高血糖诱导的氧化应激通过 ROS 介导的 Bcl-2/CytC/AIF 通路加剧了耳蜗血管纹周细胞线粒体凋亡损伤。

IF 5.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Redox Report Pub Date : 2024-12-01 Epub Date: 2024-08-02 DOI:10.1080/13510002.2024.2382943
Tian-Feng Shi, Zan Zhou, Wen-Jun Jiang, Tian-Lan Huang, Jun-Qiang Si, Li Li
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引用次数: 0

摘要

目的:糖尿病与听力损失密切相关,但其确切机制仍不清楚。耳蜗血管纹和周细胞对听力至关重要。本研究探讨了高血糖是否会通过氧化应激导致的 ROS 水平升高诱导耳蜗血管纹和周细胞凋亡,从而影响听力损失:我们在 C57BL/6J 小鼠中建立了 II 型糖尿病模型,并使用听性脑干反应(ABR)、伊文思蓝染色、HE 染色、免疫组织化学和免疫荧光观察听力、血-迷宫屏障(BLB)通透性、血管横纹形态和细胞凋亡蛋白表达的变化。将原代培养的血管横纹周细胞置于高糖条件下,使用流式细胞术、Annexin V-FITC、Hoechst 33342染色、Western印迹、Mitosox和JC-1探针评估细胞凋亡水平:结果:糖尿病小鼠的听阈下降、血管纹密度降低、氧化应激增加、细胞凋亡和抗氧化剂水平降低。高糖暴露增加了周细胞的凋亡和 ROS 含量,同时线粒体膜电位降低,AIF 和细胞色素 C (CytC) 从线粒体释放到细胞质中。加入氧化清除剂可减少AIF和CytC的释放,从而减少周细胞凋亡:讨论:高血糖可通过氧化应激诱导耳蜗纹状体周细胞线粒体凋亡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hyperglycemia-induced oxidative stress exacerbates mitochondrial apoptosis damage to cochlear stria vascularis pericytes via the ROS-mediated Bcl-2/CytC/AIF pathway.

Objectives: Diabetes is closely linked to hearing loss, yet the exact mechanisms remain unclear. Cochlear stria vascularis and pericytes (PCs) are crucial for hearing. This study investigates whether high glucose induces apoptosis in the cochlear stria vascularis and pericytes via elevated ROS levels due to oxidative stress, impacting hearing loss.

Methods: We established a type II diabetes model in C57BL/6J mice and used auditory brainstem response (ABR), Evans blue staining, HE staining, immunohistochemistry, and immunofluorescence to observe changes in hearing, blood-labyrinth barrier (BLB) permeability, stria vascularis morphology, and apoptosis protein expression. Primary cultured stria vascularis pericytes were subjected to high glucose, and apoptosis levels were assessed using flow cytometry, Annexin V-FITC, Hoechst 33342 staining, Western blot, Mitosox, and JC-1 probes.

Results: Diabetic mice showed decreased hearing thresholds, reduced stria vascularis density, increased oxidative stress, cell apoptosis, and decreased antioxidant levels. High glucose exposure increased apoptosis and ROS content in pericytes, while mitochondrial membrane potential decreased, with AIF and cytochrome C (CytC) released from mitochondria to the cytoplasm. Adding oxidative scavengers reduced AIF and CytC release, decreasing pericyte apoptosis.

Discussion: Hyperglycemia may induce mitochondrial apoptosis of cochlear stria vascularis pericytes through oxidative stress.

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来源期刊
Redox Report
Redox Report 生物-生化与分子生物学
CiteScore
6.10
自引率
0.00%
发文量
28
审稿时长
>12 weeks
期刊介绍: Redox Report is a multidisciplinary peer-reviewed open access journal focusing on the role of free radicals, oxidative stress, activated oxygen, perioxidative and redox processes, primarily in the human environment and human pathology. Relevant papers on the animal and plant environment, biology and pathology will also be included. While emphasis is placed upon methodological and intellectual advances underpinned by new data, the journal offers scope for review, hypotheses, critiques and other forms of discussion.
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