Article (Scientific journals)
OAG induces an additional PKC-, PI3K-, and Rac2-mediated signaling pathway up-regulating NOX2 activity, independently of Ca 2+ entry
BRÉCHARD, Sabrina; SALSMANN, Alexandre; TSCHIRHART, Eric
2009In Journal of Leukocyte Biology, 85 (4), p. 638-647
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Abstract :
[en] The requirement of calcium ion (Ca(2)(+)) entry for neutrophil NADPH oxidase (NOX2) regulation is clearly established. However, its role in the signaling pathway leading to NOX2 activation is still elusive. 1-oleoyl-2-acetyl-sn-glycerol (OAG) causes an increase in NOX2 activity and has been shown to directly modulate Ca(2)(+) channels unrelated to the well-known store-operated Ca(2)(+) entry (SOCE) mechanism. In our study, we have investigated the potential role of OAG in Ca(2)(+) influx-mediated NOX2 activity in neutrophil-like-differentiated HL-60 cells to further characterize second signals involved in the regulation of NOX2. OAG inhibited fMLF- and thapsigargin-induced Ca(2)(+) entry, a phenomenon that was not restored by protein kinase C (PKC) or PI3K blockade. Addition of OAG resulted in a rapid decrease of maximal intracellular Ca(2)(+) concentration induced by thapsigargin. Both results suggest that OAG has an inhibitory effect, independent of PI3K and PKC, on the regulation of SOCE. In contrast to SOCE inhibition, OAG-induced NOX2 activation was mediated by PKC and PI3K. Our data establish that both kinases exert their effects through the regulation of Rac2 activity. In addition, OAG potentiated the effect of fMLF on the activation of NOX2 and led to a discernible activity of NOX2 upon thapsigargin stimulation. In conclusion, our results demonstrate that an additional PKC- and/or PI3K-dependent signal may act in synergy with Ca(2)(+) influx to trigger NOX2 activation.
Disciplines :
Biochemistry, biophysics & molecular biology
Identifiers :
UNILU:UL-ARTICLE-2013-026
Author, co-author :
BRÉCHARD, Sabrina ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
SALSMANN, Alexandre ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
TSCHIRHART, Eric ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Language :
English
Title :
OAG induces an additional PKC-, PI3K-, and Rac2-mediated signaling pathway up-regulating NOX2 activity, independently of Ca 2+ entry
Publication date :
2009
Journal title :
Journal of Leukocyte Biology
ISSN :
0741-5400
Publisher :
Wiley Liss, Inc., New York, United States - New York
Volume :
85
Issue :
4
Pages :
638-647
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 13 September 2013

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