Moravcová Simona, Filipovská Eva, Spišská Veronika, Svobodová Irena, Novotný Jiří, Bendová Zdeňka
Department of Physiology, Faculty of Science, Charles University, 128 43 Prague, Czech Republic.
Department of Sleep Medicine and Chronobiology, National Institute of Mental Health, 250 67 Klecany, Czech Republic.
Life (Basel). 2021 Oct 18;11(10):1105. doi: 10.3390/life11101105.
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 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 expression and STAT3 phosphorylation, but it did not significantly affect AANAT expression or activity. Simultaneous LPS administration and silencing enhanced the transcription and AANAT activity to a similar extent as inhibition without LPS co-administration. Furthermore, we describe the circadian rhythmicity in 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.
在啮齿动物中，松果体产生褪黑素是通过来自视交叉上核的肾上腺素能信号以及对其合成过程中的主要酶——芳基烷基胺-N-乙酰基转移酶（AANAT）的调节来控制的。在本研究中，我们发现，使用小干扰RNA（siRNA）或STAT3抑制剂WP1066和AZD1480沉默信号转导和转录激活因子3（STAT3）后，异丙肾上腺素诱导的松果体表达增加以及夜间AANAT活性增强。体内这种AANAT活性增强并未干扰光诱导的AANAT抑制作用。全身或体外给予脂多糖（LPS）可显著增加表达和STAT3磷酸化，但对AANAT表达或活性无显著影响。同时给予LPS和进行沉默与不联合给予LPS时抑制作用相比，在相似程度上增强了转录和AANAT活性。此外，我们描述了大鼠松果体中STAT3蛋白表达及其磷酸化形式的昼夜节律性。我们的数据表明，松果体中夜间较高的内源性STAT3水平会减缓或阻碍去甲肾上腺素诱导的AANAT激活过程，或影响AANAT酶的稳定性。
