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. 1970 Nov 30;132(6):1138–1152. doi: 10.1084/jem.132.6.1138

ACTION OF DIPHTHERIA TOXIN IN THE GUINEA PIG

Joel B Baseman 1, A M Pappenheimer Jr 1, D M Gill 1, Annabel A Harper 1
PMCID: PMC2180503  PMID: 5511567

Abstract

The blood clearance and distribution in the tissues of 125I after intravenous injection of small doses (1.5–5 MLD or 0.08–0.25 µg) of 125I-labeled diphtheria toxin has been followed in guinea pigs and rabbits and compared with the fate of equivalent amounts of injected 125I-labeled toxoid and bovine serum albumin. Toxoid disappeared most rapidly from the blood stream and label accumulated and was retained in liver, spleen, and especially in kidney. Both toxin and BSA behaved differently. Label was found widely distributed among all the organs except the nervous system and its rate of disappearance from the tissues paralleled its disappearance from the circulation. There was no evidence for any particular affinity of toxin for muscle tissue or for a "target" organ. Previous reports by others that toxin causes specific and selective impairment of protein synthesis in muscle tissue were not confirmed. On the contrary, both in guinea pigs and rabbits, a reduced rate of protein synthesis was observed in all tissues that had taken up the toxin label. In tissues removed from intoxicated animals of both species there was an associated reduction in aminoacyl transferase 2 content. It is concluded that the primary action of diphtheria toxin in the living animal is to effect the inactivation of aminoacyl transferase 2. The resulting inhibition in rate of protein synthesis leads to morphologic damage in all tissues reached by the toxin and ultimately to death of the animal.

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Selected References

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

  1. Bonventre P. F., Imhoff J. G. Studies on the mode of action of diphtheria toxin. I. Protein synthesis in guinea pig tissues. J Exp Med. 1966 Dec 1;124(6):1107–1122. doi: 10.1084/jem.124.6.1107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bowman C. G., Bonventre P. F. Studies on the mode of action of diphtheria toxin. III. Effect on subcellular components of protein synthesis from the tissues of intoxicated guinea pigs and rats. J Exp Med. 1970 Apr 1;131(4):659–674. doi: 10.1084/jem.131.4.659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Fazzini G., Cioni P., Fonnesu-Severi C. Incorporazione di glicina-1-14C in vitro nelle proteine di fegato, rene e cuore di animali trattati con tossine batteriche. Sperimentale. 1966 Jul-Aug;116(4):235–245. [PubMed] [Google Scholar]
  4. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gill D. M., Pappenheimer A. M., Jr, Baseman J. B. Studies on transferase II using diphtheria toxin. Cold Spring Harb Symp Quant Biol. 1969;34:595–602. doi: 10.1101/sqb.1969.034.01.068. [DOI] [PubMed] [Google Scholar]
  6. Gill D. M., Pappenheimer A. M., Jr, Brown R., Kurnick J. T. Studies on the mode of action of diphtheria toxin. VII. Toxin-stimulated hydrolysis of nicotinamide adenine dinucleotide in mammalian cell extracts. J Exp Med. 1969 Jan 1;129(1):1–21. doi: 10.1084/jem.129.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Goor R. S., Pappenheimer A. M., Jr Studies on the mode of action of diphtheria toxin. 3. Site of toxin action in cell-free extracts. J Exp Med. 1967 Nov 1;126(5):899–912. doi: 10.1084/jem.126.5.899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Honjo T., Nishizuka Y., Hayaishi O. Diphtheria toxin-dependent adenosine diphosphate ribosylation of aminoacyl transferase II and inhibition of protein synthesis. J Biol Chem. 1968 Jun 25;243(12):3553–3555. [PubMed] [Google Scholar]
  9. Jacobs J. M., Cavanagh J. B., Mellick R. S. Intraneural injection of diphtheria toxin. Br J Exp Pathol. 1966 Oct;47(5):507–517. [PMC free article] [PubMed] [Google Scholar]
  10. KATO I., PAPPENHEIMER A. M., Jr An early effect of diphtheria toxin on the metabolism of mammalian cells growing in culture. J Exp Med. 1960 Aug 1;112:329–349. doi: 10.1084/jem.112.2.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Moehring J. M., Moehring T. J. The response of cultured mammalian cells to diphtheria toxin. II. The resistant cell: enhancement of toxin action by poly-L-ornithine. J Exp Med. 1968 Mar 1;127(3):541–554. doi: 10.1084/jem.127.3.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Moehring T. J., Moehring J. M., Kuchler R. J., Solotorovsky M. The response of cultured mammalian cells to diphtheria toxin. I. Amino acid transport, accumulation, and incorporation in normal and intoxicated sensitive cells. J Exp Med. 1967 Sep 1;126(3):407–422. doi: 10.1084/jem.126.3.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nishizuka Y., Ueda K., Honjo T., Hayaishi O. Enzymic adenosine diphosphate ribosylation of histone and poly adenosine diphosphate ribose synthesis in rat liver nuclei. J Biol Chem. 1968 Jul 10;243(13):3765–3767. [PubMed] [Google Scholar]
  14. Pappenheimer A. M., Jr, Brown R. Studies on the mode of action of diphtheria toxin. VI. Site of the action of toxin in living cells. J Exp Med. 1968 Jun 1;127(6):1073–1086. doi: 10.1084/jem.127.6.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. STRAUSS N., HENDEE E. D. The effect of diphtheria toxin on the metabolism of HeLa cells. J Exp Med. 1959 Feb 1;109(2):145–163. doi: 10.1084/jem.109.2.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Schimke R. T., Ganschow R., Doyle D., Arias I. M. Regulation of protein turnover in mammalian tissues. Fed Proc. 1968 Sep-Oct;27(5):1223–1230. [PubMed] [Google Scholar]
  17. TALLAN H. H., MOORE S., STEIN W. H. Studies on the free amino acids and related compounds in the tissues of the cat. J Biol Chem. 1954 Dec;211(2):927–939. [PubMed] [Google Scholar]

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