Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1989 Sep 15;262(3):989–992. doi: 10.1042/bj2620989

Cholesterol and bile acid synthesis in Hep G2 cells. Metabolic effects of 26- and 7 alpha-hydroxycholesterol.

N B Javitt 1, K Budai 1
PMCID: PMC1133372  PMID: 2556116

Abstract

1. Using a human hepatoma (Hep G2) cell line that continually synthesizes 3 beta-hydroxy-5-cholenoic acid, lithocholic acid, chenodeoxycholic acid and cholic acid we have determined the metabolism and biological effects of 26-hydroxycholesterol and 7 alpha-hydroxycholesterol. 2. Addition of 26-hydroxycholesterol to the medium (6 microM) downregulated cholesterol and chenodeoxycholic acid synthesis. 3. The predominant metabolite of 26-hydroxycholesterol was 3 beta-hydroxy-5-cholenoic acid. 4. Cholesterol synthesis was not affected by the addition of 7 alpha-hydroxycholesterol (6 and 12 microM). The predominant metabolite of 7 alpha-hydroxycholesterol was chenodeoxycholic acid. 5. In Hep G2 cells 7 alpha-hydroxylation of 26-hydroxycholesterol is not well expressed.

Full text

PDF
989

Selected References

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

  1. ABEL L. L., LEVY B. B., BRODIE B. B., KENDALL F. E. A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity. J Biol Chem. 1952 Mar;195(1):357–366. [PubMed] [Google Scholar]
  2. Ali S. S., Javitt N. B. Quantitative estimation os bile salts in serum. Can J Biochem. 1970 Sep;48(9):1054–1057. doi: 10.1139/o70-166. [DOI] [PubMed] [Google Scholar]
  3. Anderson K. E., Kok E., Javitt N. B. Bile acid synthesis in man: metabolism of 7 -hydroxycholesterol- 14 C and 26-hydroxycholesterol- 3 H. J Clin Invest. 1972 Jan;51(1):112–117. doi: 10.1172/JCI106780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Axelson M., Mörk B., Sjövall J. Occurrence of 3 beta-hydroxy-5-cholestenoic acid, 3 beta,7 alpha-dihydroxy-5-cholestenoic acid, and 7 alpha-hydroxy-3-oxo-4-cholestenoic acid as normal constituents in human blood. J Lipid Res. 1988 May;29(5):629–641. [PubMed] [Google Scholar]
  5. Ayaki Y., Kok E., Javitt N. B. Cholic acid synthesis from 26-hydroxycholesterol and 3-hydroxy-5-cholestenoic acid in the rabbit. J Biol Chem. 1989 Mar 5;264(7):3818–3821. [PubMed] [Google Scholar]
  6. Cighetti G., Bosisio E., Galli G., Galli Kienle M. The effect of cholestyramine on liver HMG-CoA reductase and cholesterol 7 alpha-hydroxylase in various laboratory animals. Life Sci. 1983 Dec 19;33(25):2483–2488. doi: 10.1016/0024-3205(83)90156-x. [DOI] [PubMed] [Google Scholar]
  7. Esterman A. L., Cohen B. I., Javitt N. B. Cholesterol metabolism: use of D2O for determination of synthesis rate in cell culture. J Lipid Res. 1985 Aug;26(8):950–954. [PubMed] [Google Scholar]
  8. Everson G. T., Polokoff M. A. HepG2. A human hepatoblastoma cell line exhibiting defects in bile acid synthesis and conjugation. J Biol Chem. 1986 Feb 15;261(5):2197–2201. [PubMed] [Google Scholar]
  9. Javitt N. B., Emerman S. Metabolic pathways of bile acid formation in the rat. Mt Sinai J Med. 1970 Jul-Aug;37(4):477–481. [PubMed] [Google Scholar]
  10. Javitt N. B., Kok E., Burstein S., Cohen B., Kutscher J. 26-Hydroxycholesterol. Identification and quantitation in human serum. J Biol Chem. 1981 Dec 25;256(24):12644–12646. [PubMed] [Google Scholar]
  11. Javitt N. B., Kok E., Cohen B., Burstein S. Cerebrotendinous xanthomatosis: reduced serum 26-hydroxycholesterol. J Lipid Res. 1982 May;23(4):627–630. [PubMed] [Google Scholar]
  12. Javitt N. B., Pfeffer R., Kok E., Burstein S., Cohen B. I., Budai K. Bile acid synthesis in cell culture. J Biol Chem. 1989 Jun 25;264(18):10384–10387. [PubMed] [Google Scholar]
  13. Knowles B. B., Howe C. C., Aden D. P. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science. 1980 Jul 25;209(4455):497–499. doi: 10.1126/science.6248960. [DOI] [PubMed] [Google Scholar]
  14. Koopman B. J., van der Molen J. C., Wolthers B. G., Vanderpas J. B. Determination of some hydroxycholesterols in human serum samples. J Chromatogr. 1987 Apr 24;416(1):1–13. doi: 10.1016/0378-4347(87)80479-6. [DOI] [PubMed] [Google Scholar]
  15. Miao E., Wilson S. R., Javitt N. B. Cholesterol metabolism. Effect of 26-thiacholesterol and 26-aminocholesterol, analogues of 26-hydroxycholesterol, on cholesterol synthesis and low-density-lipoprotein-receptor binding. Biochem J. 1988 Nov 1;255(3):1049–1052. doi: 10.1042/bj2551049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mitropoulos K. A., Myant N. B., Gompertz D. The formation of propionate from the side-chain of cholesterol in an infant with an inborn error in the metabolism of propionate. Biochem J. 1970 Jul;118(3):551–552. doi: 10.1042/bj1180551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Salen G., Grundy S. M. The metabolism of cholestanol, cholesterol, and bile acids in cerebrotendinous xanthomatosis. J Clin Invest. 1973 Nov;52(11):2822–2835. doi: 10.1172/JCI107478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Setchell K. D., Worthington J. A rapid method for the quantitative extraction of bile acids and their conjugates from serum using commercially available reverse-phase octadecylsilane bonded silica cartridges. Clin Chim Acta. 1982 Oct 27;125(2):135–144. doi: 10.1016/0009-8981(82)90190-5. [DOI] [PubMed] [Google Scholar]
  19. Sugiyama K., Okuyama S., Imoto M., Okumura K., Takagi K., Satake T. Clinical evaluation of serum 3 beta-hydroxy-5-cholenoic acid in hepatobiliary diseases. Gastroenterol Jpn. 1986 Dec;21(6):608–616. doi: 10.1007/BF02774489. [DOI] [PubMed] [Google Scholar]
  20. Wachtel N., Emerman S., Javitt N. B. Metabolism of cholest-5-ene-3 beta, 26-diol in the rat and hamster. J Biol Chem. 1968 Oct 10;243(19):5207–5212. [PubMed] [Google Scholar]

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

RESOURCES