Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1976 Jul 1;70(1):20–32. doi: 10.1083/jcb.70.1.20

Growth control of differentiated fetal rat hepatocytes in primary monolayer culture. IX. Specific inhibition of DNA synthesis initiation by very low density lipoprotein and possible significance to the problem of liver regeneration

PMCID: PMC2109804  PMID: 180032

Abstract

Rat serum very low density lipoprotein (VLDL) inhibits initiation of DNA synthesis in fetal rat hepatocyte cultures; cells engaged in synthesizing DNA resist inhibition. VLDL action is specific and apparently blocks prereplicative protein synthesis. These and other results, from studies of altered blood VLDL levels and [3H] thymidine incorporation into isolated liver nuclei in 70% hepatectomized normal and mutant hyperlipoproteinemic rats, as well as from infusion studies with a "mitogenic" hormone solution, suggest that hepatic VLDL metabolism is linked to the suppression of hepatocyte proliferation.

Full Text

The Full Text of this article is available as a PDF (956.1 KB).

Selected References

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

  1. BUCHER N. L. R., SCOTT J. F., AUB J. C. Regeneration of the liver in parabiotic rats. Cancer Res. 1951 Jun;11(6):457–465. [PubMed] [Google Scholar]
  2. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bissell D. M., Hammaker L. E., Meyer U. A. Parenchymal cells from adult rat liver in nonproliferating monolayer culture. I. Functional studies. J Cell Biol. 1973 Dec;59(3):722–734. doi: 10.1083/jcb.59.3.722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blobel G., Potter V. R. Nuclei from rat liver: isolation method that combines purity with high yield. Science. 1966 Dec 30;154(3757):1662–1665. doi: 10.1126/science.154.3757.1662. [DOI] [PubMed] [Google Scholar]
  5. Brady R. O., Borek C., Bradley R. M. Composition and synthesis of gangliosides in rat hepatocyte and hepatoma cell lines. J Biol Chem. 1969 Dec 10;244(23):6552–6554. [PubMed] [Google Scholar]
  6. Bruckdorfer K. R., Graham J. M., Green C. The incorporation of steroid molecules into lecithin sols, beta-lipoproteins and cellular membranes. Eur J Biochem. 1968 May;4(4):512–518. doi: 10.1111/j.1432-1033.1968.tb00242.x. [DOI] [PubMed] [Google Scholar]
  7. Bucher M. L., Swaffield M. N. Regulation of hepatic regeneration in rats by synergistic action of insulin and glucagon. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1157–1160. doi: 10.1073/pnas.72.3.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eaton R. P. Hypolipemic action of glucagon in experimental endogenous lipemia in the rat. J Lipid Res. 1973 May;14(3):312–318. [PubMed] [Google Scholar]
  9. Fidge N. H., Poulis P. Studies on the radioiodination of very low density lipoprotein obtained from different mammalian species. Clin Chim Acta. 1974 Mar;52(1):15–26. doi: 10.1016/0009-8981(74)90383-0. [DOI] [PubMed] [Google Scholar]
  10. Fielding C. J., Shore V. G., Fielding P. E. A protein cofactor of lecithin:cholesterol acyltransferase. Biochem Biophys Res Commun. 1972 Feb 25;46(4):1493–1498. doi: 10.1016/0006-291x(72)90776-0. [DOI] [PubMed] [Google Scholar]
  11. GLINOS A. D. Environmental feedback control of cell division. Ann N Y Acad Sci. 1960 Oct 7;90:592–602. doi: 10.1111/j.1749-6632.1960.tb23275.x. [DOI] [PubMed] [Google Scholar]
  12. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Havel R. J., Fielding C. J., Olivecrona T., Shore V. G., Fielding P. E., Egelrud T. Cofactor activity of protein components of human very low density lipoproteins in the hydrolysis of triglycerides by lipoproteins lipase from different sources. Biochemistry. 1973 Apr 24;12(9):1828–1833. doi: 10.1021/bi00733a026. [DOI] [PubMed] [Google Scholar]
  14. Holley R. W., Kiernan J. A. "Contact inhibition" of cell division in 3T3 cells. Proc Natl Acad Sci U S A. 1968 May;60(1):300–304. doi: 10.1073/pnas.60.1.300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jones A. L., Ockner R. K. An electron microscopic study of endogenous very low density lipoprotein production in the intestine of rat and man. J Lipid Res. 1971 Sep;12(5):580–589. [PubMed] [Google Scholar]
  16. Koch K., Leffert H. L. Growth control of differentiated fetal rat hepatocytes in primary monolayer culture. VI. Studies with conditioned medium and its functional interactions with serum factors. J Cell Biol. 1974 Sep;62(3):780–791. doi: 10.1083/jcb.62.3.780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Koga S., Horwitz D. L., Scanu A. M. Isolation and properties of lipoproteins from normal rat serum. J Lipid Res. 1969 Sep;10(5):577–588. [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. Growth control of differentiated fetal rat hepatocytes in primary monolayer culture. V. Occurrence in dialyzed fetal bovine serum of macromolecules having both positive and negative growth regulatory functions. J Cell Biol. 1974 Sep;62(3):767–779. doi: 10.1083/jcb.62.3.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Leffert H. L. Growth control of differentiated fetal rat hepatocytes in primary monolayer culture. VII. Hormonal control of DNA synthesis and its possible significance to the problem of liver regeneration. J Cell Biol. 1974 Sep;62(3):792–801. doi: 10.1083/jcb.62.3.792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Leffert H. L., Paul D. Serum dependent growth of primary cultured differentiated fetal rat hepatocytes in arginine-deficient medium. J Cell Physiol. 1973 Feb;81(1):113–124. doi: 10.1002/jcp.1040810114. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Leffert H. L., Sell S. Alpha1-fetoprotein biosynthesis during the growth cycle of differentiated fetal rat hepatocytes in primary monolayer culture. J Cell Biol. 1974 Jun;61(3):823–829. doi: 10.1083/jcb.61.3.823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Leffert H., Alexander N. M., Faloona G., Rubalcava B., Unger R. Specific endocrine and hormonal receptor changes associated with liver regeneration in adult rats. Proc Natl Acad Sci U S A. 1975 Oct;72(10):4033–4036. doi: 10.1073/pnas.72.10.4033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Paul D., Leffert H., Sato G., Holley R. W. Stimulation of DNA and protein synthesis in fetal-rat liver cells by serum from partially hepatectomized rats. Proc Natl Acad Sci U S A. 1972 Feb;69(2):374–377. doi: 10.1073/pnas.69.2.374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. ROGERS A. E., SHAKA J. A., PECHET G., MACDONALD R. A. Regeneration of the liver. Absence of a "humoral factor" affecting hepatic regeneration in parabiotic rats. Am J Pathol. 1961 Nov;39:561–578. [PMC free article] [PubMed] [Google Scholar]
  27. Ross R., Glomset J. A. Atherosclerosis and the arterial smooth muscle cell: Proliferation of smooth muscle is a key event in the genesis of the lesions of atherosclerosis. Science. 1973 Jun 29;180(4093):1332–1339. doi: 10.1126/science.180.4093.1332. [DOI] [PubMed] [Google Scholar]
  28. Schonfeld G., Felski C., Howald M. A. Characterization of the plasma lipoproteins of the genetically obese hyperlipoproteinemic Zucker fatty rat. J Lipid Res. 1974 Sep;15(5):457–464. [PubMed] [Google Scholar]
  29. Schonfeld G., Pfleger B. Overproduction of very low-density lipoproteins by livers of genetically obese rats. Am J Physiol. 1971 May;220(5):1178–1181. doi: 10.1152/ajplegacy.1971.220.5.1178. [DOI] [PubMed] [Google Scholar]
  30. Sell S., Skelly H., Leffert H. L., Muller-Eberhard U., Kida S. Relationship of the biosynthesis of alpha-fetoprotein, albumin, hemopexin, and haptoglobin to the growth state of fetal rat hepatocyte cultures. Ann N Y Acad Sci. 1975 Aug 22;259:45–58. doi: 10.1111/j.1749-6632.1975.tb25401.x. [DOI] [PubMed] [Google Scholar]
  31. Short J., Brown R. F., Husakova A., Gilbertson J. R., Zemel R., Lieberman I. Induction of deoxyribonucleic acid synthesis in the liver of the intact animal. J Biol Chem. 1972 Mar 25;247(6):1757–1766. [PubMed] [Google Scholar]
  32. Simard A., Corneille L., Deschamps Y., Verly W. G. Inhibition of cell proliferation in the livers of hepatectomized rats by a rabbit hepatic chalone. Proc Natl Acad Sci U S A. 1974 May;71(5):1763–1766. doi: 10.1073/pnas.71.5.1763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Starzl T. E., Francavilla A., Halgrimson C. G., Francavilla F. R., Porter K. A., Brown T. H., Putnam C. W. The origin, hormonal nature, and action of hepatotrophic substances in portal venous blood. Surg Gynecol Obstet. 1973 Aug;137(2):179–199. [PMC free article] [PubMed] [Google Scholar]
  34. Stein O., Stein Y. Lipid synthesis, intracellular transport, storage, and secretion. I. Electron microscopic radioautographic study of liver after injection of tritiated palmitate or glycerol in fasted and ethanol-treated rats. J Cell Biol. 1967 May;33(2):319–339. doi: 10.1083/jcb.33.2.319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Verly W. G., Deschamps Y., Pushpathadam J., Desrosiers M. The hepatic chalone. I. Assay method for the hormone and purification of the rabbit liver chalone. Can J Biochem. 1971 Dec;49(12):1376–1383. doi: 10.1139/o71-198. [DOI] [PubMed] [Google Scholar]
  36. Veser J., Frank W. Stimulierung von Kulturen embryonaler Rattenzellen durch Kälberserum. IV. Isolierung eines aktiven Proteins sowie Anreicherung einer zwieten wirksamen Fraktion aus fötalem Kälberserum. Z Naturforsch B. 1972 Dec;27(12):1573–1574. [PubMed] [Google Scholar]
  37. Watkins M. L., Fizette N., Heimberg M. Sexual influences on hepatic secretion of triglyceride. Biochim Biophys Acta. 1972 Sep 7;280(1):82–85. doi: 10.1016/0005-2760(72)90214-7. [DOI] [PubMed] [Google Scholar]
  38. Weber M. J. Hexose transport in normal and in Rous sarcoma virus-transformed cells. J Biol Chem. 1973 May 10;248(9):2978–2983. [PubMed] [Google Scholar]
  39. Weinstein D. B., Marsh J. B., Glick M. C., Warren L. Membranes of animal cells. IV. Lipids of the L cell and its surface membrane. J Biol Chem. 1969 Aug 10;244(15):4103–4111. [PubMed] [Google Scholar]
  40. Weinstein D. B., Marsh J. B., Glick M. C., Warren L. Membranes of animal cells. VI. The glycolipids of the L cell and its surface membrane. J Biol Chem. 1970 Aug 10;245(15):3928–3937. [PubMed] [Google Scholar]
  41. Zucker L. M., Antoniades H. N. Insulin and obesity in the Zucker genetically obese rat "fatty". Endocrinology. 1972 May;90(5):1320–1330. doi: 10.1210/endo-90-5-1320. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES