MICROARRAY EXPRESSION PROFILING IN THE USE OF NEW ORAL DRUGS FOR ANEMIA: AN APPLICATION TO DOPING DETECTION / 体力科学

ABSTRACT

Erythropoietin (EPO) promotes red blood cell production thereby raising oxygen transport ability. <i>Epo</i> gene expression is positively controlled by hypoxia-inducible factor (HIF) through the HIF binding site in an <i>Epo</i> gene enhancer; and negatively controlled by GATA, which binds to the GATA site in the <i>Epo</i> 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 (<i>Lpo</i>) only in the mice treated with K-11706, and decreased expression of Oncostatin M (<i>Osm</i>) 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.