| Neutral lipid trafficking regulates alveolar type II cell surfactant phospholipid and surfactant protein expression. | |
MedLine Citation:
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PMID: 21721951 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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ABSTRACT Adipocyte differentiation-related protein (ADRP) is a critically important protein that mediates lipid uptake, and is highly expressed in lung lipofibroblasts (LIFs). Triacylglycerol secreted from the pulmonary circulation and stored in lipid storage droplets is a robust hormonal-, growth factor-, and stretch-regulated precursor for surfactant phospholipid synthesis by alveolar type II epithelial (ATII) cells. A549 lung epithelial cells rapidly take up green fluorescent protein (GFP)-ADRP fusion protein-associated lipid droplets (LDs) in a dose-dependent manner. The LDs initially localize to the perinuclear region of the cell, followed by localization in the cytoplasm. Uptake of ADRP-LDs causes a time- and dose-dependent increase in surfactant protein-B (SP-B) expression. This mechanism can be inhibited by either actinomycin D or cycloheximide, indicating that ADRP-LDs induce newly synthesized SP-B. ADRP-LDs concomitantly stimulate saturated phosphatidylcholine (satPC) synthesis by A549 cells, which is inhibited by ADRP antibody, indicating that this is a receptor-mediated mechanism. Intravenous administration of GFP-ADRP LDs to adult rats results in dose-dependent increases in lung ADRP and SP-B expression. These data indicate that lipofibroblast-derived ADRP coordinates ATII cells' synthesis of the surfactant phospholipid-protein complex by stimulating both satPC and SP-B. The authors propose, therefore, that ADRP is the physiologic determinant for the elusive coordinated, stoichiometric synthesis of surfactant phospholipid and protein by pulmonary ATII cells. |
Authors:
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John Torday; Virender Rohan |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-1 |
Journal Detail:
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Title: Experimental lung research Volume: - ISSN: 1521-0499 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8004944 Medline TA: Exp Lung Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center , Torrance, California , USA. |
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