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石榴皮提取物通过调节小鼠耳蜗中PNUTS/PP1的活性减轻D-半乳糖诱导的氧化应激和听力损失。

Pomegranate peel extract attenuates D-galactose-induced oxidative stress and hearing loss by regulating PNUTS/PP1 activity in the mouse cochlea.

作者信息

Liu Shuangyue, Xu Tao, Wu Xidi, Lin Yuhan, Bao Dongyan, Di Yang, Ma Tingting, Dang Yan, Jia Peili, Xian Jianqiao, Wang Aimei, Liu Yongxin

机构信息

Department of Physiology, Jinzhou Medical University, Jinzhou, P.R. China.

Life Science Institute, Jinzhou Medical University, Jinzhou, P.R. China.

出版信息

Neurobiol Aging. 2017 Nov;59:30-40. doi: 10.1016/j.neurobiolaging.2017.07.007. Epub 2017 Jul 25.

Abstract

Oxidative stress is considered to be a major contributor to age-related hearing loss (ARHL). Here, we investigated whether pomegranate peel extract (PPE) protected against hearing loss by decreased oxidative stress in the cochlea of D-galactose-induced accelerated aging mice. The aging mice exhibited an increase in hearing threshold shifts and hair cells loss, which were improved in the PPE-treated aging mice. The aging mice also exhibited an increase in 4-hydroxynonenal, the expression of protein phosphatase 1 nuclear targeting subunit (PNUTS), p53 and caspase-3, and a decrease in protein phosphatase 1 (PP1) and MDM2 in the cochlea. PPE treatment reversed the changes in aforementioned molecules. Our results suggested that PPE can protect against ARHL, the underlying mechanisms may involve in the inhibition of oxidative damage of cochlea, possibly by regulating PNUTS/PP1 pathway. The results from the present study provide a new therapeutic strategy to use PPE for prevention of ARHL.

摘要

氧化应激被认为是与年龄相关的听力损失(ARHL)的主要促成因素。在此,我们研究了石榴皮提取物(PPE)是否通过降低D-半乳糖诱导的加速衰老小鼠耳蜗中的氧化应激来预防听力损失。衰老小鼠表现出听力阈值偏移增加和毛细胞损失,而PPE处理的衰老小鼠中这些情况得到改善。衰老小鼠耳蜗中4-羟基壬烯醛、蛋白磷酸酶1核靶向亚基(PNUTS)、p53和半胱天冬酶-3的表达也增加,而蛋白磷酸酶1(PP1)和MDM2减少。PPE处理逆转了上述分子的变化。我们的结果表明,PPE可以预防ARHL,其潜在机制可能涉及抑制耳蜗的氧化损伤,可能是通过调节PNUTS/PP1途径。本研究结果为使用PPE预防ARHL提供了一种新的治疗策略。

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