LOSS OF GLUCOSE-TRANSPORT IN DEVELOPING AVIAN RED-CELLS

Although red cells are generally associated with significant glucose t ransport and dependence on glycolysis, the mature red cells of some sp ecies (e.g. pig) show very low glucose transport, The generally low le vel of glucose transport in mature mammalian red cells is the result o f maturational development, since it has been shown that even in red c ells which have negligible glucose transport (e.g. pig red cells) the corresponding reticulocytes have significant glucose transport activit y. The reticulocytes of the chicken, however, show minimal glucose tra nsport activity. But this also is the result of maturational developme nt. since chicken bone marrow red cells do transport glucose which dim inishes upon cell maturation in vitro, The erythroblast chicken cell l ine, HD3, has high glucose transport activity which is lost upon induc tion to the red cell phenotype. Growing HD3 cells have much higher lev els of transport than native chicken bone marrow cells and this is ass ociated in part with elevation of glucose transporter (GLUT) mRNAs as a consequence of the expression of the v-erbA and v-erbB oncogenes, Bo th native bone marrow red cells and HD3 cells, when incubated in vitro under renditions where maturation occurs, show substantial losses of GLUT mRNA and GLUT proteins, To assess whether the inducers of maturat ion (hemin and butyrate) affect only the normally expressed GLUTs, chi cken GLUT3 expressed from a different promoter was introduced into the HD3 cell by retroviral infection, Both the endogenous and erogenous t ransporters were lost upon cell differentiation and maturation, leavin g a cell with low glucose transport activity. Conversely, in growing c ells, butyrate had a pronounced effect on the elevation of the GLUT3 m RNA, especially on the exogenous GLUT3 mRNA, and elevated glucose tran sport prior to differentiation. These results are consistent with the conclusion that chicken red cell development involves a requirement to reduce glucose transport activity. The near absence of glucose transp ort in the embryonic chicken red cell is thus due to a loss of this tr ansporter during early development which occurs at an earlier developm ental stage in the chicken red cell than in the mammalian red cell.