scholarly journals Melatonin: an endogenous negative modulator of 12-lipoxygenation in the rat pineal gland

1999 ◽  
Vol 344 (2) ◽  
pp. 487-493 ◽  
Author(s):  
Hongjian ZHANG ◽  
Mohammed AKBAR ◽  
Hee-Yong KIM
Keyword(s):  
Pineal Gland ◽  
Negative Ion ◽  
Dark Phase ◽  
Exogenous Melatonin ◽  
Protein Levels ◽  
Endogenous Modulator ◽  
12 Lipoxygenase ◽  
Rat Pineal Gland ◽  
Melatonin Production

Major biochemical activities of the pineal gland include melatonin biosynthesis and 12-lipoxygenation. In this paper, we provide evidence in vivo that melatonin regulates 12-lipoxygenation via 12-lipoxygenase (LOX) expression. The relationship between these two biochemical activities was established by monitoring levels of endogenous melatonin and a 12-LOX metabolite, 12-hydroxyeicosatetraenoic acid (12-HETE), in the rat pineal gland both during the light-dark cycle and after isoproterenol injection using GC/MS with negative ion chemical ionization. As pineal melatonin production reflected a typical diurnal variation, 12-HETE levels showed an off-phase diurnal pattern in relation to melatonin levels. Intravenous administration of isoproterenol, which has been shown to elevate melatonin production, decreased the 12-HETE level significantly. The reduction of 12-HETE levels during the dark phase and after isoproterenol injection was accompanied by decreases in 12-LOX mRNA and protein levels. Direct administration of melatonin to rats by intravenous injection decreased pineal 12-LOX protein levels significantly, indicating that melatonin plays a role in down-regulating 12-LOX expression. When pineal glands were incubated with exogenous melatonin in culture, time-dependent reduction of 12-LOX protein levels was observed. The melatonin-induced reduction in 12-LOX protein was abolished in the presence of the melatonin receptor antagonist luzindole, establishing further the role of melatonin in this process. Incubation of pineal homogenates with exogenous melatonin partially inhibited 12-LOX activity. Taken together, an inverse relationship exists in the endogenous production of 12-HETE, 12-LOX mRNA and protein with respect to melatonin production in the rat pineal gland. Melatonin decreased both 12-LOX mRNA and protein levels in addition to 12-LOX enzyme activity, indicating that melatonin is an endogenous modulator of pineal 12-lipoxygenation.

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

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1105
Author(s):  
Simona Moravcová ◽  
Eva Filipovská ◽  
Veronika Spišská ◽  
Irena Svobodová ◽  
Jiří Novotný ◽  
...  
Keyword(s):  
Pineal Gland ◽  
Enzyme Stability ◽  
Suprachiasmatic Nuclei ◽  
Stat3 Phosphorylation ◽  
Activity Enhancement ◽  
Transcription 3 ◽  
Rat Pineal Gland ◽  
Melatonin Production

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.

scholarly journals Proteomic analysis of day–night variations in protein levels in the rat pineal gland

PROTEOMICS ◽  
2007 ◽  
Vol 7 (12) ◽  
pp. 2009-2018 ◽  
Author(s):  
Morten Møller ◽  
Thomas Sparre ◽  
Nicolai Bache ◽  
Peter Roepstorff ◽  
Henrik Vorum
Keyword(s):  
Pineal Gland ◽  
Proteomic Analysis ◽  
Protein Levels ◽  
Rat Pineal Gland

Norepinephrine Release in the Rat Pineal Gland: The Input from the Biological Clock Measured by In Vivo Microdialysis

2002 ◽  
Vol 66 (2) ◽  
pp. 748-755 ◽  
Author(s):  
W. J. Drijfhout ◽  
A. G. Van Der Linde ◽  
S. E. Kooi ◽  
C. J. Grol ◽  
B. H. C. Westerink
Keyword(s):  
Pineal Gland ◽  
Biological Clock ◽  
In Vivo Microdialysis ◽  
Norepinephrine Release ◽  
Rat Pineal Gland

scholarly journals Effects of Diazepam Administration on Melatonin Synthesis in the Rat Pineal Gland in Vivo.

1991 ◽  
Vol 39 (10) ◽  
pp. 2674-2676 ◽  
Author(s):  
Hiroyuki WAKABAYASHI ◽  
Kenji SHIMADA ◽  
Tetsuo SATOH
Keyword(s):  
Pineal Gland ◽  
Melatonin Synthesis ◽  
Rat Pineal Gland

scholarly journals Leptin Modulates Norepinephrine-Mediated Melatonin Synthesis in Cultured Rat Pineal Gland

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Rodrigo Antonio Peliciari-Garcia ◽  
Jéssica Andrade-Silva ◽  
José Cipolla-Neto ◽  
Carla Roberta de Oliveira Carvalho
Keyword(s):  
Pineal Gland ◽  
Leptin Receptor ◽  
Pineal Melatonin ◽  
Melatonin Synthesis ◽  
Inducible Camp Early Repressor ◽  
Per Se ◽  
Isoform B ◽  
Rat Pineal Gland

Pineal melatonin synthesis can be modulated by many peptides, including insulin. Because melatonin appears to alter leptin synthesis, in this work we aimed to investigate whether leptin would have a role on norepinephrine- (NE-)mediated melatonin synthesis in cultured rat pineal glands. According to our data, cultured rat pineal glands express leptin receptor isoform b (Ob-Rb). Pineal expression ofOb-RbmRNA was also observedin vivo. Administration of leptin (1 nM) associated with NE (1 µM) reduced melatonin content as well as arylalkylamine-N-acetyl transferase (AANAT) activity and expression in cultured pineal glands. Leptin treatment per se induced the expression of STAT3 in cultured pineal glands, but STAT3 does not participate in the leptin modulation of NE-mediated pineal melatonin synthesis. In addition, the expression of inducible cAMP early repressor (ICER) was further induced by leptin challenge when associated with NE. In conclusion, leptin inhibition of pineal melatonin synthesis appears to be mediated by a reduction in AANAT activity and expression as well as by increased expression ofIcermRNA. Peptidergic signaling within the pineal gland appears to be one of the most important signals which modulates melatonin synthesis; leptin, as a member of this system, is not an exception.

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