Retinoic acid increases glucocorticoid receptor phosphorylation via cyclin-dependent kinase 5
Retinoic acid increases glucocorticoid receptor phosphorylation via cyclin-dependent kinase 5
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DOI：
10.1016/j.mcn.2017.05.001
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发表时间：
2017-07-01
影响因子：
3.5
通讯作者：
Corcuff, Jean-Benoit
中科院分区：
文献类型：
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作者：
Brossaud, Julie;Roumes, Helene;Corcuff, Jean-Benoit
糖皮质激素受体（GR）的功能是由磷酸化调节。由于维甲酸（RA）可激活胞浆中的GR磷酸化激酶，因此我们研究了长期糖皮质激素（GR）抑制下RA是否能调节神经细胞GR的磷酸化。地塞米松（Dex）联合RA处理4 d后，发现RA可增强Dex诱导的海马HT 22细胞核GR丝氨酸220（（pSer 220）GR）磷酸化。这种处理增加了p35/p25蛋白质的细胞质比率，p35/p25蛋白质是主要的CDK 5辅因子。Roscovitine，一种CDK 5抑制剂，或一种针对CDK 5的siRNA，阻止了RA增强GR磷酸化的作用，并抵消了RA对GR敏感的靶蛋白如BDNF或组织转氨酶的作用，这些数据有助于理解RA和糖皮质激素信号通路之间的相互作用，这两种通路对成人大脑都有很强的影响。(C)2017爱思唯尔公司All rights reserved.
Glucocorticoid receptor (GR) function is modulated by phosphorylation. As retinoic acid (RA) can activate some cytoplasmic kinases able to phosphorylate GR, we investigated whether RA could modulate GR phosphorylation in neuronal cells in a context of long-term glucocorticoid exposure.A 4-day treatment of dexamethasone (Dex) plus RA, showed that RA potentiated the (Dex)-induced phosphorylation on GR Serine 220 ((pSer220)GR) in the nucleus of a hippocampal HT22 cell line. This treatment increased the cytoplasmic ratio of p35/p25 proteins, which are major CDK5 cofactors. Roscovitine, a pharmacological CDK5 inhibitor, or a siRNA against CDK5 prevented RA potentiation of GR phosphorylation.Furthermore, roscovitine counter-acted the effect of RA on GR sensitive target proteins such as BDNF or tissue-transglutaminase.These data help understanding the interaction between RA- and glucocorticoid-signalling pathways, both of which have strong influences on the adult brain. (C) 2017 Elsevier Inc. All rights reserved.