Enhancement of low density lipoprotein binding to both low density lipoprotein receptor-positive and- negative cells by tetracycline antibiotics

Some tetracycline (TC) antibiotics, including TC and anhydrotetracycline, have been found to enhance specific binding of low density lipoprotein (LDL) to both LDL receptor-positive and-negative cells at relatively higher concentrations. When incubated at 37°C, the ability of LDL receptor-negative human fibroblasts to bind ¹²⁵I-LDL was increased from<2 to 45 ng/mg by 170 μM TC. In normal human fibroblasts and Hep G2 cells, ¹²⁵I-LDL binding was elevated 1.4- to 2-fold by 113 μM TC. The ¹²⁵I-LDL binding in the presence of TC was diminished by both heparin and EDTA. The enhancement by TC was not observed when ¹²⁵I-LDL binding was assayed at 4°C. TC enhanced LDL binding to paraformaldehyde-fixed Hep G2 cells, excluding LDL receptor induction in the mechanism. These results demonstrated that TC enhanced cellular LDL binding through a process not involving functional LDL receptors.