Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1980 Feb 1;84(2):225–234. doi: 10.1083/jcb.84.2.225

Effects of sodium butyrate on the membrane glycoconjugates of murine sarcoma virus-transformed rat cells

PMCID: PMC2110554  PMID: 7380882

Abstract

The temporal relationship between butyrate-induced cellular flattening of murine sarcoma virus-transformed rat cells (MSV-NRK) and alterations in certain surface-associated biochemical markers of transformation, e.g., surface glycopeptides, glycolipids, fibronectin, hexose uptake, and cell-substrate adhesion was examined. The induction of elevated levels of the ganglioside GM3 and of a GDla-like ganglioside were observed to precede or to parallel cellular flattening. Likewise, enhanced incorporation of radioisotopically labeled fucose into a novel fucose-containing component, i.e., glucopyranosyl (1 leads to 3) fucopyranosyl-threonine, was also observed to occur at an early stage of cellular flattening. In contrast, a shift in the molecular weight distribution of trypsin-sensitive, surface fucopeptides was observed to occur at a late stage of cellular flattening. Moreover, surface fibronectin was not detectable in the butyrate-flattened MSV-NRK cells despite the fact that the cells manifested significantly enhanced cell- substrate adhesion. Thus, butyrate appears to be a useful tool for understanding the sequential changes associated with expression of the transformed phenotype of MSV-NRK cells.

Full Text

The Full Text of this article is available as a PDF (750.1 KB).

Selected References

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

  1. Ali I. U., Hynes R. O. Effects of cytochalasin B and colchicine on attachment of a major surface protein of fibroblasts. Biochim Biophys Acta. 1977 Nov 15;471(1):16–24. doi: 10.1016/0005-2736(77)90388-1. [DOI] [PubMed] [Google Scholar]
  2. Ali I. U., Mautner V., Lanza R., Hynes R. O. Restoration of normal morphology, adhesion and cytoskeleton in transformed cells by addition of a transformation-sensitive surface protein. Cell. 1977 May;11(1):115–126. doi: 10.1016/0092-8674(77)90322-1. [DOI] [PubMed] [Google Scholar]
  3. Altenburg B. C., Via D. P., Steiner S. H. Modification of the phenotype of murine sarcoma virus-transformed cells by sodium butyrate. Effects on morphology and cytoskeletal elements. Exp Cell Res. 1976 Oct 15;102(2):223–231. doi: 10.1016/0014-4827(76)90036-7. [DOI] [PubMed] [Google Scholar]
  4. Birdwell C. R., Gospodarowicz D., Nicolson G. L. Identification, localization, and role of fibronectin in cultured bovine endothelial cells. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3273–3277. doi: 10.1073/pnas.75.7.3273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bonner W. M., Laskey R. A. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
  6. Brady R. O., Fishman P. H. Biosynthesis of glycolipids in virus-transformed cells. Biochim Biophys Acta. 1974 Sep 9;355(2):121–148. doi: 10.1016/0304-419x(74)90001-8. [DOI] [PubMed] [Google Scholar]
  7. Buck C. A., Glick M. C., Warren L. Effect of growth on the glycoproteins from the surface of control and Rous sarcoma virus transformed hamster cells. Biochemistry. 1971 May 25;10(11):2176–2180. doi: 10.1021/bi00787a034. [DOI] [PubMed] [Google Scholar]
  8. Buck C. A., Glick M. C., Warren L. Glycopeptides from the surface of control and virus-transformed cells. Science. 1971 Apr 9;172(3979):169–171. doi: 10.1126/science.172.3979.169. [DOI] [PubMed] [Google Scholar]
  9. Chen L. B., Gallimore P. H., McDougall J. K. Correlation between tumor induction and the large external transformation sensitive protein on the cell surface. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3570–3574. doi: 10.1073/pnas.73.10.3570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Culp L. A. Electrophoretic analysis of substrate-attached proteins from normal and virus-transformed cells. Biochemistry. 1976 Sep 7;15(18):4094–4104. doi: 10.1021/bi00663a028. [DOI] [PubMed] [Google Scholar]
  11. Deutsch S. I., Silvers D. N., Cox R. P., Griffin M. J., Ghosh N. K. Ultrastructural and enzymic modulation of HeLa cells induced by sodium butyrate and the effects of cytochalasin B and colcemid. J Cell Sci. 1976 Jul;21(2):391–406. doi: 10.1242/jcs.21.2.391. [DOI] [PubMed] [Google Scholar]
  12. FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
  13. Fishman P. H., Bradley R. M., Henneberry R. C. Butyrate-induced glycolipid biosynthesis in HeLa cells: properties of the induced sialyltransferase. Arch Biochem Biophys. 1976 Feb;172(2):618–626. doi: 10.1016/0003-9861(76)90116-8. [DOI] [PubMed] [Google Scholar]
  14. Fishman P. H., Simmons J. L., Brady R. O., Freese E. Induction of glycolipid biosynthesis by sodium butyrate in HeLa cells. Biochem Biophys Res Commun. 1974 Jul 10;59(1):292–299. doi: 10.1016/s0006-291x(74)80205-6. [DOI] [PubMed] [Google Scholar]
  15. Ghosh N. K., Cox R. P. Induction of human follicle-stimulating hormone in HeLa cells by sodium butyrate. Nature. 1977 Jun 2;267(5610):435–437. doi: 10.1038/267435a0. [DOI] [PubMed] [Google Scholar]
  16. Ghosh N. K., Deutsch S. I., Griffin M. J., Cox R. P. Regulation of growth and morphological modulation of HeLa65 cells in monolayer culture by dibutyryl cyclic AMP, butyrate and their analogs. J Cell Physiol. 1975 Dec;86 (Suppl 2)(3 Pt 2):663–672. doi: 10.1002/jcp.1040860511. [DOI] [PubMed] [Google Scholar]
  17. Ginsburg E., Salomon D., Sreevalsan T., Freese E. Growth inhibition and morphological changes caused by lipophilic acids in mammalian cells. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2457–2461. doi: 10.1073/pnas.70.8.2457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Griffin M. J., Price G. H., Bazzell K. L. A study of adenosine 3':5'-cyclic monophosphate, sodium butyrate and cortisol as inducers of HeLa alkaline phosphatase. Arch Biochem Biophys. 1974 Oct;164(2):619–623. doi: 10.1016/0003-9861(74)90073-3. [DOI] [PubMed] [Google Scholar]
  19. Hakomori S. I., Wyke J. A., Vogt P. K. Glycolipids of chick embryo fibroblasts infected with temperature-sensitive mutants of avian sarcoma viruses. Virology. 1977 Feb;76(2):485–493. doi: 10.1016/0042-6822(77)90231-8. [DOI] [PubMed] [Google Scholar]
  20. Henneberry R. C., Fishman P. H. Morphological and biochemical differentiation in HeLa cells. Effects of cycloheximide on butyrate-induced process formation and ganglioside metabolism. Exp Cell Res. 1976 Nov;103(1):55–62. doi: 10.1016/0014-4827(76)90240-8. [DOI] [PubMed] [Google Scholar]
  21. Hynes R. O. Alteration of cell-surface proteins by viral transformation and by proteolysis. Proc Natl Acad Sci U S A. 1973 Nov;70(11):3170–3174. doi: 10.1073/pnas.70.11.3170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hynes R. O. Cell surface proteins and malignant transformation. Biochim Biophys Acta. 1976 Apr 30;458(1):73–107. doi: 10.1016/0304-419x(76)90015-9. [DOI] [PubMed] [Google Scholar]
  23. Hök M., Rubin K., Oldberg A., Obrink B., Vaheri A. Cold-insoluble globulin mediates the adhesion of rat liver cells to plastic Petri dishes. Biochem Biophys Res Commun. 1977 Dec 7;79(3):726–733. doi: 10.1016/0006-291x(77)91172-x. [DOI] [PubMed] [Google Scholar]
  24. Koyama H., Ono T. Induction by short-chain fatty acids of alkaline phosphatase activity in cultured mammalian cells. J Cell Physiol. 1976 May;88(1):49–56. doi: 10.1002/jcp.1040880107. [DOI] [PubMed] [Google Scholar]
  25. Kurkinen M., Wartiovaara J., Vaheri A. Cytochalasin B releases a major surface-associated glycoprotein, fibronectin, from cultured fibroblasts. Exp Cell Res. 1978 Jan;111(1):127–137. doi: 10.1016/0014-4827(78)90243-4. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  28. Langenbach R., Malick L., Kennedy S. Ganglioside and morphological changes in mouse embryo cells with time. Cancer Lett. 1978 Jan;4(1):13–19. doi: 10.1016/s0304-3835(78)93082-3. [DOI] [PubMed] [Google Scholar]
  29. Larriba G., Klinger M., Sramek S., Steiner S. Noval fucose-containing components from rat tissues. Biochem Biophys Res Commun. 1977 Jul 11;77(1):79–85. doi: 10.1016/s0006-291x(77)80167-8. [DOI] [PubMed] [Google Scholar]
  30. Larriba G. O-glycosidically linked fucose in high molecular weight glycoproteins, in normal and virus-transformed rat cells. FEBS Lett. 1978 Nov 1;95(1):190–193. doi: 10.1016/0014-5793(78)80081-7. [DOI] [PubMed] [Google Scholar]
  31. Leder A., Leder P. Butyric acid, a potent inducer of erythroid differentiation in cultured erythroleukemic cells. Cell. 1975 Jul;5(3):319–322. doi: 10.1016/0092-8674(75)90107-5. [DOI] [PubMed] [Google Scholar]
  32. Pearlstein E. Plasma membrane glycoprotein which mediates adhesion of fibroblasts to collagen. Nature. 1976 Aug 5;262(5568):497–500. doi: 10.1038/262497a0. [DOI] [PubMed] [Google Scholar]
  33. Pouysségur J. M., Pastan I. Mutants of Balb/c 3T3 fibroblasts defective in adhesiveness to substratum: evidence for alteration in cell surface proteins. Proc Natl Acad Sci U S A. 1976 Feb;73(2):544–548. doi: 10.1073/pnas.73.2.544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Pouysségur J., Pastan I. Mutants of mouse fibroblasts altered in the synthesis of cell surface glycoproteins. Preliminary evidence for a defect in the acetylation of glucosamine 6-phosphate. J Biol Chem. 1977 Mar 10;252(5):1639–1646. [PubMed] [Google Scholar]
  35. Pouysségur J., Willingham M., Pastan I. Role of cell surface carbohydrates and proteins in cell behavior: studies on the biochemical reversion of an N-acetylglucosamine-deficient fibroblast mutant. Proc Natl Acad Sci U S A. 1977 Jan;74(1):243–247. doi: 10.1073/pnas.74.1.243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Prasad K. N., Sinha P. K. Effect of sodium butyrate on mammalian cells in culture: a review. In Vitro. 1976 Feb;12(2):125–132. doi: 10.1007/BF02796360. [DOI] [PubMed] [Google Scholar]
  37. Richardson C. L., Baker S. R., Morré D. J., Keenan T. W. Glycosphingolipid synthesis and tumorigenesis. A role for the Golgi apparatus in the origin of specific receptor molecules of the mammalian cell surface. Biochim Biophys Acta. 1975 Dec 31;417(3-4):175–186. doi: 10.1016/0304-419x(75)90009-8. [DOI] [PubMed] [Google Scholar]
  38. Riggs M. G., Whittaker R. G., Neumann J. R., Ingram V. M. n-Butyrate causes histone modification in HeLa and Friend erythroleukaemia cells. Nature. 1977 Aug 4;268(5619):462–464. doi: 10.1038/268462a0. [DOI] [PubMed] [Google Scholar]
  39. SVENNERHOLM L. Quantitative estimation of sialic acids. II. A colorimetric resorcinol-hydrochloric acid method. Biochim Biophys Acta. 1957 Jun;24(3):604–611. doi: 10.1016/0006-3002(57)90254-8. [DOI] [PubMed] [Google Scholar]
  40. SVENNERHOLM L. THE GANGLIOSIDES. J Lipid Res. 1964 Apr;5:145–155. [PubMed] [Google Scholar]
  41. Simmons J. L., Fishman P. H., Freese E., Brady R. O. Morphological alterations and ganglioside sialyltransferase activity induced by small fatty acids in HeLa cells. J Cell Biol. 1975 Aug;66(2):414–424. doi: 10.1083/jcb.66.2.414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Steiner S. M., Melnick J. L., Kit S., Somers K. D. Fucosylglycolipids in cells transformed by a temperature-sensitive mutant of murine sarcoma virus. Nature. 1974 Apr 19;248(5450):682–684. doi: 10.1038/248682a0. [DOI] [PubMed] [Google Scholar]
  43. Steiner S., Brennan P. J., Melnick J. L. Fucosylglycolipid metabolism in oncornavirus-transformed cell lines. Nat New Biol. 1973 Sep 5;245(140):19–21. doi: 10.1038/newbio245019a0. [DOI] [PubMed] [Google Scholar]
  44. Steiner S., Steiner M. R. Fucolipid patterns of cell lines transformed by highly and weakly tumorigenic simian virus 40 and herpes simplex virus. Intervirology. 1975;6(1):32–41. doi: 10.1159/000149451. [DOI] [PubMed] [Google Scholar]
  45. Tallman J. F., Smith C. C., Henneberry R. C. Induction of functional beta-adrenergic receptors in HeLa cells. Proc Natl Acad Sci U S A. 1977 Mar;74(3):873–877. doi: 10.1073/pnas.74.3.873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Vaheri A., Ruoslahti E., Linder E., Wartiovaara J., Keski-Oja J., Kuusela P., Saksela O. Fibroblast surface antigen (SF): molecular properties, distribution in vitro and in vivo, and altered expression in transformed cells. J Supramol Struct. 1976;4(1):63–70. doi: 10.1002/jss.400040107. [DOI] [PubMed] [Google Scholar]
  47. Yamada K. M., Yamada S. S., Pastan I. Cell surface protein partially restores morphology, adhesiveness, and contact inhibition of movement to transformed fibroblasts. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1217–1221. doi: 10.1073/pnas.73.4.1217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Yamada K. M., Yamada S. S., Pastan I. The major cell surface glycoprotein of chick embryo fibroblasts is an agglutinin. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3158–3162. doi: 10.1073/pnas.72.8.3158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Zetter B. R., Chen L. B., Buchanan J. M. Effects of protease treatment on growth, morphology, adhesion, and cell surface proteins of secondary chick embryo fibroblasts. Cell. 1976 Mar;7(3):407–412. doi: 10.1016/0092-8674(76)90170-7. [DOI] [PubMed] [Google Scholar]
  50. Zigmond S. H., Otto J. J., Bryan J. Organization of myosin in a submembranous sheath in well-spread human fibroblasts. Exp Cell Res. 1979 Mar 15;119(2):205–219. doi: 10.1016/0014-4827(79)90349-5. [DOI] [PubMed] [Google Scholar]

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

RESOURCES