出版社:American Society for Biochemistry and Molecular Biology
摘要:Human StarD5 belongs to the StarD4 subfamily of START (for steroidogenicacute regulatory lipid transfer) domain proteins. We previouslyreported that StarD5 is located in the cytosolic fraction ofhuman liver and binds cholesterol and 25-hydroxycholesterol.After overexpression of the gene encoding StarD5 in primaryrat hepatocytes, free cholesterol accumulated in intracellularmembranes. These findings suggested StarD5 to be a directionalcytosolic sterol transporter. The objective of this study wasto determine the localization of StarD5 in human liver. Westernblot analysis confirmed StarD5's presence in the liver but notin human hepatocytes. Immunohistochemistry studies showed StarD5localized within sinusoidal lining cells in the human liverand colocalized with CD68, a marker for Kupffer cells. Westernblot analyses identified the presence of StarD5 in monocytesand macrophages as well as mast cells, basophils, and promyelocyticcells, but not in human hepatocytes, endothelial cells, fibroblasts,osteocytes, astrocytes, or brain tissue. Cell fractionationand immunocytochemistry studies on THP-1 macrophages localizedStarD5 to the cytosol and supported an association with theGolgi. The presence of this cholesterol/25-hydroxycholesterol-bindingprotein in cells related to inflammatory processes providesnew clues to the role of this protein in free sterol transportin the cells and in lipid-mediated atherogenesis.Supplementary key words liver • Kupffer cells • macrophages • sterol transporter