Bioactive lipoxygenase metabolites stimulation of NADPH oxidases and reactive oxygen species |
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Authors: | Kyung-Jin Cho Ji-Min Seo Jae-Hong Kim |
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Institution: | (1) Cardiovascular Division, King’s College London British Heart Foundation Centre of Research Excellence, London, SE5 9NU, UK |
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Abstract: | In mammalian cells, reactive oxygen species (ROS) are produced via a variety of cellular oxidative processes, including the
activity of NADPH oxidases (NOX), the activity of xanthine oxidases, the metabolism of arachidonic acid (AA) by lipoxygenases
(LOX) and cyclooxygenases (COX), and the mitochondrial respiratory chain. Although NOX-generated ROS are the best characterized
examples of ROS in mammalian cells, ROS are also generated by the oxidative metabolism (e.g., via LOX and COX) of AA that
is released from the membrane phospholipids via the activity of cytosolic phospholipase A2 (cPLA2). Recently, growing evidence suggests that LOX- and COX-generated AA metabolites can induce ROS generation by stimulating
NOX and that a potential signaling connection exits between the LOX/COX metabolites and NOX. In this review, we discuss the
results of recent studies that report the generation of ROS by LOX metabolites, especially 5-LOX metabolites, via NOX stimulation.
In particular, we have focused on the contribution of leukotriene B4 (LTB4), a potent bioactive eicosanoid that is derived from 5-LOX, and its receptors, BLT1 and BLT2, to NOX stimulation through
a signaling mechanism that leads to ROS generation. |
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Keywords: | BLT2 eicosanoids lipoxygenase NOX ROS |
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