Sonna Larry A, Cullivan Michael L, Sheldon Holly K, Pratt Richard E, Lilly Craig M
Thermal and Mountain Medicine Division, United States Army Research Institute of Environmental Medicine, Natick, MA 01760, USA.
Physiol Genomics. 2003 Feb 6;12(3):195-207. doi: 10.1152/physiolgenomics.00104.2002.
The full extent to which hypoxia produces gene expression changes in human cells is unknown. We used late-generation oligonucleotide arrays to catalog hypoxia-induced changes in gene expression in HepG2 cells. Five paired sets of cultures were subjected to either control (room air-5% CO(2)) or hypoxic (1% O(2)-5% CO(2)) conditions for 24 h, and RNA was analyzed on an Affymetrix cDNA array containing approximately 12,600 sequences. A statistically significant change in expression was shown by 2,908 sequences (1,255 increased and 1,653 decreased). The observed changes were highly concordant with published literature on hypoxic stress but showed relatively little overlap (12-22%) with changes in gene expression that have been reported to occur after heat stress in other systems. Of note, of these 2,908 sequences, only 387 (213 increased and 174 decreased) both exhibited changes in expression of twofold or greater and were highly expressed in at least three of the five experiments. We conclude that the effect of hypoxia on gene expression by HepG2 cells is broad, has a significant component of downregulation, and includes a relatively small number of genes whose response is truly independent of cell and stress type.
缺氧在人类细胞中引起基因表达变化的完整程度尚不清楚。我们使用新一代寡核苷酸阵列来梳理缺氧诱导的HepG2细胞基因表达变化。五组配对培养物分别置于对照（室内空气-5%二氧化碳）或缺氧（1%氧气-5%二氧化碳）条件下24小时，然后在包含约12,600个序列的Affymetrix cDNA阵列上分析RNA。2,908个序列显示出具有统计学意义的表达变化（1,255个增加，1,653个减少）。观察到的变化与关于缺氧应激的已发表文献高度一致，但与其他系统中热应激后报道的基因表达变化的重叠相对较少（12 - 22%）。值得注意的是，在这2,908个序列中，只有387个（213个增加，174个减少）在五个实验中的至少三个实验中既表现出两倍或更大的表达变化，又具有高表达。我们得出结论，缺氧对HepG2细胞基因表达的影响是广泛的，有显著的下调成分，并且包括相对少数其反应真正独立于细胞和应激类型的基因。
