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Alterations of hepatic acetyl-CoA carboxylase by 2,3,7,8-tetrachlorodibenzo-p-dioxin

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Lipids

Abstract

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on acetyl-CoA carboxylase (ACC) activity and synthesis was examined. Male Wistar rats received a singlei. p. injection of TCDD (53 μg/kg), and nine days later body weight, liver weight, hepatic lipid, ACC activity and mass were determined and compared to pair-fed controls. Body weights of TCDD-treated animals decreased, while liver weights increased resulting in an increase in liver to body weight ratios. ACC activity was decreased by 65%, however sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western analysis using a biotin specific probe revealed that ACC protein levels were not appreciably changed. In addition, there was a large increase in exogenous lipid material in TCDD-treated livers as determined by osmium tetroxide staining. These data suggest that the decrease in ACC activity may be due to direct inhibition of the enzyme by negative allosteric interactions with free fatty acids released from adipose tissue that subsequently accumulate in liver.

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Abbreviations

ACC:

acetyl-CoA carboxylase

FAS:

fatty acid synthase

MPO:

1-methyl-2-pyrrolidinone

PC:

pyrivate carboxylase

SDS-PAGE:

sodium dodecyl sulfate-polyacrylamide gel electrophoresis

TCDD:

2,3,7,8-tetrachlorodibenzo-p-dioxin

References

  1. Hodgson, E., and Levi, P.E. (1987)A Textbook of Modern Toxicology, p. 212, Elsevier, New York.

    Google Scholar 

  2. Murphy, S.D. (1986)Toxicology: The Basic Science of Poisons (Klaassen, C.D., Amdur, M.O., and Doull, J.D., eds.), pp. 554–555 Macmillan Publishing Co., New York.

    Google Scholar 

  3. Wagner, S.L. (1983) inClinical Toxicology of Agricultural Chemicals, pp. 138–155, Noyes Data Corp., Park Ridge.

    Google Scholar 

  4. Neal, R.A., Beatty, P.W., and Gasiewicz, T.A. (1979)Drug. Met. Rev. 13, 1315.

    Google Scholar 

  5. Poland, A., and Knutson, J.C. (1982)Ann. Rev. Pharmacol. Toxicol. 22, 517–554.

    Article  CAS  Google Scholar 

  6. Potter, C.L., Sipes, I.G., and Russell, D.H. (1983)Toxicol. Appl. Pharmacol. 69, 89–95.

    Article  PubMed  CAS  Google Scholar 

  7. Rozman, K., Rozman, R., and Greim, H. (1984)Toxicol. Appl. Pharmacol. 72, 372–376.

    Article  PubMed  CAS  Google Scholar 

  8. Rozman, K., and Greim, H. (1986)Arch. Toxicol. 59, 211–215.

    Article  PubMed  CAS  Google Scholar 

  9. Potter, C.L., Moore, R.W., Inhorn, S.L., Hagen, T.C., and Peterson, R.E. (1986)Toxicol. Appl. Pharmacol. 84, 45–55.

    Article  PubMed  CAS  Google Scholar 

  10. Gorski, J.R., and Rozman, K. (1987)Toxicology 44, 297–307.

    Article  PubMed  CAS  Google Scholar 

  11. Muzi, G., Gorski, J.R., and Rozman, K. (1987)Arch. Toxicol. 61, 34–39.

    Article  PubMed  CAS  Google Scholar 

  12. Romkes, M., Piskorska-Pliszczynska, J., and Safe, S. (1987)Toxicol. Appl. Pharmacol. 87, 306–314.

    Article  PubMed  CAS  Google Scholar 

  13. McConkey, D.J., Hartzell, P., Duddy, S.K., Hakansson, H., and Orrenius, S. (1988)Science 242, 256–258.

    Article  PubMed  CAS  Google Scholar 

  14. Wahba, Z.Z., Lawson, T.A., and Stohs, S.J. (1988)Cancer Lett. 29, 281–286.

    Article  Google Scholar 

  15. Ganong, W.F. (1983) inReview of Medical Physiology, pp. 221–253, Lange.

  16. Rozman, K., Ernst, S.W., and Weber, L.W.D. (1989)The Toxicologist. 9, 118.

    Google Scholar 

  17. Lakshman, M.R., Campbell, B.S., Chirtel, S.J., and Ekarohita, N. (1988)Lipids 23, 904–906.

    Article  PubMed  CAS  Google Scholar 

  18. Gorski, J.R., Weber, L.W.D., and Rozman, K. (1988)Arch. Toxicol. 62, 146–151.

    Article  PubMed  CAS  Google Scholar 

  19. Goodridge, A.G., Back, D.W., Wilson, S.B., and Goldman, M.J. (1988)Ann. N.Y. Acad. Sci. 478, 46–62.

    Google Scholar 

  20. Freytag, S.O., and Collier, K.J. (1984)J. Biol. Chem. 259, 12831–12837.

    PubMed  CAS  Google Scholar 

  21. Wakil, S.J. (1988)Ann. N.Y. Acad. Sci. 478, 203–219.

    Google Scholar 

  22. Roth, W., Voorman, R., and Aust, S.D. (1988)Toxicol. Appl. Pharmacol. 92, 65–74.

    Article  PubMed  CAS  Google Scholar 

  23. Burton, J.D., Gronwald, J.W., Somers, D.A., Connelly, J.A., Gengenbach, B.G., and Wyse, D.L. (1987)Biochem. Biophys. Res. Commun. 148, 1039–1044.

    Article  PubMed  CAS  Google Scholar 

  24. Harwood, J.L. (1988)TIBS 13, 330–331.

    PubMed  CAS  Google Scholar 

  25. Secor, J., and Cseke, C. (1988)Plant Physiol. 86, 10–12.

    Article  PubMed  CAS  Google Scholar 

  26. Lakshman, M.R., Chirtel, S.J., Chambers, L.L., and Coutlakis, P.J. (1989)J. Pharmacol. Exp. Ther. 248, 62–66.

    PubMed  CAS  Google Scholar 

  27. Witteres, L.A., and Vogt, B. (1981)J. Lipid Res. 22, 364–369.

    Google Scholar 

  28. Mallory, F.B. (1961)Pathological Technique, pp. 118–120, Hafner Publishing Co., New York.

    Google Scholar 

  29. McKim, Jr., J.M., Schaup, H.W., Marien, K., and Selivonchick, D.P. (1989)Lipids 24, 187–192.

    Article  PubMed  CAS  Google Scholar 

  30. Allred, J.B., and Roehrig, K.L. (1978)J. Biol. Chem. 253, 4826–4829.

    PubMed  CAS  Google Scholar 

  31. Ballard, F.J., and Hanson, R.W. (1967)Biochem. J. 104, 866–871.

    PubMed  CAS  Google Scholar 

  32. Hames, B.J. (1981)Gel Electrophoresis of Proteins: A Practical Approach (Hames, B.D., and Rickwood, D., eds.) pp. 26–27, IRL Press, Oxford.

    Google Scholar 

  33. Swift, L.L., Gasiewicz, T.A., Dunn, G.D., Soule, P.D., and Neal, R.A. (1981)Toxicol. Appl. Pharmacol. 59, 489–499.

    Article  PubMed  CAS  Google Scholar 

  34. Hardie, D.G., and Cohen, P. (1978)J. Biochem. 92, 25–34.

    CAS  Google Scholar 

  35. Haystead, T.A.J., and Hardie, D.G. (1986)J. Biochem. 234, 279–284.

    CAS  Google Scholar 

  36. Albro, P.W., Corbett, J.T., Harris, M., and Lawson, L.D. (1978)Chem. Biol. Inter. 23, 315–330.

    Article  CAS  Google Scholar 

  37. Goodridge, A.G. (1985) inBiochemistry of Lipids and Membranes (Vance, D.E., and Vance, J.E., eds.) pp. 143–180, The Benjamin/Cummings Pub. Co., Menlo Park.

    Google Scholar 

  38. Towle, H.C., and Mariash, C.N. (1986)Fed. Proc. 45, 2406–2411.

    PubMed  CAS  Google Scholar 

  39. Goodridge, A.G. (1986)Fed. Proc. 45, 2399–2405.

    PubMed  CAS  Google Scholar 

  40. Lebofsky, M., Weber, L.W.D., Greim, H., and Rozman, K. (1989)The Toxicologist 9, 118.

    Google Scholar 

  41. Thampy, K.G., and Wakil, S.J. (1988)J. Biol. Chem. 263, 6447–6453.

    PubMed  CAS  Google Scholar 

  42. Thampy, K.G., and Wakil, S.J. (1988)J. Biol. Chem. 263, 6454–6458.

    PubMed  CAS  Google Scholar 

  43. Hardie, D.G., Carling, D., and Sim, A.T.R. (1989)TIBS 14, 20–23.

    CAS  Google Scholar 

  44. Carling, D., Zammit, V.A., and Hardie, D.G. (1987)FEBS Lett. 223, 217–222.

    Article  PubMed  CAS  Google Scholar 

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McKim, J.M., Marien, K., Schaup, H.W. et al. Alterations of hepatic acetyl-CoA carboxylase by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Lipids 26, 521–525 (1991). https://doi.org/10.1007/BF02536597

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  • DOI: https://doi.org/10.1007/BF02536597

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