PDF(Pubmed)
Abstract：
The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate (ATP) by supporting cells in the Kölliker\'s organ. However, the mechanisms responsible for initiating spontaneous ATP release have not been determined. Our previous study revealed that telomerase reverse transcriptase (TERT) is expressed in the basilar membrane during the first postnatal week. Its role in cochlear development remains unclear. In this study, we investigated the expression and role of TERT in postnatal cochlea supporting cells. Our results revealed that in postnatal cochlear Kölliker\'s organ supporting cells, TERT shifts from the nucleus into the cytoplasm over time. We found that the TERT translocation tendency in postnatal cochlear supporting cells in vitro coincided with that observed in vivo. Further analysis showed that TERT in the cytoplasm was mainly located in mitochondria in the absence of oxidative stress or apoptosis, suggesting that TERT in mitochondria plays roles other than antioxidant or anti-apoptotic functions. We observed increased ATP synthesis, release and activation of purine signaling systems in supporting cells during the first 10 postnatal days. The phenomenon that TERT translocation coincided with changes in ATP synthesis, release and activation of the purine signaling system in postnatal cochlear supporting cells suggested that TERT may be involved in regulating ATP release and activation of the purine signaling system. Our study provides a new research direction for exploring the spontaneous electrical activity of the cochlea during the early postnatal period.
摘要：
发育中的听觉系统中自发的电活动爆发源于通过支持科利克器官中的细胞而周期性释放的三磷酸腺苷（ATP）。然而,启动自发ATP释放的机制尚未确定.我们先前的研究表明，端粒酶逆转录酶（TERT）在出生后的第一周在基底膜中表达。其在耳蜗发育中的作用尚不清楚。在这项研究中,我们研究了TERT在出生后耳蜗支持细胞中的表达和作用。我们的结果显示，在出生后的耳蜗科利克的器官支持细胞，TERT随时间从细胞核转移到细胞质中。我们发现，体外出生后耳蜗支持细胞的TERT易位趋势与体内观察到的趋势一致。进一步分析表明，在无氧化应激或凋亡的情况下，细胞质中的TERT主要位于线粒体，提示线粒体中的TERT发挥抗氧化或抗凋亡功能以外的作用。我们观察到ATP合成增加，在出生后的前10天，支持细胞中嘌呤信号系统的释放和激活。TERT易位与ATP合成变化同时发生的现象，出生后耳蜗支持细胞中嘌呤信号系统的释放和激活表明TERT可能参与调节ATP释放和嘌呤信号系统的激活。本研究为探索出生后早期耳蜗的自发电活动提供了新的研究方向。
