title: Dipalmitoyl-phosphatidylcholine biosynthesis is induced by non-injurious mechanical stretch in a model of alveolar type II cells.
abstract: 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, Ca²⁺-independent phospholipase A₂ (aiPLA₂) 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 aiPLA₂ enzymatic activities and gene expression. Finally, incubation of the cells with MJ33 suppressed aiPLA₂ 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.
authors.affiliation: Department of Chemistry, Laboratory of Biochemistry, School of Science, University of Ioannina, Ioannina, Greece.
authors.forename: Despoina
authors.initials: D
authors.lastname: Pantazi
authors.forename: Eirini
authors.initials: E
authors.lastname: Kitsiouli
authors.forename: Athanasios
authors.initials: A
authors.lastname: Karkabounas
authors.forename: Theoni
authors.initials: T
authors.lastname: Trangas
authors.forename: George
authors.initials: G
authors.lastname: Nakos
authors.forename: Marilena E
authors.initials: ME
authors.lastname: Lekka
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000096:biosynthesis*; D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects; D002470:Cell Survival; D002798:Diacylglycerol Cholinephosphotransferase / Q000378:metabolism; D005786:Gene Expression Regulation; D005994:Glycerophosphates / Q000494:pharmacology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D054465:Peroxiredoxin VI / Q000235:genetics; D054467:Phospholipases A2 / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D005994:Glycerophosphates; D010743:Phospholipids; D013109:Sphingomyelins; C078587:1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol; D015060:1,2-Dipalmitoylphosphatidylcholine; D007770:L-Lactate Dehydrogenase; C515977:PRDX6 protein, human; D054465:Peroxiredoxin VI; D008243:1-Acylglycerophosphocholine O-Acyltransferase; C526202:Lpcat1 protein, human; D002798:Diacylglycerol Cholinephosphotransferase; D054467:Phospholipases A2