Regulation of NADPH Oxidase Activity in Phagocytes

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.

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MODULATION OF NADPH OXIDASE ACTIVITY

Journal of Hypertension ◽

10.1097/00004872-201106001-00907 ◽

2011 ◽

Vol 29 ◽

pp. e315

Author(s):

A. Schulz ◽

V. Jankowski ◽

W. Zidek ◽

J. Jankowski

Keyword(s):

Nadph Oxidase ◽

Oxidase Activity ◽

Nadph Oxidase Activity

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Attenuation of renal excretory responses to ANG II during inhibition of superoxide dismutase in anesthetized rats

AJP Renal Physiology ◽

10.1152/ajprenal.00511.2009 ◽

2010 ◽

Vol 298 (2) ◽

pp. F401-F407 ◽

Cited By ~ 2

Author(s):

Md. Abdul Hye Khan ◽

Mohammed Toriqul Islam ◽

Alexander Castillo ◽

Dewan Syed Abdul Majid

Keyword(s):

Superoxide Dismutase ◽

Nadph Oxidase ◽

Oxidase Activity ◽

Ang Ii ◽

Sod Activity ◽

Doppler Flowmetry ◽

Nadph Oxidase Activity ◽

Blood Flows ◽

Renal Responses

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

Brain Research ◽

10.1016/j.brainres.2006.06.082 ◽

2006 ◽

Vol 1111 (1) ◽

pp. 111-116 ◽

Cited By ~ 51

Author(s):

Alyson A. Miller ◽

Gregory J. Dusting ◽

Carli L. Roulston ◽

Christopher G. Sobey

Keyword(s):

Nadph Oxidase ◽

Oxidase Activity ◽

Cerebral Arteries ◽

Nadph Oxidase Activity

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Peroxiredoxin 6 translocates to the plasma membrane during neutrophil activation and is required for optimal NADPH oxidase activity

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ◽

10.1016/j.bbamcr.2011.11.014 ◽

2012 ◽

Vol 1823 (2) ◽

pp. 306-315 ◽

Cited By ~ 39

Author(s):

Daniel R. Ambruso ◽

Michael A. Ellison ◽

Gail W. Thurman ◽

Thomas L. Leto

Keyword(s):

Plasma Membrane ◽

Nadph Oxidase ◽

Oxidase Activity ◽

Neutrophil Activation ◽

Peroxiredoxin 6 ◽

Nadph Oxidase Activity

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Abstract 776: Protein Disulfide Isomerase Is Involved In Redox Regulation Of Nitric Oxide Output During Laminar Shear Stress In Endothelial Cells

Circulation ◽

10.1161/circ.116.suppl_16.ii_149-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Denise C Fernandes ◽

Celio X Santos ◽

Hanjoong Jo ◽

Francisco R Laurindo

Keyword(s):

Endothelial Cells ◽

Nadph Oxidase ◽

Oxidase Activity ◽

Membrane Fraction ◽

Protein Disulfide Isomerase ◽

Disulfide Isomerase ◽

Nadph Oxidase Activity ◽

Caveolin 1 ◽

Protein Disulfide ◽

Laminar Shear

While anti-atherogenic effects of sustained laminar shear (LS) involve NO release from eNOS, increases in LS trigger transient superoxide production via NADPH oxidase. Recently, we showed that NADPH oxidase undergoes thiol-dependent regulation by the thioredoxin superfamily chaperone Protein Disulfide Isomerase (PDI). PDI is known to promote NO internalization via trans-nitrosation reactions. We hypothesized that PDI-dependent support of NADPH oxidase activity affects NO output during sustained LS. Cultured rabbit aortic endothelial cells (RAEC) submitted to LS (15 dynes/cm 2 ) in a cone-plate system for 18h exhibited (vs. static controls): Decreased (~50%) superoxide production (HPLC analysis of DHE oxidation); Decreased (~20%) NADPH-triggered hydrogen peroxide production in membrane fraction (Amplex Red assay); Decreased mRNA expression of Nox1 (67%) and Nox4 (45%) (real-time QPCR); Increased eNOS expression (~50%, western blot) and nitrite levels in culture medium (Δ = 7.1±2.5[SD] μM, NO Analyzer and Griess reaction); Decrease in total and membrane fraction PDI protein expression (~20%) without changes in membrane fraction/total ratio of PDI. RAEC were transfected with c-myc -tagged plasmid coding for wild-type (WT) PDI or PDI mutated in 4 thioredoxin-motif cysteine residues. Forced expression (2-fold) of mutated but not WT PDI led to increase in nitrite output after LS (18h) (Δmutated = 17.2±3.3 μM vs. ΔWT = 7.0±1.9 μM, n=3, p<0.02). Confocal microscopy indicated similar subcellular localization between WT and mutated PDI. PDI co-imunoprecipitated with p22phox NADPH oxidase subunit, but not with eNOS or caveolin-1, either in static condition or after LS. Fractionation studies in sucrose gradients showed that PDI is distributed throughout several fractions in static conditions, including caveolin-1-enriched fractions, but migrates to higher-density fractions, not containing caveolin-1, during sustained LS. These results suggest that PDI is involved in regulation of NO output during LS via its effects on NADPH oxidase activity.

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