AANAT
Serotonin N-acetyltransferase (EC 2.3.1.87) (Serotonin acetylase) (Aralkylamine N-acetyltransferase) (AA-NAT) [SNAT]
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Melatonin, a neuroendocrine hormone synthesized by the pineal gland and cholangiocytes, decreases biliary hyperplasia and liver fibrosis during cholestasis-induced biliary injury via melatonin-dependent autocrine signaling through increased biliary arylalkylamine N-acetyltransferase (AANAT) expression and melatonin secretion, downregulation of miR-200b and specific circadian clock genes. Melatonin synthesis is decreased by pinealectomy (PINX) or chronic exposure to light. We evaluated the effect of PINX or prolonged light exposure on melatonin-dependent modulation of biliary damage/ductular reaction/liver fibrosis. Studies were performed in male rats with/without BDL for 1 week with 12:12 h dark/light cycles, continuous light or after 1 week of PINX. The expression of AANAT and melatonin levels in serum and cholangiocyte supernatant were increased in BDL rats, while decreased in BDL rats following PINX or continuous light exposure. BDL-induced increase in serum chemistry, ductular reaction, liver fibrosis, inflammation, angiogenesis and ROS generation were significantly enhanced by PINX or light exposure. Concomitant with enhanced liver fibrosis, we observed increased biliary senescence and enhanced clock genes and miR-200b expression in total liver and cholangiocytes. In vitro, the expression of AANAT, clock genes and miR-200b was increased in PSC human cholangiocyte cell lines (hPSCL). The proliferation and activation of HHStecs (human hepatic stellate cell lines) were increased after stimulating with BDL cholangiocyte supernatant and further enhanced when stimulated with BDL rats following PINX or continuous light exposure cholangiocyte supernatant via intracellular ROS generation. Conclusion: Melatonin plays an important role in the protection of liver against cholestasis-induced damage and ductular reaction.
MeSH Terms
- Animals
- Arylalkylamine N-Acetyltransferase
- Bile Ducts, Intrahepatic
- CLOCK Proteins
- Cell Line
- Cell Proliferation
- Cholestasis
- Epithelial Cells
- Gene Expression Regulation
- Hepatic Stellate Cells
- Humans
- Kupffer Cells
- Light
- Liver
- Liver Cirrhosis
- Male
- Melatonin
- MicroRNAs
- Pineal Gland
- Pinealectomy
- Primary Cell Culture
- Rats
- Rats, Inbred F344
- Signal Transduction
Keywords
- Arylalkylamine N-acetyltransferase
- Clock genes
- Melatonin receptors
- Reactive oxygen species
- Senescence
Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin Ð); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Biomarkers
- Cell Proliferation
- Cells, Cultured
- Female
- Humans
- Male
- Middle Aged
- Pineal Gland
- Signal Transduction
- Thymus Gland
Keywords
- Gerotarget
- aging
- melatonin
- neuroendocrine-immune
- pineal
- thymus
Melatonin affects diverse physiological functions through its receptor and plays an important role in the central nervous system. In the present study, we compared immunoreactivity patterns of arylalkylamine N-acetyltransferase (AANAT), an enzyme essential for melatonin synthesis, and melatonin receptor type 1B (MT2) in the spinal cord of young adult (2~3 years) and aged (10~12 years) beagle dogs using immunohistochemistry and Western blotting. AANAT-specific immunoreactivity was observed in the nuclei of spinal neurons, and was significantly increased in aged dog spinal neurons compared to young adult spinal neurons. MT2-specific immunoreactivity was found in the cytoplasm of spinal neurons, and was predominantly increased in the margin of the neuron cytoplasm in aged spinal cord compared to that in the young adult dogs. These increased levels of AANAT and MT2 immunoreactivity in aged spinal cord might be a feature of normal aging and associated with a feedback mechanism that compensates for decreased production of melatonin during aging.
MeSH Terms
- Age Factors
- Aging
- Animals
- Arylalkylamine N-Acetyltransferase
- Blotting, Western
- Dogs
- Fluorescent Antibody Technique
- Male
- Receptor, Melatonin, MT2
- Spinal Cord
Keywords
- aging
- beagle dog
- melatonin receptor
- spinal gray matter
- spinal neurons
20-hydroxyecdysone (20E) and the juvenile hormone (JH) have an age-specific effect on total dopamine (DA) content in Drosophila (Gruntenko and Rauschenbach 2008). Earlier we studied the mechanism of influence of 20E and JH on DA metabolism in young females (Rauschenbach et al. in J Insect Physiol 53:587-591, 2007a: Arch Insect Biochem Physiol 65:95-102, 2008a; Gruntenko et al. in Arch Insect Biochem Physiol 72:263-269, 2009). Here we investigate the effects of 20E and JH on the activities of the alkaline phosphatase (ALP), tyrosine hydroxylase (TH) and DA-dependent arylalkylamine N-acetyltransferase (AANAT) in mature females of wild type D. virilis under normal conditions and under heat stress (38°C). 20E feeding of the flies led to a substantial decrease in ALP and TH activities and to an increase in AANAT activity in mature females. JH application resulted in an increasing of ALP and TH activities, but did not influence AANAT activity in mature females. A rise in JH and 20E levels was found to change ALP and TH stress reactivities. Mechanisms of age-specific regulation of DA level by 20E and JH in Drosophila females are discussed.
MeSH Terms
- Aging
- Alkaline Phosphatase
- Animals
- Arylalkylamine N-Acetyltransferase
- Dopamine
- Drosophila
- Ecdysterone
- Female
- Juvenile Hormones
- Tyrosine 3-Monooxygenase
The role of arylalkylamine N-acetyltransferase (AANAT) in neuronal functioning has been suggested based on biochemical assays; only scarce evidence indicates neuronal expression of the mRNA encoding for this enzyme that catalyzes the conversion of serotonin into N-acetylserotonin. Using a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay with internal standards, and an in-situ RT-PCR hybridization assay we found evidence for the expression of AANAT in the rat brain. In the localization studies, the most prominent AANAT mRNA signal was found in the granule neurons of the hippocampus, the olfactory bulb, and the cerebellum, and in the gray matter of the spinal cord. Diurnal differences in AANAT mRNA content were observed in the pineal gland but not in the hippocampus; the content of AANAT mRNA was lower both in the pineal gland and the hippocampus of old (24 months) compared with young (2 months) rats. These data are consistent with the hypothesis that AANAT may play a physiological role in mammalian central nervous system neurons. Further studies are warranted into the possible functional significance of neuronal expression of AANAT mRNA.
MeSH Terms
- Aging
- Animals
- Arylamine N-Acetyltransferase
- Brain
- Cerebellum
- Circadian Rhythm
- Gene Expression
- Hippocampus
- Male
- Melatonin
- Neurons
- Olfactory Bulb
- Pineal Gland
- RNA, Messenger
- Rats
- Rats, Inbred F344
- Rats, Sprague-Dawley
- Serotonin
- Spinal Cord