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. 1987 May;79(5):1493–1497. doi: 10.1172/JCI112979

n-Butyrate inhibition of hyaluronate synthesis in cultured human fibroblasts.

T J Smith
PMCID: PMC424425  PMID: 3106417

Abstract

The effects of the short-chain aliphatic carboxylic acid, n-butyrate, on glycosaminoglycan (GAG) accumulation were studied in cultured human skin fibroblasts. Normal fibroblast cultures were grown to confluence, shifted to a medium without or with n-butyrate for 24 h, labeled with either [3H]acetate or [3H]glucosamine and analyzed for [3H]GAG and [3H]hyaluronate accumulation. Accumulation was stimulated at low concentrations (0.1-1 mM) by up to 27%. Higher concentrations of n-butyrate (greater than 1 mM) inhibited [3H]GAG by up to 70-90%. This effect was maximal at 10 mM and half-maximal at 3 mM. Propionate had similar effects but was less potent. Parallel studies conducted in colonic fibroblasts revealed that n-butyrate could markedly inhibit [3H]GAG accumulation in that cell type as well. These effects were rapid, occurring within 3 h of treatment, and were reversible. Chondroitin sulfate accumulation was unaffected by the compound. A pulse-chase study failed to demonstrate any effect on [3H]GAG degradation.

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Selected References

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

  1. Arbogast B., Hopwood J. J., Dorfman A. Absence of hyaluronidase in cultured human skin fibroblasts. Biochem Biophys Res Commun. 1975 Nov 3;67(1):376–382. doi: 10.1016/0006-291x(75)90326-5. [DOI] [PubMed] [Google Scholar]
  2. Boffa L. C., Gruss R. J., Allfrey V. G. Manifold effects of sodium butyrate on nuclear function. Selective and reversible inhibition of phosphorylation of histones H1 and H2A and impaired methylation of lysine and arginine residues in nuclear protein fractions. J Biol Chem. 1981 Sep 25;256(18):9612–9621. [PubMed] [Google Scholar]
  3. Boffa L. C., Vidali G., Mann R. S., Allfrey V. G. Suppression of histone deacetylation in vivo and in vitro by sodium butyrate. J Biol Chem. 1978 May 25;253(10):3364–3366. [PubMed] [Google Scholar]
  4. Christman J. K., Weich N., Schoenbrun B., Schneiderman N., Acs G. Hypomethylation of DNA during differentiation of Friend erythroleukemia cells. J Cell Biol. 1980 Aug;86(2):366–370. doi: 10.1083/jcb.86.2.366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cousens L. S., Gallwitz D., Alberts B. M. Different accessibilities in chromatin to histone acetylase. J Biol Chem. 1979 Mar 10;254(5):1716–1723. [PubMed] [Google Scholar]
  6. Cummings J. H. Short chain fatty acids in the human colon. Gut. 1981 Sep;22(9):763–779. doi: 10.1136/gut.22.9.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Helson L., Lai K., Young C. W. Papaverine-induced changes in cultured human melanoma cells. Biochem Pharmacol. 1974 Oct 15;23(20):2917–2920. doi: 10.1016/0006-2952(74)90066-5. [DOI] [PubMed] [Google Scholar]
  10. Hopwood J. J., Dorfman A. Glycosaminoglycan synthesis by cultured human skin fibroblasts after transformation with simian virus 40. J Biol Chem. 1977 Jul 25;252(14):4777–4785. [PubMed] [Google Scholar]
  11. Johnson G. S., Friedman R. M., Pastan I. Restoration of several morphological characteristics of normal fibroblasts in sarcoma cells treated with adenosine-3':5'-cyclic monphosphate and its derivatives. Proc Natl Acad Sci U S A. 1971 Feb;68(2):425–429. doi: 10.1073/pnas.68.2.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kruh J. Effects of sodium butyrate, a new pharmacological agent, on cells in culture. Mol Cell Biochem. 1982 Feb 5;42(2):65–82. doi: 10.1007/BF00222695. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Lamberg S. I., Dorfman A. Synthesis and degradation of hyaluronic acid in the cultured fibroblasts of Marfan's disease. J Clin Invest. 1973 Oct;52(10):2428–2433. doi: 10.1172/JCI107433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Littlefield B. A., Cidlowski N. B., Cidlowski J. A. Modulation of glucocorticoid effects and steroid receptor binding in butyrate-treated HeLa S3 cells. Arch Biochem Biophys. 1980 Apr 15;201(1):174–184. doi: 10.1016/0003-9861(80)90500-7. [DOI] [PubMed] [Google Scholar]
  16. McNeil N. I., Cummings J. H., James W. P. Short chain fatty acid absorption by the human large intestine. Gut. 1978 Sep;19(9):819–822. doi: 10.1136/gut.19.9.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Philipson L. H., Schwartz N. B. Subcellular localization of hyaluronate synthetase in oligodendroglioma cells. J Biol Chem. 1984 Apr 25;259(8):5017–5023. [PubMed] [Google Scholar]
  18. Prasad K. N., Gilmer K., Kumar S. Morphologically "differentiated" mouse neuroblastoma cells induced by noncyclic AMP agents: levels of cyclic AMP, nucleic acid and protein. Proc Soc Exp Biol Med. 1973 Sep;143(4):1168–1171. doi: 10.3181/00379727-143-37493. [DOI] [PubMed] [Google Scholar]
  19. Prasad K. N., Mandal B. Catechol-o-methyl-transferase activity in dibutyryl cyclic AMP, prostaglandin and x-ray -induced differentiated neuroblastoma cell culture. Exp Cell Res. 1972 Oct;74(2):532–534. doi: 10.1016/0014-4827(72)90412-0. [DOI] [PubMed] [Google Scholar]
  20. Prasad K. N., Mandal B. Choline acetyltransferase level in cyclic AMP and x-ray induced morphologically differentiated neuroblastoma cells in culture. Cytobios. 1973 Sep-Oct;8(29):75–80. [PubMed] [Google Scholar]
  21. Prasad K. N., Vernadakis A. Morphological and biochemical study in x-ray- and dibutyryl cyclic AMP-induced differentiated neuroblastoma cells. Exp Cell Res. 1972 Jan;70(1):27–32. doi: 10.1016/0014-4827(72)90177-2. [DOI] [PubMed] [Google Scholar]
  22. Rastl E., Swetly P. Expression of poly(adenosine diphosphate-ribose) polymerase activity in erythroleukemic mouse cells during cell cycle and erythropoietic differentiation. J Biol Chem. 1978 Jun 25;253(12):4333–4340. [PubMed] [Google Scholar]
  23. Richelson E. Stimulation of tyrosine hydroxylase activity in an adrenergic clone of mouse neuroblastoma by dibutyryl cyclic AMP. Nat New Biol. 1973 Apr 11;242(119):175–177. doi: 10.1038/newbio242175a0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Ruppin H., Bar-Meir S., Soergel K. H., Wood C. M., Schmitt M. G., Jr Absorption of short-chain fatty acids by the colon. Gastroenterology. 1980 Jun;78(6):1500–1507. [PubMed] [Google Scholar]
  26. Samuels H. H., Stanley F., Casanova J., Shao T. C. Thyroid hormone nuclear receptor levels are influenced by the acetylation of chromatin-associated proteins. J Biol Chem. 1980 Mar 25;255(6):2499–2508. [PubMed] [Google Scholar]
  27. Sealy L., Chalkley R. The effect of sodium butyrate on histone modification. Cell. 1978 May;14(1):115–121. doi: 10.1016/0092-8674(78)90306-9. [DOI] [PubMed] [Google Scholar]
  28. Smith T. J. Dexamethasone regulation of glycosaminoglycan synthesis in cultured human skin fibroblasts. Similar effects of glucocorticoid and thyroid hormones. J Clin Invest. 1984 Dec;74(6):2157–2163. doi: 10.1172/JCI111642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Smith T. J., Horwitz A. L., Refetoff S. The effect of thyroid hormone on glycosaminoglycan accumulation in human skin fibroblasts. Endocrinology. 1981 Jun;108(6):2397–2399. doi: 10.1210/endo-108-6-2397. [DOI] [PubMed] [Google Scholar]
  30. Smith T. J., Murata Y., Horwitz A. L., Philipson L., Refetoff S. Regulation of glycosaminoglycan synthesis by thyroid hormone in vitro. J Clin Invest. 1982 Nov;70(5):1066–1073. doi: 10.1172/JCI110694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Stanley F., Samuels H. H. n-Butyrate effects thyroid hormone stimulation of prolactin production and mRNA levels in GH1 cells. J Biol Chem. 1984 Aug 10;259(15):9768–9775. [PubMed] [Google Scholar]
  32. Turakainen H., Larjava H., Saarni H., Penttinen R. Synthesis of hyaluronic acid and collagen in skin fibroblasts cultured from patients with osteogenesis imperfecta. Biochim Biophys Acta. 1980 Apr 3;628(4):388–397. doi: 10.1016/0304-4165(80)90388-8. [DOI] [PubMed] [Google Scholar]
  33. Waymire J. C., Weiner N., Prasad K. N. Regulation of tyrosine hydroxylase activity in cultured mouse neuroblastoma cells: elevation induced by analogs of adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1972 Aug;69(8):2241–2245. doi: 10.1073/pnas.69.8.2241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. de Hemptinne A., Marrannes R., Vanheel B. Influence of organic acids on intracellular pH. Am J Physiol. 1983 Sep;245(3):C178–C183. doi: 10.1152/ajpcell.1983.245.3.C178. [DOI] [PubMed] [Google Scholar]

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