Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1990 Jan 1;265(1):101–107. doi: 10.1042/bj2650101

Transient activation of topoisomerase I in leukotriene D4 signal transduction in human cells.

M R Mattern 1, S Mong 1, S M Mong 1, J O Bartus 1, H M Sarau 1, M A Clark 1, J J Foley 1, S T Crooke 1
PMCID: PMC1136619  PMID: 2154178

Abstract

U937 human monoblast cells incubated with leukotriene D4 (LTD4) rapidly released arachidonic acid metabolites into the culture medium. Release was suppressed by the high-affinity LTD4 receptor antagonist SK&F 104353. Arachidonic acid release induced by LTD4 has been linked to a rapid induction of gene expression, and the propagation of the receptor binding signal is probably associated with enzymes that regulate gene expression. We have studied the participation of DNA topoisomerase I in LTD4 signal transduction. LTD4-specific release of arachidonic acid metabolites was inhibited (60-80%) by the topoisomerase I inhibitor camptothecin. LTD4 increased protein-linked DNA strand breakage induced by camptothecin in U937 cells; this enhancement was prevented by coincubation of the cells with LTD4 plus the receptor antagonist SK&F 104353. In addition, LTD4 produced a rapid transient increase in extractable topoisomerase I activity, which was maximum within the first 10 min after addition of LTD4 to the culture medium. Incubation of cultures for greater than 10 min with LTD4 before the addition of camptothecin resulted in no enhancement of camptothecin-induced DNA strand breakage, consistent with a reversal of topoisomerase I activation. Staurosporine, an inhibitor of protein kinase C, blocked LTD4-induced arachidonic acid release and attenuated the effect of LTD4 on camptothecin-induced DNA strand breakage. These results are consistent with the view that the regulation of topoisomerase I activity is involved in the propagation of LTD4-mediated signals in U937 cells.

Full text

PDF
107

Images in this article

104Fig. 3.
on p.104

Selected References

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

  1. Ackerman P., Glover C. V., Osheroff N. Phosphorylation of DNA topoisomerase II by casein kinase II: modulation of eukaryotic topoisomerase II activity in vitro. Proc Natl Acad Sci U S A. 1985 May;82(10):3164–3168. doi: 10.1073/pnas.82.10.3164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brill S. J., DiNardo S., Voelkel-Meiman K., Sternglanz R. Need for DNA topoisomerase activity as a swivel for DNA replication for transcription of ribosomal RNA. 1987 Mar 26-Apr 1Nature. 326(6111):414–416. doi: 10.1038/326414a0. [DOI] [PubMed] [Google Scholar]
  3. Chen G. L., Yang L., Rowe T. C., Halligan B. D., Tewey K. M., Liu L. F. Nonintercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II. J Biol Chem. 1984 Nov 10;259(21):13560–13566. [PubMed] [Google Scholar]
  4. Clark M. A., Chen M. J., Crooke S. T., Bomalaski J. S. Tumour necrosis factor (cachectin) induces phospholipase A2 activity and synthesis of a phospholipase A2-activating protein in endothelial cells. Biochem J. 1988 Feb 15;250(1):125–132. doi: 10.1042/bj2500125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clark M. A., Conway T. M., Shorr R. G., Crooke S. T. Identification and isolation of a mammalian protein which is antigenically and functionally related to the phospholipase A2 stimulatory peptide melittin. J Biol Chem. 1987 Mar 25;262(9):4402–4406. [PubMed] [Google Scholar]
  6. Clark M. A., Cook M., Mong S., Crooke S. T. The binding of leukotriene C4 and leukotriene D4 to membranes of a smooth muscle cell line (BC3H1) and evidence that leukotriene induced contraction in these cells is mediated by thromboxane, protein and RNA syntheses. Eur J Pharmacol. 1985 Oct 22;116(3):207–220. doi: 10.1016/0014-2999(85)90155-4. [DOI] [PubMed] [Google Scholar]
  7. Clark M. A., Littlejohn D., Conway T. M., Mong S., Steiner S., Crooke S. T. Leukotriene D4 treatment of bovine aortic endothelial cells and murine smooth muscle cells in culture results in an increase in phospholipase A2 activity. J Biol Chem. 1986 Aug 15;261(23):10713–10718. [PubMed] [Google Scholar]
  8. Gilmour D. S., Elgin S. C. Localization of specific topoisomerase I interactions within the transcribed region of active heat shock genes by using the inhibitor camptothecin. Mol Cell Biol. 1987 Jan;7(1):141–148. doi: 10.1128/mcb.7.1.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gleason J. G., Hall R. F., Perchonock C. D., Erhard K. F., Frazee J. S., Ku T. W., Kondrad K., McCarthy M. E., Mong S., Crooke S. T. High-affinity leukotriene receptor antagonists. Synthesis and pharmacological characterization of 2-hydroxy-3-[(2-carboxyethyl)thio]-3-[2-(8-phenyloctyl)phenyl] propanoic acid. J Med Chem. 1987 Jun;30(6):959–961. doi: 10.1021/jm00389a001. [DOI] [PubMed] [Google Scholar]
  10. Hsiang Y. H., Hertzberg R., Hecht S., Liu L. F. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem. 1985 Nov 25;260(27):14873–14878. [PubMed] [Google Scholar]
  11. Hsiang Y. H., Liu L. F. Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin. Cancer Res. 1988 Apr 1;48(7):1722–1726. [PubMed] [Google Scholar]
  12. Kawahara Y., Sunako M., Tsuda T., Fukuzaki H., Fukumoto Y., Takai Y. Angiotensin II induces expression of the c-fos gene through protein kinase C activation and calcium ion mobilization in cultured vascular smooth muscle cells. Biochem Biophys Res Commun. 1988 Jan 15;150(1):52–59. doi: 10.1016/0006-291x(88)90485-8. [DOI] [PubMed] [Google Scholar]
  13. Kohn K. W., Erickson L. C., Ewig R. A., Friedman C. A. Fractionation of DNA from mammalian cells by alkaline elution. Biochemistry. 1976 Oct 19;15(21):4629–4637. doi: 10.1021/bi00666a013. [DOI] [PubMed] [Google Scholar]
  14. Lau L. F., Nathans D. Identification of a set of genes expressed during the G0/G1 transition of cultured mouse cells. EMBO J. 1985 Dec 1;4(12):3145–3151. doi: 10.1002/j.1460-2075.1985.tb04057.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mattern M. R., Mong S. M., Bartus H. F., Mirabelli C. K., Crooke S. T., Johnson R. K. Relationship between the intracellular effects of camptothecin and the inhibition of DNA topoisomerase I in cultured L1210 cells. Cancer Res. 1987 Apr 1;47(7):1793–1798. [PubMed] [Google Scholar]
  16. Mong S., Hoffman K., Wu H. L., Crooke S. T. Leukotriene-induced hydrolysis of inositol lipids in guinea pig lung: mechanism of signal transduction for leukotriene-D4 receptors. Mol Pharmacol. 1987 Jan;31(1):35–41. [PubMed] [Google Scholar]
  17. Mong S., Miller J., Wu H. L., Crooke S. T. Leukotriene D4 receptor-mediated hydrolysis of phosphoinositide and mobilization of calcium in sheep tracheal smooth muscle cells. J Pharmacol Exp Ther. 1988 Feb;244(2):508–515. [PubMed] [Google Scholar]
  18. Mong S., Wu H. L., Clark M. A., Gleason J. G., Crooke S. T. Leukotriene D4 receptor-mediated synthesis and release of arachidonic acid metabolites in guinea pig lung: induction of thromboxane and prostacyclin biosynthesis by leukotriene D4. J Pharmacol Exp Ther. 1986 Oct;239(1):63–70. [PubMed] [Google Scholar]
  19. Nambi P., Watt R., Whitman M., Aiyar N., Moore J. P., Evan G. I., Crooke S. Induction of c-fos protein by activation of vasopressin receptors in smooth muscle cells. FEBS Lett. 1989 Mar 13;245(1-2):61–64. doi: 10.1016/0014-5793(89)80192-9. [DOI] [PubMed] [Google Scholar]
  20. Rowe T. C., Wang J. C., Liu L. F. In vivo localization of DNA topoisomerase II cleavage sites on Drosophila heat shock chromatin. Mol Cell Biol. 1986 Apr;6(4):985–992. doi: 10.1128/mcb.6.4.985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sahyoun N., Wolf M., Besterman J., Hsieh T., Sander M., LeVine H., 3rd, Chang K. J., Cuatrecasas P. Protein kinase C phosphorylates topoisomerase II: topoisomerase activation and its possible role in phorbol ester-induced differentiation of HL-60 cells. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1603–1607. doi: 10.1073/pnas.83.6.1603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sarau H. M., Mong S., Foley J. J., Wu H. L., Crooke S. T. Identification and characterization of leukotriene D4 receptors and signal transduction processes in rat basophilic leukemia cells. J Biol Chem. 1987 Mar 25;262(9):4034–4041. [PubMed] [Google Scholar]
  23. Stewart A. F., Schütz G. Camptothecin-induced in vivo topoisomerase I cleavages in the transcriptionally active tyrosine aminotransferase gene. Cell. 1987 Sep 25;50(7):1109–1117. doi: 10.1016/0092-8674(87)90177-2. [DOI] [PubMed] [Google Scholar]
  24. Tamaoki T., Nomoto H., Takahashi I., Kato Y., Morimoto M., Tomita F. Staurosporine, a potent inhibitor of phospholipid/Ca++dependent protein kinase. Biochem Biophys Res Commun. 1986 Mar 13;135(2):397–402. doi: 10.1016/0006-291x(86)90008-2. [DOI] [PubMed] [Google Scholar]
  25. Vegesna R. V., Mong S., Crooke S. T. Leukotriene D4-induced activation of protein kinase C in rat basophilic leukemia cells. Eur J Pharmacol. 1988 Mar 15;147(3):387–396. doi: 10.1016/0014-2999(88)90173-2. [DOI] [PubMed] [Google Scholar]
  26. Vegesna R. V., Wu H. L., Mong S., Crooke S. T. Staurosporine inhibits protein kinase C and prevents phorbol ester-mediated leukotriene D4 receptor desensitization in RBL-1 cells. Mol Pharmacol. 1988 May;33(5):537–542. [PubMed] [Google Scholar]
  27. Vosberg H. P. DNA topoisomerases: enzymes that control DNA conformation. Curr Top Microbiol Immunol. 1985;114:19–102. doi: 10.1007/978-3-642-70227-3_2. [DOI] [PubMed] [Google Scholar]
  28. Wang J. C. DNA topoisomerases. Annu Rev Biochem. 1985;54:665–697. doi: 10.1146/annurev.bi.54.070185.003313. [DOI] [PubMed] [Google Scholar]
  29. Yang L., Rowe T. C., Liu L. F. Identification of DNA topoisomerase II as an intracellular target of antitumor epipodophyllotoxins in simian virus 40-infected monkey cells. Cancer Res. 1985 Nov;45(11 Pt 2):5872–5876. [PubMed] [Google Scholar]

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

RESOURCES