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Guthmann, F; Schachtrup, C; Tölle, A; Wissel, H; Binas, B; Kondo, H; Owada, Y; Spener, F; Rüstow, B.
Phenotype of palmitic acid transport and of signalling in alveolar type II cells from E/H-FABP double-knockout mice: contribution of caveolin-1 and PPARgamma.
Biochim Biophys Acta. 2004; 1636(2-3):196-204
Doi: 10.1016/j.bbalip.2003.10.015
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PubMed
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- Co-Autor*innen der Med Uni Graz
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Spener Friedrich
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- Abstract:
- Based on the assumption that fatty-acid-binding proteins (FABPs) of the epidermal-type (E-FABP) and heart-type (H-FABP) in murine alveolar type II (TII) cells mediate the synthesis of dipalmitoyl phosphatidylcholine (DPPC), the main surfactant phospholipid, we analysed TII cells isolated from wild-type (wt) and E/H-FABP double-knockout (double-ko) mice. Application of labelled palmitic acid to these cells revealed a drop in uptake, beta-oxidation, and incorporation into neutral lipids and total phosphatidylcholine (PC) of TII cells from double-ko mice. Whereas incorporation of labelled palmitic acid into DPPC remained unchanged, degradation studies demonstrated a substantial shift in DPPC synthesis from de novo to reacylation. In addition, increased expression of mRNAs and proteins of caveolin-1 and PPARgamma, and an increase of the mRNA encoding fatty acid translocase (FAT) was observed in the double-ko phenotype. As caveolin-1 interacted with PPARgamma, we assumed that FAT, caveolin-1, and PPARgamma form a signalling chain for fatty acid or drug. Consequently, PPARgamma-selective pioglitazone was added to the diet of double-ko mice. We found that further activation of PPARgamma could 'heal' the E/H-FABP double-ko effect in these TII cells as transport and utilisation of labelled palmitic acid restored a wt phenocopy. This indicated that E-FABP and/or H-FABP are involved in the mediation of DPPC synthesis in wt TII cells.
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Animals -
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Base Sequence -
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Biological Transport -
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Carrier Proteins - genetics Carrier Proteins - physiology
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Caveolin 1 -
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Caveolins - physiology
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DNA Primers -
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Fatty Acid-Binding Proteins -
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Mice -
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Mice, Knockout -
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Nerve Tissue Proteins -
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Palmitic Acid - metabolism
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Polymerase Chain Reaction -
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Pulmonary Alveoli - metabolism
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RNA, Messenger - genetics
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Receptors, Cytoplasmic and Nuclear - physiology
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Transcription Factors - physiology
- Find related publications in this database (Keywords)
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caveolin-1
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fatty-acid-binding protein
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fatty acid signalling
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knockout mouse
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peroxisome proliferator activated receptor
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surfactant