Example：10.1021/acsami.1c06204 or Chem. Rev., 2007, 107, 2411-2502
Proteasome inhibition induces macrophage apoptosis via mitochondrial dysfunction Journal of Biochemical and Molecular Toxicology (IF3.642), Pub Date : 2021-08-21, DOI: 10.1002/jbt.22894 Jieyan Wang, Yingling Wang, Shihan He, Zhu Wang, Qiong Deng, Hui Liang
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.