The E-loop Is Involved in Hydrogen Peroxide Formation by the NADPH Oxidase Nox4

Takac, Ina; Schröder, Katrin; Zhang, Leilei; Lardy, Bernard; Anilkumar, Narayana; Lambeth, J. David; Shah, Ajay M.; Morel, Françoise; Brandes, Ralf P.

doi:10.1074/jbc.m110.192138

Cited by 469 publications

(410 citation statements)

References 34 publications

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“…Alternatively, Takac and his colleagues [43] have shown that disulfide bridges formed by two cysteines C226 and C270 may be involved in the maintenance of the extracellular E-loop integrity. Indeed, the disruption of the bridge by mutagenesis modified notably Nox4 ROS production [43].…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the disruption of the bridge by mutagenesis modified notably Nox4 ROS production [43]. Disulfide bridges with a standard redox potential (E 0 ) of À180 mV [47] could be reduced by NADPH, NADH and b-mercaptoethanol that possess a lower E 0 (À324, À320, and À253 mV, respectively) [48].…”

Section: Discussionmentioning

confidence: 99%

“…A recent study [43] showed that structural modifications of the E-loop, by deletion or exchange of cysteine, had an impact on the production rate and nature of ROS generated. The authors hypothesized that extracellular cysteines C226 and C270 might form a disulfide bridge that modulates Nox4 ROS production.…”

Section: Redox Regulation Of Nox4 Activitymentioning

confidence: 99%

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Quinone compounds regulate the level of ROS production by the NADPH oxidase Nox4

Nguyen

Lardy

Rousset

et al. 2013

Biochemical Pharmacology

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NADPH oxidase Nox4 is expressed in a wide range of tissues and plays a role in cellular signaling by providing reactive oxygen species (ROS) as intracellular messengers. Nox4 oxidase activity is thought to be constitutive and regulated at the transcriptional level; however, we challenge this point of view and suggest that specific quinone derivatives could modulate this activity. In fact, we demonstrated a significant stimulation of Nox4 activity by 4 quinone derivatives (AA-861, tBuBHQ, tBuBQ, and duroquinone) observed in 3 different cellular models, HEK293E, T-REx™, and chondrocyte cell lines. Our results indicate that the effect is specific toward Nox4 versus Nox2. Furthermore, we showed that NAD(P)H:quinone oxidoreductase (NQO1) may participate in this stimulation. Interestingly, Nox4 activity is also stimulated by reducing agents that possibly act by reducing the disulfide bridge (Cys226, Cys270) located in the extracellular E-loop of Nox4. Such model of Nox4 activity regulation could provide new insight into the understanding of the molecular mechanism of the electron transfer through the enzyme, i.e., its potential redox regulation, and could also define new therapeutic targets in diseases in which quinones and Nox4 are implicated

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Quinone compounds regulate the level of ROS production by the NADPH oxidase Nox4

Nguyen

Lardy

Rousset

et al. 2013

Biochemical Pharmacology

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“…H 2 O 2 has been suggested to be a redox signalling molecule93 that can interact with redox‐sensitive components or pathways, activating various transcription factors in skeletal muscle 94. In addition to SOD‐dependent production of H 2 O 2 , a number of enzyme systems also generate H 2 O 2 including NOX4,95, 96 urate and amino acid oxidases 97. Moreover, recent evidence supports endoplasmic reticulum (ER) H 2 O 2 generation in vivo 98 via thiol‐disulfide exchange mechanisms 99.…”

Section: Chemistry Of Reactive Oxygen and Nitrogen Species Produced Bmentioning

confidence: 99%

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Sakellariou

Lightfoot

Earl

et al. 2017

J cachexia sarcopenia muscle

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Skeletal muscle is a major site of metabolic activity and is the most abundant tissue in the human body. Age‐related muscle atrophy (sarcopenia) and weakness, characterized by progressive loss of lean muscle mass and function, is a major contributor to morbidity and has a profound effect on the quality of life of older people. With a continuously growing older population (estimated 2 billion of people aged >60 by 2050), demand for medical and social care due to functional deficits, associated with neuromuscular ageing, will inevitably increase. Despite the importance of this ‘epidemic’ problem, the primary biochemical and molecular mechanisms underlying age‐related deficits in neuromuscular integrity and function have not been fully determined. Skeletal muscle generates reactive oxygen and nitrogen species (RONS) from a variety of subcellular sources, and age‐associated oxidative damage has been suggested to be a major factor contributing to the initiation and progression of muscle atrophy inherent with ageing. RONS can modulate a variety of intracellular signal transduction processes, and disruption of these events over time due to altered redox control has been proposed as an underlying mechanism of ageing. The role of oxidants in ageing has been extensively examined in different model organisms that have undergone genetic manipulations with inconsistent findings. Transgenic and knockout rodent studies have provided insight into the function of RONS regulatory systems in neuromuscular ageing. This review summarizes almost 30 years of research in the field of redox homeostasis and muscle ageing, providing a detailed discussion of the experimental approaches that have been undertaken in murine models to examine the role of redox regulation in age‐related muscle atrophy and weakness.

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“…-and/or H 2 O 2 are generated by membrane located endothelial and vascular NAPDH oxidases [66], consecutively leading to HO . formation [67].…”

Section: No-mediated Vasorelaxant Potency and Antioxidant Properties mentioning

confidence: 99%

On the vasoprotective mechanisms underlying novel β-phosphorylated nitrones: Focus on free radical characterization, scavenging and NO-donation in a biological model of oxidative stress

Cassien

Petrocchi

Thétiot-Laurent

et al. 2016

European Journal of Medicinal Chemistry

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A series of new hybrid 2-(diethoxyphosphoryl)-N-(benzylidene)propan-2-amine oxide derivatives with different aromatic substitution (PPNs) were synthesized. These molecules were evaluated for their EPR spin trapping potential and NO donation properties in vitro, their cytotoxicity and on precontracted rat aortic rings. A subfamily of the new PPNs featured an antioxidant moiety occurring in natural phenolic acids. From the experimental screening of these hydroxyphenyl-and methoxyphenyl-substituted PPNs, biocompatible nitrones 4d, 4g−i deriving from caffeic, gallic, ferulic and sinapic acids, which combined improved EPR probing of ROS formation, vasorelaxant action and antioxidant potency, might be potential drug candidate alternatives to PBN and its analogues.

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The E-loop Is Involved in Hydrogen Peroxide Formation by the NADPH Oxidase Nox4

Cited by 469 publications

References 34 publications

Quinone compounds regulate the level of ROS production by the NADPH oxidase Nox4

Quinone compounds regulate the level of ROS production by the NADPH oxidase Nox4

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

On the vasoprotective mechanisms underlying novel β-phosphorylated nitrones: Focus on free radical characterization, scavenging and NO-donation in a biological model of oxidative stress

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