Retinoic acid-induced HL-60 cell differentiation is augmented by copper supplementation.
The objective of this study was to determine how copper influences the ability of HL-60 cells to differentiate into cells of the granulocytic lineage. We hypothesized that granulopoiesis requires copper because copper-deficient humans become neutropenic. Differentiation of HL-60 cells along the granulocytic lineage with retinoic acid was enhanced by copper. The results showed a greater number of cells were more differentiated when copper was added to the medium for 96 h. The respiratory burst activity of retinoic acid-induced cells was increased by copper supplementation, but intracellular superoxide anion generation was not affected. Supplementation with copper resulted in more cell-associated copper in both noninduced and induced cells; however, the induced cells accumulated three times more copper than the noninduced cells. Even though the amount of copper associated with retinoic acid-treated cells was greater than in untreated cells, the activity of a copper-requiring enzyme, copper/zinc superoxide dismutase, was significantly lower. Copper supplementation increased the activity of this enzyme in both retinoic acid-treated and untreated cells. Cytochrome c oxidase activity was not affected by retinoic acid treatment or by copper supplementation. Copper seems to play a specific role during the early stages of granulocyte differentiation.
Bae
B
B
Food Science and Human Nutrition Department, University of Florida, Gainesville 32611.
Percival
S S
SS
D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D003300:Copper / Q000378:metabolism / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000502:physiology; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects* / Q000502:physiology; D013482:Superoxide Dismutase / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D013481:Superoxides; D009580:Nitroblue Tetrazolium; D014212:Tretinoin; D003300:Copper; D013482:Superoxide Dismutase; D003576:Electron Transport Complex IV