Zimmermann L J, Lee W S, Post M
Neonatal Research Division, Hospital for Sick Children, University of Toronto, Ontario, Canada.
Pediatr Res. 1995 Dec;38(6):864-9. doi: 10.1203/00006450-199512000-00007.
phosphocholine cytidylyltransferase (CT) catalyses a rate regulatory step in the de novo synthesis of surfactant phosphatidylcholine (PC). We have previously shown that CT activity increases during late gestation in alveolar type II cells, and that this increase is most pronounced in microsomes. As it is known that CT is activated by lipids, we investigated the lipid activation of CT in fetal type II cells during late gestation. The degree of activation of cytosolic CT by PC/oleic acid (OA) (1:1 molar ratio) vesicles was gestation-dependent (a 3-fold stimulation on d 18 and a 1.5-fold stimulation on d 21). In contrast, microsomal CT activation by PC/OA vesicles (1.5-fold) remained constant with advancing gestation. Lipids extracted from microsomes of fetal type II cells of different gestational ages (d 18-21) did not differ in their ability to activate either cytosolic CT of d 18 or 21 fetal type II cells, purified CT from adult lung, or delipidated purified CT. In contrast, lipids extracted from cytosol of fetal type II cells of different gestational ages (d 18 and 21) differed in their ability to activate either delipidated cytosolic CT of fetal type II cells, or delipidated purified CT from adult lung. Day 21 cytosolic lipids activated CT more than d 18 cytosolic lipids. Both cytosolic and purified CT, when delipidated by acetone/butanol extraction, showed reduced activities. Several lipids were tested for their ability to activate cytosolic CT. Acidic phospholipids and the mixture of PC/OA (1:1) were the strongest stimulators of cytosolic CT activity. We conclude that cytosolic but not microsomal lipids are involved in the developmental activation of cytosolic CT in fetal type II cells at late gestation.
磷酸胆碱胞苷转移酶（CT）催化表面活性物质磷脂酰胆碱（PC）从头合成中的一个速率调节步骤。我们之前已经表明，CT活性在妊娠后期的II型肺泡细胞中增加，并且这种增加在微粒体中最为明显。由于已知CT被脂质激活，我们研究了妊娠后期胎儿II型细胞中CT的脂质激活情况。PC/油酸（OA）（1:1摩尔比）囊泡对胞质CT的激活程度与妊娠相关（在第18天有3倍的刺激，在第21天有1.5倍的刺激）。相比之下，PC/OA囊泡对微粒体CT的激活（1.5倍）随着妊娠进展保持恒定。从不同胎龄（第18 - 21天）的胎儿II型细胞微粒体中提取的脂质，在激活第18天或第21天胎儿II型细胞的胞质CT、成年肺的纯化CT或脱脂纯化CT的能力上没有差异。相比之下，从不同胎龄（第18天和第21天）的胎儿II型细胞胞质中提取的脂质，在激活胎儿II型细胞的脱脂胞质CT或成年肺的脱脂纯化CT的能力上有所不同。第21天的胞质脂质比第18天的胞质脂质更能激活CT。当通过丙酮/丁醇提取进行脱脂时，胞质CT和纯化CT的活性均降低。测试了几种脂质激活胞质CT的能力。酸性磷脂和PC/OA（1:1）混合物是胞质CT活性最强的刺激剂。我们得出结论，胞质脂质而非微粒体脂质参与妊娠后期胎儿II型细胞中胞质CT的发育激活。
