The Key laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi, China.
Life Sci. 2012 May 15;90(17-18):673-81. doi: 10.1016/j.lfs.2012.03.011. Epub 2012 Mar 29.
Trichosanthin (TCS) is a type I ribosome-inactivating protein. We have previously shown that TCS induces a more potent apoptosis in infected cells over uninfected cells, but the mechanism underlying it is unclear. In this study, we explored the anti-HSV-1 mechanism of TCS through the nuclear factor-κB (NF-κB) and p53 pathways in human epithelial carcinoma (HEp-2) cells with wild type p53.
The western blot, electrophoretic mobility shift assay, chromatin immunoprecipitation assay, enzyme-linked immunosorbent assay and cytokinesis-block micronucleus were applied in this study.
It was shown that TCS inhibited the HSV-1-induced NF-κB activation. Meanwhile, in HSV-1 infected cells, TCS treatment activated significantly more p53 and BAX, with no DNA damage and less S phase arrest compared with uninfected cells. The activation of BAX in infected cells correlated with the cell death signaling of p53.
Taken together, these results suggest that the anti-HSV-1 effect of TCS is related to its suppression of NF-κB activation and regulation of p53-dependent cell death in infected cells.
天花粉蛋白（TCS）是一种 I 型核糖体失活蛋白。我们之前的研究表明，TCS 在感染细胞中诱导比未感染细胞更强的细胞凋亡，但其中的机制尚不清楚。在这项研究中，我们通过野生型 p53 的人上皮癌细胞（HEp-2）中核因子-κB（NF-κB）和 p53 通路探索了 TCS 抗 HSV-1 的机制。
本研究应用了 Western blot、电泳迁移率变动分析、染色质免疫沉淀分析、酶联免疫吸附试验和胞质分裂阻断微核试验。
结果表明，TCS 抑制了 HSV-1 诱导的 NF-κB 激活。同时，与未感染细胞相比，在 HSV-1 感染细胞中，TCS 处理后 p53 和 BAX 的激活显著增加，没有 DNA 损伤，S 期阻滞减少。感染细胞中 BAX 的激活与 p53 依赖性细胞死亡的信号转导有关。
综上所述，这些结果表明 TCS 的抗 HSV-1 作用与其抑制 NF-κB 激活和调节感染细胞中 p53 依赖性细胞死亡有关。
