Subcellular Localization of the 15-Lipoxygenase in Mammalian Cells

Abstract

15-lipoxygenases are capable of oxygenating not only free polyenoic fatty acids but also complex substrates such as biomembranes (Kühn et al., 1990) and lipoproteins (Belkner et al., 1993). The enzyme is expressed in high yield in rabbit reticulocytes, in human airway epithelial cells and eosinophils and in smaller amounts in other mammalian cells (for review see Ford-Hutchinson, 1991a). In contrast to the 5-lipoxygenase which is involved in the biosynthesis of mediators in inflammatory and allergic processes (Samuelsson et al., 1987), the biological role of the 15-lipoxygenase pathway is not well understood. Its capability of oxygenating biomembranes (Kühn et al., 1990) and the biological dynamics of the enzyme in rabbit reticulocytes (Rapoport and Schewe, 1986) suggested a role in the programed breakdown of mitochondria during late erythropoiesis. Recently, a role of the 15-lipoxygenase in atherogenesis has been suggested (Ylä-Herttuala et al., 1991). The human 5-lipoxygenase which is synthesized as a cytosolic protein in resting white blood cells translocates to the nuclear envelope when the cells were stimulated with calcium ionophore (Woods et al., 1993). In the translocation process a special 5-lipoxygenase activating protein (FLAP) is involved as a docking protein for the lipoxygenase (Ford-Hutchinson, 1991b).