Reactive Oxygen Species-Mediated Mitophagy and Cell Apoptosis are Involved in the Toxicity of Aluminum Chloride Exposure in GC-2spd
Reactive Oxygen Species-Mediated Mitophagy and Cell Apoptosis are Involved in the Toxicity of Aluminum Chloride Exposure in GC-2spd
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DOI：
10.1007/s12011-023-03848-0
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发表时间：
2023-09-15
影响因子：
3.9
通讯作者：
Chen，Wen-cheng
中科院分区：
文献类型：
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作者：
Peng，Hui-xin;Chai，Fu;Chen，Wen-cheng
氯化铝是一种常见于日常生活和各种材料中的无机高分子混凝剂。虽然男性生殖毒性与AlCl3接触有关，但其潜在机制仍不清楚。本研究旨在研究AlCl3暴露对睾丸组织和小鼠精母细胞有丝分裂和线粒体凋亡的影响。用多功能酶标记仪测定AlCl3暴露后GC-2spd中的ROS和ATP水平。激光共聚焦显微镜观察线粒体膜电位和TUNEL的变化，Western印迹分析线粒体吞噬和凋亡相关蛋白的表达。我们的结果表明，AlCl3暴露扰乱了睾丸组织的有丝分裂，并增加了凋亡相关蛋白的表达。在体外实验中，AlCl3可诱导Gc-2spd细胞产生ROS，抑制细胞存活率和ATP的产生，并引起细胞基质金属蛋白酶的减少，导致细胞有丝分裂和细胞凋亡。N-乙酰半胱氨酸(NAC)的干预减少了ROS的产生，部分恢复了线粒体的功能，从而逆转了由此产生的有丝分裂和细胞凋亡。我们的发现提供了证据，证明ROS介导的有丝分裂和细胞凋亡在AlCl3暴露的GC-2spd的毒性中起着关键作用。这些结果有助于了解AlCl3暴露对男性生殖毒性的影响，并为今后该领域的研究提供基础。
Aluminum chloride is an inorganic polymeric coagulant commonly found in daily life and various materials. Although male reproductive toxicity has been associated with AlCl3exposure, the underlying mechanism remains unclear. This study aimed to examine the impact of AlCl3exposure on mitophagy and mitochondrial apoptosis in testicular tissue and mouse spermatocytes. Reactive oxygen species (ROS) and ATP levels were measured in GC-2spd after AlCl3exposure 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 AlCl3exposure disrupted mitophagy and increased apoptosis-related protein expression in testicular tissues. In the in vitro experiments, AlCl3exposure 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 AlCl3exposure in GC-2spd. These results contribute to the understanding of male reproductive toxicity caused by AlCl3exposure and offer a foundation for future research in this area.