Regulation of fetal lung disaturated phosphatidylcholine synthesis by de novo palmitate supply

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 (t½ 48 h) compared with that on day 18 (t½ 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.

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De novo phosphatidylcholine synthesis is required for autophagosome membrane formation and maintenance during autophagy

Autophagy ◽

10.1080/15548627.2019.1659608 ◽

2019 ◽

Vol 16 (6) ◽

pp. 1044-1060 ◽

Cited By ~ 14

Author(s):

Gabriela Andrejeva ◽

Sharon Gowan ◽

Gigin Lin ◽

Anne-Christine LF Wong Te Fong ◽

Elham Shamsaei ◽

...

Keyword(s):

De Novo ◽

Membrane Formation ◽

Phosphatidylcholine Synthesis

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Leptin mediates the parathyroid hormone-related protein paracrine stimulation of fetal lung maturation

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2002.282.3.l405 ◽

2002 ◽

Vol 282 (3) ◽

pp. L405-L410 ◽

Cited By ~ 109

Author(s):

J. S. Torday ◽

H. Sun ◽

L. Wang ◽

E. Torres

Keyword(s):

De Novo ◽

Fetal Lung ◽

Lung Fibroblasts ◽

Type Ii ◽

Rat Lung ◽

Parathyroid Hormone Related Protein ◽

Fetal Rat ◽

Type Ii Cell ◽

Leptin Expression ◽

Stimulation Of

Developing rat lung lipofibroblasts express leptin beginning on embryonic day (E) 17, increasing 7- to 10-fold by E20. Leptin and its receptor are expressed mutually exclusively by fetal lung fibroblasts and type II cells, suggesting a paracrine signaling “loop.” This hypothesized mechanism is supported by the following experimental data: 1) leptin stimulates the de novo synthesis of surfactant phospholipid by both fetal rat type II cells (400% · 100 ng−1 · ml−1 · 24 h−1) and adult human airway epithelial cells (85% · 100 ng−1 · 24 h−1); 2) leptin is secreted by lipofibroblasts in amounts that stimulate type II cell surfactant phospholipid synthesis in vitro; 3) epithelial cell secretions such as parathyroid hormone-related protein (PTHrP), PGE2, and dexamethasone stimulate leptin expression by fetal rat lung fibroblasts; 4) PTHrP or leptin stimulate the de novo synthesis of surfactant phospholipid (2- to 2.5-fold/24 h) and the expression of surfactant protein B (SP-B; >25-fold/24 h) by fetal rat lung explants, an effect that is blocked by a leptin antibody; and 5) a PTHrP receptor antagonist inhibits the expression of leptin mRNA by explants but does not inhibit leptin stimulation of surfactant phospholipid or SP-B expression, indicating that PTHrP paracrine stimulation of type II cell maturation requires leptin expression by lipofibroblasts. This is the first demonstration of a paracrine loop that functionally cooperates to induce alveolar acinar lung development.

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Regulation of phosphatidylcholine synthesis in fetal type II cells by CTP:phosphocholine cytidylyltransferase

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1993.264.6.l575 ◽

1993 ◽

Vol 264 (6) ◽

pp. L575-L580 ◽

Cited By ~ 4

Author(s):

L. J. Zimmermann ◽

M. Hogan ◽

K. S. Carlson ◽

B. T. Smith ◽

M. Post

Keyword(s):

De Novo ◽

Late Gestation ◽

Molar Ratio ◽

Type Ii Cells ◽

Type Ii ◽

Developmental Profile ◽

Ctp:Phosphocholine Cytidylyltransferase ◽

Fetal Rat ◽

Saturated Form ◽

Phosphatidylcholine Synthesis

Phosphatidylcholine synthesis increases in fetal rat type II cells during late gestation, as demonstrated by an increased incorporation of radiolabeled palmitate, glycerol, acetate, and choline into phosphatidylcholine. However, the percentage of phosphatidylcholine present in the saturated form remains essentially constant. The developmental profile of the enzymes of the CDP-choline pathway suggests that CTP:choline-phosphate cytidylyltransferase catalyses a rate regulatory step in de novo phosphatidylcholine synthesis by fetal type II cells. When cytidylyltransferase activity is assayed in different subcellular fractions, the greatest increase, as a function of development, is found in microsomes. This developmental increase is accompanied by a shift in subcellular distribution of cytidylyltransferase activity from cytosol to microsomes in fetal type II cells during late gestation. This shift is evident even when cytidylyltransferase activity is assayed in the presence of 0.5 mM phosphatidylcholine/oleic acid (1/1 molar ratio) vesicles. We speculate that either a subcellular translocation of CTP:phosphocholine cytidylyltransferase from cytosol to microsomes or an increase in cytidylyltransferase gene expression are responsible for the developmental increase of de novo phosphatidylcholine synthesis by fetal type II cells.

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Biogenesis of mitochondria. Phospholipid synthesis in vitro by yeast mitochondrial and microsomal fractions

Biochemical Journal ◽

10.1042/bj1440265 ◽

1974 ◽

Vol 144 (2) ◽

pp. 265-275 ◽

Cited By ~ 71

Author(s):

G S Cobon ◽

P D Crowfoot ◽

A W Linnane

Keyword(s):

Phosphatidic Acid ◽

Microsomal Fraction ◽

De Novo ◽

Specific Activity ◽

Neutral Lipids ◽

Mitochondrial Fraction ◽

Biogenesis Of Mitochondria ◽

Glycerolipid Synthesis ◽

Phosphatidylcholine Synthesis

The ability in vitro of yeast mitochondrial and microsomal fractions to synthesize lipid de novo was measured. The major phospholipids synthesized from sn-[2-3H]glycerol 3-phosphate by the two microsomal fractions were phosphatidylserine, phosphatidylinositol and phosphatidic acid. The mitochondrial fraction, which had a higher specific activity for total glycerolipid synthesis, synthesized phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine and phosphatidic acid, together with smaller amounts of neutral lipids and diphosphatidylglycerol. Phosphatidylcholine synthesis from both S-adenosyl[Me-14C]methionine and CDP-[Me-14C]choline appeared to be localized in the microsomal fraction.

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