Metabolic changes in LDL receptors and an appearance of scavenger receptors after phorbol ester-induced differentiation of U937 cells.
Metabolic changes in lipoprotein receptors after cell differentiation were investigated using U937 cells, a human tumor cell line with monoblastic characteristics. After inducing the differentiation of U937 cells into monocyte-macrophage-like cells using TPA (12-tetradecanoyl-phorbol-13-acetate), the incorpotation of [14C]oleate into cellular cholesteryl [14C]oleate was increased in comparison with U937 cells when incubated with r-beta VLDL, h-VLDL or h-LDL. A marked down-regulation of LDL receptors was observed in U937 cells upon addition of 25-hydroxycholesterol. However, this down-regulation of LDL receptors was poor in monocyte-macrophage-like cells that had been induced to differentiate from U937 cells with TPA. Acyl coenzyme A:cholesterol acyltransferase activity was increased after TPA-induced differentiation of U-937 cells. The incorporation of [14C]oleate into cellular cholesteryl [14C]oleate was also increased when incubated with acetylated h-LDL in monocyte-macrophage-like cells in comparison with U937 cells. These results suggest that a poor down-regulation of LDL receptors, which is attributable to increased acyl coenzyme A:cholesterol acyltransferase activity, and scavenger receptors are induced and that these metabolic changes in lipoprotein receptors and an increased acyl coenzyme A:cholesterol acyltransferase activity contribute to cholesterol ester accumulation in monocyte-macrophage-like cells.
Hayashi
K
K
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Dojo
S
S
Hirata
Y
Y
Ohtani
H
H
Nakashima
K
K
Nishio
E
E
Kurushima
H
H
Saeki
M
M
Kajiyama
G
G
D000214:Acyl Coenzyme A / Q000502:physiology; D000818:Animals; D002417:Cattle; D002454:Cell Differentiation; D015536:Down-Regulation; D006801:Humans; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism*; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism*; D009829:Oleic Acids / Q000378:metabolism; D010703:Phorbol Esters; D011973:Receptors, LDL / Q000378:metabolism*; D002785:Sterol O-Acyltransferase / Q000502:physiology; D014407:Tumor Cells, Cultured
D000214:Acyl Coenzyme A; D009829:Oleic Acids; D010703:Phorbol Esters; D011973:Receptors, LDL; D002785:Sterol O-Acyltransferase