Effect of Prnp gene to prion protein expression

一些作者先前使用永生化朊蛋白基因（Prnp）缺陷的神经元细胞证明了细胞朊蛋白（PrP ^c）与凋亡之间的关系。然而，PrP ^c阻止细胞凋亡的机制仍不清楚。在这项研究中，作者使用凋亡相关基因的基因转移分析了Prnp ^<-/->细胞的凋亡。用bcl-2、bcl-x_L或编码Cu/Zn超氧化物歧化酶（SOD）的SOD-1转染Prnp ^<-/->细胞，可抑制血清剥夺诱导的细胞凋亡。由于血清剥夺降低了-Prnp ^<-/->细胞中的Bcl-2和Bcl-x_L蛋白，因此认为这些细胞通过由Bcl-2家族和细胞内超氧化物调节的凋亡途径死亡。Prnp的重新引入可上调SOD活性并消除超氧阴离子的产生，而不引起Bcl-2、Bcl-x_L和Cu/Zn SOD表达水平的变化。由于PrP ^c在八肽重复序列中与铜结合，这些结果表明PrP ^c通过上调SOD活性抑制细胞凋亡，而SOD活性的上调是由于铜代谢调节所致。

Some of the authors previously demonstrated the relation between cellular prion protein (PrP^c) and apoptosis using immortalized prion protein gene (Prnp)-deficient neuronal cells. However, the mechanism(s) by which PrP^c prevents apoptosis remains unclear. In this study, the authors analyzed apoptosis of Prnp^<-/-> cells using gene transfer of apoptosis-related genes. Transfection of Prnp^<-/-> cells with bcl-2, bcl-x_L or SOD-1, which encodes Cu/Zn superoxide dismutase (SOD), inhibited apoptosis induced by serum deprivation. As serum deprivation decreased Bcl-2 and Bcl-x_L proteins in-Prnp^<-/-> cells, these cells are thought to die via apoptosis pathways regulated by the Bcl-2 family and intracellular superoxides. Re-introduction of Prnp upregulated SOD activity and eliminated superoxide anion generation without inducing changes hi Bcl-2, Bcl-x_L and Cu/Zn SOD expression levels. As PrP^c was bound to copper in the octapeptide repeats, these results suggested that PrP^c inhibited apoptosis by upregulation of SOD activity due to copper metabolism regulation.