出版社：American Society for Biochemistry and Molecular Biology
摘要：Adipose differentiation-related protein (ADRP) is a major proteinassociated with lipid droplets in various types of cells, includingmacrophage-derived foam cells and liver cells. However, therole of ADRP in the processes of formation and regression ofthese cells is not understood. When J774 murine macrophageswere incubated with either VLDL or oleic acid, their contentof both ADRP and triacylglycerol (TG) increased 3- to 4-fold.Induction of ADRP during TG accumulation was also observed inoleic acid-treated HuH-7 human liver cells. Addition of triacsinC, a potent inhibitor of acyl-CoA synthase, for 6 h decreasedthe amount of TG in VLDL-induced foam cells and oleic acid-treatedliver cells; it decreased the amount of ADRP protein in parallel,indicating the amount of ADRP reduced during regression of thelipid-storing cells. Addition of a proteasome inhibitor duringtriacsin C treatment abolished the ADRP decrease and accumulatedpolyubiquitinated ADRP. In addition, the proteasome inhibitorreversed not only the degradation of ADRP but also TG reductionby triacsin C. These results suggest that cellular amounts ofADRP and TG regulate each other and that the ubiquitin-proteasomesystem is involved in degradation of ADRP during regressionof lipid-storing cells.Supplementary key words lipid droplets • adipose differentiation-related protein • macrophages • liver cells • triacylglycerol • VLDL
Abbreviations: AcLDL, acetylated LDL; ADRP, adipose differentiation-related protein; ALP, alkaline phosphatase; FC, free cholesterol; LPDS, lipoprotein-deficient serum; LPS, lipopolysaccharide; mAb, monoclonal antibody; OxLDL, oxidized LDL; pAb, polyclonal antibody; PNS, postnuclear supernatant; TC, total cholesterol; TG, triacylglycerol
