Vitamin E deficiency reduces surfactant lipid biosynthesis in alveolar type II cells.
Reactive oxygen species play an important role in development of lung injury. Neonates exhibit a high risk of developing acute and/or chronic lung disorder, often associated with surfactant deficiency, and in parallel they show low vitamin E concentration. We investigated whether the vitamin E status of adult rats affects the content of phospholipids (PL) in bronchoalveolar lavage and alveolar type II cells. Phosphatidylcholine (PtdCho) is the dominant and functional most important PL in lung surfactant. Therefore, we determined its formation via de novo synthesis and reacylation of lyso-PtdCho in type II cells. Vitamin E depletion caused a decrease of PL content in bronchoalveolar lavage and type II cells and decreased glycerol-3-phosphate O-acyltransferase (G3P-AT) activity, de novo synthesis of PtdCho, and reacylation of lyso-PtdCho in type II cells. Preincubation of type II cell homogenates with dithiothreitol restored the activity of G3P-AT and de novo synthesis but inhibited reacylation. Reacylation was strongly reduced by chelerythrine-mediated inhibition of protein kinase C. We conclude that antioxidant and PKC-modulating properties of vitamin E regulate de novo synthesis of PtdCho and reacylation of lyso-PtdCho in alveolar type II cells. Vitamin E depletion reduced the two pathways of PL synthesis and caused a decrease of PL content in alveolar surfactant of rats.
Guthmann
Florian
F
Clinic of Neonatology, Humboldt-Universität zu Berlin, Charité Campus Mitte, Berlin, Germany
Kolleck
Ingrid
I
Schachtrup
Christian
C
Schlame
Michael
M
Spener
Friedrich
F
Rüstow
Bernd
B
D000215:Acylation; D000470:Alkaloids; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D053119:Benzophenanthridines; D015153:Blotting, Western; D018893:Bronchoalveolar Lavage; D018955:CD36 Antigens; D002478:Cells, Cultured; D004032:Diet; D004229:Dithiothreitol / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D027361:Organic Anion Transporters / Q000378:metabolism; D019308:Palmitic Acid / Q000378:metabolism; D010617:Phenanthridines / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014811:Vitamin E Deficiency / Q000378:metabolism*
D000470:Alkaloids; D000975:Antioxidants; D053119:Benzophenanthridines; D018955:CD36 Antigens; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D027361:Organic Anion Transporters; D010617:Phenanthridines; D010713:Phosphatidylcholines; D010743:Phospholipids; D011663:Pulmonary Surfactants; D019308:Palmitic Acid; C016299:chelerythrine; D005992:Glycerol-3-Phosphate O-Acyltransferase; D011493:Protein Kinase C; D005978:Glutathione; D004229:Dithiothreitol