Disease relevance of Aanat

• We further demonstrated that skin, melanomas, spleen, pituitary, and eye but not heart expressed arylalkylamine N-acetyltransferase mRNA [1].
• After decapitation the pineal gland was rapidly dissected out, followed by measurements of one of the melatonin-forming enzymes, serotonin N-acetyltransferase (NAT) activity [2].
• Biochemical correlates of neuroendocrine/gonadal function and nocturnal levels of serotonin N-acetyltransferase (NAT) activity were determined in partially nephrectomized (PNx), male, Long Evans rats following a 5-week period of chronic renal insufficiency (CRI) [3].

Psychiatry related information on Aanat

• We found that periodic maternal deprivation (PMD) was able to cause a phase shift of serotonin N-acetyltransferase (NAT) in neonatal blinded rat pups [4].

High impact information on Aanat

• Diurnal variation in mRNA encoding serotonin N-acetyltransferase in pineal gland [5].
• Melatonin production: proteasomal proteolysis in serotonin N-acetyltransferase regulation [6].
• Vasoactive intestinal polypeptide stimulated serotonin N-acetyltransferase activity in rat pineal glands in organ culture by a postsynaptic action that was independent of the beta-receptor [7].
• Environmental lighting regulates numerous circadian rhythms, including the cycle in pineal serotonin N-acetyltransferase activity [8].
• Pineal serotonin N-acetyltransferase activity: abrupt decrease in adenosine 3',5'-monophosphate may be signal for "turnoff" [9].

Biological context of Aanat

• More important, our data demonstrate that dopamine rhythmicity is not necessary for generating the circadian rhythm of Aanat mRNA in the photoreceptors [10].
• Rhythmic serotonin N-acetyltransferase mRNA degradation is essential for the maintenance of its circadian oscillation [11].
• While cAMP-induced CREB phosphorylation appears to be a prerequisite for AA-NAT and ICER gene expression, it is not known whether CREB phosphorylation accounts for the full cAMP response of the two genes [12].
• The mechanisms responsible for downregulation of Aanat transcription are less clear [13].
• This finding suggests that the c-FOS/c-JUN dimer is required for transcriptional activation of the Aanat gene [14].

Anatomical context of Aanat

• In this study, we identify three proteins from pineal glands that associate with cis-acting elements within species-specific AANAT 3' untranslated regions to mediate mRNA degradation [11].
• The circadian rhythm in the levels of Aanat mRNA in the rat retina persists after the suprachiasmatic nucleus (SCN) of the hypothalamus has been lesioned, indicative of its relative independence from the master clock in the brain [15].
• When COS-7 cells transfected with AANAT cDNA were treated with phorbol 12-myristate 13-acetate (PMA), both the activity and protein level of AANAT were increased [16].
• After removal of superior cervical ganglia, the daily rhythm in arylalkylamine N-acetyltransferase mRNA was abolished in both the superficial and deep pineal indicating that the rhythm is driven by sympathetic input in the entire pineal complex [17].
• In addition, the day-time pineal arylalkylamine N-acetyltransferase mRNA expression in ganglionectomized rats persisted after adrenal gland removal but was reduced by 50% after propranolol injection [17].

Associations of Aanat with chemical compounds

• To date, our understanding of the oscillatory mechanism of melatonin has been limited to autoregulatory transcriptional and posttranslational regulations of AANAT mRNA [11].
• In comparison, SB202474, the inactive analog, had no effect on NE or (Bu)(2)cAMP-stimulated AA-NAT activity or protein level [18].
• Cotreatment with SB202190, a selective p38(MAPK) inhibitor, although having no effect on AA-NAT activity or protein level 3 h after NE treatment, caused a sustained increase in AA-NAT activity and protein level after 6 h of NE treatment [18].
• Similar results were obtained when AA-NAT was induced by (Bu)(2)cAMP or when SB203580 was used to inhibit p38(MAPK) [18].
• Serine/threonine phosphatase inhibitors decrease adrenergic arylalkylamine n-acetyltransferase induction in the rat pineal gland [19].
• Consistent with the enhancing role of hnRNP Q in AANAT IRES activities, knockdown of the hnRNP Q level elicited a dramatic decrease of peak amplitude in the AANAT protein profile parallel to reduced melatonin production in pinealocytes [20].

Regulatory relationships of Aanat

• Inhibition of p38 mitogen-activated protein kinase enhances adrenergic-stimulated arylalkylamine N-acetyltransferase activity in rat pinealocytes [18].
• Accumulation of rat pineal serotonin N-acetyltransferase mRNA induced by pituitary adenylate cyclase activating polypeptide and vasoactive intestinal peptide in vitro [21].
• GRF and secretin were less potent than VIP in inducing AA-NAT gene expression and cAMP efflux [21].
• Isoproterenol did not affect the TRH content of pineal glands in vitro; nor did TRH or T3 affect basal or stimulated activities of serotonin N-acetyltransferase, the presumed controlling enzyme in melatonin production [22].

Other interactions of Aanat

• The AA-NAT mRNA varied similar to the Per2 mRNA changes [23].
• Therefore, the regulatory role of pineal serine/threonine phosphatases in adrenergically stimulated AA-NAT expression probably does not depend on ICER or Fra-2 [19].
• Lack of effect of oxytocin on the numbers of "synaptic" ribbons, cyclic guanosine monophosphate and serotonin N-acetyltransferase activity in organ-cultured pineals of three strains of rats [24].
• The diurnal time course of pineal melatonin synthesis was analyzed simultaneously in the arginine vasopressin (AVP)-deficient Brattleboro rat (BB), the Long-Evans (LE) and Sprague-Dawley (SD) rat by means of radioenzymatic determination of the rate-limiting enzyme serotonin-N-acetyltransferase (NAT) and the melatonin content over a period of 24 h [25].
• The inhibitory effect of proteasomal inhibition on adrenergic-induced Aanat transcription appears specific for Aanat because it has no effect on the adrenergic induction of mitogen-activated protein kinase phosphatase-1 (mkp-1) [26].

Analytical, diagnostic and therapeutic context of Aanat

• Reverse transcriptase-polymerase chain reaction (RT-PCR) data indicate that okadaic acid exerts its effect on cAMP-dependent AA-NAT induction by downregulating the amount of AA-NAT transcript [19].
• To identify which amino acids were phosphorylated by PKC, several conserved Thr and Ser residues in AANAT were targeted for site-directed mutagenesis [16].
• To find out whether there is non-noradrenergic regulation of in vivo pineal metabolism, the mRNA encoding the enzyme arylalkylamine N-acetyltransferase was studied using the highly sensitive technique of in situ hybridization [17].
• They were sacrificed 18 hours after the last injection, and their hippocampi were processed for a quantitative reverse-transcription/polymerase-chain reaction assay of AA-NAT and cyclophilin (cyc) messenger (m)RNAs [27].
• Rat pineal serotonin N-acetyltransferase (EC 2.3.1.87) activity is isolated in two molecular forms (Mr approximately equal to 10,000 and 95,000) by high performance size exclusion liquid chromatography in the presence of ammonium acetate (0.1 M, pH 6.5) [28].

References