Lipopolysaccharide (LPS) as a component of the outer structure of cell wall of gram-negative bacteria, could induce apoptosis in the intestinal endocrine cell line STC-1. However, the signaling cascades involved in this process have not been elucidated. Hence, we investigated the mechanism of cell apoptosis and hyposecretion of glucagon-like peptide 1 (GLP-1) induced by LPS in the GLUTag enteroendocrine cell line. LPS decreased the cell viability of GLUTag cells, up-regulated the TNF-α level, induced the apoptosis and down-regulated the mRNA and protein levels of GLP-1. In addition, TNF-α promoted LPS-induced apoptosis of GLUTag cells through mediating the formation of the RIP1/RIP3 necrosome. RIP1 and RIP3 knockdown increased cell viability, the mRNA and protein levels of GLP-1 and the mTOR signaling pathway-related proteins (p-mTOR and p-S6), and decreased the relative caspase 3/7 activity, cell apoptosis and ROS production. Further studies showed that ROS inhibited the mTOR signaling pathway. Moreover, the antioxidant N-acetyl-l-cysteine increased cell viability, GLP-1 expressions and the mTOR signaling pathway-related proteins, and inhibited the ROS production. However, the mTOR specific inhibitor (Rapa) reversed all these above effects. Taken together, our result revealed that LPS induced the apoptosis of GLUTag cells and GLP-1 hyposecretion through the RIP/ROS/mTOR pathway.

中文翻译：

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LPS经由RIP / ROS / mTOR途径诱导GLUTag细胞凋亡和GLP-1分泌不足。

脂多糖（LPS）作为革兰氏阴性细菌细胞壁外部结构的组成部分，可以诱导肠道内分泌细胞系STC-1凋亡。但是，尚未阐明此过程中涉及的信号级联。因此，我们研究了LPS诱导的GLUTag肠内分泌细胞系中细胞凋亡和胰高血糖素样肽1（GLP-1）分泌不足的机制。LPS降低了GLUTag细胞的细胞活力，上调了TNF-α的水平，诱导了细胞凋亡，并下调了GLP-1的mRNA和蛋白水平。此外，TNF-α通过介导RIP1 / RIP3坏死体的形成促进LPS诱导的GLUTag细胞凋亡。RIP1和RIP3敲低可提高细胞活力，GLP-1的mRNA和蛋白水平以及与mTOR信号通路相关的蛋白（p-mTOR和p-S6），并降低了相对半胱天冬酶3/7活性，细胞凋亡和ROS的产生。进一步的研究表明，ROS抑制了mTOR信号通路。此外，抗氧化剂N-乙酰基-1-半胱氨酸增加细胞活力，GLP-1表达和mTOR信号通路相关蛋白，并抑制ROS的产生。但是，mTOR特异性抑制剂（Rapa）可以逆转上述所有作用。两者合计，我们的结果表明，脂多糖通过RIP / ROS / mTOR途径诱导GLUTag细胞凋亡和GLP-1分泌不足。并抑制了ROS的产生。但是，mTOR特异性抑制剂（Rapa）可以逆转上述所有作用。两者合计，我们的结果表明，脂多糖通过RIP / ROS / mTOR途径诱导GLUTag细胞凋亡和GLP-1分泌不足。并抑制了ROS的产生。但是，mTOR特异性抑制剂（Rapa）可以逆转上述所有作用。两者合计，我们的结果表明，脂多糖通过RIP / ROS / mTOR途径诱导GLUTag细胞凋亡和GLP-1分泌不足。