中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (5): 1119-1125.doi: 10.4103/1673-5374.382862

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

出生后耳蜗支持细胞中端粒酶逆转录酶易位与ATP释放有关

  

  • 出版日期:2024-05-15 发布日期:2023-10-31
  • 基金资助:
    国家自然科学基金项目(81870732,82171161,81900933,82000978)

Translocation of telomerase reverse transcriptase coincided with ATP release in postnatal cochlear supporting cells

Yukai Zhang#, Keyong Tian#, Wei Wei#, Wenjuan Mi, Fei Lu, Zhenzhen Liu, Qingwen Zhu, Xinyu Zhang, Panling Geng, Jianhua Qiu, Yongli Song*, Dingjun Zha*   

  1. Department of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province, China
  • Online:2024-05-15 Published:2023-10-31
  • Contact: Dingjun Zha, MD, zhadjun@fmmu.edu.cn; Yongli Song, MD, syljudy@163.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81870732 (to DZ), 82171161 (to DZ), 81900933 (to YS), and 82000978 (to ZL).

摘要:

听觉系统发育中的自发性电活动起源于耳蜗Kölliker器支持细胞周期性自发释放的ATP。然而,启动ATP自发释放的机制尚未确定。作者既往研究已证实,端粒酶逆转录酶在出生后第1周即可在基底膜表达,但其在耳蜗发育中的作用尚不清楚,此次实验分析了在出生后耳蜗支持细胞中端粒酶逆转录酶的表达和作用。结果表明,在出生后小鼠耳蜗Kölliker器的支持细胞中的端粒酶逆转录酶,会随着耳蜗发育的成熟,从细胞核向细胞质中转位,且体外培养的耳蜗支持细胞中端粒酶逆转录酶易位趋势与体内相一致。进入线粒体的端粒酶逆转录酶主要定位在线粒体,但没有发挥经典的抗氧化或抗凋亡的作用。令人惊讶的是,在端粒酶逆转录酶转位期间,支持细胞中的ATP合成和嘌呤信号系统的激活增加。出生后耳蜗支持细胞中端粒酶逆转录酶转位与ATP释放以及嘌呤信号系统激活同时发生的现象表明,转位期可能参与调节ATP释放和激活嘌呤信号系统。这项研究可为探索出生后早期耳蜗自发性电活动提供了新的研究方向。

https://orcid.org/0000-0002-2115-6624 (Yukai Zhang); https://orcid.org/0000-0002-9380-9209 (Dingjun Zha); https://orcid.org/0000-0002-8870-308X (Yongli Song)

关键词: 耳蜗, 支持细胞, 线粒体功能, ATP释放, Ca2+瞬变, 活性氧, 细胞凋亡, 自发性电活动

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.

Key words: apoptosis, ATP release, Ca2+ transients, cochlea, mitochondrial function, reactive oxygen species, spontaneous electrical activity, supporting cells