Dysfunction of the ubiquitin–proteasome system has been linked to the pathogenesis of a variety of diseases. Proteasome inhibition not only exerts antitumor effects but also affects inflammatory signaling pathways. MG132, a proteasome inhibitor, has been shown to induce tumor cell apoptosis. However, its role in the induction of macrophage apoptosis remains unknown. In our study, we investigated the mechanism of the proapoptotic effects of MG132 in macrophages. Our data showed that MG132 treatment induced mitochondrial reactive oxygen species (ROS) generation and loss of mitochondrial membrane potential in macrophages. We found that proteasome inhibition induced a significant increase in the apoptosis rate, as evidenced by cleavage of caspase-3 and cleavage of poly(ADP-ribose) polymerase (PARP). Moreover, (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenyl-phosphonium chloride (Mito-TEMPO) attenuated MG132-induced apoptosis. In conclusion, proteasome inhibition by MG132 can induce macrophage apoptosis by promoting the production of ROS and mitochondrial dysfunction.

中文翻译：

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蛋白酶体抑制通过线粒体功能障碍诱导巨噬细胞凋亡

泛素-蛋白酶体系统的功能障碍与多种疾病的发病机制有关。蛋白酶体抑制不仅发挥抗肿瘤作用，而且影响炎症信号通路。MG132 是一种蛋白酶体抑制剂，已被证明可诱导肿瘤细胞凋亡。然而，它在诱导巨噬细胞凋亡中的作用仍然未知。在我们的研究中，我们研究了 MG132 在巨噬细胞中的促凋亡作用机制。我们的数据显示，MG132 处理诱导巨噬细胞中线粒体活性氧 (ROS) 的产生和线粒体膜电位的丧失。我们发现蛋白酶体抑制诱导细胞凋亡率显着增加，这可以通过 caspase-3 的切割和聚（ADP-核糖）聚合酶 (PARP) 的切割来证明。此外，(2-(2,2,6, 6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenyl-phosphonium chloride (Mito-TEMPO) 减弱 MG132 诱导的细胞凋亡。总之，MG132对蛋白酶体的抑制可以通过促进ROS的产生和线粒体功能障碍来诱导巨噬细胞凋亡。