Functional ABCG1 expression induces apoptosis in macrophages and other cell types

László Seres, Judit Cserepes, N. Elkind, D. Törőcsik, L. Nagy, B. Sarkadi, L. Homolya

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The expression of the ATP-binding cassette transporter ABCG1 is greatly increased in macrophages by cholesterol loading via the activation of the nuclear receptor LXR. Several recent studies demonstrated that ABCG1 expression is associated with increased cholesterol efflux from macrophages to high-density lipoprotein, suggesting an atheroprotective role for this protein. Our present study uncovers an as yet not described cellular function of ABCG1. Here we demonstrate that elevated expression of human ABCG1 is associated with apoptotic cell death in macrophages and also in other cell types. We found that overexpression of the wild type protein results in phosphatidyl serine (PS) translocation, caspase 3 activation, and subsequent cell death, whereas neither the inactive mutant variant of ABCG1 (ABCG1K124M) nor the ABCG2 multidrug transporter had such effect. Induction of ABCG1 expression by LXR activation in Thp1 cells and in human monocyte-derived macrophages was accompanied by a significant increase in the number of apoptotic cells. Thyroxin and benzamil, previously identified inhibitors of ABCG1 function, selectively prevented ABCG1-promoted apoptosis in transfected cells as well as in LXR-induced macrophages. Collectively, our results suggest a causative relationship between ABCG1 function and apoptotic cell death, and may offer new insights into the role of ABCG1 in atherogenesis.

Original languageEnglish
Pages (from-to)2378-2387
Number of pages10
JournalBBA - Biomembranes
Volume1778
Issue number10
DOIs
Publication statusPublished - Oct 2008

Fingerprint

Macrophages
Apoptosis
Cell death
Cell Death
Chemical activation
Cholesterol
ATP-Binding Cassette Transporters
Phosphatidylserines
HDL Lipoproteins
Cytoplasmic and Nuclear Receptors
Thyroxine
Caspase 3
Atherosclerosis
Proteins
Cell Count
Cells

Keywords

  • ABC transporter
  • Annexin V binding
  • Atherosclerosis
  • LXR-ligand
  • Macrophage

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Biophysics

Cite this

Functional ABCG1 expression induces apoptosis in macrophages and other cell types. / Seres, László; Cserepes, Judit; Elkind, N.; Törőcsik, D.; Nagy, L.; Sarkadi, B.; Homolya, L.

In: BBA - Biomembranes, Vol. 1778, No. 10, 10.2008, p. 2378-2387.

Research output: Contribution to journalArticle

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