Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets

被引:749
作者
Drummond, Grant R. [1 ]
Selemidis, Stavros [1 ]
Griendling, Kathy K. [2 ]
Sobey, Christopher G. [1 ]
机构
[1] Monash Univ, Dept Pharmacol, Vasc Biol & Immunopharmacol Grp, Clayton, Vic 3800, Australia
[2] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA
关键词
SMOOTH-MUSCLE-CELLS; CHRONIC GRANULOMATOUS-DISEASE; NITRIC-OXIDE SYNTHASE; II-INDUCED HYPERTENSION; SRC HOMOLOGY-3 DOMAINS; TANDEM SH3 DOMAINS; PHOSPHORYLATION-INDUCED ACTIVATION; DEPENDENT CHRONIC HYPERTENSION; NMDA RECEPTOR ACTIVATION; RAT CAROTID-ARTERY;
D O I
10.1038/nrd3403
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
NADPH oxidases are a family of enzymes that generate reactive oxygen species (ROS). The NOX1 (NADPH oxidase 1) and NOX2 oxidases are the major sources of ROS in the artery wall in conditions such as hypertension, hypercholesterolaemia, diabetes and ageing, and so they are important contributors to the oxidative stress, endothelial dysfunction and vascular inflammation that underlies arterial remodelling and atherogenesis. In this Review, we advance the concept that compared to the use of conventional antioxidants, inhibiting NOX1 and NOX2 oxidases is a superior approach for combating oxidative stress. We briefly describe some common and emerging putative NADPH oxidase inhibitors. In addition, we highlight the crucial role of the NADPH oxidase regulatory subunit, p47phox, in the activity of vascular NOX1 and NOX2 oxidases, and suggest how a better understanding of its specific molecular interactions may enable the development of novel isoform-selective drugs to prevent or treat cardiovascular diseases. © 2011 Macmillan Publishers Limited. All rights reserved.
引用
收藏
页码:453 / 471
页数:19
相关论文
共 227 条
[1]   Mechanism for phosphorylation-induced activation of the phagocyte NADPH oxidase protein p47 phox - Triple replacement of serines 303, 304, and 328 with aspartates disrupts the SH3 domain-mediated intramolecular interaction in p47 phox, thereby activating the oxidase [J].
Ago, T ;
Nunoi, H ;
Ito, T ;
Sumimoto, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (47) :33644-33653
[2]   Phosphorylation of p47phox directs phox homology domain from SH3 domain toward phosphoinositides, leading to phagocyte NADPH oxidase activation [J].
Ago, T ;
Kuribayashi, F ;
Hiroaki, H ;
Takeya, R ;
Ito, T ;
Kohda, D ;
Sumimoto, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (08) :4474-4479
[3]   Increased expression of gp91phox homologues of NAD(P)H oxidase in the aortic media during chronic hypertension: Involvement of the renin-angiotensin system [J].
Akasaki, Takashi ;
Ohya, Yusuke ;
Kuroda, Junya ;
Eto, Kimika ;
Abe, Isao ;
Sumimoto, Hideki ;
Iida, Mitsuo .
HYPERTENSION RESEARCH, 2006, 29 (10) :813-820
[4]   Noxal is a central component of the smooth muscle NADPH oxidase in mice [J].
Ambasta, Rashmi K. ;
Schreiber, Judith G. ;
Janiszewski, Mariano ;
Busse, Rudi ;
Brandes, Ralf P. .
FREE RADICAL BIOLOGY AND MEDICINE, 2006, 41 (02) :193-201
[5]   Direct interaction of the novel nox proteins with p22phox is required for the formation of a functionally active NADPH oxidase [J].
Ambasta, RK ;
Kumar, P ;
Griendling, KK ;
Schmidt, HHHW ;
Busse, R ;
Brandes, RP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (44) :45935-45941
[6]   NF-κB regulates phagocytic NADPH oxidase by inducing the expression of gp91phox [J].
Anrather, J ;
Racchumi, G ;
Iadecola, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (09) :5657-5667
[7]   Elicitation of reactive oxygen species in Chlamydia pneumoniae-stimulated macrophages:: a Ca2+-dependent process involving simultaneous activation of NADPH oxidase and cytochrome oxidase genes [J].
Azenabor, AA ;
Yang, S ;
Job, G ;
Adedokun, OO .
MEDICAL MICROBIOLOGY AND IMMUNOLOGY, 2005, 194 (1-2) :91-103
[8]   Macrophages Generate Reactive Oxygen Species in Response to Minimally Oxidized Low-Density Lipoprotein Toll-Like Receptor 4-and Spleen Tyrosine Kinase-Dependent Activation of NADPH Oxidase 2 [J].
Bae, Yun Soo ;
Lee, Jee Hyun ;
Choi, Soo Ho ;
Kim, Sunah ;
Almazan, Felicidad ;
Witztum, Joseph L. ;
Miller, Yury I. .
CIRCULATION RESEARCH, 2009, 104 (02) :210-U147
[9]   NOX3, a superoxide-generating NADPH oxidase of the inner ear [J].
Bánfi, B ;
Malgrange, B ;
Knisz, J ;
Steger, K ;
Dubois-Dauphin, M ;
Krause, KH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (44) :46065-46072
[10]   Two novel proteins activate superoxide generation by the NADPH oxidase NOX1 [J].
Bánfi, B ;
Clark, RA ;
Steger, K ;
Krause, KH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (06) :3510-3513