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K. Gertz, U. Laufs, U. Lindauer, G. Nickenig, M. Böhm, U. Dirnagl, M. Endres (2003)
Withdrawal of Statin Treatment Abrogates Stroke Protection in MiceStroke: Journal of the American Heart Association, 34
J. Liao (2002)
Beyond lipid lowering: the role of statins in vascular protection.International journal of cardiology, 86 1
B. White, J. Sullivan, D. DeGracia, B. O’Neil, R. Neumar, L. Grossman, J. Rafols, G. Krause (2000)
Brain ischemia and reperfusion: molecular mechanisms of neuronal injuryJournal of the Neurological Sciences, 179
S. Wassmann, U. Laufs, K. Müller, C. Konkol, K. Ahlbory, A. Bäumer, W. Linz, M. Böhm, G. Nickenig (2002)
Cellular Antioxidant Effects of Atorvastatin In Vitro and In VivoArteriosclerosis, Thrombosis, and Vascular Biology: Journal of the American Heart Association, 22
K. Shatwell, A. Segal (1996)
NADPH oxidase.The international journal of biochemistry & cell biology, 28 11
L. Virág, É. Szabó, P. Gergely, C. Szabó (2003)
Peroxynitrite-induced cytotoxicity: mechanism and opportunities for intervention.Toxicology letters, 140-141
(2004)
Curr Opin Immunol
Y. Rikitake, S. Kawashima, S. Takeshita, T. Yamashita, Hiroshi Azumi, M. Yasuhara, H. Nishi, N. Inoue, M. Yokoyama (2001)
Anti-oxidative properties of fluvastatin, an HMG-CoA reductase inhibitor, contribute to prevention of atherosclerosis in cholesterol-fed rabbits.Atherosclerosis, 154 1
H. Cai, K. Griendling, D. Harrison (2003)
The vascular NAD(P)H oxidases as therapeutic targets in cardiovascular diseases.Trends in pharmacological sciences, 24 9
F. Yu, T. Sugawara, P. Chan (2003)
Treatment with dihydroethidium reduces infarct size after transient focal cerebral ischemia in miceBrain Research, 978
Motohisa Suzuki, M. Tabuchi, M. Ikeda, T. Tomita (2002)
Concurrent formation of peroxynitrite with the expression of inducible nitric oxide synthase in the brain during middle cerebral artery occlusion and reperfusion in ratsBrain Research, 951
(2005)
1131 Inhibition of brain GTP cyclohydrolase I and tetrahydrobiopterin attenuates cerebral infarction via reducing iNOS and peroxynitrite in ischemic strokeJournal of the Neurological Sciences, 238
Lixin Li, S. Watts, A. Banes, J. Galligan, G. Fink, Alex Chen (2003)
NADPH Oxidase–Derived Superoxide Augments Endothelin-1–Induced Venoconstriction in Mineralocorticoid HypertensionHypertension: Journal of The American Heart Association, 42
Lixin Li, Elahé Crockett, Donna Wang, J. Galligan, G. Fink, Alex Chen (2002)
Gene Transfer of Endothelial NO Synthase and Manganese Superoxide Dismutase on Arterial Vascular Cell Adhesion Molecule-1 Expression and Superoxide Production in Deoxycorticosterone Acetate-Salt HypertensionArteriosclerosis, Thrombosis, and Vascular Biology: Journal of the American Heart Association, 22
H. Kontos (2001)
Oxygen radicals in cerebral ischemia: the 2001 Willis lecture.Stroke, 32 11
G. Kidd, Hua Hong, A. Majid, D. Kaufman, Alex Chen (2005)
Inhibition of Brain GTP Cyclohydrolase I and Tetrahydrobiopterin Attenuates Cerebral Infarction via Reducing Inducible NO Synthase and Peroxynitrite in Ischemic StrokeStroke, 36
I. Kusaka, G. Kusaka, Changman Zhou, M. Ishikawa, A. Nanda, D. Granger, John Zhang, Jiping Tang (2004)
Role of AT1 receptors and NAD(P)H oxidase in diabetes-aggravated ischemic brain injury.American journal of physiology. Heart and circulatory physiology, 286 6
C. Walder, S. Green, W. Darbonne, Joanne Mathias, J. Rae, M. Dinauer, J. Curnutte, G. Thomas (1997)
Ischemic stroke injury is reduced in mice lacking a functional NADPH oxidase.Stroke, 28 11
K. O'Neil, F. Miller, T. Barder, D. Lubman (2003)
Profiling the progression of cancer: Separation of microsomal proteins in MCF10 breast epithelial cell lines using nonporous chromatophoresisPROTEOMICS, 3
E. Veselov (1946)
[Protection from mice].Gigiena i sanitariia, 11 3
H. Hirabayashi, S. Takizawa, N. Fukuyama, H. Nakazawa, Y. Shinohara (2000)
Nitrotyrosine generation via inducible nitric oxide synthase in vascular wall in focal ischemia-reperfusionBrain Research, 852
V. Bianca, S. Dusi, E. Bianchini, I. Prà, F. Rossi (1999)
beta-amyloid activates the O-2 forming NADPH oxidase in microglia, monocytes, and neutrophils. A possible inflammatory mechanism of neuronal damage in Alzheimer's disease.The Journal of biological chemistry, 274 22
N. Thakur, Toshio Hayashi, Daigo Sumi, Hatsuyo Kano, Taku Tsunekawa, Akihisa Iguchi (2001)
HMG-CoA reductase inhibitor stabilizes rabbit atheroma by increasing basal NO and decreasing superoxide.American journal of physiology. Heart and circulatory physiology, 281 1
S. Ashwal, Beatriz Tone, H. Tian, D. Cole, W. Pearce (1998)
Core and penumbral nitric oxide synthase activity during cerebral ischemia and reperfusion.Stroke, 29 5
F. Serrano, Nutan Kolluri, F. Wientjes, J. Card, E. Klann (2003)
NADPH oxidase immunoreactivity in the mouse brainBrain Research, 988
R. Fabian, J. Perez-Polo, T. Kent (2000)
Electrochemical monitoring of superoxide anion production and cerebral blood flow: Effect of interleukin‐1β pretreatment in a model of focal ischemia and reperfusionJournal of Neuroscience Research, 60
Statins have recently been shown to exert neuronal protection in ischemic stroke. Reactive oxygen species, specifically superoxide formed during the early phase of reperfusion, augment neuronal injury. NADPH oxidase is a key enzyme for superoxide production. The present study tested the hypothesis that atorvastatin protects against cerebral infarction via inhibition of NADPH oxidase-derived superoxide in transient focal ischemia. Transient focal ischemia was created in halothane-anesthetized adult male Sprague-Dawley rats (250–300 g) by middle cerebral artery occlusion (MCAO). Atorvastatin (Lipitor, 10 mg/kg sc) was administered three times before MCAO. Infarct volume was measured by triphenyltetrazolium chloride staining. NADPH oxidase enzymatic activity and superoxide levels were quantified in the ischemic core and penumbral regions by lucigenin (5 µM)-enhanced chemiluminescence. Expression of NADPH oxidase membrane subunit gp91 phox and membrane-translocated subunit p47 phox and small GTPase Rac-1 was analyzed by Western blot. NADPH oxidase activity and superoxide levels increased after reperfusion and peaked within 2 h of reperfusion in the penumbra, but not in the ischemic core, in MCAO rats. Atorvastatin pretreatment prevented these increases, blunted expression of membrane subunit gp91 phox , and prevented translocation of cytoplasmic subunit p47 phox to the membrane in the penumbra 2 h after reperfusion. Consequently, cerebral infarct volume was significantly reduced in atorvastatin-treated compared with nontreated MCAO rats 24 h after reperfusion. These results indicate that atorvastatin protects against cerebral infarction via inhibition of NADPH oxidase-derived superoxide in transient focal ischemia. transient focal ischemia; neuronal injury; inducible nitric oxide synthase; oxidative stress; statins Address for reprint requests and other correspondence: A. F. Chen, Depts. of Pharmacology and Neurology, B403 Life Sciences Bldg., Michigan State Univ., East Lansing, MI 48824-1317 (e-mail: chenal@msu.edu )
AJP - Heart and Circulatory Physiology – The American Physiological Society
Published: Nov 1, 2006
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