Regulation of cellular 15-lipoxygenase activity on pretranslational, translational, and posttranslational levels

Lipids. 1999;34 Suppl:S273-9. doi: 10.1007/BF02562317.

Abstract

In mammalian cells, enzymatic lipid peroxidation catalyzed by 12/15-lipoxygenases is regulated by pretranslational, translational, and posttranslational processes. In rabbits, rats, and mice induction of experimental anemia leads to a systemic up-regulation of 12/15-lipoxygenases expression. In addition, interleukins-4 and -13 were identified as strong up-regulators of this enzyme in human and murine monocyte/macrophages and in the lung carcinoma cell line A549, and the interleukin-4(13) cell surface receptor as well as the signal transducer and activator of transcription 6 (STATG) appears to be involved in the signal transduction cascade. On the level of translation, 15-lipoxygenase synthesis is blocked by the binding of regulatory proteins to a characteristic guanine-cytosine-rich repetitive element in the 3'-untranslated region of the rabbit 15-lipoxygenase mRNA, and the formation of such 15-lipoxygenase mRNA/protein complexes was identified as molecular reason for the translational inactivity of the 15-lipoxygenase mRNA in immature red blood cells. However, proteolytic breakdown of the regulatory proteins which were recently identified as hnRNP K and hnRNP E1 overcomes translational inhibition during later stages of reticulocyte maturation. For maximal intracellular activity, 12/15-lipoxygenases require a rise in cytosolic calcium concentration inducing a translocation of the enzyme from the cytosol to cellular membranes as well as small amounts of preformed hydroperoxides which act as essential activators of the enzymes. 12/15-Lipoxygenases undergo irreversible suicide inactivation during fatty acid oxygenation, and this process may be considered an element of down-regulation of enzyme activity. Suicide inactivation and proteolytic breakdown may contribute to the disappearance of functional 12/15-lipoxygenase at later stages of erythropoiesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anemia / blood
  • Anemia / enzymology
  • Animals
  • Arachidonate 15-Lipoxygenase / blood*
  • Arachidonate 15-Lipoxygenase / genetics*
  • Erythrocytes / enzymology*
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Mice
  • Protein Biosynthesis*
  • Protein Processing, Post-Translational*
  • Rabbits
  • Rats
  • Reticulocytes / enzymology
  • Transcription, Genetic*
  • Tumor Cells, Cultured

Substances

  • Arachidonate 15-Lipoxygenase