The Circadian Rhythms of STAT3 in the Rat Pineal Gland and Its Involvement in Arylalkylamine-N-Acetyltransferase Regulation.

Simona Moravcová,Jiří Novotný,Veronika Spišská,Eva Filipovská,Irena Svobodová,Zdeňka Bendová

doi:10.3390/life11101105

Simona Moravcová, Jiří Novotný + Show 4 more

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https://doi.org/10.3390/life11101105

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Journal: Life	Publication Date: Oct 18, 2021
Citations: 4	License type: CC BY 4.0

Affiliation: Charles University, National Institute of Mental Health

Abstract

In rodents, the melatonin production by the pineal gland is controlled through adrenergic signaling from the suprachiasmatic nuclei and regulation of the principal enzyme in its synthesis, arylalkylamine-N-acetyltransferase (AANAT). In the present study, we identified increased isoprenaline-induced aa-nat expression and nocturnal AANAT activity in the pineal glands in response to the silencing of the signal transducer and activator of transcription 3 (STAT3) with siRNA or STAT3 inhibitors WP1066 and AZD1480. This AANAT activity enhancement in vivo did not interfere with light-induced AANAT suppression. Systemic or in vitro lipopolysaccharide (LPS) administration markedly increased Stat3 expression and STAT3 phosphorylation, but it did not significantly affect AANAT expression or activity. Simultaneous LPS administration and Stat3 silencing enhanced the aa-nat transcription and AANAT activity to a similar extent as Stat3 inhibition without LPS co-administration. Furthermore, we describe the circadian rhythmicity in Stat3 expression and the phosphorylated form of STAT3 protein in the rat pineal gland. Our data suggest that the higher nocturnal endogenous level of STAT3 in the pineal gland decelerates or hampers the process of NA-induced AANAT activation or affects the AANAT enzyme stability.

Highlights

The pineal gland is a neuroendocrine organ whose primary function is the nocturnal production of melatonin, a neurohormone with widespread biological impact
The significant rhythmicity was confirmed for the level of the pSTAT3(y)
0.5 mm search of the role of signal transducer and activator of transcription 3 (STAT3) in pineal physiology, we focused on its effect—the on area demonstrated in representative autoradiographs themelatonin right

Summary

Introduction

The pineal gland is a neuroendocrine organ whose primary function is the nocturnal production of melatonin, a neurohormone with widespread biological impact. The SCN causes an increase in activity of the postganglionic sympathetic fibers and release of noradrenaline (NA) into pineal parenchyma, where it binds to β-AR receptors on pinealocytes. Activation of the intracellular cAMP signaling pathway that leads to phosphorylation of the cAMP response element-binding protein (CREB) and to initiation of aa-nat transcription [3,4]. This results in a >100-fold increase in aa-nat mRNA level after the onset of darkness, followed by a similar magnitude of increases in AANAT protein level and enzyme activity [5]

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