Longo C A, Tyler D, Mallampalli R K
Department of Internal Medicine, and the Department of Veterans Affairs Medical Center, The University of Iowa College of Medicine, Iowa City 52242, USA.
Am J Respir Cell Mol Biol. 1997 May;16(5):605-12. doi: 10.1165/ajrcmb.16.5.9160843.
We investigated several indices involved in sphingomyelin metabolism in developing rat lung. The levels of sphingomyelin gradually increased during lung maturation, with highest levels observed postnatally. The content of sphingosine and ceramide, biologically active sphingomyelin degradation products, did not significantly change in microsomes during the prenatal period, but increased to peak levels in neonatal and adult lung, respectively. Sphingosine content increased 6-fold between the fetal (Day 21) and neonatal period. The developmental profiles of two enzymes involved in sphingomyelin synthesis, serine palmitoyltransferase and sphingomyelin synthase, were similar. Serine palmitoyltransferase activity increased progressively from the fetal to neonatal period, and plateaued at high levels in the adult lung. The activity of serine palmitoyltransferase correlated with the levels of endogenous sphingolipid in lung tissue. Sphingomyelin synthase activity also increased during fetal lung development, but attained highest levels at Day 21 gestation; postnatally, enzyme activity was detected at lower levels. The activities of the sphingolipid hydrolases, acid and neutral sphingomyelinase and acid and alkaline ceramidase, were elevated in fetal lung, thereafter declining to low levels after birth. Studies conducted in alveolar macrophages, fibroblasts, and alveolar type II epithelial cells revealed that these developmental changes in enzyme activities in lung tissue were also occuring globally at the cellular level and were not restricted to any specific cell population. These studies suggest that the developmental increase in lung sphingomyelin content is due to coordinate regulation of enzymes involved in the biosynthesis and degradation of sphingomyelin. These observations also suggest a regulatory role for serine palmitoyltransferase in the generation of long chain sphingoid bases.
我们研究了发育中的大鼠肺中参与鞘磷脂代谢的几个指标。在肺成熟过程中，鞘磷脂水平逐渐升高，出生后达到最高水平。鞘氨醇和神经酰胺是具有生物活性的鞘磷脂降解产物，其在产前阶段微粒体中的含量没有显著变化，但在新生儿和成年肺中分别增加至峰值水平。在胎儿期（第21天）到新生儿期之间，鞘氨醇含量增加了6倍。参与鞘磷脂合成的两种酶，丝氨酸棕榈酰转移酶和鞘磷脂合酶的发育模式相似。从胎儿期到新生儿期，丝氨酸棕榈酰转移酶的活性逐渐增加，并在成年肺中稳定在较高水平。丝氨酸棕榈酰转移酶的活性与肺组织中内源性鞘脂的水平相关。鞘磷脂合酶的活性在胎儿肺发育过程中也增加，但在妊娠第21天达到最高水平；出生后，酶活性检测到较低水平。鞘脂水解酶，酸性和中性鞘磷脂酶以及酸性和碱性神经酰胺酶的活性在胎儿肺中升高，出生后下降至低水平。在肺泡巨噬细胞、成纤维细胞和肺泡II型上皮细胞中进行的研究表明，肺组织中这些酶活性的发育变化在细胞水平上也是全局发生的，并不局限于任何特定的细胞群体。这些研究表明，肺鞘磷脂含量的发育性增加是由于参与鞘磷脂生物合成和降解的酶的协调调节。这些观察结果还表明丝氨酸棕榈酰转移酶在长链鞘氨醇碱基生成中起调节作用。
