COPPER UPTAKE AND INTRACELLULAR-DISTRIBUTION DURING RETINOIC ACID-INDUCED DIFFERENTIATION OF HL-60 CELLS

Because neutropenia is a sign of copper deficiency, the HL-60 cell fin e was used to examine copper distribution during cellular differentiat ion This study measured the accumulation and distribution of copper in differentiating (retinoic acid-treated) and nondifferentiating (untre ated) HL-60 cells by radiolabeling the cells with Cu-67. The intracell ular distribution of total copper as well as Cu-67 was examined Retino ic acid-treated cells had twice as much copper as control cells. Coppe r uptake from Cu-67 labeled ceruloplasmin was greater in retinoic acid -treated cells at 24 and 48 ht after induction compared with the contr ol cells. The intracellular distribution of Cu-67 was found predominan tly in high molecular weight fractions (100,000 D) and a low molecular weight fraction (20,000 D). The high molecular weight protein had gre ater Cu-67 associated with it in the retinoic acid-treated cells than in the untreated control cells. This protein may be responsible for th e greater levels of copper found in the retinoic acid treated cells. C opper uptake is clearly regulated during the process of differentiatio n.