Phorbol esters inhibit the binding of low-density lipoproteins (LDL) to U-937 monocytelike cells.
The present study demonstrates that U-937 monocytelike human cells possess specific LDL receptors. 125I-LDL binds at 4 degrees C on the cell surface. The bound molecules are releasable by heparin. The reaction requires Ca2+ and the binding sites are sensitive to proteolysis. Unlabeled LDL compete with 125I-LDL, whereas HDL are ineffective. At 37 degrees C, LDL are internalized and degraded by a chloroquine-sensitive pathway. Tumor-promoting phorbol esters inhibit the binding of 125I-LDL to its receptor on U-937 cells. This inhibition exhibits temperature, time, and concentration dependence. At 37 degrees C, inhibition is 50% at 5 X 10(-9) M of TPA. After removal of phorbol esters, treated cells recover their 125I-LDL-binding activity in 60 min. The inhibitory activities of various phorbol esters are proportional to their tumor-promoting activities. Inhibition appears to be due to a reduction in the number of available LDL receptors rather than a decrease in receptor affinity.
D002460:Cell Line; D006801:Humans; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D011973:Receptors, LDL / Q000187:drug effects
D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D010703:Phorbol Esters; D010704:Phorbols; D011973:Receptors, LDL