Acoustic overstimulation modifies Mcl-1 expression in cochlear sensory epithelial cells.
Acoustic overstimulation modifies Mcl-1 expression in cochlear sensory epithelial cells.
复制标题
DOI：
10.1002/jnr.22333
复制
发表时间：
2010-06
影响因子：
4.2
通讯作者：
Cai, Qunfeng
中科院分区：
文献类型：
--
作者：
Hu, Bo Hua;Cai, Qunfeng
细胞-细胞连接以及细胞与细胞外基质之间的连接对于维持耳蜗的结构和功能完整性是必不可少的，并且也是声损伤的主要目标。虽然形态学评估揭示了噪音创伤后耳蜗的粘附功能障碍，但导致粘附破坏的分子机制尚不清楚。在此，我们筛选了49个粘附相关基因在正常大鼠耳蜗中的转录表达，并测量了声学创伤后耳蜗发病早期阶段的表达变化。我们发现，来自四个粘附家族的基因，包括免疫球蛋白超家族和整合素，钙粘蛋白和选择素家族，在正常耳蜗中表达。暴露于120 dB声压级（SPL）的强烈噪声2小时引起的网站特定的变化，在顶端和基底节的感觉上皮细胞的表达水平。表达的变化，发生在耳蜗感觉上皮是双相的，早期上调2小时后噪声暴露和随后的下调1天后曝光。重要的是，七个基因（Sgce，Sell，Itga 5，Itgal，Selp，Cntn 1和Col 5a 1）的表达水平的改变与听觉脑干反应（ABR）的阈值偏移水平有关，ABR是反映耳蜗功能变化的指标。值得注意的是，显示表达变化的基因表现出不同的组成型表达水平，属于多个粘附基因家族。在时间的方式（2小时与1天）和空间的方式（顶端和基底的感觉上皮细胞以及侧壁组织）在多个家族的粘附基因的表达变化的发现表明，声过度刺激引起的粘附基因，这可能涉及多个粘附相关的信号通路的复杂反应。
Cell–cell junctions and junctions between cells and extracellular matrix are essential for maintenance of the structural and functional integrity of the cochlea, and are also a major target of acoustic trauma. While morphological assessments have revealed adhesion dysfunction in noise-traumatized cochleae, the molecular mechanisms responsible for adhesion disruption are not clear. Here, we screened the transcriptional expression of 49 adhesion-related genes in normal rat cochleae and measured the expression changes in the early phases of cochlear pathogenesis after acoustic trauma. We found that genes from four adhesion families, including the immunoglobulin superfamily and the integrin, cadherin, and selectin families, are expressed in the normal cochlea. Exposure to an intense noise at 120 dB sound pressure level (SPL) for 2 h caused site-specific changes in expression levels in the apical and the basal sections of the sensory epithelium. Expression changes that occurred in the cochlear sensory epithelium were biphasic, with early upregulation at 2 h post-noise exposure and subsequent downregulation at 1 day post-exposure. Importantly, the altered expression level of seven genes (Sgce, Sell, Itga5, Itgal, Selp, Cntn1 and Col5a1) is related to the level of threshold shift of the auditory brainstem response (ABR), an index reflecting functional change in the cochlea. Notably, the genes showing expression changes exhibited diverse constitutive expression levels and belong to multiple adhesion gene families. The finding of expression changes in multiple families of adhesion genes in a temporal fashion (2 h vs. 1 day) and a spatial fashion (the apical and the basal sensory epithelia as well as the lateral wall tissue) suggests that acoustic overstimulation provokes a complex response in adhesion genes, which likely involves multiple adhesion-related signaling pathways.
登录
查看更多内容
影响因子：
56.9
作者：
Opferman, JT;Iwasaki, H;Korsmeyer, SJ
通讯作者：
Korsmeyer, SJ
影响因子：
2.8
作者：
Hu, BH;Henderson, D;Nicotera, TM
通讯作者：
Nicotera, TM
影响因子：
32.4
作者：
LINETTE, GP;GRUSBY, MJ;KORSMEYER, SJ
通讯作者：
KORSMEYER, SJ
影响因子：
2.8
作者：
Coling, Donald E.;Ding, Dalian;Salvi, Richard J.
通讯作者：
Salvi, Richard J.
影响因子：
4.8
作者：
Clohessy, JG;Zhuang, JG;Brady, HJM
通讯作者：
Brady, HJM