Differential regulation of the STARD1 subfamily of START lipid trafficking proteins in human macrophages.
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.
Borthwick
Faye
F
Vascular Biology Group, Glasgow Caledonian University, Glasgow, UK.
Taylor
Janice M
JM
Bartholomew
Chris
C
Graham
Annette
A
D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002777:Cholestanols / Q000494:pharmacology; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D005487:Foam Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism; D000071518:Liver X Receptors; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D051779:Sterol Regulatory Element Binding Proteins / Q000235:genetics / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000494:pharmacology; D000098682:Steroidogenic Acute Regulatory Protein
D002352:Carrier Proteins; D002777:Cholestanols; D004268:DNA-Binding Proteins; C107473:LY 295427; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; D008565:Membrane Proteins; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D010750:Phosphoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D047488:Retinoid X Receptors; C105684:STARD3 protein, human; D051779:Sterol Regulatory Element Binding Proteins; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C099252:oxidized low density lipoprotein; D000098682:Steroidogenic Acute Regulatory Protein; D002784:Cholesterol