Oxidative and endoplasmic reticulum stress in diabetes-related hearing loss: Protective effects of thioredoxin.

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Life sciences Pub Date : 2024-11-06 DOI:10.1016/j.lfs.2024.123223

Meng Xu, Shiwen Zhong, Na Zhu, Sifan Wang, Jingyi Wang, Xiang Li, Xiang Ren, Hui Kong

{"title":"Oxidative and endoplasmic reticulum stress in diabetes-related hearing loss: Protective effects of thioredoxin.","authors":"Meng Xu, Shiwen Zhong, Na Zhu, Sifan Wang, Jingyi Wang, Xiang Li, Xiang Ren, Hui Kong","doi":"10.1016/j.lfs.2024.123223","DOIUrl":null,"url":null,"abstract":"<p><p>Diabetes mellitus (DM) induces complex physiological changes in the inner ear environment. This study investigates the roles of oxidative stress (OS) and endoplasmic reticulum stress (ERS) in diabetic hearing loss and explores the potential of thioredoxin (Trx) in regulating OS, ERS, and apoptosis-related factors to mitigate the progression of hearing impairment. We conducted auditory and serological assessments in 63 patients with type 2 diabetes and 30 healthy controls. Type 2 diabetes models were induced in wild-type and Trx transgenic (Tg) mice, with auditory brainstem response (ABR) used to evaluate hearing changes. Cochlear tissues were isolated to analyse markers of apoptosis, OS, and ERS. Both patients with diabetes and mouse models exhibited hearing loss, alongside increased serum levels of Trx1, TXNIP, and AOPP, indicating oxidative damage. H&E and succinate dehydrogenase (SDH) staining revealed varying degrees of hair cell loss from the base to the apex of the cochlea in diabetic mice, with decreased expression of the hair cell protein prestin gene. Notably, Tg mice showed significant delay in hearing loss progression. In vitro, advanced glycation end-products (AGEs) induced OS and ERS in cochlear-like HEI-OC1 cells, while Trx overexpression enhanced Nrf2 activity, alleviating AGE-induced cellular stress. In conclusion, Trx exhibits protective effects against diabetes-related hearing loss, potentially by enhancing Nrf2/HO-1/SOD2 function to reduce OS and ERS.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.lfs.2024.123223","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

Diabetes mellitus (DM) induces complex physiological changes in the inner ear environment. This study investigates the roles of oxidative stress (OS) and endoplasmic reticulum stress (ERS) in diabetic hearing loss and explores the potential of thioredoxin (Trx) in regulating OS, ERS, and apoptosis-related factors to mitigate the progression of hearing impairment. We conducted auditory and serological assessments in 63 patients with type 2 diabetes and 30 healthy controls. Type 2 diabetes models were induced in wild-type and Trx transgenic (Tg) mice, with auditory brainstem response (ABR) used to evaluate hearing changes. Cochlear tissues were isolated to analyse markers of apoptosis, OS, and ERS. Both patients with diabetes and mouse models exhibited hearing loss, alongside increased serum levels of Trx1, TXNIP, and AOPP, indicating oxidative damage. H&E and succinate dehydrogenase (SDH) staining revealed varying degrees of hair cell loss from the base to the apex of the cochlea in diabetic mice, with decreased expression of the hair cell protein prestin gene. Notably, Tg mice showed significant delay in hearing loss progression. In vitro, advanced glycation end-products (AGEs) induced OS and ERS in cochlear-like HEI-OC1 cells, while Trx overexpression enhanced Nrf2 activity, alleviating AGE-induced cellular stress. In conclusion, Trx exhibits protective effects against diabetes-related hearing loss, potentially by enhancing Nrf2/HO-1/SOD2 function to reduce OS and ERS.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

糖尿病相关性听力损失中的氧化应激和内质网应激：硫氧还蛋白的保护作用

糖尿病（DM）会导致内耳环境发生复杂的生理变化。本研究调查了氧化应激（OS）和内质网应激（ERS）在糖尿病听力损失中的作用，并探讨了硫氧还蛋白（Trx）在调节OS、ERS和细胞凋亡相关因子以减轻听力损伤进展方面的潜力。我们对 63 名 2 型糖尿病患者和 30 名健康对照者进行了听觉和血清学评估。在野生型小鼠和 Trx 转基因（Tg）小鼠中诱导 2 型糖尿病模型，用听觉脑干反应（ABR）评估听力变化。分离耳蜗组织以分析凋亡、OS和ERS的标记物。糖尿病患者和小鼠模型都表现出听力损失，同时血清中的 Trx1、TXNIP 和 AOPP 水平升高，表明存在氧化损伤。H&E和琥珀酸脱氢酶（SDH）染色显示，糖尿病小鼠耳蜗从基底到顶端都有不同程度的毛细胞缺失，毛细胞蛋白prestin基因的表达也有所下降。值得注意的是，Tg 小鼠的听力损失进展明显延迟。在体外，高级糖化终产物（AGEs）诱导耳蜗类 HEI-OC1 细胞出现 OS 和 ERS，而过量表达 Trx 能增强 Nrf2 的活性，减轻 AGE 诱导的细胞压力。总之，Trx对糖尿病相关听力损失具有保护作用，可能是通过增强Nrf2/HO-1/SOD2的功能来减少OS和ERS。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.