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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Biological Transport / drug effects
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Biological Transport / physiology
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Differentiation / drug effects
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Cell Differentiation / physiology
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Cell Line
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Cholestanols / pharmacology
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Cholesterol / genetics
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Cholesterol / metabolism*
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DNA-Binding Proteins / agonists
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Foam Cells / cytology
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Foam Cells / metabolism*
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology*
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Humans
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Lipoproteins, LDL / genetics
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Lipoproteins, LDL / metabolism
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Liver X Receptors
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Orphan Nuclear Receptors
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PPAR gamma / agonists
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PPAR gamma / genetics
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PPAR gamma / metabolism
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Receptors, Cytoplasmic and Nuclear / agonists
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism
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Retinoid X Receptors / agonists
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Retinoid X Receptors / genetics
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Retinoid X Receptors / metabolism
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Steroidogenic Acute Regulatory Protein
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Sterol Regulatory Element Binding Proteins / genetics
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Sterol Regulatory Element Binding Proteins / metabolism
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beta-Cyclodextrins / pharmacology
Substances
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Carrier Proteins
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Cholestanols
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DNA-Binding Proteins
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LY 295427
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Lipoproteins, LDL
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Liver X Receptors
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Membrane Proteins
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Orphan Nuclear Receptors
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PPAR gamma
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Phosphoproteins
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Receptors, Cytoplasmic and Nuclear
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Retinoid X Receptors
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STARD3 protein, human
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Sterol Regulatory Element Binding Proteins
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beta-Cyclodextrins
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methyl-beta-cyclodextrin
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oxidized low density lipoprotein
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Steroidogenic Acute Regulatory Protein
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Cholesterol