论文部分内容阅读
在生理条件下,pH的稳定是细胞生长、增殖和凋亡的一个重要影响因素。一旦pH平衡被打破,细胞的功能和生存将会受到影响。然而,适度的酸中毒能提高细胞对有害应激的耐受,从而增加细胞在有害环境中的生存能力。在本研究中,我们用一种无脊椎动物水蚤作为模式动物,发现酸预处理能提高水蚤在严重缺氧条件下的耐受,同时,酸预处理明显地增加了低氧诱导因子(HIF)的表达。HIF拮抗剂echinomycin和磷酸腺苷激活的蛋白激酶(AMPK)拮抗剂Compound C能有效的抑制酸预处理引起的水蚤对低氧的耐受和酸预处理介导的HIF的表达增高;而哺乳动物的雷帕霉素靶蛋白(mTOR)拮抗剂temsirolimus虽然抑制了酸预处理介导的HIF的表达增高,但却提高了酸预处理所引起的水蚤对低氧的耐受。因此,酸预处理对水蚤的保护作用不仅依赖于HIF的表达上调,也与AMPK和mTOR信号途径有关。
Under physiological conditions, pH stability is an important factor in cell growth, proliferation and apoptosis. Once the pH balance is broken, cell function and survival will be affected. However, moderate acidosis can increase the tolerance of cells to harmful stresses, thereby increasing the viability of cells in harmful environments. In this study, we used an invertebrate Daphnia as a model animal and found that acid pretreatment increased water flea tolerance under severe hypoxia, while acid pretreatment significantly increased hypoxia-inducible factor ( HIF) expression. HIF antagonist echinomycin and AMPK antagonist Compound C can effectively inhibit the hypoxia tolerance caused by acid pretreatment and acid pretreatment-mediated HIF expression increased; while lactation Although the antagonist of temsirolimus, an animal target of mTOR antagonism, inhibited the increase of HIF induced by acid pretreatment, it increased the hypoxia tolerance of Daphnia caused by acid pretreatment. Thus, the protective effect of acid pretreatment on Daphnia not only depends on the up-regulation of HIF but also on the AMPK and mTOR signaling pathways.