Deletion of the transmembrane transporter ABCG1 results in progressive pulmonary lipidosis.

Deletion of the transmembrane transporter ABCG1 results in progressive pulmonary lipidosis. Research Abstract Details 

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Deletion of the transmembrane transporter ABCG1 results in progressive pulmonary lipidosis. Abstract Text:

Angel ,Paul Tarr,Charisse S Vales,Joy Frank,Thomas K Shimotake,Sam Hawgood,Peter A Edwards,

We show that mice lacking the ATP-binding cassette transmembrane transporter ABCG1 show progressive and age-dependent severe pulmonary lipidosis that recapitulates the phenotypes of different respiratory syndromes in both humans and mice. The lungs of chow-fed Abcg1(-/-) mice, >6-months old, exhibit extensive subpleural cellular accumulation, macrophage, and pneumocyte type 2 hypertrophy, massive lipid deposition in both macrophages and pneumocytes and increased levels of surfactant. No such abnormalities are observed at 3 months of age. However, gene expression profiling reveals significant changes in the levels of mRNAs encoding key genes involved in lipid metabolism in both 3- and 8-month-old Abcg1(-/-) mice. These data suggest that the lungs of young Abcg1(-/-) mice maintain normal lipid levels by repressing lipid biosynthetic pathways and that such compensation is inadequate as the mice mature. Studies with A-549 cells, a model for pneumocytes type 2, demonstrate that overexpression of ABCG1 specifically stimulates the efflux of cellular cholesterol by a process that is dependent upon phospholipid secretion. In addition, we demonstrate that Abcg1(-/-), but not wild-type macrophages, accumulate cholesterol ester droplets when incubated with surfactant. Together, these data provide a mechanism to explain the lipid accumulation in the lungs of Abcg1(-/-)mice. In summary, our results demonstrate that ABCG1 plays essential roles in pulmonary lipid homeostasis.

Deletion of the transmembrane transporter ABCG1 results in progressive pulmonary lipidosis. Publishing Authors By Initials

A ,P Tarr,CS Vales,J Frank,TK Shimotake,S Hawgood,PA Edwards,

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Deletion of the transmembrane transporter ABCG1 results in progressive pulmonary lipidosis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 281

Page Numbers: 29401-10

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ISSN: 0021-9258

DAY: 3

MONTH: 08

YEAR: 2006

Deletion of the transmembrane transporter ABCG1 results in progressive pulmonary lipidosis. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

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Grant and Affiliation Information for Deletion of the transmembrane transporter ABCG1 results in progressive pulmonary lipidosis.

AFFILIATION: Department of Biological Chemistry, University o California, Los Angeles 90095, USA.

Country: United States

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MEDLINETA: J Biol Chem

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