Uptake of retinyl ester in HL-60 cells via the low-density-lipoprotein-receptor pathway.
Newly absorbed retinol is transported in association with chylomicrons and their remnants. In addition, after intake of high doses of retinol, significant amounts are also found in low-density lipoprotein (LDL). As both chylomicron remnants and LDL may be taken up by cells via the LDL receptor, and retinoids inhibit proliferation of some leukaemic cells, we have studied the uptake of retinol in leukaemic cells via the LDL-receptor pathway. HL-60 cells contain saturable binding sites for LDL. The binding of LDL to its receptor has a dissociation constant of about 3.2 x 10(-9) M, and the number of receptors per cell was calculated to be about 2700. Uptake of 125I-LDL by HL-60 cells was increased 2-fold by preincubating the cells with mevinolin. The presence of specific receptors for LDL on HL-60 cells was further confirmed by the finding that exogenous LDL cholesterol was able to up-regulate the ACAT (acyl-CoA: cholesterol acyltransferase) activity of HL-60 cells. We then tested the uptake of retinyl ester in leukaemic cells via the LDL-receptor pathway. HL-60 cells were incubated with LDL or chylomicron remnants labelled with [3H]retinyl palmitate. Uptake of retinyl ester associated with both LDL and chylomicron remnants was observed. Furthermore, the presence of excess LDL decreased the uptake by 75-100%, supporting the hypothesis that the uptake of retinyl ester occurred via the LDL receptor in HL-60 cells.
Wathne
K O
KO
Institute for Nutrition Research, School of Medicine, University of Oslo, Norway.
Carlander
B
B
Norum
K R
KR
Blomhoff
R
R
D002460:Cell Line; D004224:Diterpenes; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008148:Lovastatin / Q000494:pharmacology; D012176:Retinoids / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000378:metabolism*; D000084562:Retinyl Esters; D002785:Sterol O-Acyltransferase / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014801:Vitamin A / Q000031:analogs & derivatives / Q000378:metabolism
D004224:Diterpenes; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D012176:Retinoids; D012177:Retinol-Binding Proteins; D000084562:Retinyl Esters; C022081:retinyl ester lipoprotein complex; D014801:Vitamin A; C014794:retinol palmitate; D008148:Lovastatin; D002785:Sterol O-Acyltransferase