scholarly journals Melatonin Synthesis Enzymes in Macaca mulatta: Focus on Arylalkylamine N-Acetyltransferase (EC 2.3.1.87)

2002 ◽  
Vol 87 (10) ◽  
pp. 4699-4706 ◽  
Author(s):  
Steven L. Coon ◽  
Elena del Olmo ◽  
W. Scott Young ◽  
David C. Klein

Arylalkylamine N-acetyltransferase (AANAT; serotonin N-acetyltransferase, EC 2.3.1.87) plays a unique transduction role in vertebrate physiology as the key interface between melatonin production and regulatory mechanisms. Circulating melatonin is elevated at night in all vertebrates, because AANAT activity increases in the pineal gland in response to signals from the circadian clock. Circadian regulation of melatonin synthesis is implicated in a variety of human problems, including jet lag, shift work, insomnia, and abnormal activity rhythms in blind persons. In this report AANAT was studied in the rhesus macaque to better understand human melatonin regulation. AANAT mRNA is abundant in the pineal gland and retina, but not elsewhere; AANAT mRNA is uniformly distributed in the pineal gland, but is limited primarily to the photoreceptor outer segments in the retina. Day and night levels of pineal and retinal AANAT mRNA are similar. In contrast, AANAT activity and protein increase more than 4-fold at night in both tissues. The activity of hydroxyindole-O-methyltransferase, the last enzyme in melatonin synthesis, is tonically high in the pineal gland, but is nearly undetectable in the retina; hydroxyindole O-methyltransferase mRNA levels exhibited a similar pattern. This supports the view that the source of circulating melatonin in primates is the pineal gland. The discovery in this study that rhesus pineal AANAT mRNA is high at all times is of special importance because it shows that posttranscriptional control of this enzyme plays a dominant role in regulating melatonin synthesis.

2021 ◽  
Vol 4 (1) ◽  
pp. 99-114
Author(s):  
Janaína B Garcia ◽  
Fernanda G Do Amaral ◽  
Daniela C Buonfiglio ◽  
Rafaela FA Vendrame ◽  
Patrícia L Alves ◽  
...  

The pineal gland synthesizes melatonin exclusively at night, which gives melatonin the characteristic of a temporal synchronizer of the physiological systems. Melatonin is a regulator of insulin activities centrally and also peripherally and its synthesis is reduced in diabetes.  Since monosodium glutamate (MSG) is often used to induce the type 2 diabetic and metabolic syndrome in animal models, the purpose of this work is to evaluate the potential effects of MSG given to neonates on the pineal melatonin synthesis in different aged male and female rats. Wistar rats were subcutaneously injected with MSG (4mg/g/day) or saline solution (0.9%) from the second to eighth post-natal day. The circadian profiles both melatonin levels and AANAT activity were monitored at different ages. Body weight, naso-anal length, adipose tissues weight, GTT, ITT and serum insulin levels were also evaluated. Typical obesity with the neonatal MSG treatment was observed, indicated by a great increase in adipose depots without a concurrent increase in body weight. MSG treatment did not cause hyperglycemia or glucose intolerance, but induced insulin resistance. An increase of melatonin synthesis at ZT 15 with phase advance was observed in in some animals. The AANAT activity was positively parallel to the melatonin circadian profile. It seems that MSG causes hypothalamic obesity which may increase AANAT activity and melatonin production in pineal gland. These effects were not temporally correlated with insulin resistance and hyperinsulinemia indicating the hypothalamic lesions, particularly in arcuate nucleus induced by MSG in early age, as the principal cause of the increase in melatonin production.


2000 ◽  
Vol 351 (3) ◽  
pp. 709-716 ◽  
Author(s):  
Beibei LI ◽  
Hongjian ZHANG ◽  
Mohammed AKBAR ◽  
Hee-Yong KIM

In this paper evidence that supports a new role for melatonin as a negative endogenous regulator of cytosolic phospholipase A2 (cPLA2) is presented. When rat pineal glands were incubated in culture, time-dependent release of arachidonic acid (AA) was observed, which was significantly inhibited by a known 85-kDa cPLA2 inhibitor, methyl arachidonyl fluorophosphonate. Co-incubation with melatonin inhibited the AA release in a concentration-dependent manner, and this decrease was accompanied by a reduction of cPLA2 protein and mRNA expression. Melatonin-receptor agonists, 2-iodo-N-butanoyl-5-methoxytryptamine and 5-methoxycarbonylamino-N-acetyltryptamine, also decreased AA release and cPLA2 protein and mRNA levels, while pre-incubation with the melatonin receptor antagonists luzindole and 2-phenylmelatonin abolished the melatonin effect. In vivo, as melatonin production reflected a typical diurnal variation, endogenous non-esterified AA and cPLA2 mRNA levels in the rat pineal gland showed an off-phase diurnal pattern in relation to melatonin levels. Intravenous administration of isoproterenol, which has been shown to elevate melatonin production, also decreased the levels of non-esterified AA and cPLA2 mRNA significantly. Direct administration of melatonin to rats by intravenous injection decreased the levels of non-esterified AA, cPLA2 protein and mRNA in rat pineal glands. In conclusion, melatonin endogenously down-regulates cPLA2 expression, presumably through melatonin-receptor-mediated processes.


2019 ◽  
Vol 25 ◽  
pp. 3605-3616 ◽  
Author(s):  
Fang Zhao ◽  
Chen Ma ◽  
Guodong Zhao ◽  
Gen Wang ◽  
Xiaobin Li ◽  
...  

2015 ◽  
Vol 14 (11) ◽  
pp. 1991-1997 ◽  
Author(s):  
Masaki Torii ◽  
Daisuke Kojima ◽  
Akiyuki Nishimura ◽  
Hiroshi Itoh ◽  
Yoshitaka Fukada

A comparative study of non-visual opsins expressed in the chicken pineal gland showed that melanopsins and pinopsins photoactivate mutually different G protein pathways, which regulate melatonin production.


2019 ◽  
Vol 66 (3) ◽  
pp. e12552 ◽  
Author(s):  
Jingtao Qiu ◽  
Jinglin Zhang ◽  
Yewen Zhou ◽  
Xin Li ◽  
Hongjiao Li ◽  
...  

Endocrinology ◽  
2006 ◽  
Vol 147 (11) ◽  
pp. 5052-5060 ◽  
Author(s):  
Natalia Sinitskaya ◽  
Anthony Salingre ◽  
Paul Klosen ◽  
Florent G. Revel ◽  
Paul Pévet ◽  
...  

Species differences have been reported for the nighttime regulation of arylalkylamine N-acetyltransferase (AA-NAT), the melatonin rhythm-generating enzyme. In particular, de novo synthesis of stimulatory transcription factors is required for Aa-nat transcription in the Syrian hamster but not in the rat pineal gland. The present work investigated the contribution of phosphorylated cAMP-responsive element-binding protein, c-FOS, c-JUN, and JUN-B in the regulation of Aa-nat transcription in Syrian hamsters compared with rats. The nighttime pattern of cAMP-responsive element-binding protein phosphorylation and regulation by norepinephrine observed in the Syrian hamster was similar to those reported in the rat. On the contrary, strong divergences in c-FOS, c-JUN, and JUN-B expression were observed between both species. In Syrian hamster, predominant expression of c-FOS and c-JUN was observed at the beginning of night, whereas a predominant expression of c-JUN and JUN-B was observed in the late night in rat. The early peak of c-FOS and c-JUN, known to form a stimulatory transcription dimer, suggests that they are involved in the nighttime stimulation of Aa-nat transcription. Indeed, early-night administration of a protein synthesis inhibitor (cycloheximide) markedly decreased AA-NAT mRNA levels in Syrian hamster. In the rat, high levels of JUN-B and c-JUN, constituting an inhibitory transcription dimer, are probably involved in the late-night inhibition of Aa-nat transcription. Early-night administration of cycloheximide actually increased AA-NAT mRNA levels toward the late night. Therefore, composition and timing of the pineal activator protein-1 complexes differ between rat and Syrian hamster and may be an activator (Syrian hamster) or an inhibitor (rat) of Aa-nat transcription.


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