scholarly journals Advanced Oxidation Protein Products Promote Inflammation in Diabetic Kidney through Activation of Renal Nicotinamide Adenine Dinucleotide Phosphate Oxidase

Endocrinology ◽  
2008 ◽  
Vol 149 (4) ◽  
pp. 1829-1839 ◽  
Author(s):  
Xiao Yun Shi ◽  
Fan Fan Hou ◽  
Hong Xin Niu ◽  
Guo Bao Wang ◽  
Di Xie ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Advanced Oxidation ◽  
Diabetic Rats ◽  
Nicotinamide Adenine ◽  
Control Group ◽  
Advanced Oxidation Protein Products ◽  
Renal Inflammation ◽  
Diabetic Kidney

The involvement of inflammatory processes has been recognized in development and/or progression of diabetic nephropathy. However, the mechanisms involved in the pathogenesis of renal inflammation have not been completely understood. In this study, we tested the hypothesis that accumulation of advanced oxidation protein products (AOPPs), which occurs in diabetes, may promote inflammatory responses in diabetic kidney. Streptozotocin-induced diabetic rats were randomized to iv injection of vehicle, native rat serum albumin (RSA), and AOPPs-modified RSA (AOPPs-RSA) in the presence or absence of oral administration of apocynin. A control group was followed concurrently. Compared with RSA- or vehicle-treated diabetic rats, AOPPs-RSA-treated animals displayed significant increase in renal macrophage infiltration and overexpression of monocyte chemoattractant protein-1 and TGF-β1. This was associated with deteriorated structural and functional abnormalities of diabetic kidney, such as glomerular hypertrophy, fibronectin accumulation, and albuminuria. AOPP challenge significantly increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent superoxide generation in renal homogenates and up-regulated membrane expression of renal NADPH oxidase subunits p47phox and gp91phox. All these AOPPs-induced perturbations in diabetic kidney could be prevented by the NADPH oxidase inhibitor apocynin. These data suggest that chronic accumulation of AOPPs may promote renal inflammation in diabetes probably through activation of renal NADPH oxidase.

NADPH oxidase promotes NF-κB activation and proliferation in human airway smooth muscle

2002 ◽  
Vol 282 (4) ◽  
pp. L782-L795 ◽  
Author(s):  
Sukhdev S. Brar ◽  
Thomas P. Kennedy ◽  
Anne B. Sturrock ◽  
Thomas P. Huecksteadt ◽  
Mark T. Quinn ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Nadph Oxidase ◽  
Airway Smooth Muscle ◽  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Nuclear Factor Κb ◽  
Nicotinamide Adenine ◽  
Phagocytic Cells ◽  
Diphenylene Iodonium ◽  
Reduced Nicotinamide Adenine Dinucleotide

Evidence is rapidly accumulating that low-activity-reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases homologous to that in phagocytic cells generate reactive oxygen species as signaling intermediates in both endothelium and vascular smooth muscle. We therefore explored the possibility of such an oxidase regulating growth of airway smooth muscle (AWSM). Proliferation of human AWSM cells in culture was inhibited by the antioxidants catalase and N-acetylcysteine, and by the flavoprotein inhibitor diphenylene iodonium (DPI). Membranes prepared from human AWSM cells generated superoxide anion (O[Formula: see text]) measured by superoxide dismutase-inhibitable lucigenin chemiluminescence, with a distinct preference for NADPH instead of reduced nicotinamide adenine dinucleotide as substrate. Chemiluminescence was also inhibited by DPI, suggesting the presence of a flavoprotein containing oxidase generating O[Formula: see text] as a signaling molecule for cell growth. Examination of human AWSM cells by reverse transcriptase-polymerase chain reaction consistently demonstrated transcripts with sequences identical to those reported for p22phox. Transfection with p22phoxantisense oligonucleotides reduced human AWSM proliferation. Inhibition of NADPH oxidase activity with DPI prevented serum-induced activation of nuclear factor-κB (NF-κB), and overexpression of a superrepressor form of the NF-κB inhibitor IκBα significantly reduced human AWSM growth. These findings suggest that an NADPH oxidase containing p22phoxregulates growth-factor responsive human AWSM proliferation, and that the oxidase signals in part through activation of the prototypical redox-regulated transcription factor NF-κB.

Transient Association of the Nicotinamide Adenine Dinucleotide Phosphate Oxidase Subunits p47phox and p67phox With Phagosomes in Neutrophils From Patients With X-Linked Chronic Granulomatous Disease

Blood ◽  
1999 ◽  
Vol 93 (10) ◽  
pp. 3521-3530 ◽  
Author(s):  
Lee-Ann H. Allen ◽  
Frank R. DeLeo ◽  
Annabelle Gallois ◽  
Satoshi Toyoshima ◽  
Kensuke Suzuki ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Nicotinamide Adenine Dinucleotide ◽  
Polymorphonuclear Leukocytes ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Actin Binding ◽  
Nicotinamide Adenine ◽  
Cell Periphery ◽  
Granulomatous Disease ◽  
Flavocytochrome B

Optimal microbicidal activity of polymorphonuclear leukocytes (PMNs) requires recruitment of a functional nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to the phagosome. In this study, we used a synchronized phagocytosis assay and immunofluorescence microscopy (IFM) to examine the association of cytosolic NADPH oxidase subunits with phagosomes containing opsonized zymosan (OpZ). Ingestion of OpZ began within 30 seconds of particle binding and forming phagosomes were enriched for both F-actin and the actin-binding protein p57. NADPH oxidase subunits p47phox and p67phox were also recruited to forming phagosomes and were retained on mature phagosomes for at least 15 minutes. Colocalization of F-actin, p57, and p47phox on phagosomes was confirmed by immunoblotting. Translocation of p67phox, but not p57, to forming phagosomes was deficient in PMNs lacking p47phox. Surprisingly, we found that in PMNs from six individuals with X-linked chronic granulomatous disease (CGD), p47phox and p67phox accumulated in the periphagosomal area during ingestion of OpZ. However, in marked contrast to normal PMNs, p47phox and p67phox were shed from nascent phagosomes along with F-actin and p57 once OpZ was internalized (≈5 minutes). These data support a model in which flavocytochrome b is required for stable membrane binding of p47phox and p67phox, but not their association with the cytoskeleton or transport to the cell periphery.

Transient congenital hypothyroidism caused by compound heterozygous mutations affecting the NADPH-oxidase domain of DUOX2

2016 ◽  
Vol 29 (3) ◽  
Author(s):  
Atsuko Yoshizawa-Ogasawara ◽  
Kiyomi Abe ◽  
Sayaka Ogikubo ◽  
Satoshi Narumi ◽  
Tomonobu Hasegawa ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Congenital Hypothyroidism ◽  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Nicotinamide Adenine ◽  
Compound Heterozygous ◽  
Loss Of Function ◽  
Dual Oxidase ◽  
Compound Heterozygous Mutations ◽  
Transient Congenital Hypothyroidism

AbstractHere, we describe three cases of loss-of-function mutations in the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase (NOX) domain of dual oxidase 2 (

scholarly journals Metabolic changes in the lymphocytes during influenza

2012 ◽  
Vol 93 (4) ◽  
pp. 580-584
Author(s):  
I V Sergeeva ◽  
N I Kamzalakova ◽  
E P Tikhonova ◽  
G V Bulygin
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Tricarboxylic Acid Cycle ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Tricarboxylic Acid ◽  
Nicotinamide Adenine ◽  
Control Group ◽  
Healthy Individuals ◽  
Acid Cycle ◽  
Intracellular Enzymes ◽  
Glucose 6 Phosphate Dehydrogenase

Aim. To assess the nature and intensity of metabolic processes in lymphocytes of patients with influenza according to the activity of intracellular enzymes in comparison to the severity of the disease. Methods. Determined were the enzymatic parameters of lymphocytes of 45 patients aged 18 to 42 years with a diagnosis of «influenza». Two groups of patients were formed: with moderate (24 patients) and severe (21 patients) course of the disease. Used as controls were the values the activity of intracellular enzymes of lymphocytes of 37 practically healthy individuals of comparable age. Results. In patients with a moderately severe course of the influenza compared with the controls noted was a significant increase in activity of glucose-6-phosphate dehydrogenase (3.17±0.53 and 2.74±0.31 mkE/10 000 cells, p 0.05) and glycerol-3-phosphate dehydrogenase (57.33±±5.65 and 0.84±0.16 mkE/10 000 cells respectively, p 0.001). The activity of lactate dehydrogenase was lower in patients than in controls (0.40±0.08 and 0.84±0.08 mkE/10 000 cells respectively, p 0.001). Indicators of nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate dependant isocitrate dehydrogenases in lymphocytes of patients were lower than in the controls: the first indicator in the patients was 0.17±0.02 mkE/10 000 cells, in controls - 1.95±0.25 mkE/10 000 cells (p 0.001), and for the second indicator these values were respectively 0.09±0.01 and 31.02±±2.20 mkE/10 000 cells (p 0.001). In patients with a moderately severe course of influenza the activity of nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate dependant glutamate dehydrogenases was significantly higher compared with healthy individuals: 63.67±5.32 and 0.34±0.06 mkE/10 000 cells, 1.45±0.18 and 0.11±0.02 mkE/10 000 cells respectively (p 0.001). The activity of nicotinamide adenine dinucleotide dependant malate dehydrogenase in patients was equal to 86.46±12.30 mkE/10 000 cells (in the control group 84.16±13.70 mkE/10 000 cells), and the activity of nicotinamide adenine dinucleotide phosphate dependant malate dehydrogenase was equal to 1.34±±0.25 mkE/10 000 cells (in the control group 0.33±0.07 mkE/10 000 cells, p 0.001). The activity of glutathione reductase was also higher in patients with the moderately severe course of the influenza: 5.86±0.25 mkE/10 000 cells, while the value in healthy individuals was 1.28±0.30 mkE/10 000 cells (p 0.001). In the group of patients with a severe course of influenza the activity of almost all (except for glucose-6-phosphate dehydrogenase) enzymes was higher than during the moderately severe course of disease. Conclusion. At the peak of the diseases noted were opposite changes in the activity of reactions of the pentose phosphate cycle and glycolysis. With a high functional load on the cells there is a significant reduction in the intensity of the reactions of the initial phase of the tricarboxylic acid cycle, which reduces the energy efficiency of the cycle, while the intense influx of metabolites to supply the tricarboxylic acid cycle with substrates of the amino acid metabolism provides enhanced transport of amino acids into the lymphocytes.

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