The vascular NADPH oxidase subunit p47phox is involved in redox-mediated gene expression.
An NADPH oxidase is thought to be a main source of vascular superoxide (O(2)(-)) production. The functional role of this oxidase, however, and the contribution of the different subunits of the enzyme to cellular signaling are still incompletely understood. We determined the role of the p47phox subunit of the oxidase in O(2)(-) generation and signaling in aortic rings and cultured smooth muscle cells (SMC) from wild-type (WT) and p47phox-deficient (p47phox -/-) mice. Basal O(2)(-) levels in aortae of p47phox -/- mice were lower than those in WT aortae. Infusion of [val(5)]-angiotensin II increased O(2)(-) levels in aortae from WT more than in aortae from p47phox -/- mice. O(2)(-) generation was similar in quiescent SMC from WT and p47phox -/- mice. However, exposure to thrombin selectively increased O(2)(-) generation in VSMC from WT, but not from p47phox -/- mice. Thrombin-activated redox-mediated signal transduction and gene expression was attenuated in VSMC from p47phox -/- compared to cells from WT mice as determined by p38 MAP kinase activation and VEGF gene expression. We conclude that p47phox is important for vascular ROS production and redox-modulated signaling and gene expression in VSMC.
Brandes
Ralf P
RP
Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Frankfurt am Main, Germany. R.Brandes@em.uni-frankfurt.de
Miller
Francis J
FJ
Beer
Stefani
S
Haendeler
Judith
J
Hoffmann
Jörg
J
Ha
Tulinh
T
Holland
Steven M
SM
Görlach
Agnes
A
Busse
Rudi
R
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism; D004996:Ethidium / Q000031:analogs & derivatives*; D005260:Female; D015870:Gene Expression; D015151:Immunoblotting; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D019255:NADPH Oxidases / Q000502:physiology*; D010084:Oxidation-Reduction; D010750:Phosphoproteins / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D048051:p38 Mitogen-Activated Protein Kinases
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D010750:Phosphoproteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C067883:dihydroethidium; D013481:Superoxides; D000804:Angiotensin II; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D013917:Thrombin; D004996:Ethidium