Article (Scientific journals)
iPLA 2 , a novel determinant in Ca2+ - and phosphorylation-dependent S100A8/A9 regulated NOX2 activity
Schenten, Véronique; Bréchard, Sabrina; Plançon, Sébastien et al.
2010In Biochimica et Biophysica Acta-Molecular Cell Research, 1803 (7), p. 840-847
Peer reviewed
 

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Abstract :
[en] The neutrophil NADPH oxidase (NOX2) is a key enzyme responsible for host defense against invading pathogens, via the production of reactive oxygen species. Dysfunction of NOX2 can contribute to inflammatory processes, which could lead to the development of diseases such as atherosclerosis. In this paper, we characterize a pathway leading to NOX2 activation in which iPLA(2)-regulated p38 MAPK activity is a key regulator of S100A8/A9 translocation via S100A9 phosphorylation. Studies in cell-free or recombinant systems involved two Ca2+-binding proteins of the S100 family, namely S100A8 and S100A9, in NOX2 activation dependent on intracellular Ca2+ concentration ([Ca2+](i)) elevation. Using differentiated HL-60 cells as a model of neutrophils, we provide evidence that [Ca2+](i)-regulated S100A8/A9 translocation is mediated by an increase in [Ca2+](i) through intracellular Ca2+ store depletion. Moreover, we confirm that p38 MAPK induces S100A9 phosphorylation, a mandatory precondition for S100 translocation. Based on a pharmacological approach and an siRNA strategy, we identify iPLA(2) as a new molecular player aiding S100 translocation and NOX2 activity. Inhibition of p38 MAPK activity and S100A9 phosphorylation by bromoenol lactone, a selective inhibitor of iPLA(2), indicated that p38 MAPK-mediated S100A9 phosphorylation is dependent on iPLA(2). In conclusion, we have characterized a pathway leading to NOX2 activation in which iPLA(2)-regulated p38 MAPK activity is a key regulator of S100A8/A9 translocation via S100A9 phosphorylation.
Disciplines :
Biochemistry, biophysics & molecular biology
Identifiers :
UNILU:UL-ARTICLE-2013-022
Author, co-author :
Schenten, Véronique ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Bréchard, Sabrina ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Plançon, Sébastien ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Melchior, Chantal ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Frippiat, Jean-Pol;  Lorraine University, Vandoeuvre-lès-Nancy, France
Tschirhart, Eric ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Language :
English
Title :
iPLA 2 , a novel determinant in Ca2+ - and phosphorylation-dependent S100A8/A9 regulated NOX2 activity
Publication date :
2010
Journal title :
Biochimica et Biophysica Acta-Molecular Cell Research
ISSN :
0167-4889
Publisher :
Elsevier Science, Amsterdam, Unknown/unspecified
Volume :
1803
Issue :
7
Pages :
840-847
Peer reviewed :
Peer reviewed
Available on ORBilu :
since 13 September 2013

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