Medical School, Southeast University, Nanjing, 210009, China.
Medical School, Southeast University, Nanjing, 210009, China.
Biochem Biophys Res Commun. 2021 Jan 1;534:248-253. doi: 10.1016/j.bbrc.2020.11.102. Epub 2020 Dec 3.
We here investigated molecular basis of notch receptor GLP-1 in controlling simulated microgravity stress in Caenorhabditis elegans. glp-1 expression was decreased by simulated microgravity. Meanwhile, glp-1 mutation caused resistance to toxicity of simulated microgravity. GLP-1 acted in germline cells to control toxicity of simulated microgravity. In germline cells, RNAi knockdown of glp-1 increased daf-16 expression. RNAi knockdown of daf-16 suppressed resistance to toxicity of simulated microgravity in glp-1 mutant. In simulated microgravity treated worms, germline RNAi knockdown of glp-1 decreased expressions of daf-28, ins-39, and ins-8 encoding insulin peptides, and resistance to simulated microgravity toxicity could be detected in daf-28(RNAi), ins-39(RNAi), and ins-8(RNAi) worms. In simulated microgravity treated worms, RNAi knockdown of daf-28, ins-39, or ins-8 in germline cells further increased expression and nucleus localization of transcriptional factor DAF-16 in intestinal cells. Therefore, the GLP-1-activated germline-intestine communication of insulin signaling is required for control of simulated microgravity toxicity in C. elegans.
我们在此研究了 Notch 受体 GLP-1 在控制秀丽隐杆线虫模拟微重力应激中的分子基础。模拟微重力会降低 glp-1 的表达。同时，glp-1 突变会导致对模拟微重力毒性的抗性。GLP-1 在生殖细胞中起作用，以控制模拟微重力的毒性。在生殖细胞中，glp-1 的 RNAi 敲低会增加 daf-16 的表达。glp-1 突变体中，daf-16 的 RNAi 敲低会抑制对模拟微重力毒性的抗性。在模拟微重力处理的线虫中，生殖细胞中的 glp-1 RNAi 敲低会降低编码胰岛素肽的 daf-28、ins-39 和 ins-8 的表达，并且可以在 daf-28(RNAi)、ins-39(RNAi)和 ins-8(RNAi)线虫中检测到对模拟微重力毒性的抗性。在模拟微重力处理的线虫中，生殖细胞中 daf-28、ins-39 或 ins-8 的 RNAi 敲低进一步增加了肠道细胞中转录因子 DAF-16 的表达和核定位。因此，GLP-1 激活的生殖细胞-肠通讯胰岛素信号通路对于控制秀丽隐杆线虫模拟微重力毒性是必需的。
