FEBS Letters
Volume 583, Issue 7 , Pages 1147-1153, 2 April 2009

Differential regulation of the STARD1 subfamily of START lipid trafficking proteins in human macrophages

Edited by Laszlo Nagy

  • Faye Borthwick

      Affiliations

    • Vascular Biology Group, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, UK
    • ,
  • Janice M. Taylor

      Affiliations

    • Vascular Biology Group, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, UK
    • ,
  • Chris Bartholomew

      Affiliations

    • Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, UK
    • ,
  • Annette Graham

      Affiliations

    • Vascular Biology Group, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, UK
    • Corresponding Author InformationCorresponding author. Fax: +44 (0) 141 3208.

Received 25 November 2008; received in revised form 17 February 2009; accepted 27 February 2009. published online 09 March 2009.

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.

Keywords: Atherosclerosis, Macrophage, ‘Foam cell’, Steroidogenic acute regulatory protein (StAR/STARD1), STARD3/metastatic lymph node 64 (MLN64), Liver X receptor, Peroxisome proliferator activated receptor, Retinoic acid X receptor, Sterol regulatory element binding protein

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PII: S0014-5793(09)00173-2

doi:10.1016/j.febslet.2009.02.042

FEBS Letters
Volume 583, Issue 7 , Pages 1147-1153, 2 April 2009

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