scholarly journals Thyroid Hormone-Induced Cytosol-to-Nuclear Translocation of Rat Liver Nrf2 Is Dependent on Kupffer Cell Functioning

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Luis A. Videla ◽  
Pamela Cornejo ◽  
Pamela Romanque ◽  
Catherine Santibáñez ◽  
Iván Castillo ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Kupffer Cell ◽  
Respiratory Burst ◽  
Oxidase Inhibitor ◽  
Burst Activity ◽  
Oxygen Species ◽  
Respiratory Burst Activity ◽  
Nadph Oxidase Inhibitor ◽  
Nrf2 Activation

L-3,3′,5-triiodothyronine (T3) administration upregulates nuclear factor-E2-related factor 2 (Nrf2) in rat liver, which is redox-sensitive transcription factor mediating cytoprotection. In this work, we studied the role of Kupffer cell respiratory burst activity, a process related to reactive oxygen species generation and liver homeostasis, in Nrf2 activation using the macrophage inactivator gadolinium chloride (GdCl3; 10 mg/kg i.v. 72 h before T3[0.1 mg/kg i.p.]) or NADPH oxidase inhibitor apocynin (1.5 mmol/L added to the drinking water for 7 days before T3), and determinations were performed 2 h after T3. T3increased nuclear/cytosolic Nrf2 content ratio and levels of heme oxygenase 1 (HO-1), catalytic subunit of glutamate cysteine ligase, and thioredoxin (Western blot) over control values, proteins whose gene transcription is induced by Nrf2. These changes were suppressed by GdCl3treatment prior to T3, an agent-eliciting Kupffer-cell depletion, inhibition of colloidal carbon phagocytosis, and the associated respiratory burst activity, with enhancement in nuclear inhibitor of Nrf2 kelch-like ECH-associated protein 1 (Keap1)/Nrf2 content ratios suggesting Nrf2 degradation. Under these conditions, T3-induced tumor necrosis factor-α(TNF-α) response was eliminated by previous GdCl3administration. Similar to GdCl3, apocynin given before T3significantly reduced liver Nrf2 activation and HO-1 expression, a NADPH oxidase inhibitor eliciting abolishment of colloidal carbon-induced respiratory burst activity without altering carbon phagocytosis. It is concluded that Kupffer cell functioning is essential for upregulation of liver Nrf2-signaling pathway by T3. This contention is supported by suppression of the respiratory burst activity of Kupffer cells and the associated reactive oxygen species production by GdCl3or apocynin given prior to T3, thus hindering Nrf2 activation.

Reduction in Impulse Noise-Induced Permanent Threshold Shift with Intracochlear Application of an NADPH Oxidase Inhibitor

2013 ◽  
Vol 24 (06) ◽  
pp. 461-473 ◽  
Author(s):  
Eric C. Bielefeld
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Impulse Noise ◽  
Noise Exposure ◽  
Oxidase Inhibitor ◽  
Threshold Shift ◽  
Distilled Water ◽  
Oxygen Species ◽  
Nadph Oxidase Inhibitor ◽  
Continuous Noise

Background: Toxic levels of reactive oxygen species are key contributors to the lesion of dead outer hair cells (OHCs) seen in the cochlea after noise exposure. The current study follows previous work in which paraquat was used to demonstrate that NADPH oxidase is active in the cochlea and can contribute to cochlear reactive oxygen species formation and hair cell loss. Purpose: The current study was undertaken to test whether pharmacological blockade of NADPH oxidase in the cochlea would lead to reduced noise-induced hearing loss and OHC death. Study Sample: A total of 18 chinchillas (36 ears) were assessed in the study. Intervention: AEBSF (4-[2-aminoethyl]benzenesulfonyl fluoride), an inhibitor of NADPH oxidase activation, was dissolved in distilled water and delivered into the cochlea via diffusion across the round window membrane. The contralateral ears received distilled water as a vehicle control. Following treatment, chinchillas were exposed to one of two noises: a 4 kHz octave band noise at 106 dB SPL for 6 hr or an impulse noise that consisted of 75 pairs of 155 dB pSPL impulses. Data Collection and Analysis: Pre– and post–noise exposure, thresholds of the auditory brainstem response at 2–8 kHz were measured. Postmortem OHC counts were conducted at the conclusion of the study. Two- and three-factor ANOVAs were used for statistical analysis of the OHC losses and ABR threshold shifts induced by the noise exposures. Results: Permanent threshold shift from the impulse noise was reduced in the ears treated with the NADPH oxidase inhibitor, but no differences were found in the groups exposed to the continuous noise. OHC losses were not statistically different between the treated and untreated ears for either noise exposure. Conclusions: The results suggest that NADPH oxidase-mediated superoxide has a role in cochlear damage from impulse noise, and pharmacologic inhibition of NADPH oxidase can reduce cochlear susceptibility to noise damage. The lack of protection from the longer-duration continuous noise can be attributed to a number of possibilities related to dose level and delivery schedule.

scholarly journals The respiratory explosion activity of neutrophils in blood from patients with Graves' disease manifestation

2017 ◽  
Vol 63 (1) ◽  
pp. 4-8
Author(s):  
Sergey A. Dogadin ◽  
Margarita A. Dudina ◽  
Andrey A. Savchenko ◽  
Vladimir A. Mankovskiy ◽  
Ivan I. Gvozdev
Keyword(s):  
Reactive Oxygen Species ◽  
Respiratory Burst ◽  
Area Under The Curve ◽  
Reactive Oxygen ◽  
Maximum Level ◽  
Burst Activity ◽  
Graves Disease ◽  
Oxygen Species ◽  
Respiratory Burst Activity ◽  
Disease Manifestation

  Objective. To study respiratory burst activity in neutrophilic granulocytes in the onset of Graves’ disease (GD). Material and methods. Twenty-six females aged 18—55 years (mean age, 40.7±13.2 years), with the diagnosis of Graves’ disease verified for the first time, were enrolled in this study. Spontaneous and zymosan-induced chemiluminescence (CL) was assessed using a CL3606 36-channel analyzer for 90 min. The following parameters of the chemiluminescence curve were determined: time to attain the maximum (Tmax), the maximum intensity (Imax), and the area under the curve (S). Results. Patients with GD and lucigenin-dependent CL of neutrophils exhibited decreased zymosan-induced CL and the increased Imax of luminol-dependent spontaneous and zymosan-induced CL of neutrophils. Association between the anti-TPO level in blood serum with Tmax (r=–0,70; р=0.036) and Imax of luminol-dependent induced CL (r=–0.72; р=0.030) was found. The maximum level of synthesis of secondary reactive oxygen species (ROS) was found to be elevated in patients with GP both at relative rest and upon antigen-induced respiratory burst. Conclusion. In patients with GD, respiratory burst activity in neutrophils increases due to synthesis of secondary reactive oxygen species. Upon the onset of GD, already at the stage of subclinical thyrotoxicosis, the association between the indices of respiratory burst in neutrophils and thyroid hormones is lost but there emerges a relationship between the CL response and anti-TPO concentration.

scholarly journals Vascular Lipotoxicity: Endothelial Dysfunction via Fatty-Acid-Induced Reactive Oxygen Species Overproduction in Obese Zucker Diabetic Fatty Rats

Endocrinology ◽  
2007 ◽  
Vol 148 (1) ◽  
pp. 160-165 ◽  
Author(s):  
Ichiro Chinen ◽  
Michio Shimabukuro ◽  
Ken Yamakawa ◽  
Namio Higa ◽  
Toshihiro Matsuzaki ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Reactive Oxygen ◽  
Oxidase Inhibitor ◽  
Ros Production ◽  
Oxygen Species ◽  
Oxidase Subunit ◽  
Nadph Oxidase Inhibitor ◽  
Zdf Rats

Vascular endothelial dysfunction has been demonstrated in obesity, but the molecular basis for this link has not been clarified. We examined the role of free fatty acids (FFA) on vascular reactivity in the obese fa/fa Zucker diabetic fatty (ZDF) rat. Addition of acetylcholine produced a dose-dependent relaxation in aortic rings of ZDF and lean +/+ rats, but the ED50 value was higher in ZDF (−6.80 ± 0.05 vs. −7.11 ± 0.05 log10 mol/liter, P = 0.033). A 2-wk treatment with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, pitavastatin (3 mg/kg/d) or a reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin (5 mmol/liter in drinking water), improved the response in ZDF (ED50, −7.16 ± 0.03 and −7.14 ± 0.05 log10 mol/liter, P = 0.008 and P = 0.015 vs. vehicle, respectively). Vasodilator response to sodium nitroprusside was identical between ZDF and +/+ rats. Vascular reactive oxygen species (ROS) levels and NADPH oxidase activity in aorta were increased in ZDF rats but were decreased by pitavastatin. In in vitro cell culture, intracellular ROS signal and NADPH oxidase subunit mRNA were increased by palmitate, but this palmitate-induced ROS production was inhibited by NADPH oxidase inhibitor or pitavastatin. In conclusion, FFA-induced NADPH oxidase subunit overexpression and ROS production could be involved in the endothelial dysfunction seen in obese ZDF rats, and this could be protected by pitavastatin or NADPH oxidase inhibitors.

Abstract 38: Reactive Oxygen Species Contribute To Aneurysmal Rupture in Mice

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Kenji Shimada ◽  
Yoshiteru Tada ◽  
Kosuke Wada ◽  
Mari Kudo ◽  
Shoko Murakami ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Xanthine Oxidase ◽  
Intracranial Aneurysms ◽  
Oxidase Inhibitor ◽  
Oxygen Species ◽  
Gelatinase Activity ◽  
Xanthine Oxidase Inhibitor ◽  
Aneurysmal Rupture ◽  
Nadph Oxidase Inhibitor ◽  
Superoxide Scavenger

Background and Purpose: Inflammation and apoptosis are recognized as key factors for aneurysmal rupture. Reactive oxygen species (ROS) mediates both inflammation and apoptosis in vascular walls. Therefore, we hypothesized that ROS produced by xanthine oxidase and NADPH oxidase contributes to aneurysmal rupture. Recently we have demonstrated the feasibility of using a mouse model of intracranial aneurysms to test pharmacological therapies for the prevention of aneurysmal rupture. We tested the hypothesis by using this newly established mouse model. Methods: Intracranial aneurysms were induced in male mice using a combination of a single injection of elastase into the cerebrospinal fluid and the deoxycorticosterone acetate (DOCA) salt hypertension. Six days after aneurysm induction, we started 2-week treatment with vehicle (n=27), a superoxide scavenger (tempol; n=13), a xanthine oxidase inhibitor (oxypurinol; n=15), and a NADPH oxidase inhibitor (apocynin; n=16). Aneurysmal rupture was detected by neurological symptoms and confirmed by the presence of intracranial aneurysms with subarachnoid hemorrhage. Dihydroethidium staining and in situ zymography were performed to detect superoxide production and gelatinase activity, respectively. Results: A superoxide scavenger (tempol) significantly reduced rupture rate (vehicle vs. tempol: 74% vs. 27%, P < 0.05) (Figure1). It reduced superoxide production and gelatinase activity in aneurysmal walls (Figure2). Furthermore, the xanthine oxidase inhibitor (oxypurinol), and the NADPH oxidase inhibitor (apocynin) reduced the rupture rate (vehicle vs. oxypurinol: 74% vs. 30%, P< 0.05, vehicle vs. apocynin: 74% vs. 33%, P < 0.05). Conclusion: Our results indicate that superoxide produced by xanthine oxidase and NADPH oxidase contributes to aneurysmal rupture, by activating matrix metalloproteinases.

Coronary endothelial dysfunction after cardiomyocyte-specific mineralocorticoid receptor overexpression

2011 ◽  
Vol 300 (6) ◽  
pp. H2035-H2043 ◽  
Author(s):  
Julie Favre ◽  
Ji Gao ◽  
An Di Zhang ◽  
Isabelle Remy-Jouet ◽  
Antoine Ouvrard-Pascaud ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Coronary Arteries ◽  
Mineralocorticoid Receptor ◽  
Vascular Dysfunction ◽  
Reactive Oxygen ◽  
Oxidase Inhibitor ◽  
Oxygen Species ◽  
Coronary Endothelial Dysfunction

The deleterious effects of aldosterone excess demonstrated in cardiovascular diseases might be linked in part to coronary vascular dysfunction. However, whether such vascular dysfunction is a cause or a consequence of the changes occurring in the cardiomyocytes is unclear. Moreover, the possible link between mineralocorticoid receptor (MR)-mediated effects on the cardiomyocyte and the coronary arteries is unknown. Thus we used a mouse model with conditional, cardiomyocyte-specific overexpression of human MR (hMR) and observed the effects on endothelial function in isolated coronary segments. hMR overexpression decreased the nitric oxide (NO)-mediated relaxing responses to acetylcholine in coronary arteries (but not in peripheral arteries), and this was prevented by a 1-mo treatment either with an MR antagonist, vitamin E/vitamin C, or a NADPH oxidase inhibitor. hMR overexpression did not affect coronary endothelial NO synthase content nor its level of phosphorylation on serine 1177, but increased cardiac levels of reactive oxygen species, cardiac NADPH oxidase (NOX) activity, and expression of the NOX subunit gp91phox, which was limited to endothelial cells. Thus an increase in hMR activation, restricted to cardiomyocytes, is sufficient to induce a severe coronary endothelial dysfunction. We suggest a new paracrine mechanism by which cardiomyocytes trigger a NOX-dependent, reactive oxygen species-mediated coronary endothelial dysfunction.

Involvement of Reactive Oxygen Species in the Induction of (S)-N-p-Coumaroyloctopamine Accumulation by β-1,3-Glucooligosaccharide Elicitors in Potato Tuber Tissues

2001 ◽  
Vol 56 (3-4) ◽  
pp. 228-234 ◽  
Author(s):  
Fumio Matsuda ◽  
Hisashi Miyagawa ◽  
Tamio Ueno
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Potato Tuber ◽  
Serine Protease ◽  
Reactive Oxygen ◽  
Oxidase Inhibitor ◽  
Oxygen Species ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor

Abstract Treatment of potato tuber tissues with β-1,3-glucooligosaccharide induces accumulation of (S)-N-p-coumaroyloctopamine (p-CO). We examined the role of reactive oxygen species (ROS) and nitric oxide (NO) in the signal transduction leading to p-CO accumulation. Induction was suppressed by an NADPH -oxidase inhibitor, diphenyleneiodonium chloride, and oxygen radical scavengers. H2O2 was generated in the tuber tissue within a few minutes of treatment with β-1,3-glucooligosaccharide. On the other hand, treatment with NO specific scavenger, nitric oxide synthase inhibitor, and serine protease inhibitor did not inhibit p -CO induction. Our findings suggest that ROS generated by the action o f NADPH -oxidase play an important role in this system, while NO and serine protease are unlikely to be involved in this process.

scholarly journals NADPH oxidase-derived reactive oxygen species in skeletal muscle modulates the exercise pressor reflex

2009 ◽  
Vol 107 (2) ◽  
pp. 450-459 ◽  
Author(s):  
Han-Jun Wang ◽  
Yan-Xia Pan ◽  
Wei-Zhong Wang ◽  
Irving H. Zucker ◽  
Wei Wang
Keyword(s):  
Blood Pressure ◽  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Pressor Response ◽  
Oxidase Inhibitor ◽  
Oxygen Species ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex ◽  
Stimulation Of

Muscle metabolic by-products during exercise, such as K+, lactic acid, ATP, H+, and phosphate, are well established to be involved in the reflex cardiovascular response to static muscle contraction. However, the role of muscle reactive oxygen species (ROS), a metabolic by-product during muscle contraction, in the exercise pressor reflex (EPR) has not been investigated in detail. In the present study, we evaluated the role of muscle ROS in the EPR in a decerebrate rat model. We hypothesized that muscle NADPH oxidase-derived ROS contributes to sensitization of the EPR. Thus the rise in blood pressure and heart rate in response to a 30-s static contraction induced by electrical stimulation of L4/L5 ventral roots was compared before and after hindlimb arterial infusion of the redox agents: diethyldithiocarbamate, a superoxide dismutase inhibitor; the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidine 1-oxyl (tempol); the free radical scavenger dimethylthiourea; a NADPH oxidase inhibitor, apocynin; and a xanthine oxidase inhibitor, allopurinol. The EPR-induced pressor response was augmented after treatment with diethyldithiocarbamate and was attenuated after treatment with tempol, dimethylthiourea, and apocynin. Treatment with allopurinol did not affect the EPR function. None of the drug's affected the EPR heart rate response. In addition, neither the pressor response to electrical stimulation of the central end of dorsal roots, nor femoral blood flow was affected by any treatment. These data suggest that NADPH oxidase-derived muscle ROS plays an excitatory role in the EPR control of blood pressure.

scholarly journals Voltage-Gated Proton Channels Find Their Dream Job Managing the Respiratory Burst in Phagocytes

Physiology ◽  
2010 ◽  
Vol 25 (1) ◽  
pp. 27-40 ◽  
Author(s):  
Thomas E. DeCoursey
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Respiratory Burst ◽  
Proton Channel ◽  
Oxygen Species ◽  
Proton Extrusion ◽  
Proton Channels ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
Voltage Sensing Domain

The voltage-gated proton channel bears surprising resemblance to the voltage-sensing domain (S1–S4) of other voltage-gated ion channels but is a dimer with two conduction pathways. The proton channel seems designed for efficient proton extrusion from cells. In phagocytes, it facilitates the production of reactive oxygen species by NADPH oxidase.

D5 dopamine receptor regulation of reactive oxygen species production, NADPH oxidase, and blood pressure

2006 ◽  
Vol 290 (1) ◽  
pp. R96-R104 ◽  
Author(s):  
Zhiwei Yang ◽  
Laureano D. Asico ◽  
Peiying Yu ◽  
Zheng Wang ◽  
John E. Jones ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Reactive Oxygen ◽  
Receptor Activation ◽  
Oxidase Inhibitor ◽  
Ros Production ◽  
Oxygen Species ◽  
Nadph Oxidase Activity

Activation of D1-like receptors (D1 and/or D5) induces antioxidant responses; however, the mechanism(s) involved in their antioxidant actions are not known. We hypothesized that stimulation of the D5 receptor inhibits NADPH oxidase activity, and thus the production of reactive oxygen species (ROS). We investigated this issue in D5 receptor-deficient (D5−/−) and wild-type (D5+/+) mice. NADPH oxidase protein expression (gp91phox, p47phox, and Nox 4) and activity in kidney and brain, as well as plasma thiobarbituric acid-reactive substances (TBARS) were higher in D5−/− than in D5+/+ mice. Furthermore, apocynin, an NADPH oxidase inhibitor, normalized blood pressure, renal NADPH oxidase activity, and plasma TBARS in D5−/− mice. In HEK-293 cells that heterologously expressed human D5 receptor, its agonist fenoldopam decreased NADPH oxidase activity, expression of one of its subunits (gp91phox), and ROS production. The inhibitory effect of the D5 receptor activation on NADPH oxidase activity was independent of cAMP/PKA but was partially dependent on phospholipase D2. The ability of D5 receptor stimulation to decrease ROS production may explain, in part, the antihypertensive action of D5 receptor activation.

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