Altered lung phospholipid metabolism in mice with targeted deletion of lysosomal-type phospholipase A21
Lung surfactant dipalmitoylphosphatidylcholine (DPPC) is endocytosed by alveolar epithelial cells and degraded by lysosomal-type phospholipase A2 (aiPLA2). This enzyme is identical to peroxiredoxin 6 (Prdx6), a bifunctional protein with PLA2 and GSH peroxidase activities. Lung phospholipid was studi...
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| Format: | Article |
| Language: | English |
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Elsevier
2005-06-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520330297 |
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| author | Aron B. Fisher Chandra Dodia Sheldon I. Feinstein Ye-Shih Ho |
| author_facet | Aron B. Fisher Chandra Dodia Sheldon I. Feinstein Ye-Shih Ho |
| author_sort | Aron B. Fisher |
| collection | DOAJ |
| description | Lung surfactant dipalmitoylphosphatidylcholine (DPPC) is endocytosed by alveolar epithelial cells and degraded by lysosomal-type phospholipase A2 (aiPLA2). This enzyme is identical to peroxiredoxin 6 (Prdx6), a bifunctional protein with PLA2 and GSH peroxidase activities. Lung phospholipid was studied in Prdx6 knockout (Prdx6−/−) mice. The normalized content of total phospholipid, phosphatidylcholine (PC), and disaturated phosphatidylcholine (DSPC) in bronchoalveolar lavage fluid, lung lamellar bodies, and lung homogenate was unchanged with age in wild-type mice but increased progressively in Prdx6−/− animals. Degradation of internalized [3H]DPPC in isolated mouse lungs after endotracheal instillation of unilamellar liposomes labeled with [3H]DPPC was significantly decreased at 2 h in Prdx6−/− mice (13.6 ± 0.3% vs. 26.8 ± 0.8% in the wild type), reflected by decreased dpm in the lysophosphatidylcholine and the unsaturated PC fractions. Incorporation of [14C]palmitate into DSPC at 24 h after intravenous injection was decreased by 73% in lamellar bodies and by 54% in alveolar lavage surfactant in Prdx6−/− mice, whereas incorporation of [3H]choline was decreased only slightly. Phospholipid metabolism in Prdx6−/− lungs was similar to that in wild-type lungs treated with MJ33, an inhibitor of aiPLA2 activity.These results confirm an important role for Prdx6 in lung surfactant DPPC degradation and synthesis by the reacylation pathway. |
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| id | doaj.art-6a8e7f0f56994f25bed85cb18902e872 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-21T17:36:17Z |
| publishDate | 2005-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-6a8e7f0f56994f25bed85cb18902e8722022-12-21T18:55:46ZengElsevierJournal of Lipid Research0022-22752005-06-0146612481256Altered lung phospholipid metabolism in mice with targeted deletion of lysosomal-type phospholipase A21Aron B. Fisher0Chandra Dodia1Sheldon I. Feinstein2Ye-Shih Ho3To whom correspondence should be addressed.; Institute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, PAInstitute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, PAInstitute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, PAInstitute of Environmental Health Sciences, Wayne State University, Detroit, MILung surfactant dipalmitoylphosphatidylcholine (DPPC) is endocytosed by alveolar epithelial cells and degraded by lysosomal-type phospholipase A2 (aiPLA2). This enzyme is identical to peroxiredoxin 6 (Prdx6), a bifunctional protein with PLA2 and GSH peroxidase activities. Lung phospholipid was studied in Prdx6 knockout (Prdx6−/−) mice. The normalized content of total phospholipid, phosphatidylcholine (PC), and disaturated phosphatidylcholine (DSPC) in bronchoalveolar lavage fluid, lung lamellar bodies, and lung homogenate was unchanged with age in wild-type mice but increased progressively in Prdx6−/− animals. Degradation of internalized [3H]DPPC in isolated mouse lungs after endotracheal instillation of unilamellar liposomes labeled with [3H]DPPC was significantly decreased at 2 h in Prdx6−/− mice (13.6 ± 0.3% vs. 26.8 ± 0.8% in the wild type), reflected by decreased dpm in the lysophosphatidylcholine and the unsaturated PC fractions. Incorporation of [14C]palmitate into DSPC at 24 h after intravenous injection was decreased by 73% in lamellar bodies and by 54% in alveolar lavage surfactant in Prdx6−/− mice, whereas incorporation of [3H]choline was decreased only slightly. Phospholipid metabolism in Prdx6−/− lungs was similar to that in wild-type lungs treated with MJ33, an inhibitor of aiPLA2 activity.These results confirm an important role for Prdx6 in lung surfactant DPPC degradation and synthesis by the reacylation pathway.http://www.sciencedirect.com/science/article/pii/S0022227520330297peroxiredoxin 6lung surfactantdipalmitoylphosphatidylcholinephospholipid remodelingphospholipid synthesis |
| spellingShingle | Aron B. Fisher Chandra Dodia Sheldon I. Feinstein Ye-Shih Ho Altered lung phospholipid metabolism in mice with targeted deletion of lysosomal-type phospholipase A21 Journal of Lipid Research peroxiredoxin 6 lung surfactant dipalmitoylphosphatidylcholine phospholipid remodeling phospholipid synthesis |
| title | Altered lung phospholipid metabolism in mice with targeted deletion of lysosomal-type phospholipase A21 |
| title_full | Altered lung phospholipid metabolism in mice with targeted deletion of lysosomal-type phospholipase A21 |
| title_fullStr | Altered lung phospholipid metabolism in mice with targeted deletion of lysosomal-type phospholipase A21 |
| title_full_unstemmed | Altered lung phospholipid metabolism in mice with targeted deletion of lysosomal-type phospholipase A21 |
| title_short | Altered lung phospholipid metabolism in mice with targeted deletion of lysosomal-type phospholipase A21 |
| title_sort | altered lung phospholipid metabolism in mice with targeted deletion of lysosomal type phospholipase a21 |
| topic | peroxiredoxin 6 lung surfactant dipalmitoylphosphatidylcholine phospholipid remodeling phospholipid synthesis |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520330297 |
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