Division of Life Science and Chemistry, College of Natural Science, Daejin University, Pocheon, Gyeonggido, 487-711, Republic of Korea.
J Microbiol Biotechnol. 2019 Oct 28;29(10):1675-1681. doi: 10.4014/jmb.1906.06040.
toxin A is known to cause colonic epithelial cell apoptosis, which is considered the main causative event that triggers inflammatory responses in the colon, reflecting the concept that the essential role of epithelial cells in the colon is to form a physical barrier in the gut. We previously showed that toxin A-induced colonocyte apoptosis and subsequent inflammation were dependent on prostaglandin E2 (PGE) produced in response to toxin A stimulation. However, the molecular mechanism by which PGE mediates cell apoptosis in toxin A-exposed colonocytes has remained unclear. Here, we sought to identify the signaling pathway involved in toxin A-induced, PGE-mediated colonocyte apoptosis. In non-transformed NCM460 human colonocytes, toxin A exposure strongly upregulated expression of Bak, which is known to form mitochondrial outer membrane pores, resulting in apoptosis. RT-PCR analyses revealed that this increase in Bak expression was attributable to toxin A-induced transcriptional upregulation. We also found that toxin A upregulation of Bak expression was dependent on PGE production, and further showed that this effect was recapitulated by an EP1 receptor agonist, but not by agonists of other EP receptors. Collectively, these results suggest that toxin A-induced cell apoptosis involves PGE-upregulation of Bak through the EP1 receptor.
毒素 A 已知会导致结肠上皮细胞凋亡，这被认为是触发结肠炎症反应的主要原因，反映了上皮细胞在结肠中的主要作用是在肠道中形成物理屏障的概念。我们之前表明，毒素 A 诱导的肠细胞凋亡和随后的炎症反应依赖于对毒素 A 刺激的反应产生的前列腺素 E2（PGE）。然而，PGE 介导毒素 A 暴露的肠细胞凋亡的分子机制仍不清楚。在这里，我们试图确定参与毒素 A 诱导的 PGE 介导的肠细胞凋亡的信号通路。在未转化的 NCM460 人结肠细胞中，毒素 A 暴露强烈地上调了 Bak 的表达，Bak 已知会形成线粒体外膜孔，导致细胞凋亡。RT-PCR 分析表明，Bak 表达的这种增加归因于毒素 A 诱导的转录上调。我们还发现，毒素 A 上调 Bak 表达依赖于 PGE 的产生，并且进一步表明，这种效应可以被 EP1 受体激动剂再现，但不能被其他 EP 受体的激动剂再现。总之，这些结果表明，毒素 A 诱导的细胞凋亡涉及通过 EP1 受体的 PGE 上调 Bak。
