Premium
Phorbol esters inhibit the binding of low‐density lipoproteins (LDL) to U‐937 monocytelike cells
Author(s) -
Rouis M.,
Goldstein S.,
Thomopoulos P.,
Berthelier M.,
Hervy C.,
Testa U.
Publication year - 1984
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041210313
Subject(s) - receptor , chemistry , proteolysis , phorbol ester , ldl receptor , biochemistry , phorbol , inhibitory postsynaptic potential , lipoprotein , cholesterol , protein kinase c , enzyme , biology , endocrinology
The present study demonstrates that U‐937 monocytelike human cells possess specific LDL receptors. 125 I‐LDL binds at 4°C on the cell surface. The bound molecules are releasable by heparin. The reaction requires Ca 2+ and the binding sites are sensitive to proteolysis. Unlabeled LDL compete with 125 I‐LDL, whereas HDL are ineffective. At 37°C, LDL are internalized and degraded by a chloroquine‐sensitive pathway. Tumor‐promoting phorbol esters inhibit the binding of 125 I‐LDL to its receptor on U‐937 cells. This inhibition exhibits temperature, time, and concentration dependence. At 37°C, inhibition is 50% at 5 × 10 −9 M of TPA. After removal of phorbol esters, treated cells recover their 125 I‐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.