Proteasome inhibition induces macrophage apoptosis via mitochondrial dysfunction. Issue 11 (21st August 2021)

• Record Type: Journal Article
• Authors: Wang, Jieyan; Wang, Yingling; He, Shihan; Wang, Zhu; Deng, Qiong; Liang, Hui
• Is Part Of: Journal of biochemical and molecular toxicology. Volume 35:Issue 11(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-08-21
• Subjects: apoptosis -- mitochondrial damage -- oxidative stress -- proteasome inhibition -- ROS; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Toxicology -- Periodicals; 574
• DOI: 10.1002/jbt.22894
• Languages: English
• ISSNs: 1095-6670

Abstract

Abstract: 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.