Expression and dexamethasone-induced nuclear translocation of glucocorticoid and mineralocorticoid receptors in guinea pig cochlear cells.

Expression and dexamethasone-induced nuclear translocation of glucocorticoid and mineralocorticoid receptors in guinea pig cochlear cells.
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DOI:
10.1016/j.heares.2013.01.020
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发表时间:
2013-05
期刊:
影响因子:
2.8
通讯作者:
Kalinec F
Kalinec F
中科院分区:
医学1区
文献类型:
--
作者:
Kil SH;Kalinec F

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糖皮质激素(GC)是一种强大的抗炎剂,经常用于保护听觉器官免受与各种条件相关的损伤,包括噪音暴露和耳毒性药物以及细菌和病毒感染。除了糖皮质激素受体(GC-R)之外,已知天然和合成的GC以极大的亲和力结合盐皮质激素受体(MC-R)。我们使用光和激光扫描共聚焦显微镜来研究GC-R和MC-R在豚鼠耳蜗的不同细胞群中的表达,以及用合成的GC地塞米松处理后它们向不同细胞隔室的易位。我们发现这两种类型的受体的表达在感觉内毛细胞和外毛细胞的细胞质和细胞核中,以及柱,Hensen和Deiters细胞在Corti器,内,外沟细胞,螺旋神经节神经元和几种类型的螺旋韧带和螺旋利姆布斯细胞;血管纹细胞主要表达MC-R,而IV型纤维细胞仅GC-R阳性。GC-R和MC-R也定位于柱细胞和外毛细胞的质膜或质膜附近,而GC-R仅见于Hensen细胞的质膜或质膜附近。我们研究了地塞米松处理的Hensen细胞的细胞质和细胞核中受体表达的相对水平,发现它们以剂量诱导易位的方式变化。这些结果表明GC的耳保护作用可能与耳蜗不同区域中基因组和非基因组、GC-R和MC-R介导的信号通路的协同激活有关。
Glucocorticoids (GC) are powerful anti-inflammatory agents frequently used to protect the auditory organ against damage associated with a variety of conditions, including noise exposure and ototoxic drugs as well as bacterial and viral infections. In addition to glucocorticoid receptors (GC-R), natural and synthetic GC are known to bind mineralocorticoid receptors (MC-R) with great affinity. We used light and laser scanning confocal microscopy to investigate the expression of GC-R and MC-R in different cell populations of the guinea pig cochlea, and their translocation to different cell compartments after treatment with the synthetic GC dexamethasone. We found expression of both types of receptors in the cytoplasm and nucleus of sensory inner and outer hair cells as well as pillar, Hensen and Deiters cells in the organ of Corti, inner and outer sulcus cells, spiral ganglion neurons and several types of spiral ligament and spiral limbus cells; stria vascularis cells expressed mostly MC-R whereas fibrocytes type IV were positive for GC-R only. GC-R and MC-R were also localized at or near the plasma membrane of pillar cells and outer hair cells, whereas GC-R were found at or near the plasma membrane of Hensen cells only. We investigated the relative levels of receptor expression in the cytoplasm and the nucleus of Hensen cells treated with dexamethasone, and found they varied in a way suggestive of dose-induced translocation. These results suggest that the oto-protective effects of GC could be associated with the concerted activation of genomic and non-genomic, GC-R and MC-R mediated signaling pathways in different regions of the cochlea.
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