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Articles in PresS, published online ahead of print December 3, 2002
Physiol Genomics, 10.1152/physiolgenomics.00104.2002
Submitted on August 14, 2002
Accepted on November 14, 2002
1 Thermal and Mountain Medicine Division, US Army Research Institute of Environmental Medicine, Natick, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA
2 Thermal and Mountain Medicine Division, US Army Research Institute of Environmental Medicine, Natick, MA, USA
3 Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA
4 Cardiology Division and The Gene Array Technology Center, Brigham and Women's Hospital, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: larry.sonna{at}na.amedd.army.mil.
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% CO2) or hypoxic (1% O2 / 5% CO2) conditions for 24 hours, and RNA was analyzed on an Affymetrix cDNA array containing ~12,600 sequences. 2908 sequences (1255 increased and 1653 decreased) showed a statistically significant change in expression. The observed changes were highly concordant with published literature on hypoxic stress, but showed relatively little overlap (11 - 22%) with changes in gene expression that have been reported to occur after heat stress in other systems. Of note, of these 2908 sequences, only 387 (213 increased and 174 decreased) both exhibited changes in expression of 2-fold or greater and were highly expressed in at least 3 of the 5 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.
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