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  2. Altered lung phospholipid metabolism in mice with targeted deletion of lysosomal-type phospholipase A2

Altered lung phospholipid metabolism in mice with targeted deletion of lysosomal-type phospholipase A2

  • J Lipid Res. 2005 Jun;46(6):1248-56. doi: 10.1194/jlr.M400499-JLR200.
Aron B Fisher 1 Chandra Dodia Sheldon I Feinstein Ye-Shih Ho
Affiliations

Affiliation

  • 1 Institute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA. abf@mail.med.upenn.edu
Abstract

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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