Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 2002 May 15;364(Pt 1):115–120. doi: 10.1042/bj3640115

Elevation of hepatic sulphotransferase activities in mice with resistance to cystic fibrosis.

Josie L Falany 1, Heather Greer 1, Timea Kovacs 1, Eric J Sorscher 1, Charles N Falany 1
PMCID: PMC1222552  PMID: 11988083

Abstract

The severity of intestinal disease in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) (-/-) mice has been reported to co-segregate with gene loci which contain the genes for hydroxysteroid sulphotransferase (SULT). Because of the potential involvement of steroid hormones in CF, we investigated levels of steroid SULT activity in the livers of CFTR mice to determine whether the levels of SULT activity correlate with the occurrence or severity of CF. To elucidate the possible role of SULT activity in ameliorating the deleterious effects of CF in CFTR (-/-) mice, we determined the levels of phenol SULT (PST), hydroxysteroid SULT [dehydroepiandrosterone (DHEA)-ST] and oestrogen SULT (EST) activity in control CFTR (+/+), heterozygous CFTR (+/-) and homozygous CFTR (-/-) mice, which survive to adulthood. The level of PST activity was not significantly different between any of the groups of mice, regardless of sex or genotype. Although DHEA-ST activity was significantly higher in female mice than in male mice, there was no difference in DHEA-ST activity that could be correlated with genotype. In contrast with PST and DHEA-ST activities, we found that some male and all female adult CFTR (-/-) mice had elevated, dramatically different levels of EST from both CFTR (+/+) and CFTR (+/-) mice. Results from these SULT activity experiments were confirmed by Northern-blot analysis of mouse-liver RNA. Subsequent studies with preweanling mice revealed no differences in the levels of EST that could be correlated with genotype. Thus this study indicates that EST is elevated significantly in CFTR (-/-) mice which survive to adulthood and provides important biochemical information that EST levels may be protective in CF.

Full Text

The Full Text of this article is available as a PDF (127.5 KB).

Selected References

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

  1. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  2. Coughtrie M. W., Sharp S., Maxwell K., Innes N. P. Biology and function of the reversible sulfation pathway catalysed by human sulfotransferases and sulfatases. Chem Biol Interact. 1998 Feb 20;109(1-3):3–27. doi: 10.1016/s0009-2797(97)00117-8. [DOI] [PubMed] [Google Scholar]
  3. Davis P. B. The gender gap in cystic fibrosis survival. J Gend Specif Med. 1999 Mar-Apr;2(2):47–51. [PubMed] [Google Scholar]
  4. Döring G., Krogh-Johansen H., Weidinger S., Høiby N. Allotypes of alpha 1-antitrypsin in patients with cystic fibrosis, homozygous and heterozygous for deltaF508. Pediatr Pulmonol. 1994 Jul;18(1):3–7. doi: 10.1002/ppul.1950180104. [DOI] [PubMed] [Google Scholar]
  5. Falany C. N. Enzymology of human cytosolic sulfotransferases. FASEB J. 1997 Mar;11(4):206–216. doi: 10.1096/fasebj.11.4.9068609. [DOI] [PubMed] [Google Scholar]
  6. Falany C. N., Krasnykh V., Falany J. L. Bacterial expression and characterization of a cDNA for human liver estrogen sulfotransferase. J Steroid Biochem Mol Biol. 1995 Jun;52(6):529–539. doi: 10.1016/0960-0760(95)00015-r. [DOI] [PubMed] [Google Scholar]
  7. Falany C. N., Vazquez M. E., Heroux J. A., Roth J. A. Purification and characterization of human liver phenol-sulfating phenol sulfotransferase. Arch Biochem Biophys. 1990 May 1;278(2):312–318. doi: 10.1016/0003-9861(90)90265-z. [DOI] [PubMed] [Google Scholar]
  8. Falany C. N., Vazquez M. E., Kalb J. M. Purification and characterization of human liver dehydroepiandrosterone sulphotransferase. Biochem J. 1989 Jun 15;260(3):641–646. doi: 10.1042/bj2600641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gabolde M., Guilloud-Bataille M., Feingold J., Besmond C. Association of variant alleles of mannose binding lectin with severity of pulmonary disease in cystic fibrosis: cohort study. BMJ. 1999 Oct 30;319(7218):1166–1167. doi: 10.1136/bmj.319.7218.1166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Garred P., Pressler T., Madsen H. O., Frederiksen B., Svejgaard A., Høiby N., Schwartz M., Koch C. Association of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis. J Clin Invest. 1999 Aug;104(4):431–437. doi: 10.1172/JCI6861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Her C., Wood T. C., Eichler E. E., Mohrenweiser H. W., Ramagli L. S., Siciliano M. J., Weinshilboum R. M. Human hydroxysteroid sulfotransferase SULT2B1: two enzymes encoded by a single chromosome 19 gene. Genomics. 1998 Nov 1;53(3):284–295. doi: 10.1006/geno.1998.5518. [DOI] [PubMed] [Google Scholar]
  12. Hull J., Thomson A. H. Contribution of genetic factors other than CFTR to disease severity in cystic fibrosis. Thorax. 1998 Dec;53(12):1018–1021. doi: 10.1136/thx.53.12.1018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Knowles M., Gatzy J., Boucher R. Increased bioelectric potential difference across respiratory epithelia in cystic fibrosis. N Engl J Med. 1981 Dec 17;305(25):1489–1495. doi: 10.1056/NEJM198112173052502. [DOI] [PubMed] [Google Scholar]
  14. Kong A. N., Ma M., Tao D., Yang L. Molecular cloning of cDNA encoding the phenol/aryl form of sulfotransferase (mSTp1) from mouse liver. Biochim Biophys Acta. 1993 Jan 23;1171(3):315–318. doi: 10.1016/0167-4781(93)90073-m. [DOI] [PubMed] [Google Scholar]
  15. Leiter E. H., Chapman H. D., Falany C. N. Synergism of obesity genes with hepatic steroid sulfotransferases to mediate diabetes in mice. Diabetes. 1991 Oct;40(10):1360–1363. doi: 10.2337/diab.40.10.1360. [DOI] [PubMed] [Google Scholar]
  16. Leiter E. H., Chapman H. D. Obesity-induced diabetes (diabesity) in C57BL/KsJ mice produces aberrant trans-regulation of sex steroid sulfotransferase genes. J Clin Invest. 1994 May;93(5):2007–2013. doi: 10.1172/JCI117194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Leiter E. H. The genetics of diabetes susceptibility in mice. FASEB J. 1989 Sep;3(11):2231–2241. doi: 10.1096/fasebj.3.11.2673897. [DOI] [PubMed] [Google Scholar]
  18. Mahadeva R., Stewart S., Bilton D., Lomas D. A. Alpha-1 antitrypsin deficiency alleles and severe cystic fibrosis lung disease. Thorax. 1998 Dec;53(12):1022–1024. doi: 10.1136/thx.53.12.1022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rozmahel R., Wilschanski M., Matin A., Plyte S., Oliver M., Auerbach W., Moore A., Forstner J., Durie P., Nadeau J. Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor. Nat Genet. 1996 Mar;12(3):280–287. doi: 10.1038/ng0396-280. [DOI] [PubMed] [Google Scholar]
  20. Singh A. K., Schultz B. D., Katzenellenbogen J. A., Price E. M., Bridges R. J., Bradbury N. A. Estrogen inhibition of cystic fibrosis transmembrane conductance regulator-mediated chloride secretion. J Pharmacol Exp Ther. 2000 Oct;295(1):195–204. [PubMed] [Google Scholar]
  21. Snouwaert J. N., Brigman K. K., Latour A. M., Malouf N. N., Boucher R. C., Smithies O., Koller B. H. An animal model for cystic fibrosis made by gene targeting. Science. 1992 Aug 21;257(5073):1083–1088. doi: 10.1126/science.257.5073.1083. [DOI] [PubMed] [Google Scholar]
  22. Song W. C., Moore R., McLachlan J. A., Negishi M. Molecular characterization of a testis-specific estrogen sulfotransferase and aberrant liver expression in obese and diabetogenic C57BL/KsJ-db/db mice. Endocrinology. 1995 Jun;136(6):2477–2484. doi: 10.1210/endo.136.6.7750469. [DOI] [PubMed] [Google Scholar]
  23. Song W. C., Qian Y., Sun X., Negishi M. Cellular localization and regulation of expression of testicular estrogen sulfotransferase. Endocrinology. 1997 Nov;138(11):5006–5012. doi: 10.1210/endo.138.11.5512. [DOI] [PubMed] [Google Scholar]
  24. Tesarik J., Mendoza C. Nongenomic effects of 17 beta-estradiol on maturing human oocytes: relationship to oocyte developmental potential. J Clin Endocrinol Metab. 1995 Apr;80(4):1438–1443. doi: 10.1210/jcem.80.4.7714121. [DOI] [PubMed] [Google Scholar]
  25. Turner D. M., Williams D. M., Sankaran D., Lazarus M., Sinnott P. J., Hutchinson I. V. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet. 1997 Feb;24(1):1–8. doi: 10.1111/j.1365-2370.1997.tb00001.x. [DOI] [PubMed] [Google Scholar]
  26. Weinshilboum R. M., Otterness D. M., Aksoy I. A., Wood T. C., Her C., Raftogianis R. B. Sulfation and sulfotransferases 1: Sulfotransferase molecular biology: cDNAs and genes. FASEB J. 1997 Jan;11(1):3–14. [PubMed] [Google Scholar]
  27. Wine J. J. A sensitive defense: salt and cystic fibrosis. Nat Med. 1997 May;3(5):494–495. doi: 10.1038/nm0597-494. [DOI] [PubMed] [Google Scholar]
  28. Zielenski J., Corey M., Rozmahel R., Markiewicz D., Aznarez I., Casals T., Larriba S., Mercier B., Cutting G. R., Krebsova A. Detection of a cystic fibrosis modifier locus for meconium ileus on human chromosome 19q13. Nat Genet. 1999 Jun;22(2):128–129. doi: 10.1038/9635. [DOI] [PubMed] [Google Scholar]

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

RESOURCES