Oxidative tyrosylation of high density lipoproteins impairs cholesterol efflux from mouse J774 macrophages: role of scavenger receptors, classes A and B

Abstract

Studies were designed to test whether tyrosylation of high-density lipoprotein (HDLT) modifies its metabolic features. HDLTwas less effective than native HDL in promoting cholesterol efflux from J774-AI macrophages. Cell association with fluorescent HDLT-apolipoprotein and the uptake of HDLT-[3H]cholesteryl hexadecyl ether were enhanced by 50% in comparison with native HDL. In addition, neutral cholesterol ester hydrolase (nCEH) activity in J774-AI, which controls the hydrolysis of cholesteryl ester stores to provide free cholesterol for cellular release,declined in the presence of HDLT. In vitro displacement experiments revealed the ability of HDLT to compete with oxidized and acetylated LDL, known as ligands of scavenger receptor (SR) class B type I/II. Similarly, treatment with a blocking antibody to SR-BI/II reduced the cell association of HDLT and native HDL by 50%. The addition of polyinosinic acid, an inhibitor of SR class A, reduced the cell association of HDLT without affecting that of native HDL. These findings provide evidence that HDLT can compete with modified LDL, bind SR-BI/BII and internalize cholesterol ester. Furthermore, the impaired capacity of HDLT in promoting cholesterol efflux from J774-AI was accompanied by diminished nCEH and enhanced recognition by SR-AI/II, which appears to involve the transport of cholesterol into cells.