Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1993 Apr 15;291(Pt 2):609–613. doi: 10.1042/bj2910609

Changes in levels of argininosuccinate lyase mRNA during induction by glucagon and cyclic AMP in cultured foetal-rat hepatocytes.

S Renouf 1, C Buquet 1, A Fairand 1, M Benamar 1, A Husson 1
PMCID: PMC1132567  PMID: 8387274

Abstract

During the perinatal period, the activity of the urea-cycle enzyme argininosuccinate lyase (ASL) is regulated by glucocorticoids, glucagon and insulin. In this study, the effects of glucagon and cyclic AMP (cAMP) analogues were examined on the synthesis of ASL and on the level of its corresponding mRNA in cultured foetal hepatocytes. Northern-blot analysis revealed that these agents only gave a transient induction of ASL mRNA amount, which reached a peak at 6 h and declined thereafter. This induction preceded the increase in enzyme activity and amount which could be observed for 2 or 3 days of culture. Stimulation of ASL mRNA accumulation by a combination of cAMP analogues and dexamethasone was additive, indicating that glucocorticoids and cAMP are both necessary to promote hepatocyte differentiation and that inductions could occur via independent pathways. Induction by cAMP analogues could be abolished by actinomycin D, suggesting a control mechanism at the transcriptional level. Puromycin was without effect on ASL mRNA induction by cAMP, indicating that no ongoing protein synthesis was required in the stimulation process.

Full text

PDF
609

Images in this article

611Figure 1
on p.611
611Figure 2
on p.611
612Figure 3
on p.612
612Figure 4
on p.612
612Figure 5
on p.612

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abramson R. D., Barbosa P., Kalumuck K., O'Brien W. E. Characterization of the human argininosuccinate lyase gene and analysis of exon skipping. Genomics. 1991 May;10(1):126–132. doi: 10.1016/0888-7543(91)90492-w. [DOI] [PubMed] [Google Scholar]
  2. Amaya Y., Kawamoto S., Oda T., Kuzumi T., Saheki T., Kimura S., Mori M. Molecular cloning of cDNA for argininosuccinate lyase of rat liver. Biochem Int. 1986 Sep;13(3):433–438. [PubMed] [Google Scholar]
  3. Benamar M., Gautier C., Renouf S., Fairand A., Husson A. Changes in argininosuccinate lyase gene expression in the rat liver during development. Biol Neonate. 1992;61(6):381–390. doi: 10.1159/000243825. [DOI] [PubMed] [Google Scholar]
  4. Bokar J. A., Roesler W. J., Vandenbark G. R., Kaetzel D. M., Hanson R. W., Nilson J. H. Characterization of the cAMP responsive elements from the genes for the alpha-subunit of glycoprotein hormones and phosphoenolpyruvate carboxykinase (GTP). Conserved features of nuclear protein binding between tissues and species. J Biol Chem. 1988 Dec 25;263(36):19740–19747. [PubMed] [Google Scholar]
  5. Cathala G., Savouret J. F., Mendez B., West B. L., Karin M., Martial J. A., Baxter J. D. A method for isolation of intact, translationally active ribonucleic acid. DNA. 1983;2(4):329–335. doi: 10.1089/dna.1983.2.329. [DOI] [PubMed] [Google Scholar]
  6. Chou J. Y. Regulators of fetal liver differentiation in vitro. Arch Biochem Biophys. 1988 Jun;263(2):378–386. doi: 10.1016/0003-9861(88)90649-2. [DOI] [PubMed] [Google Scholar]
  7. Cleveland D. W., Lopata M. A., MacDonald R. J., Cowan N. J., Rutter W. J., Kirschner M. W. Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes. Cell. 1980 May;20(1):95–105. doi: 10.1016/0092-8674(80)90238-x. [DOI] [PubMed] [Google Scholar]
  8. Edkins E., Rïhä N. C. Changes in the activities of the enzymes of urea synthesis caused by dexamethasone and dibutyryladenosine 3':5'-cyclic monophosphate in foetal rat liver maintained in organ culture. Biochem J. 1976 Nov 15;160(2):159–162. doi: 10.1042/bj1600159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gebhardt R., Mecke D. Permissive effect of dexamethasone on glucagon induction of urea-cycle enzymes in perifused primary monolayer cultures of rat hepatocytes. Eur J Biochem. 1979 Jun;97(1):29–35. doi: 10.1111/j.1432-1033.1979.tb13082.x. [DOI] [PubMed] [Google Scholar]
  10. Grisolía S., Timoneda J., Hernández-Yago J., Soler J., De Arriaga M. D., Wallace R. Intracellular degradation of mitochondrial enzymes. Acta Biol Med Ger. 1981;40(10-11):1407–1418. [PubMed] [Google Scholar]
  11. Husson A., Bouazza M., Buquet C., Vaillant R. Hormonal regulation of two urea-cycle enzymes in cultured foetal hepatocytes. Biochem J. 1983 Nov 15;216(2):281–285. doi: 10.1042/bj2160281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Husson A., Buquet C., Vaillant R. Induction of the five urea-cycle enzymes by glucagon in cultured foetal rat hepatocytes. Differentiation. 1987;35(3):212–218. doi: 10.1111/j.1432-0436.1987.tb00171.x. [DOI] [PubMed] [Google Scholar]
  13. Husson A., Guechairi M., Fairand A., Bouazza M., Ktorza A., Vaillant R. Effects of pancreatic hormones and glucocorticosteroids on argininosuccinate synthetase and argininosuccinase activities of rat liver during the perinatal period: in vivo and in vitro studies. Endocrinology. 1986 Sep;119(3):1171–1177. doi: 10.1210/endo-119-3-1171. [DOI] [PubMed] [Google Scholar]
  14. Husson A., Renouf S., Fairand A., Buquet C., Benamar M., Vaillant R. Expression of argininosuccinate lyase mRNA in foetal hepatocytes. Regulation by glucocorticoids and insulin. Eur J Biochem. 1990 Sep 24;192(3):677–681. doi: 10.1111/j.1432-1033.1990.tb19275.x. [DOI] [PubMed] [Google Scholar]
  15. Husson A., Vaillant R. Contrôle des activités de l'argininosuccinate synthétase, de l'argininosuccinase et de l'arginase á la naissance chez le rat. Can J Biochem. 1978 Jul;56(7):734–737. [PubMed] [Google Scholar]
  16. Husson A., Vaillant R. Effects of glucocorticosteroids and glucagon on argininosuccinate synthetase, argninosuccinase, and arginase in fetal rat liver. Endocrinology. 1982 Jan;110(1):227–232. doi: 10.1210/endo-110-1-227. [DOI] [PubMed] [Google Scholar]
  17. Johnson A. C., Lee K. L., Isham K. R., Kenney F. T. Gene-specific acquisition of hormonal responsiveness in rat liver during development. J Cell Biochem. 1988 Jun;37(2):243–253. doi: 10.1002/jcb.240370211. [DOI] [PubMed] [Google Scholar]
  18. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  19. Leffert H. L., Paul D. Studies on primary cultures of differentiated fetal liver cells. J Cell Biol. 1972 Mar;52(3):559–568. doi: 10.1083/jcb.52.3.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lin R. C., Snodgrass P. J., Rabier D. Induction of urea cycle enzymes by glucagon and dexamethasone in monolayer cultures of adult rat hepatocytes. J Biol Chem. 1982 May 10;257(9):5061–5067. [PubMed] [Google Scholar]
  21. MCLEAN P., NOVELLO F. INFLUENCE OF PANCREATIC HORMONES ON ENZYMES CONCERNED WITH UREA SYNTHESIS IN RAT LIVER. Biochem J. 1965 Feb;94:410–422. doi: 10.1042/bj0940410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Matsubasa T., Takiguchi M., Amaya Y., Matsuda I., Mori M. Structure of the rat argininosuccinate lyase gene: close similarity to chicken delta-crystallin genes. Proc Natl Acad Sci U S A. 1989 Jan;86(2):592–596. doi: 10.1073/pnas.86.2.592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mencher D., Cohen H., Benvenisty N., Meyuhas O., Reshef L. Primary activation of cytosolic phosphoenolpyruvate carboxykinase gene in fetal rat liver and the biogenesis of its mRNA. Eur J Biochem. 1984 May 15;141(1):199–203. doi: 10.1111/j.1432-1033.1984.tb08175.x. [DOI] [PubMed] [Google Scholar]
  24. Morris S. M., Jr, Moncman C. L., Kepka D. M., Nebes V. L., Diven W. F., Dizikes G. J., Cederbaum S. D., DeFranco D. Effects of deletions in mouse chromosome 7 on expression of genes encoding the urea-cycle enzymes and phosphoenolpyruvate carboxykinase (GTP) in liver, kidney, and intestine. Biochem Genet. 1988 Dec;26(11-12):769–781. doi: 10.1007/BF02395522. [DOI] [PubMed] [Google Scholar]
  25. Morris S. M., Jr, Moncman C. L., Rand K. D., Dizikes G. J., Cederbaum S. D., O'Brien W. E. Regulation of mRNA levels for five urea cycle enzymes in rat liver by diet, cyclic AMP, and glucocorticoids. Arch Biochem Biophys. 1987 Jul;256(1):343–353. doi: 10.1016/0003-9861(87)90455-3. [DOI] [PubMed] [Google Scholar]
  26. Nebes V. L., Morris S. M., Jr Regulation of messenger ribonucleic acid levels for five urea cycle enzymes in cultured rat hepatocytes. Requirements for cyclic adenosine monophosphate, glucocorticoids, and ongoing protein synthesis. Mol Endocrinol. 1988 May;2(5):444–451. doi: 10.1210/mend-2-5-444. [DOI] [PubMed] [Google Scholar]
  27. Räihä N. C., Suihkonen J. Factors influencing the development of urea-synthesizing enzymes in rat liver. Biochem J. 1968 May;107(6):793–797. doi: 10.1042/bj1070793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schmid E., Schmid W., Jantzen M., Mayer D., Jastorff B., Schütz G. Transcription activation of the tyrosine aminotransferase gene by glucocorticoids and cAMP in primary hepatocytes. Eur J Biochem. 1987 Jun 15;165(3):499–506. doi: 10.1111/j.1432-1033.1987.tb11467.x. [DOI] [PubMed] [Google Scholar]
  29. Schwartz A. L. Influence of glucagon, 6-N,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate and triamcinolone on the arginine synthetase system in perinatal rat liver. Biochem J. 1972 Jan;126(1):89–98. doi: 10.1042/bj1260089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Smith J. D., Liu A. Y. The induction, desensitization and de-induction of tyrosine aminotransferase by 8-bromo-cyclic AMP in rat hepatoma cells. Biochem J. 1988 Apr 1;251(1):261–267. doi: 10.1042/bj2510261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Snodgrass P. J., Lin R. C., Müller W. A., Aoki T. T. Induction of urea cycle enzymes of rat liver by glucagon. J Biol Chem. 1978 Apr 25;253(8):2748–2753. [PubMed] [Google Scholar]
  32. TOMLINSON S., WESTALL R. G. ARGININOSUCCINIC ACIDURIA. ARGININOSUCCINASE AND ARGINASE IN HUMAN BLOOD CELLS. Clin Sci. 1964 Apr;26:261–269. [PubMed] [Google Scholar]
  33. Takiguchi M., Haraguchi Y., Mori M. Human liver-type arginase gene: structure of the gene and analysis of the promoter region. Nucleic Acids Res. 1988 Sep 26;16(18):8789–8802. doi: 10.1093/nar/16.18.8789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tomomura M., Imamura Y., Horiuchi M., Koizumi T., Nikaido H., Hayakawa J., Saheki T. Abnormal expression of urea cycle enzyme genes in juvenile visceral steatosis (jvs) mice. Biochim Biophys Acta. 1992 Feb 14;1138(2):167–171. doi: 10.1016/0925-4439(92)90058-u. [DOI] [PubMed] [Google Scholar]
  35. Yoo-Warren H., Cimbala M. A., Felz K., Monahan J. E., Leis J. P., Hanson R. W. Identification of a DNA clone to phosphoenolpyruvate carboxykinase (GTP) from rat cytosol. Alterations in phosphoenolpyruvate carboxykinase RNA levels detectable by hybridization. J Biol Chem. 1981 Oct 25;256(20):10224–10227. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES