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Regulation of cellular 15‐lipoxygenase activity on pretranslational, translational, and posttranslational levels
Author(s) -
Kühn Hartmut,
Heydeck Dagmar,
Brinckman Roland,
Trebus Frank
Publication year - 1999
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02562317
Subject(s) - reticulocyte , translational regulation , biochemistry , lipoxygenase , post translational regulation , biology , chemistry , microbiology and biotechnology , messenger rna , enzyme , translation (biology) , phosphorylation , gene
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 gurnine‐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.