Nox4 overexpression activates reactive oxygen species and p38 MAPK in human endothelial cells.
Nicotine adenine dinucleotide phosphate (NADPH) oxidase (Nox) complexes are the main sources of reactive oxygen species (ROS) formation in the vessel wall. We have used DNA microarray, real-time PCR and Western blot to demonstrate that the subunit Nox4 is the major Nox isoform in primary human endothelial cells; we also found high levels of NADPH oxidase subunit p22(phox) expression. Nox4 was localized by laser scanning confocal microscopy within the cytoplasm of endothelial cells. Endothelial Nox4 overexpression enhanced superoxide anion formation and phosphorylation of p38 MAPK. Nox4 down-regulation by shRNA has in contrast to TGF-beta no effect on p38 MAPK phosphorylation. We conclude that Nox4 is the major Nox isoform in human endothelial cells, and forms an active complex with p22(phox). The Nox4-containing complex mediates formation of reactive oxygen species and p38 MAPK activation. This is a novel mechanism of redox-sensitive signaling in human endothelial cells.
Goettsch
Claudia
C
Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University of Technology Dresden, Fetscherstr. 74, D-01307 Dresden, Germany.
Goettsch
Winfried
W
Muller
Gregor
G
Seebach
Jochen
J
Schnittler
Hans-Joachim
HJ
Morawietz
Henning
H
D002478:Cells, Cultured; D042783:Endothelial Cells / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000096:biosynthesis* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D007527:Isoenzymes; D017382:Reactive Oxygen Species; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; C086986:CYBA protein, human; D048051:p38 Mitogen-Activated Protein Kinases