ENT Institute and Department of Otorhinolaryngology, Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200031, P.R. China.
Department of Stomatology, Key Laboratory of Oral Clinical Medicine, The Affiliated Hospital of Qingdao University, College of Stomatology, Qingdao University, Qingdao, Shandong 266000, P.R. China.
Mol Med Rep. 2020 Jan;21(1):338-346. doi: 10.3892/mmr.2019.10838. Epub 2019 Nov 20.
Several factors trigger apoptosis in cochlear hair cells. Previous studies have shown that mitochondria play key roles in apoptosis, but the role of mitochondrial deoxyribonucleic acid (mtDNA) copy number in the pathogenesis of hair cell apoptosis remains largely unknown. We used mouse cochlear hair cells and House Ear Institute‑Organ of Corti 1 (HEI‑OC1) cells to explore the relationship between mtDNA copy number and cell apoptosis. We found that the mtDNA copy number of hair cells was reduced relative to mitochondrial mass and hypothesized that increasing it might have a protective effect. We then increased the mtDNA copy number of the hair and HEI‑OC1 cells by transfecting them with an adeno‑associated virus (AAV) vector containing mitochondrial transcription factor A (TFAM). We found that the apoptosis rates decreased upon inducing apoptosis with neomycin or cisplatin (DDP). To elucidate the mechanisms, we analyzed the mitochondrial‑membrane permeability and mitochondrial function of HEI‑OC1 cells. Our results suggested that the increase in mtDNA copy number could protect hair cells and HEI‑OC1 cells against drug‑induced apoptosis by stabilizing the permeability of the mitochondrial membrane and mitochondrial function.
几种因素可触发耳蜗毛细胞凋亡。先前的研究表明，线粒体在凋亡中发挥关键作用，但线粒体 DNA（mtDNA）拷贝数在毛细胞凋亡发病机制中的作用在很大程度上仍不清楚。我们使用小鼠耳蜗毛细胞和 House Ear Institute-Organ of Corti 1（HEI-OC1）细胞来探讨 mtDNA 拷贝数与细胞凋亡之间的关系。我们发现毛细胞的 mtDNA 拷贝数相对于线粒体质量减少，并且假设增加它可能具有保护作用。然后，我们通过转染含有线粒体转录因子 A（TFAM）的腺相关病毒（AAV）载体来增加毛细胞和 HEI-OC1 细胞的 mtDNA 拷贝数。我们发现，在用新霉素或顺铂（DDP）诱导凋亡时，凋亡率降低。为了阐明机制，我们分析了 HEI-OC1 细胞的线粒体膜通透性和线粒体功能。我们的结果表明，增加 mtDNA 拷贝数可以通过稳定线粒体膜通透性和线粒体功能来保护毛细胞和 HEI-OC1 细胞免受药物诱导的凋亡。
