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Physiol. Genomics (November 15, 2001). doi:10.1152/physiolgenomics.00058.2001
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Articles in PresS, published online ahead of print November 15, 2001
Physiol Genomics, 10.1152/physiolgenomics.00058.2001
Submitted on July 16, 2001
Accepted on November 13, 2001

Gene Expression Profiles in Human Cardiac Cells Subjected to Hypoxia or Expressing a Hybrid Form of HIF-1{alpha}

Canwen Jiang1*, Hseinwie Lu1, Karen A Vincent1, Srinivas Shankara1, Adam J Belanger1, Seng H Cheng1, Geoffrey Y Akita1, Ralph A Kelly1, Mark A Goldberg1, and Richard J Gregory1

1 Genzyme Corporation, Framingham, MA, USA

* To whom correspondence should be addressed. E-mail: canwen.jiang{at}genzyme.com.

The cellular response to hypoxia depends on rapid post-translational modifications of proteins as well as regulation of gene expression. We performed serial analysis of gene expression (SAGE) on human cardiac cells under normoxia, subjected to hypoxia, or infected with Ad2/HIF-1{alpha}/VP16 (an adenoviral vector expressing a stable hybrid form of hypoxia-inducible factor 1{alpha}) or Ad2/CMVEV (an empty vector). Of the 97,646 SAGE tags that were sequenced, 27% matched GenBank entries while an additional 32% matched expressed sequence tags in UniGene. We analyzed 161 characterized genes or ESTs with a putative identification. Expression of 35, 11, and 46 was increased by hypoxia, infection with Ad2/EVCMV or Ad2/HIF-1{alpha}/VP16, respectively, compared to normoxia; conversely, 20, 11, 38 genes, respectively, were expressed at lower levels. Genes regulated by hypoxia were associated with transcription, biosynthesis, extracellular matrix formation, glycolysis, energy production, cell survival, and cell stress. Changes following infection with Ad2/HIF-1{alpha}/VP16 mimicked the hypoxic response to a certain extent. Infection with Ad2/CMVEV affected expression of genes that were associated with extracellular matrix formation, and membrane trafficking. Differential expression of select genes was confirmed using TaqMan in additional human cardiac cells and rat neonatal ventricular myocytes. These data provide insight into gene expression underlying the diverse and complex cellular response to hypoxia, expression of HIF-1{alpha}/VP16, or adenoviral infection.




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