Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Regulation of in Vivo Prostaglandin Biosynthesis by Glutathione

  • Chapter
Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 4

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 469))

Abstract

Monosodium urate crystals are a naturally occurring pro-inflammatory agent associated with the manifestations of the rheumatic disorder, gout. This disease is characterized by occasional periods of severe pain and inflammatory swelling that, if untreated, resolves spontaneously within a few days1. Although urate crystals are known to be the etiologic agent for gout, and their accumulation seems to be the major pathophysiological event leading to inflammatory episodes, additional factors influence the inflammatory response. Urate crystal deposition in joints may occur without associated inflammation2 and inflammatory attacks may remit although urate crystals are still present in the joints3. Prostaglandins (PGs) appear to play a prominent role in the onset of gout attacks because non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit PG formation, are considered the drugs of choice for the treatment of acute attacks4. Using a mouse model of urate crystal-induced peritonitis, we have found that while urate crystals triggered an initial burst of eicosanoid products, at later times additional arachidonic acid metabolism was attenuated in a fashion independent of substrate concentration5. The present study further investigate this phenomena and demonstrate that urate crystal administration resulted in five fold elevation of the intracellular and extracellular pools of reduced glutathione (GSH) and that the elevated GSH attenuated PG formation by shifting the cyclooxygenase (COX) products profile from PG to 12-hydroxyheptadecatrienoic acid (12-HHT).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Refferences

  1. Terkeltaub, R. A., M. H. Ginsberg. 1988. The inflammatory reaction of crystals. Rheum. Dis. Clin. North Am.14: 353–364

    PubMed  CAS  Google Scholar 

  2. Ortiz-Bravo, E., H. R. Schumacher. 1993. Components generated locally as well as serum alter the phlogistic effect of monosodium urate crystals in-vivo. J. Rheumatol.20: 1162–1166

    CAS  Google Scholar 

  3. Terkeltaub, R. A. 1993. Gout and mechanisms of crystal-induced inflammation. Current Opin. Rheumatol.5: 510–516

    Article  CAS  Google Scholar 

  4. Abramson, S. B. 1992. Treatment of gout and crystal arthropathies and uses and mechanisms of action of nonsteroidal anti-inflammatory drugs. Current Opin. Rheumatol.4: 295–300

    Article  CAS  Google Scholar 

  5. Margalit, A., K. L. Duffin, A. F. Shaffer, S. A. Gregory, P. C. Isakson. 1997. Altered arachidonic acid metabolism in urate crystal induced inflammation. Inflammation. 21: 205–222

    Article  PubMed  CAS  Google Scholar 

  6. Mukherjee, A. B., L. Miele, N. Pattabirman. 1994. Phospholipase A2 enzymes: regulation and physiological role. Biochem. Pharmacol. 48: 1–10

    Article  PubMed  CAS  Google Scholar 

  7. Piomelli, D. 1993. Arachidonic acid in cell signaling. Curr. Opin. Cell. Biol. 5:274–280

    Article  PubMed  CAS  Google Scholar 

  8. Herschman, H. R. 1994. Regulation of prostaglandin synthase-1 and prostaglandin synthase-2. Cancer Metas. Rev. 13: 241–256

    Article  CAS  Google Scholar 

  9. Lands, W. E. M., P. J. Marshall, R. J. Kulmacz. 1985. Hydroperoxide availability in the regulation of the arachidonate cascade. In Adv. Prostagl. Thromb. Leukotr. Res.,eds. 0. Hayaishi, S. Yamamoto, vol. 15,233–235. New-York: Raven Press

    Google Scholar 

  10. Marshall, P. J., R. J. Kulmacz, W. E. M. Lands. 1987. Constraints on prostaglandin biosynthesis in tissues. J. Biol. Chem.262: 3510–3517

    PubMed  CAS  Google Scholar 

  11. Kulmacz, R. J., R. B. Pendleton, W. E. M. Lands. 1994. Interaction between peroxidase and cyclooxygenase activities in prostaglandin-endoperoxidase synthase. J. Biol. Chem.269: 5527–5536

    PubMed  CAS  Google Scholar 

  12. Landino, L. M., B. C. Crews, M. D. Timmons, J. D. Morrow, L. J. Marnett. Peroxynitrite, the coupling product of nitric oxide and Superoxide, activates taglandin biosynthesis. Proc. Nail. Acad. Sci. USA.93: 15069–15074

    Google Scholar 

  13. Kulmacz, R. J., L.-H. Wang. 1995. Comparison of hydroperoxide initiator requirements for the cyclooxygenase activities of prostaglandin H synthase-1 and-2 J. Biol. Chem. 270: 24019–24023

    CAS  Google Scholar 

  14. Capdevila, J. H., J. D. Morrow, Y. Y. Belosludtsev, D. R. Beauchamp, R. N. DuBois, J. R. Falck. 1995. The catalytic outcome of the constitutive and the mitogen inducible isoforms of prostaglandin H2 synthase are markedly affected by glutathione and glutathione peroxidase(s). Biochemistry. 34: 3325–3337

    Article  PubMed  CAS  Google Scholar 

  15. Tripp, C. S., E. R. Unanue, P. Needleman. 1986. Monocyte migration explains the change in macrophage arachdonate metabolism during the immune response Proc. Natl. Acad. Sci. USA.83: 9655–9659

    Article  CAS  Google Scholar 

  16. Masferrer, J. L., B. S. Zweifel, P. T. Manning, S. D. Hauser, K. M. Leahy, W. G Smith, P. C. Isakson, K. Seibert. 1994. Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic. Proc. Natl. Acad Sci. USA.91: 3228–3232

    Article  PubMed  CAS  Google Scholar 

  17. Seibert, K., Y. Zhang, K. M. Leahy, S. D. Hauser, J. L. Masferrer, W. Perkins, L. Lee, P. C. Isakson. 1994. Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc. Natl. Acad. Sci. USA.91:12013–12017

    Article  PubMed  CAS  Google Scholar 

  18. Lentner, C. 1984. Pysical Chemistry Composition of Blood Hematology. Somatometric Data. In Geigy Scientific Tables,ed. C. Lentner, vol. 3, 205–215.

    Google Scholar 

  19. Basel: Ciba-Geigy Meister, A., S. S. Tate. 1976. Glutathione and related g-glutamyl compounds: biosynthesis and utilization.Ann. itRev. Biochem.45: 599–604

    Google Scholar 

  20. Morris, P. E., G. R. Bernard. 1994. Significance of glutathione in lung disease 2and implication for therapy. Am. J. Med. Sci.307: 119–1

    Article  PubMed  CAS  Google Scholar 

  21. W., A. Meister. 1985. Origin and turnover of mitochondrial glutathione. Proc. Natl. Acad. Sci. USA.82: 4668–4672

    Article  PubMed  Google Scholar 

  22. Meister, A. 1994. Glutathione-ascorbic acid antioxidant system in animals. J.Biol Chem.269: 9397–9400

    PubMed  CAS  Google Scholar 

  23. Mårtensson, J., A. Meister. 1992. Glutathione deficiency increases hepatic ascorbic acid synthesis in adult mice. Proc. Natl. Acad Sci. USA.89: 11566–11568

    Article  PubMed  Google Scholar 

  24. Shornick, L. P., M. J. Holtzman. 1993. A cryptic, microsomal-type arachidonate 12-lipoxygenase is tonically inactivated by oxidation-reduction conditions in cultured epithelial cells. J. Biol. Chem.268: 371–376

    PubMed  CAS  Google Scholar 

  25. Hagmann, W., D. Kagawa, C. Renaud, K. V. Honn. 1993. Activity and protein distribution of 12-lipoxygenase in HEL cells: induction of membrane-association by phorbol ester TPA, modulation of activity by glutathione and 12-HPODE, and Ca2+-dependent translocation to membranes. Prostaglandins46:471–477

    Article  PubMed  CAS  Google Scholar 

  26. Margalit, A., S.D. Hauser, B.S. Zweifel, M.A. Anderson, and P.C. Isakson. 1998 Regulation of prostaglandin biosynthesis in vivoby glutathione. Am. J. Phys.274:R294–R302.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Institute for Applied Biochemistry, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva, 84105, Israel

    Alon Margalit

  2. Searle Research and Development, 700 Chesterfield Parkway North, St. Louis, MO, 63198, USA

    Scott D. Hauser & Peter C. Isakson

Authors
  1. Alon Margalit
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Scott D. Hauser
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter C. Isakson
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Wayne State University School of Medicine, Detroit, Michigan, USA

    Kenneth V. Honn

  2. Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    Lawrence J. Marnett

  3. Free University Berlin, Berlin, Germany

    Santosh Nigam

  4. University of California at San Diego, San Diego, California, USA

    Edward A. Dennis

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Margalit, A., Hauser, S.D., Isakson, P.C. (1999). Regulation of in Vivo Prostaglandin Biosynthesis by Glutathione. In: Honn, K.V., Marnett, L.J., Nigam, S., Dennis, E.A. (eds) Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 4. Advances in Experimental Medicine and Biology, vol 469. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4793-8_25

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-4793-8_25

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7171-7

  • Online ISBN: 978-1-4615-4793-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation