Apoptotic outer hair cell death in the cochleae of aging Fischer 344/NHsd rats.

Apoptotic outer hair cell death in the cochleae of aging Fischer 344/NHsd rats.
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DOI:
10.1016/j.heares.2008.08.006
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发表时间:
2008-11
期刊:
影响因子:
2.8
通讯作者:
Henderson, Donald
Henderson, Donald
中科院分区:
医学1区
文献类型:
--
作者:
Hu, Bo Hua;Yang, Wei-Ping;Bielefeld, Eric C.;Li, Manna;Chen, Guang-Di;Henderson, Donald

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衰老过程中,细胞凋亡与耳蜗变性有关。为了更好地了解外毛细胞(OHC)凋亡的影响及其生物学过程,我们研究了凋亡细胞死亡对OHC病变形成的贡献,并观察了Fischer 344/NHsd大鼠中与线粒体途径相关的凋亡事件发生的时间模式,年龄范围为20-27个月。结果表明,凋亡与坏死OHCs的比例为8:1。在细胞变性过程中,Bax的表达、细胞色素c的释放和细胞核DNA断裂的开始先于核凝聚的开始。相反,caspase -3和-9的激活以及F-actin的降解发生在核凝聚开始后。本研究结果表明,核降解的起始是一个不依赖于caspase-3的过程。此外,研究发现Bax表达或细胞色素c释放的OHCs可以进入凋亡或坏死途径,这表明存在一种调节机制,引导退行性OHCs通过凋亡或坏死途径死亡。
Apoptotic cell death has been implicated in cochlear degeneration during aging. To better understand the impact and the biological process of outer hair cell (OHC) apoptosis, we investigated the contribution of apoptotic cell death to the formation of the OHC lesions, and observed the temporal patterns of the occurrence of apoptotic events associated with the mitochondrial pathway in Fischer 344/NHsd rats, with ages ranging from 20–27 months. The results showed that the ratio of apoptotic to necrotic OHCs was 8:1. During the process of cell degeneration, the onset of Bax expression, cytochrome c release, and nuclear DNA fragmentation preceded the onset of nuclear condensation. In contrast, the activation of caspases-3 and -9, as well as the degradation of F-actin, took place after the onset of nuclear condensation. The results of this study suggest that the initiation of nuclear degradation is a caspase-3-independent process. Moreover, the study revealed that OHCs with Bax expression or cytochrome c release could enter either the apoptotic or necrotic pathway, suggesting the presence of a regulatory mechanism that guides degenerating OHCs to die via either the apoptotic or necrotic pathway.
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