5-Lipoxygenase plays an essential role in 4-HNE-enhanced ROS production in murine macrophages via activation of NADPH oxidase

Abstract 4-Hydroxynonenal (HNE) mediates oxidative stress-linked pathological processes; however, its role in the generation of reactive oxygen species (ROS) in macrophages is still unclear. Thus, this study investigated the sources and mechanisms of ROS generation in macrophages stimulated with HNE...

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Published in:Free radical research 2010-07, Vol.44 (7), p.742-750
Main Authors: Yun, Mi R., Park, Hye M., Seo, Kyo W., Lee, Seung J., Im, Dong S., Kim, Chi D.
Format: Article
Language:English
Subjects:
4-Hydroxynonenal
5-lipoxygenase
Aldehydes - pharmacology
Animals
Arachidonate 5-Lipoxygenase - deficiency
Arachidonate 5-Lipoxygenase - genetics
Arachidonate 5-Lipoxygenase - physiology
Cell Line - drug effects
Cell Line - metabolism
Enzyme Activation - drug effects
Indoles - pharmacology
Leukotrienes - pharmacology
Lipoxygenase Inhibitors
Macrophages, Peritoneal - drug effects
Macrophages, Peritoneal - metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
NADPH oxidase
NADPH Oxidases - physiology
Protein Transport - drug effects
reactive oxygen species
Reactive Oxygen Species - metabolism
RNA Interference
RNA, Small Interfering - pharmacology
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Summary:Abstract 4-Hydroxynonenal (HNE) mediates oxidative stress-linked pathological processes; however, its role in the generation of reactive oxygen species (ROS) in macrophages is still unclear. Thus, this study investigated the sources and mechanisms of ROS generation in macrophages stimulated with HNE. Exposure of J774A.1 cells to HNE showed an increased production of ROS, which was attenuated by NADPH oxidase as well as 5-lipoxygenase (5-LO) inhibitors. Linked to these results, HNE increased membrane translocation of p47phox promoting NADPH oxidase activity, which was attenuated in peritoneal macrophages from 5-LO-deficient mice as well as in J774A.1 cells treated with a 5-LO inhibitor, MK886 or 5-LO siRNA. In contrast, HNE-enhanced 5-LO activity was not affected by inhibition of NADPH oxidase. Furthermore, leukotriene B4, 5-LO metabolite, was found to enhance NADPH oxidase activity in macrophages. Altogether, these results suggest that 5-LO plays a critical role in HNE-induced ROS generation in murine macrophages through activation of NADPH oxidase.
ISSN:1071-5762
1029-2470
DOI:10.3109/10715761003758122