help button home button Am J Pathol ASIP WHAT IS IT?
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Al-Shabrawey, M.
Right arrow Articles by Caldwell, R. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Al-Shabrawey, M.
Right arrow Articles by Caldwell, R. B.
(American Journal of Pathology. 2005;167:599-607.)
© 2005 American Society for Investigative Pathology

Inhibition of NAD(P)H Oxidase Activity Blocks Vascular Endothelial Growth Factor Overexpression and Neovascularization during Ischemic Retinopathy

Mohamed Al-Shabrawey*, Manuela Bartoli*{dagger}, Azza B. El-Remessy*{ddagger}, Daniel H. Platt*, Sue Matragoon{ddagger}, M. Ali Behzadian*{ddagger}, Robert W. Caldwell{ddagger} and Ruth B. Caldwell*§

From the Vascular Biology Center* and the Departments of Pathology,{dagger} Pharmacology and Toxicology,{ddagger} Cellular Biology and Anatomy,§ and Ophthalmology, The Medical College of Georgia, Augusta, Georgia

Because oxidative stress has been strongly implicated in up-regulation of vascular endothelial growth factor (VEGF) expression in ischemic retinopathy, we evaluated the role of NAD(P)H oxidase in causing VEGF overexpression and retinal neovascularization. Dihydroethidium imaging analyses showed increased superoxide formation in areas of retinal neovascularization associated with relative retinal hypoxia in a mouse model for oxygen-induced retinopathy. The effect of hypoxia in stimulating superoxide formation in retinal vascular endothelial cells was confirmed by in vitro chemiluminescence assays. The superoxide formation was blocked by specific inhibitors of NAD(P)H oxidase activity (apocynin, gp91ds-tat) indicating that NAD(P)H oxidase is a major source of superoxide formation. Western blot and immunolocalization analyses showed that retinal ischemia increased expression of the NAD(P)H oxidase catalytic subunit gp91phox, which localized primarily within vascular endothelial cells. Treatment of mice with apocynin blocked ischemia-induced increases in oxidative stress, normalized VEGF expression, and prevented retinal neovascularization. Apocynin and gp91ds-tat also blocked the action of hypoxia in causing increased VEGF expression in vitro, confirming the specific role of NAD(P)H oxidase in hypoxia-induced increases in VEGF expression. In conclusion, NAD(P)H oxidase activity is required for hypoxia-stimulated increases in VEGF expression and retinal neovascularization. Inhibition of NAD(P)H oxidase offers a new therapeutic target for the treatment of retinopathy.




This article has been cited by other articles:


Home page
 IOVSHome page
M. Al-Shabrawey, M. Rojas, T. Sanders, A. Behzadian, A. El-Remessy, M. Bartoli, A. K. Parpia, G. Liou, and R. B. Caldwell
Role of NADPH Oxidase in Retinal Vascular Inflammation
Invest. Ophthalmol. Vis. Sci., July 1, 2008; 49(7): 3239 - 3244.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
M. Al-Shabrawey, M. Bartoli, A. B. El-Remessy, G. Ma, S. Matragoon, T. Lemtalsi, R. W. Caldwell, and R. B. Caldwell
Role of NADPH Oxidase and Stat3 in Statin-Mediated Protection against Diabetic Retinopathy
Invest. Ophthalmol. Vis. Sci., July 1, 2008; 49(7): 3231 - 3238.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. J. P. Deudero, C. Caramelo, M. C. Castellanos, F. Neria, R. Fernandez-Sanchez, O. Calabia, S. Penate, and F. R. Gonzalez-Pacheco
Induction of Hypoxia-inducible Factor 1{alpha} Gene Expression by Vascular Endothelial Growth Factor
J. Biol. Chem., April 25, 2008; 283(17): 11435 - 11444.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
Y. Saito, A. Uppal, G. Byfield, S. Budd, and M. E. Hartnett
Activated NAD(P)H Oxidase from Supplemental Oxygen Induces Neovascularization Independent of VEGF in Retinopathy of Prematurity Model
Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1591 - 1598.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
L. Xia, H. Wang, S. Munk, H. Frecker, H. J. Goldberg, I. G. Fantus, and C. I. Whiteside
Reactive oxygen species, PKC-beta1, and PKC-{zeta} mediate high-glucose-induced vascular endothelial growth factor expression in mesangial cells
Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1280 - E1288.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
P. Chen, A. M. Guo, P. A. Edwards, G. Trick, and A. G. Scicli
Role of NADPH oxidase and ANG II in diabetes-induced retinal leukostasis
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2007; 293(4): R1619 - R1629.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
J. Shen, B. Xie, A. Dong, M. Swaim, S. F. Hackett, and P. A. Campochiaro
In Vivo Immunostaining Demonstrates Macrophages Associate with Growing and Regressing Vessels
Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4335 - 4341.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
A. B. El-Remessy, M. Al-Shabrawey, D. H. Platt, M. Bartoli, M. A. Behzadian, N. Ghaly, N. Tsai, K. Motamed, and R. B. Caldwell
Peroxynitrite mediates VEGF's angiogenic signal and function via a nitration-independent mechanism in endothelial cells
FASEB J, August 1, 2007; 21(10): 2528 - 2539.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
M. Ushio-Fukai
Redox signaling in angiogenesis: Role of NADPH oxidase
Cardiovasc Res, July 15, 2006; 71(2): 226 - 235.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2005 by the American Society for Investigative Pathology.