MG132 is a potent proteasome inhibitor that also inhibits calpains and lysosomal cathepsins. One of the first proteasome inhibitors to be developed, MG-132 is widely used in proteasome inhibition studies because of its high potency, high selectivity, and rapid reversibility. MG132 mechanistically acts as a proteasome inhibitor by hemiacetal formation with hydroxyl groups of active site threnonine residues.
MG132, also known as carbobenzoxy-Leu-Leu-leucinal, is a peptide aldehyde which plays a vital role in the inhibition of proteolytic activity of the 26S proteasome complex. MG132 retards the growth of HeLa cells by promoting cell cycle arrest and apoptosis. Treatment of HepG2 and HeLa cells with MG-132 triggers increased expression of MCPIP1 mRNA, which in turn increases MCPIP1 protein concentration. MCPIP1 is implicated in negative regulation of macrophage activation and differentiation of several cell types, including pre-adipocytes, neuroprogenitor cells and osteoclast precursors. MG-132 stimulates dopamine reduction and nigral dopaminergic degeneration in both cell culture and animal models of Parkinson′s disease.
Potent, membrane-permeable proteasome inhibitor. Induces neurite outgrowth in PC12 cells at 10 μM. Blocks cleavage of poly(ADP-ribose) polymerase and apoptosis in thymocytes. Proteasome inhibition induces accumulation of heat shock protein mRNA, activation of heat-shock proteins, and enhanced thermotolerance in various cell types: however, it also activates JNK-1, which initiates apoptosis in response to cell stress.