Lung phospholipid metabolism in transgenic mice overexpressing peroxiredoxin 6.
Previous studies with peroxiredoxin 6 (Prdx6) null mice demonstrated that the phospholipase A(2) activity of this enzyme plays a major role in lung phospholipid metabolism. This study evaluated lung phospholipid metabolism in transgenic mice that over-express Prdx6. Lung lysosomal type PLA(2) activity in transgenic mice was 222% of wild type in lung homogenate and 280% in isolated lamellar bodies. Total phospholipid, phosphatidylcholine (PC) and disaturated PC were decreased approximately 20-35% in bronchoalveolar lung fluid, lung homogenate, and lung lamellar bodies in transgenic mice although lung compliance and type 2 cell ultrastructure were unaltered. To study metabolism, unilamellar liposomes ((3)H-DPPC: PC: cholesterol: PG, 10: 5: 3: 2 mol fraction) were instilled endotracheally in anesthetized mice and lungs were removed for perfusion. Compared to wild type, transgenic mice showed similar net uptake of liposomes in 2 h, but significantly increased (3)H-DPPC degradation (38.9+/-1.1 vs. 29.0+/-1.3% of recovered dpm). The PLA(2) competitive inhibitor MJ33 decreased degradation to 15% of recovered dpm in both transgenic and wild type lungs. Incorporation of [(14)C] palmitate into DSPC at 24 h after its intravenous injection was markedly increased in both the lung surfactant (+100%) and lamellar bodies (+188%) while incorporation of [(3)H] choline was increased by only 10-20%. These results indicate increased DPPC degradation and synthesis by the reacylation pathway with Prdx6 overexpression and provide additional evidence that the PLA(2) activity of Prdx6 has an important role in lung surfactant turnover.
Fisher
Aron B
AB
Institute for Environmental Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6068, USA. abf@mail.med.upenn.edu
Dodia
Chandra
C
Yu
Kevin
K
Manevich
Yefim
Y
Feinstein
Sheldon I
SI
D000818:Animals; D005260:Female; D008168:Lung / Q000378:metabolism* / Q000648:ultrastructure; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010544:Peroxidases / Q000096:biosynthesis* / Q000235:genetics; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; D010743:Phospholipids / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism
D010743:Phospholipids; D011663:Pulmonary Surfactants; D010544:Peroxidases; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; C515983:Prdx6 protein, mouse