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Molecular Cloning of the Human ATP-Binding Cassette Transporter 1 (hABC1): Evidence for Sterol-Dependent Regulation in Macrophages

https://doi.org/10.1006/bbrc.1999.0406Get rights and content

Abstract

We have cloned the full-length cDNA for the human ATP binding cassette transporter 1 (hABC1). The 6603-bp open reading frame encodes a polypeptide of 2201 amino acids resulting in a deduced molecular weight of 220 kDa. The hABC1 cDNA is highly homologous (62%) to the human rim ABC transporter (ABCR). hABC1 is expressed in a variety of human tissues with highest expression levels found in placenta, liver, lung, adrenal glands, and fetal tissues. We demonstrate that the hABC1 expression is induced during differentiation of human monocytes into macrophagesin vitro.In macrophages, both the hABC1 mRNA and protein expression are upregulated in the presence of acetylated low-density lipoprotein (AcLDL). The AcLDL-induced increase in hABC1 expression is reversed by cholesterol depletion mediated by the addition of high-density lipoprotein (HDL3). Our data, demonstrating sterol-dependent regulation of hABC1 in human monocytes/macrophages, suggest a novel role for this transporter molecule in membrane lipid transport.

References (23)

  • M.F. Luciani et al.

    Genomics

    (1994)
  • M. Dean et al.

    Curr. Opin. Genet. Dev.

    (1995)
  • G.E. Tusnady et al.

    FEBS Lett.

    (1997)
  • Y. Hamon et al.

    Blood

    (1997)
  • F. Becq et al.

    J. Biol. Chem.

    (1997)
  • T. Langmann et al.

    Biochim. Biophys. Acta

    (1997)
  • S.K. Basu et al.

    J. Biol. Chem.

    (1978)
  • T. Langmann et al.

    Biochem. Biophys. Res. Commun.

    (1997)
  • C.F. Higgins

    Cell

    (1994)
  • C.F. Higgins

    Curr. Biol.

    (1994)
  • A.J. Smith et al.

    FEBS Lett.

    (1994)
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    Sequence data from this article have been deposited in the EMBL/NCBI-GenBank Data Libraries under Accession No. AJ012376.

    1

    To whom correspondence should be addressed at Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauß-Allee 11, D-93042 Regensburg, Germany. Fax: (+49)-941-944-6202. E-mail:[email protected].

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