• M Peters-Golden.
• University of Michigan Medical Center, Ann Arbor 48109-0642, USA.
• Am. J. Respir. Crit. Care Med. 1998 Jun 1;157(6 Pt 2):S227-31; discussion S231-2, S247-8.

AbstractThe initial enzymatic steps in leukotriene synthesis occur at the nuclear envelope. Cytosolic phospholipase A2 translocates from the cytoplasm to selectively hydrolyze nuclear envelope phospholipids, releasing free arachidonate. 5-Lipoxygenase-activating protein, an arachidonate transfer protein, then binds arachidonate and presents it to 5-lipoxygenase (5-LO), which catalyzes a two-step reaction to produce leukotriene A4. In resting human and rat peripheral blood neutrophils, 5-LO is localized to the cytoplasm; in rat basophilic leukemia cells and human alveolar macrophages, however, it is found predominantly in the nucleus. Immunofluorescence microscopy studies demonstrate that both cytoplasmic and nuclear 5-LO move to the nuclear envelope following cell activation. Many questions remain unanswered regarding the significance of nuclear 5-LO, potential autocrine actions of leukotrienes, and intracellular trafficking of these enzymes and their products.

16 keywords...

hide…