Hogan M, Kuliszewski M, Lee W, Post M
The Medical Research Council Group in Lung Development, Toronto, Ontario, Canada.
Biochem J. 1996 Mar 15;314 ( Pt 3)(Pt 3):799-803. doi: 10.1042/bj3140799.
Pulmonary surfactant phosphatidylcholine synthesis increases in fetal lung type II cells with advancing gestation. This increase is accompanied by an increase in gene and protein expression of CTP:phosphocholine cytidylyltransferase (CT; EC 2.7.7.15), which catalyses a regulatory step in de novo phosphatidylcholine synthesis by fetal type II cells. In the present study we investigated the role of transcriptional and post-transcriptional mechanisms in the developmental induction of CT mRNA in maturing type II cells. We found that CT mRNA increased 2-fold from days 18 to 21 of fetal rat gestation (term 22 d). This increase in CT mRNA was not accompanied by a developmental increase in CT gene transcription. However, CT mRNA was more stable on day 21 (t1/2 48 h) compared with that on day 18 (t1/2 17 h). Glucocorticoids have been shown to enhance surfactant phosphatidylcholine synthesis in fetal type II cells. Therefore we also examined the effect of maternal glucocorticoid administration to pregnant rats at 19 d of gestation on CT mRNA expression in fetal type II cells isolated 24 h later. Glucocorticoid treatment did not increase type II cell CT mRNA. As reported previously, however, glucocorticoids increased CT activity in the microsomal membrane fraction of fetal type II cells, whereas no differences in cytosolic CT activity were observed. We conclude that the developmental increase in CT mRNA in fetal type II cells is due to a decreased breakdown of the CT transcript and that glucocorticoids regulate fetal type II cell CT activity at a post-translational level.
随着妊娠进展，胎儿肺Ⅱ型细胞中肺表面活性物质磷脂酰胆碱的合成增加。这种增加伴随着CTP：磷酸胆碱胞苷转移酶（CT；EC 2.7.7.15）基因和蛋白表达的增加，该酶催化胎儿Ⅱ型细胞从头合成磷脂酰胆碱的一个调节步骤。在本研究中，我们调查了转录和转录后机制在成熟Ⅱ型细胞中CT mRNA发育诱导中的作用。我们发现，从胎鼠妊娠第18天到第21天（足月为22天），CT mRNA增加了2倍。CT mRNA的这种增加并未伴随着CT基因转录的发育性增加。然而，与第18天（半衰期17小时）相比，CT mRNA在第21天更稳定（半衰期48小时）。糖皮质激素已被证明可增强胎儿Ⅱ型细胞中表面活性物质磷脂酰胆碱的合成。因此，我们还研究了在妊娠第19天给孕鼠注射母体糖皮质激素对24小时后分离的胎儿Ⅱ型细胞中CT mRNA表达的影响。糖皮质激素处理并未增加Ⅱ型细胞CT mRNA。然而，如先前报道，糖皮质激素增加了胎儿Ⅱ型细胞微粒体膜部分的CT活性，而胞质CT活性未观察到差异。我们得出结论，胎儿Ⅱ型细胞中CT mRNA的发育性增加是由于CT转录本降解减少，并且糖皮质激素在翻译后水平调节胎儿Ⅱ型细胞CT活性。
