Oxidized LDL induces the expression of ALBP/aP2 mRNA and protein in human THP-1 macrophages

Yuchang Fu,Nanlan Luo,Maria F Lopes-Virella

doi:10.1016/s0022-2275(20)32363-4

Yuchang Fu, Nanlan Luo + Show 1 more

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https://doi.org/10.1016/s0022-2275(20)32363-4

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Abstract

The adipocyte lipid-binding protein (ALBP/aP2) belongs to a multigene family of fatty acid and retinoid transport proteins. This protein is abundantly expressed in the cytoplasm and nuclear region of adipocytes and is postulated to serve as a lipid shuttle, solubilizing hydrophobic fatty acids and delivering them to the appropriate metabolic system for utilization. This report demonstrates that human cholesterol-loaded THP-1 macrophages express ALBP/aP2 and that its expression can be stimulated by oxidized low density lipoprotein (oxLDL). The increase in mRNA expression was paralleled by a similar increase in ALBP/aP2 protein. The increase in ALBP/aP2 mRNA and protein in oxLDL-stimulated THP-1 macrophages is concentration and time dependent and is inhibited by treatment of the cells with an antioxidant inhibitor of nuclear factor-kappaB (NF-kappaB), pyrrolidine dithiocarbamate (PDTC), and with protein kinase C (PKC) inhibitors bisindolylmaleimide I and Ro-31-8220. These results suggest that activation of both NF-kappaB and PKC signaling pathways is necessary for oxLDL-induced ALBP/aP2 gene expression in THP-1 macrophages and that the upregulation of the fatty acid carrier may be a necessary event in foam cell formation.

Highlights

The adipocyte lipid-binding protein (ALBP/aP2) belongs to a multigene family of fatty acid and retinoid transport proteins
Because ALBP/aP2 plays an important role in lipid trafficking during differentiation of adipocytes, and is upregulated in monocytes treated with PPAR␥ agonists, we explored the possibility that expression of ALBP/aP2 might be stimulated in THP-1 cells by incubation of the cells with lipoproteins or lipoprotein immune complexes under conditions that lead to increased cellular lipid content
OxLDL treatment led to the highest level of ALBP/aP2 mRNA (0.65 kb) in THP-1 macrophages compared with the controls. native LDL immune complexes (nLDL-IC) and oxidized low density lipoprotein (oxLDL)-IC stimulation led to high levels of ALBP/aP2 mRNA in THP-1 macrophages when compared with the controls, native low density lipoprotein (LDL) itself did not induce the expression of ALBP/aP2 gene

Summary

Introduction

The adipocyte lipid-binding protein (ALBP/aP2) belongs to a multigene family of fatty acid and retinoid transport proteins. The increase in ALBP/aP2 mRNA and protein in oxLDL-stimulated THP-1 macrophages is concentration and time dependent and is inhibited by treatment of the cells with an antioxidant inhibitor of nuclear factor-␬B (NF-␬B), pyrrolidine dithiocarbamate (PDTC), and with protein kinase C (PKC) inhibitors bisindolylmaleimide I and Ro-318220. These results suggest that activation of both NF-␬B and PKC signaling pathways is necessary for oxLDLinduced ALBP/aP2 gene expression in THP-1 macrophages and that the upregulation of the fatty acid carrier may be a necessary event in foam cell formation.—Fu, Y., N.

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