Age-related hearing loss (ARHL) is the progressive, bilateral loss of high-frequency hearing in elderly people. Mutations in GJB2, encoding the cochlear gap junction protein connexin26 (Cx26), are the most frequent cause of hereditary deafness; however, a common molecular pathology between ARHL and GJB2-related hearing loss has not been reported. Here, we investigated the quantitative change in expression and molecular pathology of Cx26 in ARHL. We used C57BL/6J mice as a model of ARHL. Hearing levels that were evaluated by auditory brainstem response thresholds increased gradually between 4 and 32 weeks of age and increased sharply at 36 weeks. Gap junctions in the cochleae of 4-week-old mice had linear plaques along cell-cell junction sites. In contrast, the cochleae from 32-week-old mice had significantly shorter gap junctions. Severe hair cell loss was not observed during this period. Based on western blotting, Cx26 and connexin30 (Cx30) levels were significantly decreased at 32 weeks compared with 4 weeks.Moreover, Cx26 was more significantly enriched in the hydrophilic fraction at 4 weeks but was more significantly enriched in the hydrophobic fraction at 32 weeks, indicating an age-related conversion of this biochemical property. Thus, the hydrophobic conversion of Cx26 and disruption of gap junction proteins and plaques may be involved in the pathogenesis of ARHL and may occur before severe hair cell degeneration.

中文翻译：

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在与年龄有关的听力损失的早期发展中，耳蜗间隙连接蛋白的降解和修饰。

与年龄有关的听力丧失（ARHL）是老年人的高频听力的进行性双侧丧失。编码耳蜗间隙连接蛋白连接蛋白26（Cx26）的GJB2突变是遗传性耳聋的最常见原因。然而，尚未报道ARHL与GJB2相关的听力损失之间常见的分子病理学。在这里，我们调查了ARHL中Cx26表达和分子病理学的定量变化。我们使用C57BL / 6J小鼠作为ARHL的模型。通过听觉脑干反应阈值评估的听力水平在4到32周龄之间逐渐增加，在36周时急剧增加。4周龄小鼠的耳蜗中的间隙连接处沿细胞-细胞连接位点具有线性斑块。相反，来自32周龄小鼠的耳蜗的间隙连接明显较短。在此期间未观察到严重的毛细胞丢失。根据蛋白质印迹法，Cx26和connexin30（Cx30）的水平在32周时显着降低（与4周相比）;此外，Cx26在4周时更富集在亲水部分中，而在32周时更显着在疏水部分中。表明该生化特性的年龄相关转换。因此，Cx26的疏水性转化以及间隙连接蛋白和噬菌斑的破坏可能与ARHL的发病有关，并且可能在严重的毛细胞变性之前发生。Cx26在4周时更富集在亲水级分中，但在32周时更富集在疏水级分中，表明该生化特性与年龄有关。因此，Cx26的疏水性转化以及间隙连接蛋白和噬菌斑的破坏可能与ARHL的发病有关，并且可能在严重的毛细胞变性之前发生。Cx26在4周时更富集在亲水级分中，但在32周时更富集在疏水级分中，表明该生化特性与年龄有关。因此，Cx26的疏水性转化以及间隙连接蛋白和噬菌斑的破坏可能与ARHL的发病有关，并且可能在严重的毛细胞变性之前发生。