Role of the Ubiquitin C-Terminal Hydrolase L1-Modulated Ubiquitin Proteasome System in Auditory Cortex Senescence

Role of the Ubiquitin C-Terminal Hydrolase L1-Modulated Ubiquitin Proteasome System in Auditory Cortex Senescence
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泛素 C 端水解酶 L1 调节的泛素蛋白酶体系统在听觉皮层衰老中的作用

DOI:
10.1159/000468944
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发表时间:
2017-04
影响因子:
1.3
通讯作者:
Kong Wei-jia
Kong Wei-jia
中科院分区:
医学4区
文献类型:
--
作者:
Zhang Ya;Huang Xiang;Zhao Xue-yan;Hu Yu-juan;Sun Hai-ying;Kong Wei-jia

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背景/目的:近年来的研究表明,中枢性听觉障碍与神经退行性疾病密切相关。然而,中枢性老年性聋的发病机制仍不清楚。泛素C-末端水解酶L1(UCHL 1)在维持蛋白酶体活性方面很重要;然而,详细的机制尚未完全阐明。本研究旨在探讨UCHL 1在听皮层老化过程中的分子变化。方法:D-半乳糖(D-gal)诱导听皮层氧化应激和衰老,如我们以前的研究报告。原代听皮层细胞用D-半乳糖处理72小时或5天。对泛素蛋白酶体系统(UPS)相关蛋白和蛋白酶体活性进行了评价。UCHL 1过表达,并分析UCHL 1对UPS和蛋白酶体活性的影响。结果:D-半乳糖处理的初级听皮层细胞蛋白酶体活性在72 h时升高,5 d时降低。我们还发现UCHL 1的过表达增加了UPS相关蛋白UBE 1、PSMA 7、泛素化蛋白和monoubiquitin以及蛋白酶体的活性。结论:UCHL 1可能通过调节UPS相关蛋白参与听皮层衰老过程。
Background/Aims: According to recent studies, central auditory impairments are closely related to neurodegenerative diseases. However, the mechanism of central presbycusis remains unclear. Ubiquitin C-terminal hydrolase L1 (UCHL1) is important in maintaining proteasomal activity; however, the detailed mechanism has not yet been fully elucidated. This study aims to investigate the molecular alterations involved in UCHL1 regulation during auditory cortex aging. Methods:D-Galactose (D-gal) induces oxidative stress and senescence in the auditory cortex, as reported in our previous studies. Primary auditory cortex cells were treated with D-gal for 72 h or 5 days. The proteins related to the ubiquitin proteasome system (UPS) and proteasomal activities were evaluated. UCHL1 was overexpressed, and the effects of UCHL1 on the UPS and proteasomal activity were analyzed. Results: Proteasomal activity was elevated at 72 h and decreased at 5 days in D-gal-treated primary auditory cortex cells. We also found that overexpression of UCHL1 increased the UPS-related proteins UBE1, PSMA7, ubiquitinated proteins, and monoubiquitin, and proteasomal activity. Conclusion: The results suggest that UCHL1 may modify the aging process in the auditory cortex by regulating UPS- related proteins.
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影响因子: 0.8
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