion and a commonly occurring -263G/C polymorphism in the promoter region of the human AA-NAT gene. However, we found that -263G/C variant had no effect on the overnight 6-OHMS excretion. In this study, individual genotyping for -263G/C was determined by denaturing high performance liquid chromatography (DHPLC) and confirmed by sequencing. The overnight urinary 6-hydroxymelatonin sulfate (6-OHMS) excretion was quantified by enzyme-linked immunosorbent assay (ELISA).
Mol Genet Metab 2004 Jan
PMID:A naturally occurring -263G/C variant of the human AA-NAT gene and overnight melatonin production. 1472 93

Rhythms in pineal melatonin synthesis are controlled by the biological clock located in the suprachiasmatic nuclei. The endogenous clock oscillations rely upon genetic mechanisms involving clock genes coding for transcription factors working in negative and positive feedback loops. Most of these clock genes are expressed rhythmically in other tissues. Because of the peculiar role of the pineal gland in the photoneuroendocrine axis regulating biological rhythms, we studied whether clock genes are expressed in the rat pineal gland and how their expression is regulated.Per1, Per3, Cry2 and Cry1 clock genes are expressed in the pineal gland and their transcription is increased during the night. Analysis of the regulation of these pineal clock genes indicates that they may be categorized into two groups. Expression of Per1 and Cry2 genes shows the following features: (1) the 24 h rhythm persists, although damped, in constant darkness; (2) the nocturnal increase is abolished following light exposure or injection with a beta-adrenergic antagonist; and (3) the expression during daytime is stimulated by an injection with a beta-adrenergic agonist. In contrast, Per3 and Cry1 day and night mRNA levels are not responsive to adrenergic ligands (as previously reported for Per2) and daily expression of Per3 and Cry1 appears strongly damped or abolished in constant darkness. These data show that the expression of Per1 and Cry2 in the rat pineal gland is regulated by the clock-driven changes in norepinephrine, in a similar manner to the melatonin rhythm-generating enzyme arylalkylamine N-acetyltransferase. The expression of Per3 and Cry1 displays a daily rhythm not regulated by norepinephrine, suggesting the involvement of another day/night regulated transmitter(s).
Brain Res Mol Brain Res 2004 Jan 05
PMID:Daily rhythm and regulation of clock gene expression in the rat pineal gland. 1474 6

Pineal function is defined by a set of very narrowly expressed genes that encode proteins required for photoperiodic transduction and rhythmic melatonin secretion. One of these proteins is serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT), which controls the daily rhythm in melatonin production. Here, pineal-specific expression of the zebrafish aanat-2 (zfaanat-2) was studied using in vivo transient expression analyses of promoter-reporter constructs; this revealed that specificity is determined by two regions located 12 kb away from each other. One is the 5'-flanking region, and the other is a 257-bp sequence, located 6 kb downstream of the transcribed region. This 3'-sequence, designated pineal-restrictive downstream module (PRDM), has a dual function: enhancement of pineal expression and inhibition of extrapineal expression. The former is an autonomic property of PRDM whereas the later function requires interaction with the upstream regulatory region of zfaanat-2. Functional analyses of the PRDM sequence revealed that three photoreceptor conserved elements (TAATC) and a single perfect E-box (CACGTG) are crucial for the dual function of PRDM. These results indicate that pineal specificity of zfaanat-2 is determined by the dual functionality of the PRDM and the interaction between upstream regulatory region and downstream photoreceptor conserved elements and E-box element.
Mol Endocrinol 2004 May
PMID:Zebrafish serotonin-N-acetyltransferase-2 gene regulation: pineal-restrictive downstream module contains a functional E-box and three photoreceptor conserved elements. 1498 31

The nocturnal biosynthesis of melatonin in the rat pineal depends on strongly enhanced expression of the enzyme N-acetyltransferase [arylalkylamine N-acetyltransferase (AA-NAT); EC 2.3.1.87]. AA-NAT transcription is stimulated during darkness by adrenergic inputs to the pineal from the suprachiasmatic nucleus (SCN). Nocturnal activation of the AA-NAT promotor following stimulation of pinealocyte adrenoceptors involves cAMP-dependent stimulation of protein kinase A (PKA). The nocturnal rise in AA-NAT depends on the lighting conditions. As compared with light/dark (LD) 12:12, the delay between dark onset and the nocturnal rise in AA-NAT is shortened under long photoperiods and prolonged under short photoperiods. Here, we report that the rapidity of nocturnal AA-NAT induction depends on cAMP inducibility of the gene. Accordingly, cAMP produces a strong AA-NAT response in pineals obtained from rats housed under long photoperiods and a weak AA-NAT response under short photoperiods. Changes in AA-NAT inducibility are fully developed not earlier than after seven cycles. This observation suggests that long-term changes in the photoperiod are necessary to achieve full adjustment of cAMP inducibility of the gene. A direct relationship was found between cAMP-dependent AA-NAT inducibility and the pineal protein kinase A (PKA) activity. As compared to LD 12:12, PKA activity was increased under LD 20:4 and attenuated under LD 4:20. On the basis of the present findings, we suggest that the photoperiod determines the effectiveness of nocturnal AA-NAT induction by long-term modulation of the intrapineal pathway that transmits the cAMP signal to the AA-NAT gene.
Brain Res Mol Brain Res 2004 Apr 07
PMID:Rat pineal arylalkylamine-N-acetyltransferase: cyclic AMP inducibility of its gene depends on prior entrained photoperiod. 1504 65

The suprachiasmatic nucleus (SCN) of the mammalian hypothalamus contains a central circadian pacemaker, which adjusts circadian rhythms within the body to environmental light-dark cycles. It has been shown that dark exposure in the day causes phase shifts in circadian rhythms, but it does not induce changes in the melatonin levels in the pineal gland. In this study, we examined the effect of dark exposure on two "circadian clock" genes Period1 and Period2 mRNA levels in the rat SCN, and on Period1, Period2, and arylalkylamine N-acetyltransferase (Aa-Nat, the rate-limiting enzyme in melatonin synthesis) gene expression in the pineal gland. Period1 and Period2 mRNA levels were significantly decreased in the SCN after 0.5 and 2 h, respectively, therefore suggesting that changes in those mRNA levels may be the part of the mechanisms of dark-induced phase shifts. Period1 and Aa-Nat mRNA levels in the pineal gland were not affected by darkness, but Period2 was moderately affected. Since Period1 and Aa-Nat mRNA levels in the pineal gland did not respond to dark stimulation, we further examined whether the pineal gland itself is capable of responding to adrenergic stimulation at this time of the day. Isoproterenol significantly induced Period1 and Aa-Nat mRNA levels; however, it did not affect Period2. Although previous studies have reported that during the day the SCN "gates" the dark information reaching the pineal, our data demonstrate that dark information may reach the pineal during the daytime.
Brain Res Mol Brain Res 2004 Nov 04
PMID:Effect of dark exposure in the middle of the day on Period1, Period2, and arylalkylamine N-acetyltransferase mRNA levels in the rat suprachiasmatic nucleus and pineal gland. 1551 81

Alternative hypotheses propose the sister order of owls (Strigiformes) to be either day-active raptors (Falconiformes) or dark-active nightjars and allies (Caprimulgiformes). In an effort to identify molecular characters distinguishing between these hypotheses we examined a gene, arylalkylamine N-acetyltransferase (Aanat), potentially associated with the evolution of avian dark-activity. Partial Aanat coding sequences, and two introns, were obtained from the genomic DNA of 16 species: Strigiformes (four species), Falconiformes (four species), Caprimulgiformes (five species), with outgroups: Ciconiiformes (one species), Passeriformes (one species), and Apterygiformes (one species). Phylogenetic trees derived from aligned, evolutionarily conserved Aanat regions did not consistently recover clades corresponding to orders Strigiformes and Falconiformes but did place a caprimulgiform clade more distant from the strigiform and falconiform species than the latter two groups are to each other. This finding was supported by spectral analysis. The taxonomic distribution of seven intronic indels is consistent with the Aanat derived phylogenetic trees and supports conventional family-level groupings within both Strigiformes and Caprimulgiformes. The phylogenetic analyses also indicate that Caprimulgiformes is a polyphyletic grouping. In conclusion the data support, but do not conclusively prove, the proposal that Falconiformes is the sister order to Strigiformes and therefore, that the dark-activity characteristic of Strigiformes and Caprimulgiformes arose by convergent evolution.
Mol Phylogenet Evol 2004 Dec
PMID:Convergent evolution of strigiform and caprimulgiform dark-activity is supported by phylogenetic analysis using the arylalkylamine N-acetyltransferase (Aanat) gene. 1552 12


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