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Membrane Translocation of 15-Lipoxygenase in Hematopoietic
Cells Is Calcium-Dependent and Activates the Oxygenase Activity of
the Enzyme
Roland Brinckmann,
Kerstin Schnurr,
Dagmar Heydeck,
Thomas Rosenbach,
Gerhard Kolde, and
Hartmut Kühn
From the Institute of Biochemistry Pathology and Dermatological
Clinic, University Clinics Charité, Humboldt University, Berlin,
Germany.
Mammalian 15-lipoxygenases, which have been implicated in the
differentiation of hematopoietic cells are commonly regarded as
cytosolic enzymes. Studying the interaction of the purified rabbit
reticulocyte 15-lipoxygenase with various types of biomembranes, we
found that the enzyme binds to biomembranes when calcium is present in
the incubation mixture. Under these conditions, an oxidation of the
membrane lipids was observed. The membrane binding was reversible and
led to an increase in the fatty acid oxygenase activity of the enzyme.
To find out whether such a membrane binding also occurs in vivo, we
investigated the intracellular localization of the enzyme in stimulated
and resting hematopoietic cells by immunoelectron microscopy, cell
fractionation studies and activity assays. In rabbit reticulocytes, the
15-lipoxygenase was localized in the cytosol, but also bound to
intracellular membranes. This membrane binding was also reversible and
the detection of specific lipoxygenase products in the membrane lipids
indicated the in vivo activity of the enzyme on endogenous substrates.
Immunoelectron microscopy showed that in interleukin-4 -treated
monocytes, the 15-lipoxygenase was localized in the cytosol, but also
at the inner side of the plasma membrane and at the cytosolic side of intracellular vesicles. Here again, cell fractionation studies confirmed the in vivo membrane binding of the enzyme. In human eosinophils, which constitutively express the 15-lipoxygenase, the
membrane bound share of the enzyme was augmented when the cells were
stimulated with calcium ionophore. Only under these conditions,
specific lipoxygenase products were detected in the membrane lipids.
These data suggest that in hematopoietic cells the cytosolic
15-lipoxygenase translocates reversibly to the cellular membranes. This
translocation, which increases the fatty acid oxygenase activity of the
enzyme, is calcium-dependent, but may not require a special docking
protein.
Blood, Vol. 91 No. 1 (January 1), 1998:
pp. 64-74
© 1998 by The American Society of Hematology.
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