Dipalmitoyl-Phosphatidylcholine Biosynthesis is Induced by Non-Injurious Mechanical Stretch in a Model of Alveolar Type II Cells

• Published in: Lipids Vol. 48; no. 8; pp. 827 - 838
• Main Authors: Pantazi, Despoina, Kitsiouli, Eirini, Karkabounas, Athanasios, Trangas, Theoni, Nakos, George, Lekka, Marilena E.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2013; Springer Nature B.V
• Subjects: 1,2-Dipalmitoylphosphatidylcholine - biosynthesis; 1-Acylglycerophosphocholine O-Acyltransferase - genetics; 1-Acylglycerophosphocholine O-Acyltransferase - metabolism; Biomedical and Life Sciences; CDP‐choline:cholinephosphotransferase; Cell Line - drug effects; Cell Survival; Diacylglycerol Cholinephosphotransferase - metabolism; Gene Expression Regulation; Glycerophosphates - pharmacology; Humans; L-Lactate Dehydrogenase - metabolism; Life Sciences; Lipidology; Lung surfactant; Lyso‐phosphatidylcholine acyltransferase; Mechanical stretch; Medical Biochemistry; Medicinal Chemistry; Microbial Genetics and Genomics; Neurochemistry; Nutrition; Original Article; Peroxiredoxin VI - genetics; Phosphatidylcholine biosynthesis; Phospholipase A2; Phospholipases A2 - metabolism; Phospholipids - metabolism; Pulmonary Alveoli - cytology; Pulmonary Alveoli - metabolism; Sphingomyelins - metabolism; Stress, Mechanical; Lung surfactant; CDP-choline:cholinephosphotransferase; Lyso-phosphatidylcholine acyltransferase; Phospholipase A; Phosphatidylcholine biosynthesis; Mechanical stretch
• ISSN: 0024-4201; 1558-9307
• DOI: 10.1007/s11745-013-3800-8

Dipalmitoylphosphatidylcholine, (DP-PtdCho), the major phospholipid component of lung surfactant is biosynthesized via a de novo pathway, the last step of which is catalyzed by CDP-choline:cholinephosphotransferase (CPT) and two remodeling steps: a deacylation and a reacylation one, catalyzed by an acidic, Ca 2+ -independent phospholipase A 2 ( ai PLA 2 ) and a lyso-phosphatidylcholine acyltransferase (LPCAT), respectively. The aim of our study was to investigate whether a low magnitude, non-injurious static mode of mechanical stretch can induce phosphatidylcholine (PtdCho) biosynthesis and its remodeling to DP-PtdCho in the A549 cell-line, a model of alveolar type II cells. The deformation of A549 cells did not cause any release of lactate dehydrogenase, or phospholipids into the cell culture supernatants. An increase in PtdCho levels was observed after 1 h of static stretching, especially among the DP-PtdCho molecular species, as indicated by targeted lipidomics approach and site-directed fatty acyl-chain analysis. Moreover, although sphingomyelin (CerPCho) levels were unaffected, the DP-PtdCho/CerPCho ratio increased. Induction was observed in CPT, LPCAT and ai PLA 2 enzymatic activities and gene expression. Finally, incubation of the cells with MJ33 suppressed ai PLA 2 activity and DP-PtdCho production. Our data suggest that mild static mechanical stretch can promote the biosynthesis of PtdCho and its remodeling to DP-PtdCho in lung epithelial cells. Thus, low magnitude stretch could contribute to protective mechanisms rather than to injurious ones.