Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:677-683
Published online before print December 11, 2003, doi: 10.1161/01.ATV.0000112024.13727.2c
Published online before print December 11, 2003, doi: 10.1161/01.ATV.0000112024.13727.2c
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© 2004 American Heart Association, Inc.
Vascular Biology |
Distinct Subcellular Localizations of Nox1 and Nox4 in Vascular Smooth Muscle Cells
From the Division of Cardiology (L.L.H., R.E.C., K.K.G.), Department of Medicine and Department of Pathology (D.L.), Emory University, Atlanta, GA; and the Department of Veterinary Molecular Biology (M.T.Q.), Montana State University, Boseman, MT.
Correspondence to Dr Lula L. Hilenski, Emory University School of Medicine, Division of Cardiology, 1639 Pierce Dr, 319 WMRB, Atlanta, GA 30322. E-mail lhilens{at}emory.edu
Objective— Reactive oxygen species (ROS) that act as signaling molecules in vascular smooth muscle cells (VSMC) and contribute to growth, hypertrophy, and migration in atherogenesis are produced by multi-subunit NAD(P)H oxidases. Nox1 and Nox4, two homologues to the phagocytic NAD(P)H subunit gp91phox, both generate ROS in VSMC but differ in their response to growth factors. We hypothesize that the opposing functions of Nox1 and Nox4 are reflected in their differential subcellular locations.
Methods and Results— We used immunofluorescence to visualize the NAD(P)H subunits Nox1, Nox4, and p22phox in cultured rat and human VSMC. Optical sectioning using confocal microscopy showed that Nox1 is co-localized with caveolin in punctate patches on the surface and along the cellular margins, whereas Nox4 is co-localized with vinculin in focal adhesions. These immunocytochemical distributions are supported by membrane fractionation experiments. Interestingly, p22phox, a membrane subunit that interacts with the Nox proteins, is found in surface labeling and in focal adhesions in patterns similar to Nox1 and Nox4, respectively.
Conclusions— The differential roles of Nox1 and Nox4 in VSMC may be correlated with their differential compartmentalization in specific signaling domains in the membrane and focal adhesions.
Key Words: Nox1 • Nox4 • NAD(P)H oxidase • caveolae • focal adhesions
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