OBJECTIVE The purpose of this study was to evaluate the effect of 12/15-lipoxygenase (12/15LO) in macrophage ABCG1 expression and function associated with cholesterol efflux. METHODS AND RESULTS 12/15LO was stably overexpressed in J774 macrophages. 12/15LO-overexpressing macrophages had a 30% reduction in HDL-mediated cholesterol efflux, corresponding with significantly reduced ABCG1 protein ...

Signal transduction modulates expression and activity of cholesterol transporters. We recently demonstrated that the Ras/mitogen-activated protein kinase (MAPK) signaling cascade regulates protein stability of Scavenger Receptor BI (SR-BI) through Proliferator Activator Receptor (PPARα) -dependent degradation pathways. In addition, MAPK (Mek/Erk 1/2) inhibition has been shown to influence liver...

cardiovascular disease (cvd) is the leading cause of death and disability in developed countries. atherosclerosis is the major cause of cvd, accounting for about half of the attributed deaths. cholesterol homeostasis is one of the most important factors in atherosclerosis. atp-binding cassette transporters cholesterol. omega (ω) 3 fatty acids are important ligands for regulation of abc transpor...

ATP-binding cassette protein G1 (ABCG1) is important for the formation of HDL. However, the biochemical properties of ABCG1 have not been reported, and the mechanism of how ABCG1 is involved in HDL formation remains unclear. We established a procedure to express and purify human ABCG1 using the suspension-adapted human cell FreeStyle293-F. ABCG1, fused at the C terminus with green fluorescent p...

OBJECTIVE In a recent article in Arteriosclerosis, Thrombosis, and Vascular Biology, it was reported that ATP-binding cassette transporter G1 (ABCG1) containing leucine at position 550 (ABCG1-L550) was localized to the plasma membrane, whereas ABCG1-P550 (proline at position 550) was intracellular. Because the published data on the subcellular localization of ABCG1 are controversial, we perform...

Cholesterol is a critical component of cell membranes, and cellular cholesterol levels and distribution are tightly regulated in mammals. Recent evidence has revealed a critical role for pancreatic beta cell-specific cholesterol homeostasis in insulin secretion as well as in beta cell dysfunction in diabetes and the metabolic response to thiazolidinediones (TZDs), which are antidiabetic drugs. ...

OBJECTIVE Recent studies indicate that the ATP-binding cassette transporter ABCG1 can promote cholesterol efflux from macrophages to high-density lipoprotein. This study was designed to assess the in vivo role of macrophage ABCG1 in atherosclerosis. METHODS AND RESULTS Bone marrow from Abcg1-/- mice was transplanted into irradiated Ldlr-/- recipients, and atherosclerosis was evaluated by aort...

Here, we describe the initial characterization of Abcg4(-/-) mice and identify overlapping functions of ABCG4 and ABCG1 in the brain. Histological examination of tissues from Abcg4(+/-)/nlsLacZ and Abcg1(+/-)/nlsLacZ mice demonstrates that coexpression of Abcg4 and Abcg1 is restricted to neurons and astrocytes of the central nervous system (CNS). Interestingly, Abcg4 mRNA is undetectable outsid...

Although intracellular cholesterol levels are known to influence the proteolysis of beta-amyloid precursor protein (APP), the effect of specific genes that regulate cholesterol metabolism on APP processing remains poorly understood. The cholesterol transporter ABCG1 facilitates cholesterol efflux to HDL and is expressed in brain. Notably, the human ABCG1 gene maps to chromosome 21q22.3, and ind...

Abstract Extracellular matrix protein-1 (ECM1) promotes tumorigenesis in multiple organs but the mechanisms associated to ECM1 isoform subtypes have yet be clarified. We report this study that secretory ECM1a induces through GPR motif binding integrin ?X?2 and activation of AKT/FAK/Rho/cytoskeleton signaling. The ATP cassette subfamily G member 1 (ABCG1) transduces ECM1a-integrin interactive si...