scholarly journals Ca2+/Nicotinamide Adenine Dinucleotide Phosphate-Dependent H2O2 Generation Is Inhibited by Iodide in Human Thyroids

2001 ◽  
Vol 86 (9) ◽  
pp. 4339-4343 ◽  
Author(s):  
Luciene C. Cardoso ◽  
Denise C. L. Martins ◽  
Marcia D. L. Figueiredo ◽  
Doris Rosenthal ◽  
Mario Vaisman ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Thyroid Nodules ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Nadph Oxidase Activity ◽  
Thyroid Hormone Biosynthesis ◽  
H2o2 Generation ◽  
Toxic Goiter ◽  
Cold Thyroid Nodules

A calcium and NAD(P)H-dependent H2O2-generating activity has been studied in paranodular thyroid tissues from four patients with cold thyroid nodules and from nine diffuse toxic goiters. H2O2 generation was detected both in the particulate (P 3,000 g) and in the microsomal (P 100,000 g) fractions of paranodular tissue surrounding cold thyroid nodules (PN), with the same biochemical properties described for NADPH oxidase found in porcine and human thyroids. In PN tissues, the particulate NADPH oxidase activity (224 ± 38 nmol H2O2·h−1·mg−1 protein) was similar to that described for the porcine thyroid enzyme. However, no NADPH oxidase activity was detectable in the particulate fractions from eight diffuse toxic goiter patients treated with iodine before surgery; all but one also received propylthiouracil or methimazole in the preoperative period. Thyroid cytochrome c reductase (diffuse toxic goiters = 438 ± 104 nmol NADP+·h−1·mg−1 protein; PN = 78 ± 10 nmol NADP+·h−1·mg−1 protein) and thyroperoxidase (diffuse toxic goiters = 621 ± 179 U·g−1 protein; PN = 232 ± 121 U·g−1 protein) activities were unaffected by iodide. Thus, the human NADPH oxidase seems to be inhibited by iodinated compounds in vivo and probably is an enzyme involved in the Wolff-Chaikoff effect. Our findings reinforce the hypothesis that thyroid NADPH oxidase is responsible for the production of H2O2 necessary for thyroid hormone biosynthesis.

scholarly journals Effect of renin inhibition and AT1R blockade on myocardial remodeling in the transgenic Ren2 rat

2008 ◽  
Vol 295 (1) ◽  
pp. E103-E109 ◽  
Author(s):  
Adam Whaley-Connell ◽  
Javad Habibi ◽  
Shawna A. Cooper ◽  
Vincent G. DeMarco ◽  
Melvin R. Hayden ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Myocardial Remodeling ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Nadph Oxidase Activity ◽  
Renin Inhibition

Angiotensin II (Ang II) stimulation of the Ang type 1 receptor (AT1R) facilitates myocardial remodeling through NADPH oxidase-mediated generation of oxidative stress. Components of the renin-angiotensin system constitute an autocrine/paracrine unit in the myocardium, including renin, which is the rate-limiting step in the generation of Ang II. This investigation sought to determine whether cardiac oxidative stress and cellular remodeling could be attenuated by in vivo renin inhibition and/or AT1R blockade in a rodent model of chronically elevated tissue Ang II levels, the transgenic (mRen2)27 rat (Ren2). The Ren2 overexpresses the mouse renin transgene with resultant hypertension, insulin resistance, and cardiovascular damage. Young (6- to 7-wk-old) heterozygous (+/−) male Ren2 and age-matched Sprague-Dawley rats were treated with the renin inhibitor aliskiren, which has high preferential affinity for human and mouse renin, an AT1R blocker, irbesartan, or placebo for 3 wk. Myocardial NADPH oxidase activity and immunostaining for NADPH oxidase subunits and 3-nitrotyrosine were evaluated and remodeling changes assessed by light and transmission electron microscopy. Blood pressure, myocardial NADPH oxidase activity and subunit immunostaining, 3-nitrotyrosine, perivascular fibrosis, mitochondrial content, and markers of activity were significantly increased in Ren2 compared with SD littermates. Both renin inhibition and blockade of the AT1R significantly attenuated cardiac functional and structural alterations, although irbesartan treatment resulted in greater reductions of both blood pressure and markers of oxidative stress. Collectively, these data suggest that both reduce changes driven, in part, by Ang II-mediated increases in NADPH oxidase and, in part, increases in blood pressure.

scholarly journals The Post-Ischemic Increase in GluA2 Ser880 Phosphorylation Involves NADPH Oxidase

2018 ◽  
Vol 4 (1) ◽  
pp. 170-181
Author(s):  
Darrell A. Jackson ◽  
Fanny Astruc-Diaz ◽  
Nicole M. Byrnes ◽  
Phillip H. Beske
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Hippocampal Slices ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Glucose Deprivation ◽  
Subunit Composition ◽  
Stress Signaling ◽  
Scaffolding Proteins ◽  
Nadph Oxidase Activity

Most 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid receptors (AMPARs) expressed on adult hippocampal pyramidal neurons contain the edited form of GluA2 (Q607R) and are thus impermeable to Ca2+/Zn2+ entry.  Following ischemic injury, these receptors undergo a subunit composition change, switching from a GluA2-containing Ca2+/Zn2+-impermeable AMPAR to a GluA2-lacking Ca2+/Zn2+-permeable AMPAR. Recent studies indicate that an oxidative stress signaling pathway is responsible for the I/R-induced changes in AMPAR subunit composition.  Studies suggest that nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase), a superoxide generator, is the source that initiates the oxidative stress-signaling cascade during post-ischemic reperfusion. The objective of the present study was to determine if suppression of NADPH oxidase activity prevents the increase in phosphorylation and subsequent internalization of the GluA2 AMPAR subunit during reperfusion of post-ischemic hippocampal slices. In this study, we demonstrated that exposure of adult rat hippocampal slices to oxygen glucose deprivation/reperfusion (OGD/R) results in an increase in Ser880 phosphorylation of the GluA2 subunit.  The increase in Ser880 phosphorylation resulted in the dissociation of GluA2 from the scaffolding proteins Glutamate receptor-interacting protein 1 (GRIP1) and AMPAR binding protein (ABP), thus enabling the association of GluA2 with protein interacting with C kinase 1 (PICK1). OGD/R also resulted in an increase in the association of activated protein kinase C ? (PKC?) with PICK1. We have found that pharmacological inhibition of NADPH oxidase with apocynin diminishes the OGD/R-induced increase in activated PKC? association with PICK1 and subsequent Ser880 phosphorylation of GluA2. Suppression of NADPH oxidase activity also blunted OGD/R-induced decreased association of GluA2 with the scaffolding proteins GRIP1 and ABP.  Protein phosphatase 2A (PP2A), which regulates PKC? activity by dephosphorylating the kinase, was inactivated by OGD/R-induced increase in tyrosine phosphorylation of the phosphatase (Y307). Inhibition of NADPH oxidase activity ameliorated OGD/R-induced PP2A phosphorylation and inactivation. Our findings are consistent with a model of OGD/R-induced Ser880 phosphorylation of GluA2 that implicates NADPH oxidase mediated inactivation of PP2A and sustained PKC? phosphorylation of GluA2.

scholarly journals Alteration of the Gut Microbiota and Its Effect on AMPK/NADPH Oxidase Signaling Pathway in 2K1C Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Hui Yu ◽  
Lei Qin ◽  
Hai Hu ◽  
Zhanli Wang
Keyword(s):  
Gut Microbiota ◽  
Nadph Oxidase ◽  
Signaling Pathway ◽  
Oxidase Activity ◽  
High Throughput Sequencing ◽  
Plasma Concentrations ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Adenosine Monophosphate ◽  
Short Chain Fatty Acids ◽  
Nadph Oxidase Activity

Background. The purpose of this study was to evaluate the alteration of the gut microbiota and its effect on adenosine monophosphate-activated protein kinase (AMPK)/nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) signaling pathway in two-kidney one-clip (2K1C) rats. Methods. The 2K1C rat models were established. The rats were randomly divided into the following 2 groups: 2K1C group and sham group. Alterations of the gut microbiota were analyzed based on the high throughput sequencing method. Plasma concentrations of short chain fatty acids (SCFAs) were measured by chromatography. The protein expression of phosphorylated AMPK and acetyl-CoA carboxylase (ACC) was determined by western blotting. NADPH oxidase activity was measured by a luminometer. Results. Microbial community analyses revealed that the structure and composition of the gut microbiota were significantly disrupted in 2K1C rats when compared to sham rats. This disruption was associated with the drastic increase in relative abundance of the genera Prevotella and the decrease in SCFA-producing bacterial population. We further confirm that SCFAs produced by the gut microbiota influence NADPH oxidase activity through AMPK. Conclusions. Our data implicated the important role of gut microbiota in the regulation of AMPK/NADPH oxidase signaling pathway.

Potential sources of oxidative stress that induce postexercise proteinuria in rats

2008 ◽  
Vol 104 (4) ◽  
pp. 1063-1068 ◽  
Author(s):  
Günnur Koçer ◽  
Ümit Kemal Şentürk ◽  
Oktay Kuru ◽  
Filiz Gündüz
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Protein Carbonyl ◽  
Exhaustive Exercise ◽  
Carbonyl Content ◽  
Protein Carbonyl Content ◽  
Nadph Oxidase Activity ◽  
Exercise Induced

Exercise-induced proteinuria is a common consequence of physical activity and is caused predominantly by alterations in renal hemodynamics. Although it has been shown that exercise-induced oxidative stress can also contribute to the occurrence of postexercise proteinuria, the sources of reactive oxygen species that promote it are unknown. We investigated the enzymes nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and xanthine oxidase (XO) as possible sources of oxidative stress in postexercise proteinuria. First, we evaluated the effect of blocking the NADPH oxidase enzyme on postexercise proteinuria. We found a significant increase in urinary protein level, kidney thiobarbituric acid-reactive substances (TBARS), and protein carbonyl content after exhaustive exercise, and NADPH oxidase activity was induced by exercise. Rats that were treated with an NADPH oxidase inhibitor for 4 days before exhaustive exercise showed no increase in kidney TBARS or protein carbonyl derivative level and no proteinuria or NADPH oxidase activation. In the next set of experiments, we investigated the effect of XO blockage on postexercise proteinuria. Oxypurinol, an XO inhibitor was administered to rats for 3 days before exercise. Although XO inhibition significantly decreased kidney TBARS levels and protein carbonyl content in exercised rats, the inhibition did not prevent exercise-induced proteinuria. However, plasma and kidney XO activity was not induced by exercise, but rather it was suppressed under oxypurinol treatment. These results suggest that increased NADPH oxidase activity induced by exhaustive exercise is an important source of elevated oxidative, stress during exercise, which contributes to the occurrence of postexercise proteinuria.

scholarly journals Apocynin Attenuates Cerebral Infarction after Transient Focal Ischaemia in Rats

2007 ◽  
Vol 35 (4) ◽  
pp. 517-522 ◽  
Author(s):  
LL Tang ◽  
K Ye ◽  
XF Yang ◽  
JS Zheng
Keyword(s):  
Nadph Oxidase ◽  
Cerebral Infarction ◽  
Infarct Size ◽  
Oxidase Activity ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Treated Group ◽  
Oxidase Inhibitor ◽  
Sprague Dawley ◽  
Nadph Oxidase Activity ◽  
Focal Ischaemia

This study investigated whether inhibition of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase attenuates cerebral infarction after transient focal ischaemia in rats. Focal ischaemia (1.5 h) was produced in male Sprague-Dawley rats (250 − 280 g) by middle cerebral artery occlusion. Some rats also received treatment with 50 mg/kg apocynin, a NADPH oxidase inhibitor, by intraperitoneal injection 30 min prior to reperfusion. Two hours after reperfusion, brains were harvested to measure NADPH oxidase activity and superoxide levels. After 24 h, the remaining brains were harvested to investigate infarct size. NADPH oxidase activity and superoxide level were all augmented 2 h after reperfusion compared with controls. Apocynin treatment significantly reduced NADPH oxidase activity and superoxide levels. Cerebral infarct size was significantly smaller in the apocynin-treated group compared with those undergoing ischaemia/reperfusion alone. These results indicate that inhibition of NADPH oxidase attenuates cerebral infarction after transient focal ischaemia in rats, suggesting that inhibition of NADPH oxidase may provide a therapeutic strategy for ischaemic stroke.

scholarly journals Curcumin protects islet cells from glucolipotoxicity by inhibiting oxidative stress and NADPH oxidase activity both in vitro and in vivo

Islets ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 152-164 ◽  
Author(s):  
Jing Li ◽  
Ninghua Wu ◽  
Xiao Chen ◽  
Hongguang Chen ◽  
Xiaosong Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Islet Cells ◽  
Nadph Oxidase Activity

Abstract 1738: The I( f )-inhibitor Ivabradine Exerts Vascular Anti-oxidative And Anti-inflammatory Effects Selectively Mediated By Reduction Of Heart Rate

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Florian Custodis ◽  
Magnus Baumhaekel ◽  
Nils Schlimmer ◽  
Franka List ◽  
Christoph Gensch ◽  
...  
Keyword(s):  
Heart Rate ◽  
Nadph Oxidase ◽  
Atherosclerotic Plaque ◽  
Oxidase Activity ◽  
Ex Vivo ◽  
Epidemiological Studies ◽  
High Cholesterol Diet ◽  
Nadph Oxidase Activity ◽  
Group Iva

Objective: In epidemiological studies, elevated resting heart rate (HR) is associated with increased cardiovascular morbidity. We therefore characterized the effects of selective heart rate reduction by inhibition of the I (f) -current by ivabradine (IVA) in mice. Methods and Results: Male ApoE −/− mice fed a high-cholesterol diet were treated with IVA (10 mg/kg/d) or vehicle for 6 weeks (n = 10 per group). IVA reduced HR by 13.4% (472 ± 9 vs 545 ± 11 bpm, p < 0.01) but did not alter blood pressure or lipid levels. Endothelium dependent relaxation of aortic rings was significantly improved in IVA fed animals ( p < 0.01). IVA decreased atherosclerotic plaque size in the aortic root by > 40% and in the ascending aorta by > 70%, p < 0.05. HR reduction had no effect on the number of endothelial progenitor cells in the blood and the bone marrow and did not alter aortic eNOS, p-Akt, VCAM-1 or ICAM-1 expression, but decreased MCP-1 mRNA to 26 ± 7% (p < 0.05). IVA reduced vascular NADPH oxidase activity to 48 ± 6% and decreased L-012 chemiluminescence to 24 ± 9% (both p < 0.05). Lipidperoxidation was reduced to 65 ± 8% in the vasculature of the IVA group compared to vehicle treatment (p < 0.05). DHE fluorescence microscopy in aortic sections detected reduction of ROS release to 62 ± 4% in IVA treated mice (p < 0.01). The in vivo effects of IVA were absent at a dose that did not lower HR and were absent in aortic rings treated ex vivo . Protein expression of p-Akt, eNOS and p-eNOS was not altered in cultured endothelial cells (EC) by increasing doses of Iva. Similarly, NADPH oxidase activity in EC was not changed as well as the Ang II induced free radical release in vascular smooth muscle cells (DCF-fluorescence). Conclusions: Selective HR reduction improves endothelial function and reduces atherosclerotic plaque formation in ApoE −/− mice. Those effects are in part mediated by decreased markers of oxidative stress and downregulation of MCP-1. The control experiments show that a direct effect of IVA on vascular cells is unlikely and support the reduction of heart rate as the primary mechanism of action.

Sbds Deficient Neutrophils Exhibit Normal Numbers, Chemotaxis and Phagocytic Functions, but Impaired NADPH Oxidase Activity.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1634-1634
Author(s):  
Siyi Zhang ◽  
Chunxian Sun ◽  
Jian Zhong ◽  
Michael Glogauer ◽  
Johanna M. Rommens
Keyword(s):  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Ribosome Biogenesis ◽  
Pancreatic Insufficiency ◽  
Exocrine Pancreatic Insufficiency ◽  
Normal Numbers ◽  
Nadph Oxidase Activity ◽  
Conditional Allele ◽  
Conserved Gene

Abstract Shwachman-Diamond syndrome (SDS) is a recessive disease with multi-system involvement, and is characterized by hematological dysfunction, exocrine pancreatic insufficiency and skeletal abnormalities. Recurrent infections are a major cause of morbidity for SDS patients, due to neutropenia and proposed defects in neutrophil functions. SDS is caused by mutations in SBDS, a highly conserved gene that has been suggested to be involved in RNA metabolism and/or ribosome biogenesis. A conditional Cre-Lox Sbds allele was generated in the mouse using gene targeting technology, as complete ablation of Sbds has been shown to lead to early embryonic lethality. To investigate neutrophil functions and their specific sensitivity to loss of Sbds, we elected to delete the gene by breeding mice with the conditional allele to mice with Cre recombinase under the control of the lysozyme M promoter. While Sbds was confirmed to be ablated in mature neutrophils in adult offspring mice, their numbers and morphology were found to be normal in peripheral blood. Sbds-ablated neutrophils were also found to have normal chemotatic and chemokinetic abilities, and they demonstrated phagocytic function comparable to neutrophils of control mice. In contrast, NADPH oxidase activity was observed to be greatly reduced in response to phorbol-12-myristate 13-acetate stimulation, while the expression levels and phosphorylation of the NADPH oxidase complex components remained intact. To evaluate the net effect of the loss of Sbds in vivo, clearance of Pseudomonas aeruginosa from infected lungs was investigated, and found to be significantly reduced in mice with Sbds-abated neutrophils compared their wild type littermates. In summary, loss of Sbds does not to affect total peripheral neutrophil numbers directly, or chemotaxis and phagocytic abilities, but was essential for a robust NADPH oxidase response. These findings suggest that neutrophils are compromised with loss of Sbds, but that at least some of the neutrophil deficiencies of SDS patients are likely due to microenvironment deficiencies, or early hematopoiesis abnormalities.

scholarly journals Regulation of NADPH Oxidase-Mediated Superoxide Production by Acetylation and Deacetylation

2021 ◽  
Vol 12 ◽  
Author(s):  
Ning Xia ◽  
Stefan Tenzer ◽  
Oleg Lunov ◽  
Martin Karl ◽  
Thomas Simmet ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Trichostatin A ◽  
Oral Treatment ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Superoxide Production ◽  
Sirtuin 1 ◽  
Binding Potential ◽  
Free System ◽  
Nadph Oxidase Activity

Oral treatment of apolipoprotein E-knockout (ApoE-KO) mice with the putative sirtuin 1 (SIRT1) activator resveratrol led to a reduction of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in the heart. In contrast, the SIRT1 inhibitor EX527 enhanced the superoxide production in isolated human polymorphonuclear granulocytes. In human monocytic THP-1 cells, phorbol ester-stimulated superoxide production was enhanced by inhibitors of histone deacetylases (HDACs; including quisinostat, trichostatin A (TSA), PCI34051, and tubastatin A) and decreased by inhibitors of histone acetyltransferases [such as garcinol, curcumin, and histone acetyltransferase (HAT) Inhibitor II]. These results indicate that protein acetylation and deacetylation may represent crucial mechanisms regulating NADPH oxidase-mediated superoxide production. In cell-free systems, incubation of recombinant Rac1 with SIRT1 resulted in decreased Rac1 acetylation. Mass spectrometry analyses identified lysine 166 (K166) in Rac1 as a residue targeted by SIRT1. Deacetylation of Rac1 by SIRT1 markedly reduced the interaction of Rac1 with p67phox in in vitro assays. Computational modeling analyses revealed that K166 deacetylation of Rac1 led to a 5-fold reduction in its binding affinity to guanosine-5'-triphosphate, and a 21-fold decrease in its binding potential to p67phox. The latter is crucial for Rac1-mediated recruitment of p67phox to the membrane and for p67phox activation. In conclusion, both SIRT1 and non-sirtuin deacetylases play a role in regulating NADPH oxidase activity. Rac1 can be directly deacetylated by SIRT1 in a cell-free system, leading to an inhibition of Rac1-p67phox interaction. The downstream targets of non-sirtuin deacetylases are still unknown. The in vivo significance of these findings needs to be investigated in future studies.

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