Kwon Ohwon, Sartor Maureen, Tomlinson Craig R, Millard Ronald W, Olah Mark E, Sankovic John M, Banerjee Rupak K
Department of Mechanical Engineering, University of Cincinnati, Cincinnati, OH 45221, USA.
Adv Space Res. 2006;38(6):1168-1176. doi: 10.1016/j.asr.2006.02.059.
Oxygen utilization by and oxygen dependence of cellular processes may be different in biological systems that are exposed to microgravity (micro-g). A baseline in which cellular changes in oxygen sensitive molecular processes occur during micro-g conditions would be important to pursue this question. The objective of this research is to analyze oxidation-sensitive gene expression in a model cell line [rat pheochromocytoma (PC12)] under simulated micro-g conditions. The PC12 cell line is well characterized in its response to oxygen, and is widely recognized as a sensitive model for studying the responses of oxygen-sensitive molecular and cellular processes. This study uses the rotating wall vessel bioreactor (RWV) designed at NASA to simulate micro-g. Gene expression in PC12 cells in response to micro-g was analyzed by DNA microarray technology. The microarray analysis of PC12 cells cultured for 4 days under simulated micro-g under standardized oxygen environment conditions revealed more than 100 genes whose expression levels were changed at least twofold (up-regulation of 65 genes and down-regulation of 39 genes) compared with those from cells in the unit gravity (unit-g) control. This study observed that genes involved in the oxidoreductase activity category were most significantly differentially expressed under micro-g conditions. Also, known oxidation-sensitive transcription factors such as hypoxia-inducible factor-2alpha, c-myc, and the peroxisome proliferator-activated receptor-gamma were changed significantly. Our initial results from the gene expression microarray studies may provide a context in which to evaluate the effect of varying oxygen environments on the background of differential gene regulation of biological processes under variable gravity conditions.
在暴露于微重力（micro-g）的生物系统中，细胞过程的氧利用和氧依赖性可能有所不同。在微重力条件下发生氧敏感分子过程中的细胞变化的基线对于研究这个问题很重要。本研究的目的是分析模拟微重力条件下模型细胞系[大鼠嗜铬细胞瘤（PC12）]中氧化敏感基因的表达。PC12细胞系对氧的反应具有良好的特征，并且被广泛认为是研究氧敏感分子和细胞过程反应的敏感模型。本研究使用美国国家航空航天局（NASA）设计的旋转壁式生物反应器（RWV）来模拟微重力。通过DNA微阵列技术分析PC12细胞中响应微重力的基因表达。在标准化氧环境条件下，对在模拟微重力下培养4天的PC12细胞进行微阵列分析，结果显示，与单位重力（unit-g）对照中的细胞相比，有100多个基因的表达水平至少变化了两倍（65个基因上调，39个基因下调）。本研究观察到，在微重力条件下，参与氧化还原酶活性类别的基因差异表达最为显著。此外，已知的氧化敏感转录因子，如缺氧诱导因子-2α、c-myc和过氧化物酶体增殖物激活受体-γ也发生了显著变化。我们基因表达微阵列研究的初步结果可能提供一个背景，用以评估在可变重力条件下，不同氧环境对生物过程中差异基因调控背景的影响。
