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- Title
Differential regulation of the STARD1 subfamily of START lipid trafficking proteins in human macrophages
- Authors
Borthwick, Faye; Taylor, Janice M.; Bartholomew, Chris; Graham, Annette
- Abstract
Abstract: The STARD1 subfamily of ‘START’ lipid trafficking proteins can reduce macrophage lipid content and inflammatory status (STARD1; StAR), and traffic cholesterol from endosomes (STARD3/MLN64). During macrophage differentiation, STARD1 mRNA and protein increase with sterol content, while the reverse is true for STARD3. Sterol depletion (methyl beta-cyclodextrin) enhances STARD3, and represses STARD1 expression. Agonists of Liver X receptors, peroxisome proliferator activated receptor-gamma and retinoic acid X receptors increase STARD1 expression, while hypocholesterolaemic agent, LY295427, reveals both STARD1 and STARD3 as putative SREBP-target genes. Pathophysiological ‘foam cell’ formation, induced by acetylated or oxidized LDL, significantly reduced both STARD1 and STARD3 gene expression. Differential regulation of STARD1 and D3 reflects their distinct roles in macrophage cholesterol metabolism, and may inform anti-atherogenic strategies.
- Subjects
CELL differentiation; CARRIER proteins; LIPID metabolism; MACROPHAGES; CHOLESTEROL; MESSENGER RNA; GENETIC regulation; NUCLEAR receptors (Biochemistry)
- Publication
FEBS Letters, 2009, Vol 583, Issue 7, p1147
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2009.02.042