Uptake of transcobalamin II-bound cobalamin by HL-60 cells: effects of differentiation induction.
Binding and uptake of transcobalamin II-bound cobalamin by HL-60 promyelocytic leukemia cells proceed through receptor-mediated endocytosis. The affinity constant of the receptor for transcobalamin II-cobalamin was found to be 6.1 liter/nmol and the maximal rate of uptake 12 pmol/10(9) cells/h. This uptake is mediated by about 3000 receptor sites per cell. Evidence is presented that the receptor recirculates from the cell surface to the lysosomes and vice versa. Upon differentiation induction of the cells by either DMSO in granulocytic direction or by 1,25-dihydroxy-vitamin D3 in monocytic direction a rapid decline in cellular uptake and cell surface binding of the protein-bound vitamin ensues. In particular the internalization of the complex decreases faster than all other observed signs of the ongoing differentiation process, such as reduction in the OKT9-reactive transferrin receptor, increase in lineage-specific surface markers, and decrease in [3H]thymidine incorporation and actual cell proliferation. The transcobalamin II receptor on the cell surface appears to be a proliferation-associated membrane component in human leukemic cells.
Lindemans
J
J
Institute of Hematology, Erasmus University Rotterdam, The Netherlands.
Kroes
A C
AC
van Geel
J
J
van Kapel
J
J
Schoester
M
M
Abels
J
J
D002117:Calcitriol / Q000494:pharmacology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003513:Cycloheximide / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004705:Endocytosis; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology*; D008985:Monensin / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D014155:Transcobalamins / Q000378:metabolism / Q000493:pharmacokinetics*; D014407:Tumor Cells, Cultured; D014805:Vitamin B 12 / Q000378:metabolism / Q000493:pharmacokinetics*
D011956:Receptors, Cell Surface; D014155:Transcobalamins; C028176:transcobalamin receptor; D008985:Monensin; D003513:Cycloheximide; D002117:Calcitriol; D014805:Vitamin B 12; D004121:Dimethyl Sulfoxide