Expression and localization of diacylglycerol kinase ζ in guinea pig cochlea and its functional implication under noise-exposure stress conditions
Expression and localization of diacylglycerol kinase ζ in guinea pig cochlea and its functional implication under noise-exposure stress conditions
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豚鼠耳蜗中二酰甘油激酶 z 的表达和定位及其在噪声应激条件下的功能意义
DOI：
10.1007/s00418-019-01781-9
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Kakehata S
中科院分区：
文献类型：
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作者：
Shinkawa C;Ito T;Hozumi Y;Chiba M;Matsui H;Goto K;Kakehata S
耳蜗毛细胞对于听力的机械传导是必不可少的。感觉神经性听力损失可能是不可逆转的，因为毛细胞一旦受损，自我修复或再生的能力很低。为了开发预防毛细胞丢失的治疗干预措施，有必要了解耳蜗毛细胞中的信号通路及其损伤后的变化。二酰甘油激酶(DGK)通过脂类第二信使二酰甘油的磷酸化来调节细胞内的信号转导。我们以前已经报道了DGKs在病理生理条件下在不同器官中的特征表达和定位模式。然而，人们对耳蜗酶家族的形态和功能知之甚少。RT-PCR法分析表明，DGKα、DGKε和DGKζ的基因表达水平较高。免疫组织化学分析表明，正常情况下，DGKζ定位于豚鼠耳蜗内毛细胞、外毛细胞、支持细胞和螺旋神经节神经元的核。众所周知，强噪声暴露会导致耳蜗损伤，从而导致毛细胞丢失。特别是，OHC比IHC更容易受到噪声暴露的影响。我们发现在噪声暴露1周后，DGKζ在损伤敏感的毛囊中从核移位到细胞质，然后逐渐消失。与之形成鲜明对比的是，在抗损伤的IHC中，DGKζ仍留在细胞核内。这些结果表明，DGKζ胞浆易位与噪声应激条件下的细胞损伤密切相关，并参与了耳蜗外毛细胞的迟发性死亡。
Cochlear hair cells are essential for the mechanotransduction of hearing. Sensorineural hearing loss can be irreversible because hair cells have a minimal ability to repair or regenerate themselves once damaged. In order to develop therapeutic interventions to prevent hair cell loss, it is necessary to understand the signaling pathway operating in cochlear hair cells and its alteration upon damage. Diacylglycerol kinase (DGK) regulates intracellular signal transduction through phosphorylation of lipidic second messenger diacylglycerol. We have previously reported characteristic expression and localization patterns of DGKs in various organs under pathophysiological conditions. Nevertheless, little is known about morphological and functional aspects of this enzyme family in the cochlea. First RT-PCR analysis reveals predominant mRNA expression of DGKα, DGKε and DGKζ. Immunohistochemical analysis shows that DGKζ localizes to the nuclei of inner hair cells (IHCs), outer hair cells (OHCs), supporting cells and spiral ganglion neurons in guinea pig cochlea under normal conditions. It is well known that loud noise exposure induces cochlear damage, thereby resulting in hair cell loss. In particular, OHCs are highly vulnerable to noise exposure than IHCs. We found that after 1 week of noise exposure DGKζ translocates from the nucleus to the cytoplasm in damage-sensitive OHCs and gradually disappears thereafter. In sharp contrast, DGKζ remains to the nucleus in damage-resistant IHCs. These results suggest that DGKζ cytoplasmic translocation is well correlated with cellular damage under noise-exposure stress conditions and is involved in delayed cell death in cochlear outer hair cells.