Proteasome and calpain are the main nonlysosomal proteases responsible for intracellular proteolysis. MG-132 is a potent cell-permeable inhibitor of both proteasome and calpain with respective IC50 values of 0.1µM and 1.25µM. MG-132 induced neurite outgrowth in PC12 cells at a concentration of 20nM. In rabbit erythrocytes, MG-132 penetrated cell membrane and inhibited the autolysis at the dose of 100µM[3]. MG-132 also showed inhibitory activity on cell growth in both human ocular melanoma IPC227F cells and murine melanoma B16 cells with IC50 values of 42 and 77nM, respectively[4]. In airway epithelial cells, pretreatment with 10μM MG-132 for 1h inhibited TNF-α-stimulated IL-8 protein production and release. Moreover, preincubation of cells with 10μM MG-132 reversed the effects of TNF-α on the transcriptional activity of IL-8 gene, IκB degradation, and NF-κB activation[5]. In mice with hindlimb immobilization, twice-daily subcutaneous injections of MG-132 (7.5 mg/kg/dose) significantly increased the running time on treadmill as compared to DMSO-treated group. However, no significant difference in the running time of MG132- and DMSO-treated mice was observed after 11 days of remobilization[6].
作用机制
MG-132 inhibits proteasome primarily via acting on the chymotrypsin-like site in the subunit. It also inhibits the caspase-like site at high concentrations[7].
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