Limits...
Apolipoprotein C-II and lipoprotein lipase show a temporal and geographic correlation with surfactant lipid synthesis in preparation for birth.

Côté M, Provost PR, Gérard-Hudon MC, Tremblay Y - BMC Dev. Biol. (2010)

Bottom Line: The major sites of apoC-II and LPL gene expression changed over time and were found mainly in the distal epithelium at the end of gestation but not after birth.Accumulation of apoC-II in secretory granule-like structures was not systematically observed, but was found in the distal epithelium only at the end of gestation and soon after birth, mainly in epithelia with no or small lumina.We propose a model where apoC-II is retained in secretory granules in distal epithelial cells until the lumina reaches a minimum size, and is then secreted when the rate of surfactant production becomes optimal.

View Article: PubMed Central - HTML - PubMed

Affiliation: Reproduction, Perinatal and Child Health Axis, Rm T-1-49, CHUQ Research Center, Centre de Recherche en Biologie de Reproduction, Laval University, Québec City, Québec, Canada.

ABSTRACT

Background: Fatty acids are precursors in the synthesis of surfactant phospholipids. Recently, we showed expression of apolipoprotein C-II (apoC-II), the essential cofactor of lipoprotein lipase (LPL), in the fetal mouse lung and found the protein on the day of the surge of surfactant synthesis (gestation day 17.5) in secretory granule-like structures in the distal epithelium. In the present study, we will answer the following questions: Does apoC-II protein localization change according to the stage of lung development, thus according to the need in surfactant? Are LPL molecules translocated to the luminal surface of capillaries? Do the sites of apoC-II and LPL gene expression change according to the stage of lung development and to protein localization?

Results: The present study investigated whether the sites of apoC-II and LPL mRNA and protein accumulation are regulated in the mouse lung between gestation day 15 and postnatal day 10. The major sites of apoC-II and LPL gene expression changed over time and were found mainly in the distal epithelium at the end of gestation but not after birth. Accumulation of apoC-II in secretory granule-like structures was not systematically observed, but was found in the distal epithelium only at the end of gestation and soon after birth, mainly in epithelia with no or small lumina. A noticeable increase in surfactant lipid content was measured before the end of gestation day 18, which correlates temporally with the presence of apoC-II in secretory granules in distal epithelium with no or small lumina but not with large lumina. LPL was detected in capillaries at all the developmental times studied.

Conclusions: This study demonstrates that apoC-II and LPL mRNAs correlate temporally and geographically with surfactant lipid synthesis in preparation for birth and suggests that fatty acid recruitment from the circulation by apoC-II-activated LPL is regionally modulated by apoC-II secretion. We propose a model where apoC-II is retained in secretory granules in distal epithelial cells until the lumina reaches a minimum size, and is then secreted when the rate of surfactant production becomes optimal.

Show MeSH
Production of surfactant DSPC in the developing lung of Balb/C mice. Relative DSPC content (in μg inorganic phosphorus/mg dry wt) in Balb/C fetal lungs according to developmental time (day). A one-hour mating window was used (± 0.02 day). Within the developmental time window studied, DSPC varied significantly (P < 0.0001, one-way ANOVA) between GD 18.50 and 18.75 (P < 0.05, Tukey's multiple comparison test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2991289&req=5

Figure 8: Production of surfactant DSPC in the developing lung of Balb/C mice. Relative DSPC content (in μg inorganic phosphorus/mg dry wt) in Balb/C fetal lungs according to developmental time (day). A one-hour mating window was used (± 0.02 day). Within the developmental time window studied, DSPC varied significantly (P < 0.0001, one-way ANOVA) between GD 18.50 and 18.75 (P < 0.05, Tukey's multiple comparison test).

Mentions: Disaturated phosphatidylcholine (DSPC) is quantitatively the most important lipid of surfactant [19] and an increase in lung DSPC content was observed after the surge of surfactant synthesis [20]. Here, relative DSPC levels were determined in lungs from Balb/C fetal mice from GD 17.50 to 18.75 following a one hour mating window (GD ± 0.02). A marked statistically significant increase was observed between GD 18.50 and GD 18.75 (Figure 8).


Apolipoprotein C-II and lipoprotein lipase show a temporal and geographic correlation with surfactant lipid synthesis in preparation for birth.

Côté M, Provost PR, Gérard-Hudon MC, Tremblay Y - BMC Dev. Biol. (2010)

Production of surfactant DSPC in the developing lung of Balb/C mice. Relative DSPC content (in μg inorganic phosphorus/mg dry wt) in Balb/C fetal lungs according to developmental time (day). A one-hour mating window was used (± 0.02 day). Within the developmental time window studied, DSPC varied significantly (P < 0.0001, one-way ANOVA) between GD 18.50 and 18.75 (P < 0.05, Tukey's multiple comparison test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2991289&req=5

Figure 8: Production of surfactant DSPC in the developing lung of Balb/C mice. Relative DSPC content (in μg inorganic phosphorus/mg dry wt) in Balb/C fetal lungs according to developmental time (day). A one-hour mating window was used (± 0.02 day). Within the developmental time window studied, DSPC varied significantly (P < 0.0001, one-way ANOVA) between GD 18.50 and 18.75 (P < 0.05, Tukey's multiple comparison test).
Mentions: Disaturated phosphatidylcholine (DSPC) is quantitatively the most important lipid of surfactant [19] and an increase in lung DSPC content was observed after the surge of surfactant synthesis [20]. Here, relative DSPC levels were determined in lungs from Balb/C fetal mice from GD 17.50 to 18.75 following a one hour mating window (GD ± 0.02). A marked statistically significant increase was observed between GD 18.50 and GD 18.75 (Figure 8).

Bottom Line: The major sites of apoC-II and LPL gene expression changed over time and were found mainly in the distal epithelium at the end of gestation but not after birth.Accumulation of apoC-II in secretory granule-like structures was not systematically observed, but was found in the distal epithelium only at the end of gestation and soon after birth, mainly in epithelia with no or small lumina.We propose a model where apoC-II is retained in secretory granules in distal epithelial cells until the lumina reaches a minimum size, and is then secreted when the rate of surfactant production becomes optimal.

View Article: PubMed Central - HTML - PubMed

Affiliation: Reproduction, Perinatal and Child Health Axis, Rm T-1-49, CHUQ Research Center, Centre de Recherche en Biologie de Reproduction, Laval University, Québec City, Québec, Canada.

ABSTRACT

Background: Fatty acids are precursors in the synthesis of surfactant phospholipids. Recently, we showed expression of apolipoprotein C-II (apoC-II), the essential cofactor of lipoprotein lipase (LPL), in the fetal mouse lung and found the protein on the day of the surge of surfactant synthesis (gestation day 17.5) in secretory granule-like structures in the distal epithelium. In the present study, we will answer the following questions: Does apoC-II protein localization change according to the stage of lung development, thus according to the need in surfactant? Are LPL molecules translocated to the luminal surface of capillaries? Do the sites of apoC-II and LPL gene expression change according to the stage of lung development and to protein localization?

Results: The present study investigated whether the sites of apoC-II and LPL mRNA and protein accumulation are regulated in the mouse lung between gestation day 15 and postnatal day 10. The major sites of apoC-II and LPL gene expression changed over time and were found mainly in the distal epithelium at the end of gestation but not after birth. Accumulation of apoC-II in secretory granule-like structures was not systematically observed, but was found in the distal epithelium only at the end of gestation and soon after birth, mainly in epithelia with no or small lumina. A noticeable increase in surfactant lipid content was measured before the end of gestation day 18, which correlates temporally with the presence of apoC-II in secretory granules in distal epithelium with no or small lumina but not with large lumina. LPL was detected in capillaries at all the developmental times studied.

Conclusions: This study demonstrates that apoC-II and LPL mRNAs correlate temporally and geographically with surfactant lipid synthesis in preparation for birth and suggests that fatty acid recruitment from the circulation by apoC-II-activated LPL is regionally modulated by apoC-II secretion. We propose a model where apoC-II is retained in secretory granules in distal epithelial cells until the lumina reaches a minimum size, and is then secreted when the rate of surfactant production becomes optimal.

Show MeSH