Expression of neuropeptide Y and agouti-related protein mRNA stimulated by glucocorticoids is attenuated via NF-κB p65 under ER stress in mouse hypothalamic cultures
Expression of neuropeptide Y and agouti-related protein mRNA stimulated by glucocorticoids is attenuated via NF-κB p65 under ER stress in mouse hypothalamic cultures
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DOI：
10.1016/j.neulet.2013.08.040
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发表时间：
2013-10-11
影响因子：
2.5
通讯作者：
Oiso, Yutaka
中科院分区：
文献类型：
--
作者：
Hagimoto, Shigeru;Arima, Hiroshi;Oiso, Yutaka
多项证据表明下丘脑的糖皮质激素信号在能量平衡中起着重要作用，最近的研究表明下丘脑内质网应激可能影响能量平衡相关的信号。在本研究中，我们研究了内质网应激对小鼠下丘脑器官型培养中糖皮质激素信号的调节。地塞米松（dexamethasone， DEX）培养下丘脑外植体，可显著提高神经肽Y （NPY）和针刺相关蛋白（AgRP） mRNA的表达水平，而内质网应激源thapsigargin （TG）处理下丘脑外植体，可显著降低地塞米松诱导的NPY和AgRP mRNA的表达。TG处理增加了下丘脑培养物中磷酸化NF-kappa B p65的水平，NF-kappa B p65的抑制剂逆转了TG对NPY和AgRP表达的抑制作用。因此，我们的数据表明，在内质网应激下，糖皮质激素刺激的NPY和AgRP表达通过NF-kappa B p65途径减弱，并提示内质网应激与下丘脑炎症之间存在串扰。2013爱思唯尔爱尔兰有限公司版权所有。
There are several lines of evidence suggesting that glucocorticoid signaling in the hypothalamus plays an important role in energy balance, and recent studies suggest that endoplasmic reticulum (ER) stress in the hypothalamus could affect signaling related to energy balance. In the present study, we examined the regulation of glucocorticoid signaling under ER stress in mouse hypothalamic organotypic cultures. Incubation of the hypothalamic explants with dexamethasone (DEX) significantly increased expression levels of neuropeptide Y (NPY) and agouti-related protein (AgRP) mRNA, and treatment with thapsigargin (TG), an ER stressor, significantly attenuated DEX-induced NPY and AgRP mRNA expression. TG treatment increased the levels of phospho-NF-kappa B p65 in hypothalamic cultures, and inhibitors of NF-kappa B p65 reversed the inhibitory effects of TG on NPY and AgRP expression. Our data thus demonstrated that glucocorticoid-stimulated NPY and AgRP expression was attenuated via NF-kappa B p65 pathways under ER stress, and suggest crosstalk between ER stress and inflammation in the hypothalamus. (C) 2013 Elsevier Ireland Ltd. All rights reserved.