Cellular Thiols Redox Status: a Switch for NF-κB Activation During Myocardial Post-ischaemic Reperfusion

Cargnoni, Anna; Ceconi, Claudio; Gaia, Giuseppina; Agnoletti, Laura; Ferrari, Roberto

doi:10.1006/jmcc.2002.2046

Cited by 29 publications

(19 citation statements)

References 27 publications

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“…The system becomes overwhelmed (redox imbalance), leading to the activation of multiple stress-sensitive signaling pathways (nuclear factor-B, p38 mitogen-activated protein kinase, c-Jun terminal kinase/ stress-activated protein kinase, protein kinase C, advanced glycation end products/receptor for advanced glycation end products, sorbitol, and others). 190,191 In vitro studies have demonstrated that exposure of adipocytes to oxidants reduces the effect of insulin on glucose transporters; this supports the hypothesis that oxidative stress induces insulin resistance at the cellular level. 192 Furthermore, in a circular effect, glucose excess resulting from insulin resistance induces oxidative stress within the cell.…”

Section: Mitochondrial Dysfunction and Oxidative Stresssupporting

confidence: 54%

Nontraditional Risk Factors and Biomarkers for Cardiovascular Disease: Mechanistic, Research, and Clinical Considerations for Youth

Balagopal¹,

Ferranti²,

Cook³

et al. 2011

Circulation

294

239

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Abstract-The rapid increase in the prevalence and severity of obesity in children is likely to lower the age of onset and increase the incidence of cardiovascular disease worldwide. Understanding the pathophysiology and improving the clinical management of cardiovascular disease involve a knowledge of novel risk factors and biomarkers. The clinical and mechanistic roles of these novel biological factors during childhood are currently being investigated. The goals of this scientific statement are to present the existing knowledge and theoretical framework of nontraditional risk factors for cardiovascular disease as they relate to children and adolescents, to describe the relevance and weight of available experimental and clinical evidence and the therapeutic implications pertaining to nontraditional risk factors in the pediatric population, and to stimulate further research with a goal of developing valid and reliable approaches to identify and validate novel risk factors that will aid in the clinical evaluation and perhaps prediction of cardiovascular disease in the pediatric population. Although several biomarkers are promising, substantial research is required before nontraditional risk factors can be used to identify and reduce cardiovascular disease risk in children and adolescents. (Circulation. 2011;123:2749-2769.)

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Section: Mitochondrial Dysfunction and Oxidative Stresssupporting

confidence: 54%

Nontraditional Risk Factors and Biomarkers for Cardiovascular Disease: Mechanistic, Research, and Clinical Considerations for Youth

Balagopal¹,

Ferranti²,

Cook³

et al. 2011

Circulation

294

239

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“…Our results also suggest that p65 is a more sensitive target than IB␣ in regulation of NF-B activity by the mild oxidant TauCl. This is not surprising considering that reduction-oxidation of thiols modulates DNA binding activity of NF-B and subsequent NF-B transcriptional activity (Cargnoni et al, 2002;Nishi et al, 2002). We provide evidence of involvement of thiol modification (most likely oxidation) in TauCl-mediated NF-B inhibition.…”

Section: Nf-b Inhibition By 5-aminosalicyltaurinesupporting

confidence: 54%

A Molecular Mechanism for the Anti-Inflammatory Effect of Taurine-Conjugated 5-Aminosalicylic Acid in Inflamed Colon

Kim¹,

Jeon²,

Kong³

et al. 2006

Mol Pharmacol

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In previous reports, a novel colon-specific prodrug, 5-aminosalicyltaurine (5-ASA-Tau) administered orally, is successfully delivered to and liberates 5-aminosalicylic acid (5-ASA) and taurine in the inflamed large intestine of rats. Furthermore, the prodrug ameliorates the 2,4,6-trinitrobenzene-sulfonic acid-induced colitis, and taurine acts not only as a carrier but also as an active therapeutic agent. In this study, we investigated the anti-inflammatory properties of the prodrug at a molecular level. After rectal administration of taurine, formation of taurine chloramine (TauCl) in the inflamed colonic tissue was examined using high-performance liquid chromatography. In human colon epithelial cell lines, nuclear factor-B (NF-B) activity was accessed using an NF-B-dependent luciferase reporter gene. Protein levels were monitored by Western blotting. DNA binding activity of the NF-B subunit p65 was determined using a DNA binding assay kit. A millimolar level of TauCl was formed in the inflamed tissue. TauCl inhibited tumor necrosis factor (TNF)-dependent NF-B activation by modifying thiol(s) on p65 and blocking DNA binding. In addition, 5-ASA inhibited phosphorylation of p65 at serine 536, which is critical for transcriptional activity of NF-B. Furthermore, combined TauCl/5-ASA treatment additively inhibited TNF-dependent NF-B activation. Together, our data suggest that the colon-specific carrier taurine contributes to the clinical effect of the prodrug by potentiating the inhibitory effect of the active ingredient 5-ASA on a major proinflammatory signal, TNF-dependent NF-B activation in the inflamed large intestine.

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“…Cardiac cells maintain a strongly reduced state via production and enzymatic regulation of glutathione, NADPH, and thioredoxin (31). Although transient changes in redox state play a physiological role in cell signaling (32), shifts toward a persistent oxidative state are associated with injury and aging (33,34). Glutathione is the primary intracellular redox buffer.…”

Section: Discussionmentioning

confidence: 99%

Atrial Glutathione Content, Calcium Current, and Contractility

Carnes

Janssen

Ruehr

et al. 2007

Journal of Biological Chemistry

105

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Atrial fibrillation (AF) is characterized by decreased L-type calcium current (I Ca,L ) in atrial myocytes and decreased atrial contractility. Oxidant stress and redox modulation of calcium channels are implicated in these pathologic changes. We evaluated the relationship between glutathione content (the primary cellular reducing moiety) and I Ca,L in atrial specimens from AF patients undergoing cardiac surgery. Left atrial glutathione content was significantly lower in patients with either paroxysmal or persistent AF relative to control patients with no history of AF. Incubation of atrial myocytes from AF patients (but not controls) with the glutathione precursor N-acetylcysteine caused a marked increase in I Ca,L . To test the hypothesis that glutathione levels were mechanistically linked with the reduction in I Ca,L , dogs were treated for 48 h with buthionine sulfoximine, an inhibitor of glutathione synthesis. Buthionine sulfoximine treatment resulted in a 24% reduction in canine atrial glutathione content, a reduction in atrial contractility, and an attenuation of I Ca,L in the canine atrial myocytes. Incubation of these myocytes with exogenous glutathione also restored I Ca,L to normal or greater than normal levels. To probe the mechanism linking decreased glutathione levels to down-regulation of I Ca , the biotin switch technique was used to evaluate S-nitrosylation of calcium channels. S-Nitrosylation was apparent in left atrial tissues from AF patients; the extent of S-nitrosylation was inversely related to tissue glutathione content. S-Nitrosylation was also detectable in HEK cells expressing recombinant human cardiac calcium channel subunits following exposure to nitrosoglutathione. S-Nitrosylation may contribute to the glutathione-sensitive attenuation of I Ca,L observed in AF. Atrial fibrillation (AF)2 is characterized by rapid electrical activation of the atria. Persistent AF results in phenotypic electrical and structural remodeling of the atria. Calcium influx via I Ca triggers calcium release from intracellular stores and is an essential first step in excitation-contraction coupling and a critical determinant of atrial contractility. In atrial myocytes from patients with persistent AF (1) or from animals with pacinginduced AF (2), calcium current density is significantly decreased. The time course of contractile impairment following the onset of AF (3) or rapid atrial pacing (4) parallels the down-regulation of I Ca , and contractile recovery proceeding cardioversion follows a time course similar to that of reverse electrical remodeling (4). Reports characterizing the impact of AF on the expression of the calcium channel pore subunit in human AF and in experimental models have had conflicting results (5, 6); the mechanisms by which I Ca,L down-regulation occurs are not fully resolved.In a porcine model of rapid atrial pacing, superoxide production is increased (7), and nitric oxide production is decreased (8). Oxidant-generating pathways can shift the myocyte intracellular redox environment from...

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Cellular Thiols Redox Status: a Switch for NF-κB Activation During Myocardial Post-ischaemic Reperfusion

Cited by 29 publications

References 27 publications

Nontraditional Risk Factors and Biomarkers for Cardiovascular Disease: Mechanistic, Research, and Clinical Considerations for Youth

Nontraditional Risk Factors and Biomarkers for Cardiovascular Disease: Mechanistic, Research, and Clinical Considerations for Youth

A Molecular Mechanism for the Anti-Inflammatory Effect of Taurine-Conjugated 5-Aminosalicylic Acid in Inflamed Colon

Atrial Glutathione Content, Calcium Current, and Contractility

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