Effect of mechanical stress on responses of oxidative stress

氧化应激与多种人类疾病有关，包括癌症和衰老。我们报道，暴露在机械应力下会增加尿液中8-羟色胺的水平。此外，重复暴露机械应力降低了8-OHdG水平，这些观察结果表明，重复机械应力诱导了耐受性。然而，目前还没有关于机械应激耐受机制的报道，本研究分析了机械应激和氧化应激之间的反应机制。机械应力被认为是一种重要的细胞外刺激，可以促进细胞的生长和存活，影响代谢过程(包括基因表达)，并控制各种细胞类型的组织结构。成纤维细胞培养于包被胶原的弹性硅胶小室中。然后在计算机控制的拉伸装置上对细胞进行单轴拉伸。通过在培养液中添加氧化氢，细胞也暴露在氧化应激下。用基因芯片和Western blotting方法分析基因和蛋白的表达水平。我们鉴定了几个差异表达的基因和蛋白质，包括内质网应激标记葡萄糖调节蛋白78(GRP78)和ERK1。此外，击倒其中一个四叶树网状葡萄胎会导致细胞从培养装置中脱离，因此，在机械应激下对氧化应激做出反应的分子，与蛋白质表达的调节有关。

Oxidative stress have been implicated in a variety of human disorders including cancer and aging. We reported that exposure to mechanical stress increased urinaly 8-OHdG levels. Moreover repetitive exposure of mechanical stress reduced the 8-OHdG level These observations suggested that repetition of mechanical stress induced a tolerance. However, there are no reports about tolerance mechanisms about tolerance of mechanical stress.In this study, we analyzed relationship of responsive mechanisms between mechanical stress and oxidative stress. Mechanical stress is recognized as an important extracellular stimulus that promotes cellular growth and survival, influences metabolic processes (including gene expression), and governs tissue architecture in various cell types. Fibroblast cells were cultured on collagen coated elastic silicon chamber. And then, uni-axial stretch was applied to the cells by a computer-controlled stretching apparatus. Cells were also exposed to an oxidative stress by addition of hydrogen-oxide to the medium. Expression levels of genes and proteins were analyzed by cDNA array nad western blotting methods. We identified several differentially expressed genes and proteins, including the ER stress marker glucose-regulated protein 78 (GRP78) and ERK1. Moreover, knockdown of one of tetraspani web moles induced detachment of cells from a culture apparatus.Therefore, molecules which responsive to the oxidative stress during exposure to the mechanical stress, related to the regulation of protein expression.