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Related Experiment Videos

Oxysterols trigger ABCA1-mediated basolateral surfactant efflux.

Marianna Agassandian1, Satya N Mathur, Jiming Zhou

  • 1Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City 52242, USA.

American Journal of Respiratory Cell and Molecular Biology
|March 25, 2004
PubMed
Summary

Oxysterols, specifically 22-hydroxycholesterol (22HC) with retinoic acid (RA), reduce surfactant by increasing phospholipid export via the ABCA1 transporter in lung cells. This pathway impacts surfactant availability for secretion.

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Area of Science:

  • Pulmonary Biology
  • Cellular Biology
  • Lipid Metabolism

Background:

  • Surfactant, rich in disaturated phosphatidylcholine (DSPtdCho), is crucial for lung function and secreted apically by alveolar epithelia.
  • Surfactant deficiency is linked to inflammatory lung diseases, potentially due to serum lipoprotein components like oxysterols.
  • Oxysterols may impair surfactant availability by altering phosphatidylcholine (PtdCho) trafficking.

Purpose of the Study:

  • To investigate if oxysterols affect surfactant PtdCho availability by altering its cellular trafficking.
  • To determine the mechanism by which oxysterols influence PtdCho levels in lung epithelia.

Main Methods:

  • Utilized murine lung epithelial cells treated with 22-hydroxycholesterol (22HC) and 9 cis-retinoic acid (RA).

Related Experiment Videos

  • Assessed PtdCho levels and basolateral efflux.
  • Employed transcriptional activation assays, ABCA1 knockdown (siRNA), ABCA1 inhibition (glyburide), ABCA1 overexpression, and mutagenesis studies.

    • Main Results:

    • 22HC/RA decreased surfactant PtdCho levels by stimulating basolateral phospholipid export.
    • This efflux was mediated by transcriptional activation of the ATP-binding cassette transporter 1 (ABCA1) gene via a DR-4 promoter locus.
    • ABCA1 knockdown or inhibition attenuated the 22HC/RA-induced PtdCho efflux, which included DSPtdCho species.
    • ABCA1 overexpression mimicked the effect, while ABCA1 mutagenesis at Trp590 reduced PtdCho release.

    Conclusions:

    • An oxysterol-activated basolateral pathway for surfactant phospholipid export exists in lung epithelia.
    • This pathway, involving ABCA1, can reduce the availability of PtdCho for apical surfactant secretion.
    • Oxysterols may contribute to surfactant deficiency in inflammatory lung conditions by disrupting PtdCho homeostasis.