Interplay of Autophagy Inducer Rapamycin and Proteasome Inhibitor MG132 in Reduction of Foam Cell Formation and Inflammatory Cytokine Expression

Cell Transplantation
Wei ZhangQuan Zhou

Abstract

MG132 is a pivotal inhibitor of the ubiquitin-proteasome system (UPS), and rapamycin (RAPA) is an important inducer of autophagy. MG132 and RAPA have been shown to be effective agents that can cure multiple autoimmune diseases by reducing inflammation. Although individual MG132 and RAPA showed protective effects for atherosclerosis (AS), the combined effect of these two drugs and its molecular mechanism are still unclear. In this article we investigate the regulation of oxidative modification of low-density lipoprotein (ox-LDL) stress and foam cell formation in the presence of both proteasome inhibitor MG132 and the autophagy inducer RAPA to uncover the molecular mechanism underlying this process. We established the foam cells model by ox-LDL and an animal model. Then, we tested six experimental groups of MG132, RAPA, and 3MA drugs. As a result, RAPA-induced autophagy reduces accumulation of polyubiquitinated proteins and apoptosis of foam cells. The combination of MG132 with RAPA not only suppressed expression of the inflammatory cytokines and formation of macrophage foam cells, but also significantly affected the NF-κB signaling pathway and the polarization of RAW 264.7 cells. These data suggest that the combination of protea...Continue Reading

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Citations

Mar 7, 2020·Current Medicinal Chemistry·Zhi-Xiang ZhouZhi-Sheng Jiang

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Methods Mentioned

BETA
Assay
flow cytometry
protein assay
Transfections
FACS
Fluorescence imaging
confocal microscopy
ELISA

Software Mentioned

Image J
Graphpad Prism

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