ATAT1 is essential for regulation of homeostasis-retaining cellular responses in corticotrophs along hypothalamic-pituitary-adrenal axis.
ATAT1 is essential for regulation of homeostasis-retaining cellular responses in corticotrophs along hypothalamic-pituitary-adrenal axis.
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ATAT1 对于调节促肾上腺皮质激素沿下丘脑-垂体-肾上腺轴的稳态保持细胞反应至关重要。
DOI：
10.1007/s00441-017-2654-4
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发表时间：
2017
期刊：
影响因子：
3.6
通讯作者：
Hagiwara H.
中科院分区：
文献类型：
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作者：
Nakakura T;Suzuki T;Torii S;Asano-Hoshino A;Nekooki-Machida Y;Tanaka H;Arisawa K;Nishijima Y;Susa T;Okazaki T;Kiuchi Y;Hagiwara H.
促肾上腺皮质激素是一种阿黑皮质素原 (POMC) 衍生激素，由垂体前叶促肾上腺皮质激素产生和分泌，受促肾上腺皮质激素释放激素 (CRH) 和糖皮质激素调节。我们之前已经证明，肾上腺切除术会诱导促肾上腺皮质激素细胞中α-微管蛋白N-乙酰转移酶1（ATAT1）的表达和α-微管蛋白乙酰化。然而，促肾上腺皮质激素细胞中ATAT1表达的调节机制和乙酰化微管的功能尚不清楚。在这里，我们分析了 CRH 或地塞米松对小鼠促肾上腺皮质激素 AtT20 细胞系中 Atat1 表达的影响。 AtT20细胞中Atat1的表达被CRH增加而被地塞米松减少。我们分别通过实时聚合酶链反应和蛋白质印迹分析检测了Atat1敲低对POMC相关基因表达和地塞米松诱导的糖皮质激素受体（GR）核转位的影响。 Atat1敲低导致ACTH生成基因的表达显着增加，并减少地塞米松诱导的GR核转位，同时减少 Atat1 过表达导致 α-微管蛋白乙酰化和地塞米松诱导的 GR 核转位显着增加。这些结果表明乙酰化微管起到将 GR 运输到细胞核中的铁路线的作用。我们得出的结论是，ATAT1 通过细胞内反馈回路微调促肾上腺皮质激素细胞对激素刺激的细胞反应。
The production and secretion of adrenocorticotropin, a proopiomelanocortin (POMC)-derived hormone, by corticotrophs in the anterior pituitary, is regulated by corticotrophin-releasing hormone (CRH) and glucocorticoids. We have previously demonstrated that adrenalectomy induces α-tubulinN-acetyltransferase 1 (ATAT1) expression and α-tubulin acetylation in corticotrophs. However, the regulatory mechanism of ATAT1 expression and the function of acetylated microtubules in corticotrophs are unclear. Here, we analyze the effect of CRH or dexamethasone onAtat1expression in the mouse corticotroph AtT20 cell line. The expression ofAtat1was increased by CRH and decreased by dexamethasone in AtT20 cells. We examined the effect ofAtat1knockdown on the expression of POMC-associated genes and the dexamethasone-induced nuclear translocation of glucocorticoid receptor (GR) by real-time polymerase chain reaction and Western blot analysis, respectively.Atat1knockdown resulted in a significant increase in the expression of ACTH-producing genes and decreased the dexamethasone-induced nuclear translocation of GR accompanied with a reduction in α-tubulin acetylation.Atat1overexpression resulted in a significant increase in α-tubulin acetylation and the dexamethasone-induced nuclear translocation of GR. These results suggest that the acetylated microtubules function as the rail-line for the transportation of GR into the nucleus. We conclude that ATAT1 finely tunes the cellular responses of corticotrophs to hormonal stimulation through an intracellular feedback circuit.