Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiōsaka, Osaka, 577-8502, Japan.
Mol Cell Biochem. 2013 Nov;383(1-2):173-7. doi: 10.1007/s11010-013-1765-9. Epub 2013 Jul 19.
Lysophosphatidic acid (LPA) receptors (LPA1 to LPA6) indicate a variety of cellular responses, such as cell proliferation, migration, differentiation, and morphogenesis. However, the role of each LPA receptor is not functionally equivalent. Ethionine, an ethyl analog of methionine, is well known to be one of the potent liver carcinogens in rats. In this study, to assess whether ethionine may regulate cell motile activity through LPA receptors, rat liver epithelial (WB-F344) cells were treated with ethionine for 48 h. In cell motility assay with a cell culture insert, the treatment of ethionine at 1.0 and 10 μM enhanced significantly high cell motile activity, compared with untreated cells. The expression levels of LPA receptor genes in cells treated with ethionine were measured by quantitative real time RT-PCR analysis. The expression of the Lpar3 gene in ethionine-treated cells was significantly higher than that in untreated cells. Furthermore, to confirm an involvement of LPA3 on cell motility increased by ethionine, the Lpar3 knockdown cells were also used. The cell motile activity by ethionine was completely suppressed in the Lpar3 knockdown cells. These results suggest that LPA signaling through LPA3 may be involved in cell motile activity stimulated by ethionine in WB-F344 cells.
溶血磷脂酸（LPA）受体（LPA1 至 LPA6）表示各种细胞反应，例如细胞增殖、迁移、分化和形态发生。然而，每个 LPA 受体的作用并非在功能上等效。乙硫氨酸是蛋氨酸的乙基类似物，众所周知是大鼠肝脏中的一种强效致癌物质。在这项研究中，为了评估乙硫氨酸是否可以通过 LPA 受体调节细胞迁移活性，用乙硫氨酸处理大鼠肝上皮（WB-F344）细胞 48 小时。在细胞培养插入物的细胞迁移测定中，与未经处理的细胞相比，1.0 和 10 μM 的乙硫氨酸处理显著增强了高细胞迁移活性。用定量实时 RT-PCR 分析测定用乙硫氨酸处理的细胞中 LPA 受体基因的表达水平。乙硫氨酸处理细胞中 Lpar3 基因的表达明显高于未处理的细胞。此外，为了确认 LPA3 对乙硫氨酸增加的细胞迁移的参与，还使用了 Lpar3 敲低细胞。乙硫氨酸的细胞迁移活性在 Lpar3 敲低细胞中完全受到抑制。这些结果表明，LPA 信号通过 LPA3 可能参与 WB-F344 细胞中由乙硫氨酸刺激的细胞迁移活性。
