Lysosomal-type PLA2 and turnover of alveolar DPPC.
This study evaluated the role of a lysosomal-type phospholipase A2 (aiPLA(2)) in the degradation of internalized dipalmitoylphosphatidylcholine (DPPC) and in phospholipid synthesis by the rat lung. Uptake and degradation of DPPC were measured in isolated perfused rat lungs over 3 h following endotracheal instillation of [(3)H]DPPC in mixed unilamellar liposomes plus or minus MJ33, a specific inhibitor of lung aiPLA(2). Uptake of DPPC was calculated from total tissue-associated radiolabel, and degradation was calculated from the sum of radiolabel in degradation products. Both uptake and degradation were markedly stimulated by addition of 8-bromo-cAMP to the perfusate. MJ33 had no effect on DPPC uptake but decreased DPPC degradation at 3 h by approximately 40-50%. The effect of MJ33 on lung synthesis of DPPC was evaluated with intact rats over a 12- to 24-h period following intravenous injection of radiolabeled palmitate and choline. MJ33 treatment decreased palmitate incorporation into disaturated phosphatidylcholine of lamellar bodies and surfactant by approximately 65% at 24 h but had no effect on choline incorporation. This result is compatible with inhibition of the deacylation/reacylation pathway for DPPC synthesis. These results obtained with intact rat lungs indicate that aiPLA(2) is a major enzyme for degradation of internalized DPPC and also has an important role in DPPC synthesis.
Institute for Environmental Medicine, University of Pennsylvania School of Medicine, 1 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104, USA. abf@mail.med.upenn.edu
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D015060:1,2-Dipalmitoylphosphatidylcholine / Q000096:biosynthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D005994:Glycerophosphates / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005994:Glycerophosphates; D010726:Phosphodiesterase Inhibitors; C078587:1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015060:1,2-Dipalmitoylphosphatidylcholine; D010741:Phospholipases A; D054467:Phospholipases A2