Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Biochem Biophys Res Commun. 2010 Jan 22;391(4):1579-84. doi: 10.1016/j.bbrc.2009.12.006. Epub 2009 Dec 5.
Type-I ribosome-inactivating protein-trichosanthin (TCS) exhibits selective cytotoxicity toward different types of cells. It is believed that the cytotoxicity results from the inhibition of ribosomes to decrease protein synthesis, thereby indicating that there are specific mechanisms for TCS entry into target cells to reach the ribosomes. Low-density lipoprotein (LDL) receptor-related protein 1 (LRP1) is a large scavenger receptor that is responsible for the binding and endocytosis of diverse biological ligands on the cell surface. In this study, we demonstrated that 2 choriocarcinoma cell lines can significantly bind and internalize TCS. In contrast, Hela cell line displayed no obvious TCS binding and endocytosis. Furthermore LRP1 gene silencing in JAR and BeWo cell lines blocked TCS binding; TCS could also interact with LRP1.The results of our study established that LRP1 was a major receptor for phagocytosis of TCS in JAR and BeWo cell lines and might be the molecular basis of TCS abortificient and anti-choriocarcinoma activity.
I 型核糖体失活蛋白-天花粉蛋白（TCS）对不同类型的细胞表现出选择性细胞毒性。据信，这种细胞毒性是由于核糖体的抑制导致蛋白质合成减少所致，这表明 TCS 进入靶细胞到达核糖体存在特定的机制。低密度脂蛋白（LDL）受体相关蛋白 1（LRP1）是一种大型的清道夫受体，负责结合和内吞细胞表面上的各种生物配体。在这项研究中，我们证明了 2 种绒毛膜癌细胞系可以显著结合和内化 TCS。相比之下，Hela 细胞系对 TCS 的结合和内吞作用不明显。此外，LRP1 基因沉默可阻断 JAR 和 BeWo 细胞系中 TCS 的结合；TCS 还可以与 LRP1 相互作用。我们的研究结果表明，LRP1 是 JAR 和 BeWo 细胞系吞噬 TCS 的主要受体，可能是 TCS 堕胎和抗绒毛膜癌活性的分子基础。
