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神经节苷脂单唾液酸四己糖神经节苷脂通过线粒体抗氧化作用保护听觉毛细胞免受新霉素诱导的细胞毒性:一项研究。

The Ganglioside Monosialotetrahexosylganglioside Protects Auditory Hair Cells Against Neomycin-Induced Cytotoxicity Through Mitochondrial Antioxidation: An Study.

作者信息

Li Yujin, Li Ao, Wang Chao, Jin Xin, Zhang Yaoting, Lu Ling, Wang Shou-Lin, Gao Xia

机构信息

Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Clinical College of Nanjing Medical University, Nanjing, China.

Department of Otolaryngology-Head and Neck Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China.

出版信息

Front Cell Neurosci. 2021 Sep 27;15:751867. doi: 10.3389/fncel.2021.751867. eCollection 2021.

Abstract

Neomycin is a common ototoxic aminoglycoside antibiotic that causes sensory hearing disorders worldwide, and monosialotetrahexosylganglioside (GM1) is reported to have antioxidant effects that protect various cells. However, little is known about the effect of GM1 on neomycin-induced hair cell (HC) ototoxic damage and related mechanism. In this study, cochlear HC-like HEI-OC-1 cells along with whole-organ explant cultures were used to establish an neomycin-induced HC damage model, and then the apoptosis rate, the balance of oxidative and antioxidant gene expression, reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were measured. GM1 could maintain the balance of oxidative and antioxidant gene expression, inhibit the accumulation of ROS and proapoptotic gene expression, promoted antioxidant gene expression, and reduce apoptosis after neomycin exposure in HEI-OC-1 cells and cultured cochlear HCs. These results suggested that GM1 could reduce ROS aggregation, maintain mitochondrial function, and improve HC viability in the presence of neomycin, possibly through mitochondrial antioxidation. Hence, GM1 may have potential clinical value in protecting against aminoglycoside-induced HC injury.

摘要

新霉素是一种常见的耳毒性氨基糖苷类抗生素,在全球范围内可导致感觉性听力障碍,据报道单唾液酸四己糖神经节苷脂(GM1)具有保护多种细胞的抗氧化作用。然而,关于GM1对新霉素诱导的毛细胞(HC)耳毒性损伤的影响及相关机制知之甚少。在本研究中,利用耳蜗HC样HEI-OC-1细胞以及全器官外植体培养建立新霉素诱导的HC损伤模型,然后检测凋亡率、氧化与抗氧化基因表达的平衡、活性氧(ROS)水平和线粒体膜电位(MMP)。GM1可维持氧化与抗氧化基因表达的平衡,抑制ROS积累和促凋亡基因表达,促进抗氧化基因表达,并减少新霉素暴露后HEI-OC-1细胞和培养的耳蜗HC中的凋亡。这些结果表明,GM1可能通过线粒体抗氧化作用,在新霉素存在的情况下减少ROS聚集,维持线粒体功能并提高HC活力。因此,GM1在预防氨基糖苷类诱导的HC损伤方面可能具有潜在的临床价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9109/8502895/bb688ccf0cf6/fncel-15-751867-g001.jpg

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