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活性氧介导的自噬和细胞凋亡参与了氯化铝暴露对 GC-2spd 的毒性作用。

Reactive Oxygen Species-Mediated Mitophagy and Cell Apoptosis are Involved in the Toxicity of Aluminum Chloride Exposure in GC-2spd.

机构信息

The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China.

Graduate School of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China.

出版信息

Biol Trace Elem Res. 2024 Jun;202(6):2616-2629. doi: 10.1007/s12011-023-03848-0. Epub 2023 Sep 15.

DOI:10.1007/s12011-023-03848-0
PMID:37715092
Abstract

Aluminum chloride is an inorganic polymeric coagulant commonly found in daily life and various materials. Although male reproductive toxicity has been associated with AlCl exposure, the underlying mechanism remains unclear. This study aimed to examine the impact of AlCl exposure on mitophagy and mitochondrial apoptosis in testicular tissue and mouse spermatocytes. Reactive oxygen species (ROS) and ATP levels were measured in GC-2spd after AlCl exposure using a multifunctional enzyme labeler. The changes in mitochondrial membrane potential (MMP) and TUNEL were observed through confocal laser microscopy, and the expression of proteins associated with mitophagy and apoptosis was analyzed using Western blot. Our results demonstrated that AlCl exposure disrupted mitophagy and increased apoptosis-related protein expression in testicular tissues. In the in vitro experiments, AlCl exposure induced ROS production, suppressed cell viability and ATP production, and caused a decrease in MMP, leading to mitophagy and cell apoptosis in GC-2spd cells. Intervention with N-acetylcysteine (NAC) reduced ROS production and partially restored mitochondrial function, thereby reversing the resulting mitophagy and cell apoptosis. Our findings provide evidence that ROS-mediated mitophagy and cell apoptosis play a crucial role in the toxicity of AlCl exposure in GC-2spd. These results contribute to the understanding of male reproductive toxicity caused by AlCl exposure and offer a foundation for future research in this area.

摘要

氯化铝是一种常见于日常生活和各种材料中的无机聚合混凝剂。尽管已经发现 AlCl 暴露与男性生殖毒性有关,但潜在的机制仍不清楚。本研究旨在探讨 AlCl 暴露对睾丸组织和小鼠精母细胞中线粒体自噬和线粒体凋亡的影响。使用多功能酶标仪测量 AlCl 暴露后 GC-2spd 中的活性氧(ROS)和 ATP 水平。通过共聚焦激光显微镜观察线粒体膜电位(MMP)和 TUNEL 的变化,并使用 Western blot 分析与线粒体自噬和凋亡相关的蛋白质表达。我们的结果表明,AlCl 暴露破坏了睾丸组织中的线粒体自噬并增加了凋亡相关蛋白的表达。在体外实验中,AlCl 暴露诱导 ROS 产生,抑制细胞活力和 ATP 产生,并导致 MMP 降低,导致 GC-2spd 细胞中的线粒体自噬和细胞凋亡。N-乙酰半胱氨酸(NAC)的干预减少了 ROS 的产生,并部分恢复了线粒体功能,从而逆转了由此产生的线粒体自噬和细胞凋亡。我们的研究结果提供了证据表明,ROS 介导的线粒体自噬和细胞凋亡在 GC-2spd 中 AlCl 暴露的毒性中起着至关重要的作用。这些结果有助于理解 AlCl 暴露引起的男性生殖毒性,并为该领域的未来研究提供了基础。

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有机砷衍生的硫氧还蛋白和谷胱甘肽系统抑制剂ACZ2通过活性氧依赖性内质网应激诱导胃癌细胞凋亡和自噬。
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