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. 1996 Mar 15;314(Pt 3):799–803. doi: 10.1042/bj3140799

Regulation of phosphatidylcholine synthesis in maturing type II cells: increased mRNA stability of CTP:phosphocholine cytidylyltransferase.

M Hogan 1, M Kuliszewski 1, W Lee 1, M Post 1
PMCID: PMC1217127  PMID: 8615772

Abstract

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.

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Selected References

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  1. Batenburg J. J., Elfring R. H. Pre-translational regulation by glucocorticoid of fatty acid and phosphatidylcholine synthesis in type II cells from fetal rat lung. FEBS Lett. 1992 Jul 28;307(2):164–168. doi: 10.1016/0014-5793(92)80759-a. [DOI] [PubMed] [Google Scholar]
  2. Boggaram V., Margana R. K. Developmental and hormonal regulation of surfactant protein C (SP-C) gene expression in fetal lung. Role of transcription and mRNA stability. J Biol Chem. 1994 Nov 4;269(44):27767–27772. [PubMed] [Google Scholar]
  3. Buch S., Jassal D., Cannigia I., Edelson J., Han R., Liu J., Tanswell K., Post M. Ontogeny and regulation of platelet-derived growth factor gene expression in distal fetal rat lung epithelial cells. Am J Respir Cell Mol Biol. 1994 Sep;11(3):251–261. doi: 10.1165/ajrcmb.11.3.8086163. [DOI] [PubMed] [Google Scholar]
  4. Buch S., Jones C., Liu J., Han R. N., Tanswell A. K., Post M. Differential regulation of platelet-derived growth factor genes in fetal rat lung fibroblasts. Exp Cell Res. 1994 Mar;211(1):142–149. doi: 10.1006/excr.1994.1070. [DOI] [PubMed] [Google Scholar]
  5. Caniggia I., Tseu I., Han R. N., Smith B. T., Tanswell K., Post M. Spatial and temporal differences in fibroblast behavior in fetal rat lung. Am J Physiol. 1991 Dec;261(6 Pt 1):L424–L433. doi: 10.1152/ajplung.1991.261.6.L424. [DOI] [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Chu A. J., Rooney S. A. Developmental differences in activation of cholinephosphate cytidylyltransferase by lipids in rabbit lung cytosol. Biochim Biophys Acta. 1985 Jun 14;835(1):132–140. doi: 10.1016/0005-2760(85)90039-6. [DOI] [PubMed] [Google Scholar]
  8. Chu A. J., Rooney S. A. Stimulation of cholinephosphate cytidylyltransferase activity by estrogen in fetal rabbit lung is mediated by phospholipids. Biochim Biophys Acta. 1985 May 17;834(3):346–356. doi: 10.1016/0005-2760(85)90008-6. [DOI] [PubMed] [Google Scholar]
  9. Fisher J. H., McCormack F., Park S. S., Stelzner T., Shannon J. M., Hofmann T. In vivo regulation of surfactant proteins by glucocorticoids. Am J Respir Cell Mol Biol. 1991 Jul;5(1):63–70. doi: 10.1165/ajrcmb/5.1.63. [DOI] [PubMed] [Google Scholar]
  10. Fraslon-Vanhulle C., Chailley-Heu B., Batenburg J. J., Elfring R., Bourbon J. R. Ontogeny of surfactant proteins and lipid-synthesizing enzymes in cultured fetal lung epithelial cells. Am J Physiol. 1994 Oct;267(4 Pt 1):L375–L383. doi: 10.1152/ajplung.1994.267.4.L375. [DOI] [PubMed] [Google Scholar]
  11. Fraslon C., Batenburg J. J. Pre-translational regulation of lipid synthesizing enzymes and surfactant proteins in fetal rat lung in explant culture. FEBS Lett. 1993 Jul 5;325(3):285–290. doi: 10.1016/0014-5793(93)81090-m. [DOI] [PubMed] [Google Scholar]
  12. Hod Y., Hanson R. W. Cyclic AMP stabilizes the mRNA for phosphoenolpyruvate carboxykinase (GTP) against degradation. J Biol Chem. 1988 Jun 5;263(16):7747–7752. [PubMed] [Google Scholar]
  13. Hogan M., Zimmermann L. J., Wang J., Kuliszewski M., Liu J., Post M. Increased expression of CTP:phosphocholine cytidylyltransferase in maturing type II cells. Am J Physiol. 1994 Jul;267(1 Pt 1):L25–L32. doi: 10.1152/ajplung.1994.267.1.L25. [DOI] [PubMed] [Google Scholar]
  14. Jackson R. J. Cytoplasmic regulation of mRNA function: the importance of the 3' untranslated region. Cell. 1993 Jul 16;74(1):9–14. doi: 10.1016/0092-8674(93)90290-7. [DOI] [PubMed] [Google Scholar]
  15. Margana R. K., Boggaram V. Transcription and mRNA stability regulate developmental and hormonal expression of rabbit surfactant protein B gene. Am J Physiol. 1995 Mar;268(3 Pt 1):L481–L490. doi: 10.1152/ajplung.1995.268.3.L481. [DOI] [PubMed] [Google Scholar]
  16. Pelech S. L., Cook H. W., Paddon H. B., Vance D. E. Membrane-bound CTP:phosphocholine cytidylyltransferase regulates the rate of phosphatidylcholine synthesis in HeLa cells treated with unsaturated fatty acids. Biochim Biophys Acta. 1984 Oct 4;795(3):433–440. doi: 10.1016/0005-2760(84)90169-3. [DOI] [PubMed] [Google Scholar]
  17. Possmayer F. A proposed nomenclature for pulmonary surfactant-associated proteins. Am Rev Respir Dis. 1988 Oct;138(4):990–998. doi: 10.1164/ajrccm/138.4.990. [DOI] [PubMed] [Google Scholar]
  18. Post M., Barsoumian A., Smith B. T. The cellular mechanism of glucocorticoid acceleration of fetal lung maturation. Fibroblast-pneumonocyte factor stimulates choline-phosphate cytidylyltransferase activity. J Biol Chem. 1986 Feb 15;261(5):2179–2184. [PubMed] [Google Scholar]
  19. Post M. Maternal administration of dexamethasone stimulates choline-phosphate cytidylyltransferase in fetal type II cells. Biochem J. 1987 Jan 1;241(1):291–296. doi: 10.1042/bj2410291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Post M., van Golde L. M. Metabolic and developmental aspects of the pulmonary surfactant system. Biochim Biophys Acta. 1988 Jun 9;947(2):249–286. doi: 10.1016/0304-4157(88)90011-1. [DOI] [PubMed] [Google Scholar]
  21. Rooney S. A., Smart D. A., Weinhold P. A., Feldman D. A. Dexamethasone increases the activity but not the amount of choline-phosphate cytidylyltransferase in fetal rat lung. Biochim Biophys Acta. 1990 Jun 14;1044(3):385–389. doi: 10.1016/0005-2760(90)90085-c. [DOI] [PubMed] [Google Scholar]
  22. Schellhase D. E., Shannon J. M. Effects of maternal dexamethasone on expression of SP-A, SP-B, and SP-C in the fetal rat lung. Am J Respir Cell Mol Biol. 1991 Apr;4(4):304–312. doi: 10.1165/ajrcmb/4.4.304. [DOI] [PubMed] [Google Scholar]
  23. Venkatesh V. C., Iannuzzi D. M., Ertsey R., Ballard P. L. Differential glucocorticoid regulation of the pulmonary hydrophobic surfactant proteins SP-B and SP-C. Am J Respir Cell Mol Biol. 1993 Feb;8(2):222–228. doi: 10.1165/ajrcmb/8.2.222. [DOI] [PubMed] [Google Scholar]
  24. Venkatesh V. C., Planer B. C., Schwartz M., Vanderbilt J. N., White R. T., Ballard P. L. Characterization of the promoter of human pulmonary surfactant protein B gene. Am J Physiol. 1995 Apr;268(4 Pt 1):L674–L682. doi: 10.1152/ajplung.1995.268.4.L674. [DOI] [PubMed] [Google Scholar]
  25. Wang J., Kuliszewski M., Yee W., Sedlackova L., Xu J., Tseu I., Post M. Cloning and expression of glucocorticoid-induced genes in fetal rat lung fibroblasts. Transforming growth factor-beta 3. J Biol Chem. 1995 Feb 10;270(6):2722–2728. doi: 10.1074/jbc.270.6.2722. [DOI] [PubMed] [Google Scholar]
  26. Weaver T. E., Whitsett J. A. Function and regulation of expression of pulmonary surfactant-associated proteins. Biochem J. 1991 Jan 15;273(Pt 2):249–264. doi: 10.1042/bj2730249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Weinhold P. A., Rounsifer M. E., Williams S. E., Brubaker P. G., Feldman D. A. CTP:phosphorylcholine cytidylyltransferase in rat lung. The effect of free fatty acids on the translocation of activity between microsomes and cytosol. J Biol Chem. 1984 Aug 25;259(16):10315–10321. [PubMed] [Google Scholar]
  28. Xu J., Possmayer F. Exposure of rabbit fetal lung to glucocorticoids in vitro does not enhance transcription of the gene encoding pulmonary surfactant-associated protein-B (SP-B). Biochim Biophys Acta. 1993 Aug 11;1169(2):146–155. doi: 10.1016/0005-2760(93)90199-j. [DOI] [PubMed] [Google Scholar]
  29. Xu Z. X., Smart D. A., Rooney S. A. Glucocorticoid induction of fatty-acid synthase mediates the stimulatory effect of the hormone on choline-phosphate cytidylyltransferase activity in fetal rat lung. Biochim Biophys Acta. 1990 May 1;1044(1):70–76. doi: 10.1016/0005-2760(90)90220-r. [DOI] [PubMed] [Google Scholar]
  30. Xu Z. X., Stenzel W., Sasic S. M., Smart D. A., Rooney S. A. Glucocorticoid regulation of fatty acid synthase gene expression in fetal rat lung. Am J Physiol. 1993 Aug;265(2 Pt 1):L140–L147. doi: 10.1152/ajplung.1993.265.2.L140. [DOI] [PubMed] [Google Scholar]
  31. Xu Z. X., Viviano C. J., Rooney S. A. Glucocorticoid stimulation of fatty-acid synthase gene transcription in fetal lung: antagonism by retinoic acid. Am J Physiol. 1995 Apr;268(4 Pt 1):L683–L690. doi: 10.1152/ajplung.1995.268.4.L683. [DOI] [PubMed] [Google Scholar]
  32. Zimmermann L. J., Hogan M., Carlson K. S., Smith B. T., Post M. Regulation of phosphatidylcholine synthesis in fetal type II cells by CTP:phosphocholine cytidylyltransferase. Am J Physiol. 1993 Jun;264(6 Pt 1):L575–L580. doi: 10.1152/ajplung.1993.264.6.L575. [DOI] [PubMed] [Google Scholar]
  33. Zimmermann L. J., Lee W. S., Post M. Regulation of CTP:phosphocholine cytidylyltransferase by cytosolic lipids in rat type II pneumocytes during development. Pediatr Res. 1995 Dec;38(6):864–869. doi: 10.1203/00006450-199512000-00007. [DOI] [PubMed] [Google Scholar]

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