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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Central role of Sp1-regulated CD39 in hypoxia/ischemia protection
Blood, Volume 113, No. 1, Year 2009
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Description
Hypoxia is common to several inflammatory diseases, where multiple cell types release adenine-nucleotides (particularly adenosine triphosphate/adenosine diphosphate). Adenosine triphosphate/adenosine diphosphate is metabolized to adenosine through a 2-step enzymatic reaction initiated byCD39(ectonucleoside- triphosphatediphosphohydrolase- 1). Thus, extracellular adenosine becomes available to regulate multiple inflammatory endpoints. Here, we hypothesized that hypoxia transcriptionally up-regulates CD39 expression. Initial studies revealed hypoxia-dependent increases in CD39 mRNA and immunoreactivity on endothelia. Examination of the human CD39 gene promoter identified a region important in hypoxia inducibility. Multiple levels of analysis, including site-directed mutagenesis, chromatin immunoprecipitation, and inhibition by antisense, revealed a critical role for transcription-factor Sp1 in hypoxiainduction of CD39. Using a combination of cd39-/ -mice and Sp1 small interfering RNA in in vivo cardiac ischemia models revealed Sp1-mediated induction of cardiac CD39 during myocardial ischemia. In summary, these results identify a novel Sp1-dependent regulatory pathway for CD39 and indicate the likelihood that CD39 is central to protective responses to hypoxia/ischemia. © 2009 by The American Society of Hematology.
Authors & Co-Authors
Robson, Simon Christopher
United States, Boston
Harvard Medical School
Colgan, Sean P.
United States, Aurora
University of Colorado Anschutz Medical Campus
United States, Aurora
University of Colorado School of Medicine
Statistics
Citations: 195
Authors: 2
Affiliations: 4
Identifiers
Doi:
10.1182/blood-2008-06-165746
ISSN:
00064971
Research Areas
Genetics And Genomics
Noncommunicable Diseases