Intracellular Activation and Induction of 12-lipoxygenase in Mouse Peritoneal Macrophages
Upon macrophage activation, arachidonic acid is released from membrane lipids, and metabolized by cyclooxygenase (COX) and lipoxygenases.1,2 COX is the rate-limiting enzyme for the synthesis of various prostaglandins and thromboxanes, and there are two isoforms, COX-1 and COX-2.3 COX-1 is constantly expressed in resting macrophages, while COX-2 is rapidly and transiently induced by various stimuli such as cytokines and lipopolysaccharide (LPS).4 Prostaglandin E2 regulates macrophage functions including syntheses of nitric oxide5 and cytokines.6 On the other hand, 12-lipoxygenase introduces a molecular oxygen into arachidonic acid to give rise its 12-hydroperoxy derivative.7 It has been shown that this enzyme is responsible for the generation of oxidized low-density lipoprotein which is an initial event of atherosclerosis.8.9 Therefore, it is of great importance to examine intracellular activation of the 12-lipoxygenase in macrophages. For this purpose, we utilized a dichlorofluorescein dye to sensitively visualize the enzyme activity, and found that LPS induced the 12-lipoxygenase in mouse peritoneal macrophages.
KeywordsArachidonic Acid Intracellular Activation Mouse Peritoneal Macrophage Tumor Necrosis Factor Production Nordihydroguaiaretic Acid
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