The transport of glycolytic substrates into the cell is necessary for their effect on MICA expression.
A, cytochalasin B, an inhibitor of GLUT-mediated glucose transport, inhibits cell-surface MICA expression in HEK-293T cells cultured in 25 mm glucose. B, phloretin, a second GLUT transporter inhibitor, also reduces MICA expression in 25 mm glucose. C, mannose, an alternative substrate for glycolysis, induces MICA expression. The ability of fructose to induce MICA expression is limited in normal cells. D, mRNA for the fructose transporter GLUT5 is not detected in HEK-293T cells but is present in GLUT5-transfected cells. E, fructose-induced MICA expression is observed in GLUT5-transfected cells. F, the glucose analogue 2-deoxyglucose (2DG), which is not a substrate for glycolysis, does not induce MICA expression. G, 2DG inhibits MICA expression in 25 mm glucose. H, mannose does not overcome the inhibition of glucose-induced MICA expression by 2DG. RT+, with reverse transcriptase; RT−, without reverse transcriptase; dH2O, deionized H2O. Error bars, 95% confidence interval.