Fong Chi-Chun, Zhang Qi, Shi Yue-Feng, Wu Rudolf S S, Fong Wang-Fun, Yang Mengsu
Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong, SAR, China.
Toxicology. 2007 Jun 3;235(1-2):52-61. doi: 10.1016/j.tox.2007.03.006. Epub 2007 Mar 14.
Hypoxia, a decrease in oxygen tension occurring in pathological tissues, has a profound effect on macrophage functions. In this study, we have investigated cellular and molecular responses of murine macrophage-like RAW264.7 cells to low oxygen tension. Our study revealed that hypoxia induced RAW264.7 cells apoptosis and cell cycle arrest at G0/G1 phase. The result of Western blotting showed that the expression of apoptosis related signaling molecules, such as AKT and JNK was activated under hypoxia. The result of electrophoretic mobility shift assay showed that the DNA binding activity of nuclear factor kappa B (NF-kappaB) was also increased by hypoxic stimulation. Furthermore, gene expression profiles of RAW264.7 macrophages induced by hypoxia showed that hypoxia treatment may alter expression of genes related to apoptosis, survival, cell cycle, metabolism and structural matrix.
缺氧是病理组织中氧张力的降低,对巨噬细胞功能有深远影响。在本研究中,我们研究了鼠巨噬细胞样RAW264.7细胞对低氧张力的细胞和分子反应。我们的研究表明,缺氧诱导RAW264.7细胞凋亡并使细胞周期停滞在G0/G1期。蛋白质印迹结果显示,缺氧时凋亡相关信号分子如AKT和JNK的表达被激活。电泳迁移率变动分析结果显示,缺氧刺激也增加了核因子κB(NF-κB)的DNA结合活性。此外,缺氧诱导的RAW264.7巨噬细胞的基因表达谱表明,缺氧处理可能会改变与凋亡、存活、细胞周期、代谢和结构基质相关的基因表达。