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首页> 外文期刊>Chronobiology international >Rat and Syrian hamster: Two models for the regulation of AANAT gene expression
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Rat and Syrian hamster: Two models for the regulation of AANAT gene expression

机译：大鼠和叙利亚仓鼠：两种调节AANAT基因表达的模型

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The Syrian hamster is a rodent species in which the photoperiodic change in the melatonin peak duration is pivotal for the synchronization of annual functions, like reproduction. In this species, the activity of arylalkylamine N-acetyltransferase (AANAT), the key enzyme for the rhythmic synthesis of melatonin, is precisely controlled and time-gated, suggesting regulatory mechanisms different from those in the rat or mouse. At the beginning of the night, norepinephrine (NE) elicits a rapid and sustained phosphorylation of CREB into pCREB and a transient synthesis of the immediate early gene products c-FOS and c-JUN that peak 3 h after dark onset. c-FOS synthesis requires both pCREB and the pERK1/2 pathways. Interestingly, injection of the protein synthesis inhibitor cycloheximide before, but not after, the c-FOS/c-JUN peak markedly reduces Aanat mRNA levels. This finding suggests that the c-FOS/c-JUN dimer is required for transcriptional activation of the Aanat gene. During daylight, exogenous noradrenergic stimulation cannot stimulate Aanat expression and, therefore, melatonin synthesis. The inhibitory transcription factor ICER is present in the pineal gland but with highest values when AANAT may be activated, suggesting the blockade takes place upstream of Aanat expression. Preliminary experiments indicate that the diurnal inhibition of AANAT occurs at the level of the adrenergic receptor signalling pathway, but it is not known whether this is sufficient to explain the pineal resistance to NE during the daytime. Together, these findings demonstrate that AANAT regulation in the Syrian hamster requires a complex intracellular signalling cascade, different from that described in laboratory rodents like mice and rats.
机译：叙利亚仓鼠是一种啮齿动物，其中褪黑激素峰值持续时间的光周期变化对于年度功能（如繁殖）的同步至关重要。在该物种中，可以精确地控制褪黑素有节奏地合成的关键酶芳基烷基胺N-乙酰基转移酶（AANAT）的活性，并使其具有时间限制，提示其调控机制不同于大鼠或小鼠。在黑夜开始时，去甲肾上腺素（NE）引发CREB迅速且持续的磷酸化为pCREB，并立即合成了早期的基因产物c-FOS和c-JUN的合成，该产物在黑暗发作后3小时达到高峰。 c-FOS合成需要pCREB和pERK1 / 2途径。有趣的是，在c-FOS / c-JUN峰之前而非之后注射蛋白质合成抑制剂环己酰亚胺可明显降低Aanat mRNA水平。这一发现表明，c-FOS / c-JUN二聚体是Aanat基因转录激活所必需的。在白天，外源性去甲肾上腺素能刺激不能刺激Aanat表达，因此不能刺激褪黑激素的合成。抑制性转录因子ICER存在于松果体中，但当AANAT可能被激活时具有最高的值，表明该阻断发生在Aanat表达的上游。初步实验表明，AANAT的昼夜抑制作用发生在肾上腺素受体信号传导途径的水平，但是尚不清楚这是否足以解释白天松果体对NE的抵抗力。总之，这些发现表明，叙利亚仓鼠中AANAT的调控需要复杂的细胞内信号传导级联，这不同于实验室啮齿动物（如小鼠和大鼠）中所述的级联。

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