Nur77的诱导和激活是白细胞介素-1刺激AtT-20促肾上腺皮质激素细胞中阿黑皮素原所必需的。

Nur77 induction and activation are necessary for interleukin-1 stimulation of proopiomelanocortin in AtT-20 corticotrophs.

作者信息

Kovalovsky Damian, Paez Pereda Marcelo, Labeur Marta, Renner Ulrich, Holsboer Florian, Stalla Günter K, Arzt Eduardo

机构信息

Departamento de Fisiología y Biología Molecular, FCEN, Universidad de Buenos Aires and CONICET, Buenos Aires, Argentina.

出版信息

FEBS Lett. 2004 Apr 9;563(1-3):229-33. doi: 10.1016/S0014-5793(04)00303-5.

DOI:10.1016/S0014-5793(04)00303-5

Abstract

Nur77 and Nurr1 are critical for proopiomelanocortin (POMC) regulation by corticotrophin releasing hormone (CRH) in corticotrophs. We analyze the regulation and activity of Nur77 by interleukin (IL)-1 in AtT-20 corticotrophic cells and its consequences on POMC regulation. IL-1 induces Nur77 and not Nurr1 mRNA and shows an increased transcriptional activity on the NurRE site, an effect dependent of p38 protein kinase activity. A NurRE mutation abrogates POMC promoter transcription by IL-1 and a stable AtT-20 clone overexpressing a dominant negative form of Nur77 is unresponsive to IL-1-dependent POMC induction and adrenocorticotrophin (ACTH) secretion. These results demonstrate that Nur77 is essential for POMC stimulation by IL-1 in corticotrophs.

摘要

Nur77和Nurr1对于促肾上腺皮质激素释放激素（CRH）在促肾上腺皮质激素细胞中对阿黑皮素原（POMC）的调节至关重要。我们分析了白细胞介素（IL）-1对AtT-20促肾上腺皮质激素细胞中Nur77的调节和活性及其对POMC调节的影响。IL-1诱导Nur77而非Nurr1的mRNA表达，并在NurRE位点显示出增强的转录活性，这一效应依赖于p38蛋白激酶活性。NurRE突变消除了IL-1对POMC启动子的转录作用，并且过表达Nur77显性负性形式的稳定AtT-20克隆对IL-1依赖性POMC诱导和促肾上腺皮质激素（ACTH）分泌无反应。这些结果表明，Nur77对于IL-1在促肾上腺皮质激素细胞中刺激POMC至关重要。