新規経口貧血改善薬反応性遺伝子の網羅的解析　〜ドーピング検出への応用をめざして〜

概要

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Erythropoietin (EPO) promotes red blood cell production thereby raising oxygen transport ability. Epo gene expression is positively controlled by hypoxia-inducible factor (HIF) through the HIF binding site in an Epo gene enhancer; and negatively controlled by GATA, which binds to the GATA site in the Epo gene promoter. Drugs that activate HIF (FG-2216) or inhibit GATA (K-11706) increase the production of EPO. Therefore, these drugs might be illicitly used to improve performance in sports as new doping practices. To develop a system for detecting such a doping strategy, we performed DNA microarray and quantitative RT-PCR to compare the effects of FG-2216*, the derivative of FG-2216, and K-11706, on gene expression with that of recombinant human EPO (rhEPO) or hypoxia in mice. Gene expression analysis in bone marrow cells showed increased expression of Lactoperoxidase (Lpo) only in the mice treated with K-11706, and decreased expression of Oncostatin M (Osm) with FG-2216* or hypoxia, but not with K-11706. Results to date suggest that gene expression changes observed in using these drugs have the potential to yield novel biomarkers in a detection system for new illicit drug use.