期刊
BIOSCIENCE REPORTS
卷 30, 期 4, 页码 233-241出版社
PORTLAND PRESS LTD
DOI: 10.1042/BSR20090048
关键词
inducible nitric oxide synthase (iNOS); macrophage; NADPH oxidase (NOX); RAW264.7 macrophage; reactive oxygen species (ROS); respiratory burst
资金
- National Natural Science Foundation of China [30670480, 30770492]
- National Basic Research Program of China [2004CB720000, 2006CB705600, 2006CB911001]
Macrophages produce a large volume of ROS (reactive oxygen species) through respiratory burst. However, the influence of iNOS [inducible NOS (nitric oxide synthase)] activation on ROS production remains unclear. In the present study, the kinetic generation of ROS in RAW264.7 murine macrophages was monitored by chemiluminescence. PMA induces a robust chemiluminescence in RAW264.7 cells, suggesting PKC (protein kinase C)-related assembly and activation of NOX (NADPH oxidase). The effects of iNOS induction on ROS production were examined. Induction of iNOS expression in RAW264.7 cells with LPS (lipopolysaccharide; 1 mu g/ml) causes a significant increase in PMA-induced chemiluminescence, which could be enhanced by the NOS substrate, L-arginine, and could be abolished by the NOS inhibitor, L-NNA (N-G-nitro-L-arginine). Further experiments reveal that induction of iNOS expression enhances the PMA-stimulated phosphorylation of the p47(Phox) subunit of NOX, and promotes the relocalization of cytosolic p47(phox) and p67(phox) subunits to the membrane. Inhibition of PKC zeta, by its myristoylated pseudosubstrate significantly decreased the PMA-stimulated phosphorylation of the p47(phox) in LPS-pretreated cells, suggesting that PKC zeta, is involved in the iNOS-dependent assembly and activation of NOX. Taken together, the present study suggests that the induction of iNOS upregulates the PMA-induced assembly of NOX and leads to the enhanced production of ROS via a PKCL zeta-dependent mechanism.
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