Advertisement

Characterization of Epidermal 12(S) and 12(R) Lipoxygenases

  • Maeve McDonnell
  • Li Hongwei
  • Colin D. Funk
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 507)

Abstract

Lipoxygenases (LO) are a family of non-heme iron containing proteins that stereospecifically insert molecular oxygen into 1, 4-cis, cis-pentadiene containing polyunsaturated fatty acids’. They are generally classified according to their positional specificity of arachidonic acid oxygenation and cell specific expression pattern2.6. Lipoxygenase activity gives rise to a number of bioactive lipid products including leukotrienes, lipoxins and HETE’s (hydroxyeicosatetraenoic acid’s).78The major lipoxygenase forms include the neutrophil 5-LO, platelet 12-LO and reticulocyte 15LO.2’3’6’9 In recent years the lipoxygenase family has expanded by means of molecular cloning studies to include several new members. An e-12(S)LO (epidermal12(S)lipoxygenase) cDNA was cloned and functionally expressed and its gene isolated101. Two other lipoxygenases found in skin have also been cloned, a 15-LO in humans distinct from the reticulocyte enzyme4and a related phorbol ester inducible 8-LO enzyme in mouse skins. All of these lipoxygenases generate HETE metabolites of theS-stereo configuration. However, recently mammalian lipoxygenase cDNAs that generated 12(R) -HETE have been cloned and functionally expressed.12-14The epidermal 12(S) and 12-(R) lipoxygenases have yet to be characterized in any great detail.10,12-14Here, we characterize further the epidermal 12(S) and 12(R)-LO’s and attempt to elucidate the enzyme’s primary structural determinants controlling chirality of oxygen insertion.

Keywords

Hydroxyeicosatetraenoic Acid Eicosatrienoic Acid Amino Acid Stretch Methyl Arachidonate Cell Specific Expression Pattern 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    M.J. Nelson and S.P. Seitz, The structure and function of lipoxygenaseCurr.Op. Strut. Biol.4:878–884 (1994).CrossRefGoogle Scholar
  2. 2.
    C.D. Funk, The molecular biology of lipoxygenases and the quest for eicosanoid functions using lipoxygenase-deficient miceBiochim. Biophys.Acta.1304:65–84 (1996).CrossRefGoogle Scholar
  3. 3.
    Y. Takahashi, N. Ueda, and S. Yamamoto, Two immunologically and catalytically distinct arachidonate 12lipoxygenases of bovine platelets and leukocytesArch. Biochem.Biophys.266:613–621 (1988)Google Scholar
  4. 4.
    A.R. Brash, W.E. Boeglin, and M.S. Chang, Discovery of a second 15S-lipoxygenase in humansProc. Natl. Acad. Sci.USA 94:6148–6152 (1997).PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    M. Jisaka, R.B. Kim, W.E. Boeglin, L.B. Nanney, and A.R. Brash, Molecular cloning and functional expression of a phorbol ester-inducible 8S-lipoxygenase from mouse skinJ. Biol. Chem.272:2441024416 (1997).PubMedCrossRefGoogle Scholar
  6. 6.
    C.A. Rouzer and B.Samuelsson, On the nature of the 5-lipoxygenase reaction in human leukocytes:enzyme purification and requirement for multiple stimulator factorsProc. Natl. Acad. Sci/ USA82:6040–6044 (1985)CrossRefGoogle Scholar
  7. 7.
    B. Samuelsson, Leukotrienes: mediators of immediate hypersensitivity reactions and inflammationScience.220:568–575 (1983).PubMedCrossRefGoogle Scholar
  8. 8.
    B. Samuelsson, S.E. Dahlen, J.A. Lindgren, C.A. Rouzer, and C.N. Serhan, Leukotrienes and lipoxins: structures, biosynthesis, and biological effects.Science.273:1171–1176(1987).Google Scholar
  9. 9.
    M. Rapoport, T. Schewe, R. Wiesner, W. Halangk, P. Ludwig, M. Janicke-Hohne, C. Tannert, C.Hiebsch, and D.Klatt, Purification, characterization and biological dynamics of the lipoxygenase; its identity with the respiratory inhibitors of the reticulocyteEur. J. Biochem.96:545–561 (1979).PubMedCrossRefGoogle Scholar
  10. 10.
    C.D. Funk, D.S. Keeney, E.H Oliw, W.E. Boeglin, and A.R. Brash, Functional expression and cellular localization of a mouse epidermal lipoxygenaseJ. Biol. Chem.271:23338–23344 (1996).PubMedCrossRefGoogle Scholar
  11. 11.
    K.W. van Dijk, K. Steketee, L. Havekes, R. Frants, and M. Holker, Genomic and cDNA cloning of a novel mouse lipoxygenase geneBiochim. Biophys. Acta.1259:4–8 (1995).PubMedCrossRefGoogle Scholar
  12. 12.
    W.E. Boeglin, R.B.Kim, and A.R. Brash, A 12R-lipoxygenase in human skin: mechanistic evidence, molecular cloning, and expressionProc. Natl. Acad. Sci. USA95:6744–6749 (1998).PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    D. Sun, M. McDonnell, X.S. Chen, M.M. Lakkis, H. Li H, S.N. Isaacs, S.H. Elsea, P.I. Patel and C.D. Funk, Human 12(R)-lipoxygenase and the mouse ortholog. Molecular cloning, expression, and gene chromosomal assignmentJ. Biol. Chem.273:33540–33547 (1998).PubMedCrossRefGoogle Scholar
  14. 14.
    P. Krieg, M. Siebert, A. Kinzig, R. Bettenhausen, F. Marks, and G. Furstenberger, Mutine 12(R)lipoxygenase: functional expression, genomic structure and chromosomal localization.FEBS Letters.446:142–148 (1999).PubMedCrossRefGoogle Scholar
  15. 15.
    X.S. Chen, A.R. Brash, and C.D. Funk, Purification and characterization of recombinant six histidine-tagged human platelet 12-lipoxygenase expressed in a baculovirus/insect cell systemEur. J. Biochem.214:845852 (1993).PubMedCrossRefGoogle Scholar
  16. 16.
    A.Kinzig, M. Heidt, G. Furstenberger, F. Marks, and P. Krieg, cDNA cloning, genomic, and chromosomal localization of a novel murine epidermis-type lipoxygenaseGenomics58: (1992) 158–164.Google Scholar
  17. 17.
    Y.Y. Zhang, M. Hamberg, O. Râdmark, and B. Samuelsson, Stabilization of purified human 5-lipoxygenase with glutathione peroxidase and superoxide dismutaseAnal. Biochem.220:28–35 (1994).PubMedCrossRefGoogle Scholar
  18. 18.
    K. Ochi, T. Yoshimoto, S. Yamamoto, K. Taniguchi, and T. Miyamoto, Arachidonate 5-lipoxygenase of guinea pig peritonal polymorphonuclear leukocytes activation by adenosine 5’-triphosphateJ. Biol. Chem.258:5754–5758 (1983).PubMedGoogle Scholar
  19. 19.
    N. Nicolaides, Skin Lipids: their biochemical uniquenessScience 186:19–26 (1974)Google Scholar
  20. 20.
    R.D. Camp, A.I. Mallet, P.M. Woollard, S.D. Brain, A.K. Black, and M.W. Greaves, The identification of hydroxy fatty acids in psoriatic skinProstaglandins26:431–447 (1983)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Maeve McDonnell
    • 1
  • Li Hongwei
    • 1
  • Colin D. Funk
    • 1
  1. 1.Center for Experimental TherapeuticsUniversity of PennsylvaniaUSA

Personalised recommendations