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. 1968 Oct;96(4):1191–1199. doi: 10.1128/jb.96.4.1191-1199.1968

Inhibition of Hepatic Enzyme Induction as a Sensitive Assay for Endotoxin

L Joe Berry 1, Dorothy S Smythe 1, Louise S Colwell 1
PMCID: PMC252434  PMID: 4387162

Abstract

Bacterial endotoxins in mice reduced the induction by cortisone of two hepatic enzymes, tryptophan oxygenase, and phosphoenolpyruvate carboxykinase, they prevented the glyconeogenesis in liver induced by the same hormone, and they induced in intact animals the liver enzyme tyrosine-α-ketoglutarate transaminase, all in proportion to their ld50. When cortisone was given in the least amount (100 μg), it resulted in near maximal induction of tryptophan oxygenase; a smaller amount of endotoxin reduced significantly the level of enzyme than that required when 5 mg of hormone was injected. The smallest amount of endotoxin that prevented tryptophan oxygenase induction was given intravenously to adrenalectomized mice in which 25 μg of cortisone was administered. The amount (0.01 μg) is 1/40,000th of the ld50. The other metabolic processes subject to alteration by endotoxin required at least 100 to 400 times as much. This property of endotoxin can serve as a sensitive bioassay, although the dose-response curve is steep.

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Selected References

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

  1. BEATTY C. H., BOCEK R. M., PETERSON R. D. Water tolerance test for functioning adrenal cortical tissue in the rat. Am J Physiol. 1954 May;177(2):287–291. doi: 10.1152/ajplegacy.1954.177.2.287. [DOI] [PubMed] [Google Scholar]
  2. BERRY L. J. ENDOTOXIN LETHALITY AND TRYPTOPHAN PYRROLASE INDUCTION IN COLD-EXPOSED MICE. Am J Physiol. 1964 Nov;207:1058–1062. doi: 10.1152/ajplegacy.1964.207.5.1058. [DOI] [PubMed] [Google Scholar]
  3. BERRY L. J., SMYTHE D. S. EFFECTS OF BACTERIAL ENDOTOXINS ON METABOLISM. VI. THE ROLE OF TRYPTOPHAN PYRROLASE IN RESPONSE OF MICE TO ENDOTOXIN. J Exp Med. 1963 Oct 1;118:587–603. doi: 10.1084/jem.118.4.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BERRY L. J., SMYTHE D. S. EFFECTS OF BACTERIAL ENDOTOXINS ON METABOLISM. VII. ENZYME INDUCTION AND CORTISONE PROTECTION. J Exp Med. 1964 Nov 1;120:721–732. doi: 10.1084/jem.120.5.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. BERRY L. J., SMYTHE D. S., YOUNG L. G. Effects of bacterial endotoxin on metabolism. I. Carbohydrate depletion and the protective role of cortisone. J Exp Med. 1959 Sep 1;110:389–405. doi: 10.1084/jem.110.3.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Berry L. J., Smythe D. S., Colwell L. S. Inhibition of inducible liver enzymes by endotoxin and actinomycin D. J Bacteriol. 1966 Jul;92(1):107–115. doi: 10.1128/jb.92.1.107-115.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. CHEDID L., PARANT M. [Study of the tolerance of adrenalectomized mice using an endotoxin labeled with Cr-51]. Ann Inst Pasteur (Paris) 1961 Aug;101:170–177. [PubMed] [Google Scholar]
  8. Cundy K. R., Nowotny A. Comparisons of 5 toxicity parameters of Serratia marcescens endotoxins. Proc Soc Exp Biol Med. 1968 Apr;127(4):999–1003. doi: 10.3181/00379727-127-32854. [DOI] [PubMed] [Google Scholar]
  9. DUBOS R. J., SCHAEDLER R. W. The effect of bacterial endotoxins on the water intake and body weight of mice. J Exp Med. 1961 May 1;113:921–934. doi: 10.1084/jem.113.5.921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. DUFFY B. J., Jr, MORGAN H. R. ACTH and cortisone aggravation or suppression of the febrile response of rabbits to bacterial endotoxin. Proc Soc Exp Biol Med. 1951 Dec;78(3):687–689. doi: 10.3181/00379727-78-19182. [DOI] [PubMed] [Google Scholar]
  11. Eaves G. N., Berry L. J. A possible explanation for decreased tryptophan pyrrolase activity in homogenates of liver from endotoxemic mice. Proc Soc Exp Biol Med. 1966 Jun;122(2):495–499. doi: 10.3181/00379727-122-31171. [DOI] [PubMed] [Google Scholar]
  12. Eaves G. N., Berry L. J. Effect of cortisone on plasma iron concentration of normal and endotoxin-poisoned mice. Am J Physiol. 1966 Sep;211(3):800–802. doi: 10.1152/ajplegacy.1966.211.3.800. [DOI] [PubMed] [Google Scholar]
  13. FEIGELSON M., GROSS P. R., FEIGELSON P. Early effects of cortisone on nucleic acid and protein metabolism of rat liver. Biochim Biophys Acta. 1962 Apr 2;55:495–504. doi: 10.1016/0006-3002(62)90982-4. [DOI] [PubMed] [Google Scholar]
  14. FEIGELSON P., DASHMAN T., MARGOLIS F. The half-life-time of induced tryptophan peroxidase in vivo. Arch Biochem Biophys. 1959 Dec;85:478–482. doi: 10.1016/0003-9861(59)90514-4. [DOI] [PubMed] [Google Scholar]
  15. FEIGELSON P., FEIGELSON M., FANCHER C. Kinetics of liver nucleic acid turnovers during enzyme induction in the rat. Biochim Biophys Acta. 1959 Mar;32(1):133–139. doi: 10.1016/0006-3002(59)90561-x. [DOI] [PubMed] [Google Scholar]
  16. FEIGELSON P., GREENGARD O. Regulation of liver tryptophan pyrrolase activity. J Biol Chem. 1962 Jun;237:1908–1913. [PubMed] [Google Scholar]
  17. Feigelson M., Feigelson P. Relationships between hepatic enzyme induction, glutamate formation, and purine nucleotide biosynthesis in glucocorticoid action. J Biol Chem. 1966 Dec 25;241(24):5819–5826. [PubMed] [Google Scholar]
  18. GELLER P., MERRILL E. R., JAWETZ E. Effects of cortisone and antibiotics on lethal action of endotoxins in mice. Proc Soc Exp Biol Med. 1954 Aug-Sep;86(4):716–719. doi: 10.3181/00379727-86-21211. [DOI] [PubMed] [Google Scholar]
  19. Greenman D. L., Wicks W. D., Kenney F. T. Stimulation of ribonucleic acid synthesis by steroid hormones. II. High molecular weight components. J Biol Chem. 1965 Nov;240(11):4420–4426. [PubMed] [Google Scholar]
  20. KEMP A., VAN HEIJNINGEN A. J. M. K. A colorimetric micro-method for the determination of glycogen in tissues. Biochem J. 1954 Apr;56(4):646–648. doi: 10.1042/bj0560646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. KENNEY F. T., FLORA R. M. Induction of tyrosine-alpha-ketoglutarate transaminase in rat liver. I. Hormonal nature. J Biol Chem. 1961 Oct;236:2699–2702. [PubMed] [Google Scholar]
  22. KENNEY F. T., KULL F. J. HYDROCORTISONE-STIMULATED SYNTHESIS OF NUCLEAR RNA IN ENZYME INDUCTION. Proc Natl Acad Sci U S A. 1963 Sep;50:493–499. doi: 10.1073/pnas.50.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. KNOX W. E., AUERBACH V. H. The hormonal control of tryptophan peroxidase in the rat. J Biol Chem. 1955 May;214(1):307–313. [PubMed] [Google Scholar]
  24. LIN E. C., KNOX W. E. Adaptation of the rat liver tyrosine-alpha-ketoglutarate transaminase. Biochim Biophys Acta. 1957 Oct;26(1):85–88. doi: 10.1016/0006-3002(57)90057-4. [DOI] [PubMed] [Google Scholar]
  25. Moon R. J., Berry L. J. Role of tryptophan pyrrolase in endotoxin poisoning. J Bacteriol. 1968 Apr;95(4):1247–1253. doi: 10.1128/jb.95.4.1247-1253.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. NORDLIE R. C., LARDY H. A. Mammalian liver phosphoneolpyruvate carboxykinase activities. J Biol Chem. 1963 Jul;238:2259–2263. [PubMed] [Google Scholar]
  27. NORDLIE R. C., VARRICCHIO F. E., HOLTEN D. D. EFFECTS OF ALTERED HORMONAL STATES AND FASTING ON RAT-LIVER MITOCHONDRIAL PHOSPHOENOLOPYRUVATE CARBOXYKINASE LEVELS. Biochim Biophys Acta. 1965 Feb 15;97:214–221. doi: 10.1016/0304-4165(65)90085-1. [DOI] [PubMed] [Google Scholar]
  28. ROSEN F., HARDING H. R., MILHOLLAND R. J., NICHOL C. A. GLUCOCORTICOIDS AND TRANSAMINASE ACTIVITY. VI. COMPARISON OF THE ADAPTIVE INCREASES OF ALANINE- AND TYROSINE-ALPHA-KETOGLUTARATE TRANSAMINASES. J Biol Chem. 1963 Nov;238:3725–3729. [PubMed] [Google Scholar]
  29. SHRAGO E., LARDY H. A., NORDLIE R. C., FOSTER D. O. METABOLIC AND HORMONAL CONTROL OF PHOSPHOENOLPYRUVATE CARBOXYKINASE AND MALIC ENZYME IN RAT LIVER. J Biol Chem. 1963 Oct;238:3188–3192. [PubMed] [Google Scholar]
  30. WEBER G., SRIVASTAVA S. K., SINGHAL R. L. ROLE OF ENZYMES IN HOMEOSTASIS. VII. EARLY EFFECTS OF CORTICOSTEROID HORMONES ON HEPATIC GLUCONEOGENIC ENZYMES, RIBONUCLEIC ACID METABOLISM, AND AMINO ACID LEVEL. J Biol Chem. 1965 Feb;240:750–756. [PubMed] [Google Scholar]
  31. WEBER G. STUDY AND EVALUATION OF REGULATION OF ENZYME ACTIVITY AND SYNTHESIS IN MAMMALIAN LIVER. Adv Enzyme Regul. 1963;1:1–35. doi: 10.1016/0065-2571(63)90004-9. [DOI] [PubMed] [Google Scholar]

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