NADPH-oxidase activity is elevated in penumbral and non-ischemic cerebral arteries following stroke

2006 ◽  
Vol 1111 (1) ◽  
pp. 111-116 ◽  
Author(s):  
Alyson A. Miller ◽  
Gregory J. Dusting ◽  
Carli L. Roulston ◽  
Christopher G. Sobey
2009 ◽  
Vol 296 (1) ◽  
pp. H220-H225 ◽  
Author(s):  
Alyson A. Miller ◽  
Grant R. Drummond ◽  
T. Michael De Silva ◽  
Anja E. Mast ◽  
Haruyo Hickey ◽  
...  

We previously reported that NADPH oxidase activity is greater in intracranial cerebral versus systemic arteries of the rat. Here, we first tested whether NADPH oxidase activity is also greater in intracranial cerebral than systemic arteries of three other animal species, i.e., mouse, rabbit, and pig. Second, using Nox2-deficient mice, we evaluated the involvement of Nox2-containing NADPH oxidases in any such regional differences. NADPH-stimulated superoxide (O2−) production by basilar, middle cerebral arteries (MCA), and common carotid arteries (CA) and thoracic aorta (AO) from rat, mouse, rabbit, and pig was measured using lucigenin-enhanced chemiluminescence. Basal production of O2− and hydrogen peroxide (H2O2) by cerebral arteries, AO, and CA from wild-type (WT) and Nox2−/− mice was measured using L-012-enhanced chemiluminescence and Amplex Red fluorescence, respectively. Western blotting was used to measure Nox2 and SOD1–3 protein expression, and immunofluorescence was used to localize Nox2, in mouse arteries. In rats, WT mice, rabbits, and pigs, NADPH-stimulated O2− production by cerebral arteries was up to 40-fold greater than that in AO and CA. In WT mice, basal O2− and H2O2 production by cerebral arteries was ninefold and ∼2.5-fold higher, respectively, than that in AO and CA and was associated with ∼40% greater expression of Nox2 protein. Nox2 immunofluorescence was localized to the endothelium, and to a lesser extent the adventitia, in all mouse arteries and appeared to be more intense in endothelium of MCA than AO or CA. In Nox2−/− mice, NADPH-stimulated O2− production by cerebral arteries was ∼35% lower than that in WT mice, whereas Nox2 deletion had no significant effect on O2− production by AO or CA. Thus NADPH oxidase activity is greater in intracranial cerebral versus systemic arteries of several animal species and is associated with higher cerebrovascular expression and activity of Nox2.


2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Christopher Sobey ◽  
Sophocles Chrissobolis ◽  
Haruyo Hickey ◽  
Grant Drummond

2021 ◽  
Vol 11 (2) ◽  
pp. 164
Author(s):  
Jae-Hoon Jeong ◽  
Jung-Hoon Koo ◽  
Jang Soo Yook ◽  
Joon-Yong Cho ◽  
Eun-Bum Kang

Exercise and antioxidants have health benefits that improve cognitive impairment and may act synergistically. In this study, we examined the effects of treadmill exercise (TE) and mitochondria-targeted antioxidant mitoquinone (MitoQ), individually or combined, on learning and memory, mitochondrial dynamics, NADPH oxidase activity, and neuroinflammation and antioxidant activity in the hippocampus of D-galactose-induced aging rats. TE alone and TE combined with MitoQ in aging rats reduced mitochondrial fission factors (Drp1, Fis1) and increased mitochondrial fusion factors (Mfn1, Mfn2, Opa1). These groups also exhibited improved NADPH oxidase activity and antioxidant activity (SOD-2, catalase). TE or MitoQ alone decreased neuroinflammatory response (COX-2, TNF-α), but the suppression was greater with their combination. In addition, aging-increased neuroinflammation in the dentate gyrus was decreased in TE but not MitoQ treatment. Learning and memory tests showed that, contrarily, MitoQ alone demonstrated some similar effects to TE but not a definitive improvement. In conclusion, this study demonstrated that MitoQ exerted some positive effects on aging when used as an isolated treatment, but TE had a more effective role on cognitive impairment, oxidative stress, inflammation, and mitochondria dysfunction. Our findings suggest that the combination of TE and MitoQ exerted no synergistic effects and indicated regular exercise should be the first priority in neuroprotection of age-related cognitive decline.


2010 ◽  
Vol 285 (43) ◽  
pp. 33197-33208 ◽  
Author(s):  
Franck Debeurme ◽  
Antoine Picciocchi ◽  
Marie-Claire Dagher ◽  
Didier Grunwald ◽  
Sylvain Beaumel ◽  
...  

2011 ◽  
Vol 29 ◽  
pp. e315
Author(s):  
A. Schulz ◽  
V. Jankowski ◽  
W. Zidek ◽  
J. Jankowski

2010 ◽  
Vol 298 (2) ◽  
pp. F401-F407 ◽  
Author(s):  
Md. Abdul Hye Khan ◽  
Mohammed Toriqul Islam ◽  
Alexander Castillo ◽  
Dewan Syed Abdul Majid

To examine the functional interaction between superoxide dismutase (SOD) and NADPH oxidase activity, we assessed renal responses to acute intra-arterial infusion of ANG II (0.5 ng·kg−1·min−1) before and during administration of a SOD inhibitor, diethyldithiocarbamate (DETC, 0.5 mg·kg−1·min−1), in enalaprilat-pretreated (33 μg·kg−1·min−1) rats ( n = 11). Total (RBF) and regional (cortical, CBF; medullary; MBF) renal blood flows were determined by Transonic and laser-Doppler flowmetry, respectively. Renal cortical and medullary tissue NADPH oxidase activity in vitro was determined using the lucigenin-chemiluminescence method. DETC treatment alone resulted in decreases in RBF, CBF, MBF, glomerular filtration rate (GFR), urine flow (V), and sodium excretion (UNaV) as reported previously. Before DETC, ANG II infusion decreased RBF (−18 ± 3%), CBF (−16 ± 3%), MBF [−5 ± 6%; P = not significant (NS)], GFR (−31 ± 4%), V (−34 ± 2%), and UNaV (−53 ± 3%). During DETC infusion, ANG II also caused similar reductions in RBF (−20 ± 4%), CBF (−19 ± 3%), MBF (−2 ± 2; P = NS), and in GFR (−22 ± 7%), whereas renal excretory responses (V; −12 ± 2%; UNaV; −24 ± 4%) were significantly attenuated compared with those before DETC. In in vitro experiments, ANG II (100 μM) enhanced NADPH oxidase activity both in cortical [13,194 ± 1,651 vs. 20,914 ± 2,769 relative light units (RLU)/mg protein] and in medullary (21,296 ± 2,244 vs. 30,597 ± 4,250 RLU/mg protein) tissue. Application of DETC (1 mM) reduced the basal levels and prevented ANG II-induced increases in NADPH oxidase activity in both tissues. These results demonstrate that renal excretory responses to acute ANG II administration are attenuated during SOD inhibition, which seems related to a downregulation of NADPH oxidase in the deficient condition of SOD activity.


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