Guthmann Florian, Kolleck Ingrid, Schachtrup Christian, Schlame Michael, Spener Friedrich, Rüstow Bernd
Clinic of Neonatology, Humboldt-Universität zu Berlin, Charité Campus Mitte, Berlin, Germany
Free Radic Biol Med. 2003 Mar 15;34(6):663-73. doi: 10.1016/s0891-5849(02)01376-x.
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.
活性氧在肺损伤的发展过程中起重要作用。新生儿患急性和/或慢性肺部疾病的风险很高，这通常与表面活性剂缺乏有关，同时他们的维生素E浓度较低。我们研究了成年大鼠的维生素E状态是否会影响支气管肺泡灌洗和II型肺泡细胞中磷脂（PL）的含量。磷脂酰胆碱（PtdCho）是肺表面活性剂中占主导地位且功能最重要的磷脂。因此，我们通过II型细胞中从头合成和溶血磷脂酰胆碱的再酰化作用来确定其形成过程。维生素E缺乏导致支气管肺泡灌洗和II型细胞中PL含量降低，并降低了甘油-3-磷酸O-酰基转移酶（G3P-AT）的活性、PtdCho的从头合成以及II型细胞中溶血磷脂酰胆碱的再酰化作用。用二硫苏糖醇对II型细胞匀浆进行预孵育可恢复G3P-AT的活性和从头合成，但会抑制再酰化作用。白屈菜红碱介导的蛋白激酶C抑制作用可强烈降低再酰化作用。我们得出结论，维生素E的抗氧化和PKC调节特性可调节II型肺泡细胞中PtdCho的从头合成和溶血磷脂酰胆碱的再酰化作用。维生素E缺乏会减少磷脂合成的两条途径，并导致大鼠肺泡表面活性剂中磷脂含量降低。
