Modulation of glucocorticoid receptor nuclear translocation in neurons by immunophilins FKBP51 and FKBP52: implications for major depressive disorder.
Modulation of glucocorticoid receptor nuclear translocation in neurons by immunophilins FKBP51 and FKBP52: implications for major depressive disorder.
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DOI：
10.1016/j.brainres.2009.06.036
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发表时间：
2009-08-25
期刊：
影响因子：
2.9
通讯作者：
Achim CL
中科院分区：
文献类型：
--
作者：
Tatro ET;Everall IP;Kaul M;Achim CL
与下丘脑-垂体-肾上腺（HPA）轴功能障碍相关的情绪障碍是常见的精神疾病。糖皮质激素受体 (GR) 是一种类固醇激活的核受体，在与皮质醇结合后，易位到细胞核，在细胞核中靶向与神经元代谢和可塑性相关的基因。在患有重度抑郁症（MDD）的患者中，高皮质醇血症是一种常见现象。在当前的研究中，我们研究了与 FK506 结合蛋白 (FKBP) -52 和 -51 对神经元细胞培养物中皮质醇暴露的反应相关的分子事件及其对 GR 易位的影响。我们注意到 FK506 改变了 GR 的核定位并抑制了 GR 响应基因的表达。此外，编码亲免素FKBP52的FKBP4基因的si-RNA敲低可抑制皮质醇激活的GR核易位，而编码亲免素FKBP51的FKBP5基因敲低与基线GR核定位增加相关。我们认为亲免素是皮质醇-HPA 轴对压力和相关慢性脑部疾病反应的调节剂。
Mood disorders associated with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis are common psychiatric conditions. The glucocorticoid receptor (GR) is a steroid-activated nuclear receptor that, upon binding to cortisol, translocates to the nucleus where it targets genes related to neuronal metabolism and plasticity. In patients suffering from major depressive disorder (MDD), hypercortisolemia is a common finding. In the current study we investigated the molecular events associated with the FK506 binding proteins (FKBP) -52 and -51 response to cortisol exposure in neuronal cell cultures and their effect on GR translocation. We noted that FK506 altered nuclear localization of the GR and inhibited expression of GR-responsive genes. Furthermore, si-RNA knockdown of FKBP4 gene, coding for the immunophilin FKBP52, inhibited cortisol-activated GR nuclear translocation, while knockdown of FKBP5, coding for immunophilin FKBP51, was associated with increased baseline GR nuclear localization. We propose that immunophilins are modulators of the cortisol-HPA axis response to stress and related chronic brain disorders.
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影响因子：
120.7
作者：
Binder, Elisabeth B.;Bradley, Rebekah G.;Ressler, Kerry J.
通讯作者：
Ressler, Kerry J.
影响因子：
3.8
作者：
Hubler, TR;Scammell, JG
通讯作者：
Scammell, JG
影响因子：
2.9
作者：
Galigniana, MD;Harrell, JM;Pratt, WB
通讯作者：
Pratt, WB
DOI：
10.1073/pnas.0400116101
发表时间：
2004-03-02
影响因子：
11.1
作者：
Elbi, C;Walker, DA;DeFranco, DB
通讯作者：
DeFranco, DB
DOI：
10.1073/pnas.79.6.2036
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
CHROUSOS, GP;RENQUIST, D;LIPSETT, MB
通讯作者：
LIPSETT, MB