RESULTS: To test, whether low proteasomal degradation of SAA.R90S is responsible for the observed intra- and extracellular SAA accumulation, we intended to inhibit the proteasome in SAA wild type (SAA.WT) overexpressing cells with MG132. However, we observed an unexpected drastic decrease in SAA protein expression at the transcript level. NF-κB gene expression was unchanged by MG132 at the measured time point.
CONCLUSIONS: The observed results demonstrate that MG132 inhibits SAA expression at the transcript level, independent of its endogenous promoter. Further, the data might indicate that NF-κB is not involved in the observed MG132-induced inhibition of SAA expression. We, consequently, question in this brief report whether MG132 should truly be categorised as a specific ubiquitin proteasome inhibitor and recommend the usage of alternative compounds.
结果:要测试,SAA是否低蛋白酶体降解。R90S负责观察到的细胞内和细胞外SAA积累,我们打算抑制SAA野生型的蛋白酶体(SAA。WT)过表达MG132的细胞。然而,我们观察到转录水平的SAA蛋白表达出乎意料地急剧下降。在测量的时间点,NF-κB基因表达通过MG132未改变。
结论:观察到的结果表明,MG132在转录水平上抑制SAA的表达,独立于其内源性启动子。Further,数据可能表明NF-κB不参与观察到的MG132诱导的SAA表达抑制。我们,因此,在这份简短报告中,问MG132是否应该真正归类为特定的泛素蛋白酶体抑制剂,并建议使用替代化合物。