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Quantification of light-induced miniSOG superoxide production using the selective marker, 2-hydroxyethidium.
We report that miniSOG produces both 1O2 and O2•-, as can its free chromophore, flavin mononucleotide. miniSOG produced O2•- at a rate of ~4.0µmol O2•-/min/µmol photosensitizer for an excitation fluence rate of 5.9mW/mm2 at 470 ± 20nm, and the rate remained consistent across fluences (light doses). Overall, the contribution of O2•- to miniSOG phenotypes should be considered. PMID: 29353158 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - January 17, 2018 Category: Biology Authors: Barnett ME, Baran TM, Foster TH, Wojtovich AP Tags: Free Radic Biol Med Source Type: research

Nicotine induces apoptosis in human osteoblasts via a novel mechanism driven by H2O2 and entailing Glyoxalase 1-dependent MG-H1 accumulation leading to TG2-mediated NF-kB desensitization: implication for smokers-related osteoporosis.
Abstract Nicotine contained in cigarette smoke contributes to the onset of several diseases, including osteoporosis, whose emerging pathogenic mechanism is associated with osteoblasts apoptosis. Scanty information is available on the molecular mechanisms of nicotine on osteoblasts apoptosis and, consequently, on an important aspect of the pathogenesis of smokers-related osteoporosis. Glyoxalase 1 (Glo1) is the detoxification enzyme of methylglyoxal (MG), a major precursor of advanced glycation end products (AGEs), potent pro-apoptotic agents. Hydroimidazolone (MG-H1) is the major AGE derived from the spontaneous M...
Source: Free Radical Biology and Medicine - January 17, 2018 Category: Biology Authors: Marinucci L, Balloni S, Fettucciari K, Bodo M, Talesa VN, Antognelli C Tags: Free Radic Biol Med Source Type: research

Role of organic acids in the integration of cellular redox metabolism and mediation of redox signaling in photosynthetic tissues of higher plants.
Abstract Organic acids play a crucial role in numerous metabolic processes accompanied by transfer of electrons and protons and linked to the reduction/oxidation of major redox couples in plant cells, such as NAD, NADP, glutathione, and ascorbate. Fluxes though the pathways metabolizing organic acids modulate redox states in cell compartments, contribute to generation of reactive oxygen and nitrogen species, and mediate signal transduction processes. Organic acid metabolism not only functions to equilibrate the redox potential in plant cells but also functions to transfer redox equivalents between cell compartment...
Source: Free Radical Biology and Medicine - January 17, 2018 Category: Biology Authors: Igamberdiev AU, Bykova NV Tags: Free Radic Biol Med Source Type: research

Carbonic Anhydrase II Does Not Exhibit Nitrate Reductase or Nitrous Anhydrase Activity.
Abstract Carbonic anhydrase II (CA II) is a zinc metalloenzyme that catalyzes the reversible interconversion of water and CO2 to bicarbonate and a proton. CA II is abundant in most cells, and plays a role in numerous processes including gas exchange, epithelial ion transport, respiration, extra- and intracellular pH control, and vascular regulation. Beyond these CO2 and pH-linked roles, it has been postulated that CA II might also reduce nitrite (NO2-) to nitric oxide (NO), as bicarbonate and NO2- both exhibit sp2 molecular geometry and NO also plays an important role in vasodilation and regulation of blood pressu...
Source: Free Radical Biology and Medicine - January 16, 2018 Category: Biology Authors: Andring JT, Lomelino CL, Tu C, Silverman DN, McKenna R, Swenson ER Tags: Free Radic Biol Med Source Type: research

Nrf2/ARE pathway attenuates oxidative and apoptotic response in human osteoarthritis chondrocytes by activating ERK1/2/ELK1-P70S6K-P90RSK signaling axis.
Abstract Nrf2, a redox regulated transcription factor, has recently been shown to play a role in cartilage integrity but the mechanism remains largely unknown. Osteoarthritis (OA) is a multifactorial disease in which focal degradation of cartilage occurs. Here, we studied whether Nrf2 exerts chondroprotective effects by suppressing the oxidative stress and apoptosis in IL-1β stimulated human OA chondrocytes. Expression of Nrf2 and its target genes HO-1, NQO1 and SOD2 was significantly high in OA cartilage compared to normal cartilage and was also higher in damaged area compared to smooth area of OA cartilage ...
Source: Free Radical Biology and Medicine - January 12, 2018 Category: Biology Authors: Khan NM, Ahmad I, Haqqi TM Tags: Free Radic Biol Med Source Type: research

Friend or foe? Reactive oxygen species production, scavenging and signaling in plant response to environmental stresses.
Abstract In the natural environment, plants are exposed to a variety of biotic and abiotic stress conditions that trigger rapid changes in the production and scavenging of reactive oxygen species (ROS). The production and scavenging of ROS is compartmentalized, which means that, depending on stimuli type, they can be generated and eliminated in different cellular compartments such as the apoplast, plasma membrane, chloroplasts, mitochondria, peroxisomes, and endoplasmic reticulum. Although the accumulation of ROS is generally harmful to cells, ROS play an important role in signaling pathways that regulate acclimat...
Source: Free Radical Biology and Medicine - January 10, 2018 Category: Biology Authors: Czarnocka W, Karpiński S Tags: Free Radic Biol Med Source Type: research

Crosstalk between Rac1-mediated actin regulation and ROS production.
ult C Abstract The small RhoGTPase Rac1 is implicated in a variety of events related to actin cytoskeleton rearrangement. Remarkably, another event that is completely different from those related to actin regulation has the same relevance; the Rac1-mediated production of reactive oxygen species (ROS) through NADPH oxidases (NOX). Each outcome involves different Rac1 downstream effectors; on one hand, events related to the actin cytoskeleton require Rac1 to bind to WAVEs proteins and PAKs that ultimately promote actin branching and turnover, on the other, NOX-derived ROS production demands active Rac1 to be bound t...
Source: Free Radical Biology and Medicine - January 9, 2018 Category: Biology Authors: Acevedo A, González-Billault C Tags: Free Radic Biol Med Source Type: research

Selenoprotein H controls cell cycle progression and proliferation of human colorectal cancer cells.
Kipp AP Abstract Selenoprotein H (SELENOH) is supposed to be involved in redox regulation as well as in tumorigenesis. However, its role in healthy and transformed cells of the gastrointestinal tract remains elusive. We analysed SELENOH expression in cells depending on their selenium supply and differentiation status and found that SELENOH expression was increased in tumor tissue, in undifferentiated epithelial cells from mice and in colorectal cancer lines as compared to more differentiated ones. Knockdown studies in human colorectal cancer cells revealed that repression of SELENOH decreased cellular differentiat...
Source: Free Radical Biology and Medicine - January 9, 2018 Category: Biology Authors: Bertz M, Kühn K, Koeberle SC, Müller MF, Hoelzer D, Thies K, Deubel S, Thierbach R, Kipp AP Tags: Free Radic Biol Med Source Type: research

Gut Flora-Dependent Metabolite Trimethylamine-N-oxide Accelerates Endothelial Cell Senescence and Vascular Aging through Oxidative Stress.
Abstract Trimethylamine-N-oxide (TMAO), gut microbiota-dependent metabolites, has been shown to be associated with cardiovascular diseases. However, little is known about the relationship between TMAO and vascular aging. Here, we observed a change in TMAO during the aging process and the effects of TMAO on vascular aging and endothelial cell (EC) senescence. We analyzed age-related plasma levels of TMAO in young adults (18-44 years old), older adults (≥65 years old), and 1-month-old, 3-month-old, 6-month-old and 10-month-old senescence-accelerated mouse prone 8 (SAMP8) and age-matched senescence-accelerated mou...
Source: Free Radical Biology and Medicine - January 8, 2018 Category: Biology Authors: Ke Y, Li D, Zhao M, Liu C, Liu J, Zeng A, Shi X, Cheng S, Pan B, Zheng L, Hong H Tags: Free Radic Biol Med Source Type: research

An improved cell-permeable fluorogenic substrate as the basis for a highly sensitive test for NAD(P)H quinone oxidoreductase 1 (NQO1) in living cells.
In this study we have designed, produced and tested a fluorogenic coumarin conjugate which selectively releases highly fluorescent 4-methylumbelliferone (4-MU) in the presence of NQO1. It was found that measuring 4-MU release rapidly and specifically quantitated NQO1 levels in vitro and in live cells. Both the substrate and its products freely perfused through cell membranes and were non-toxic. The substrate was very specific with low background, and the assay itself could be done in less than 10minutes. This is the first assay to allow the quantitation of NQO1 in live cells which can then be retained for further experimen...
Source: Free Radical Biology and Medicine - January 8, 2018 Category: Biology Authors: Cuff S, Lewis RD, Chinje E, Jaffar M, Knox R, Weeks I Tags: Free Radic Biol Med Source Type: research

Mitochondrial Network Responses in Oxidative Physiology and Disease.
Abstract Mitochondrial activities are linked directly or indirectly to all cellular functions in aerobic eukaryotes. Omics methods enable new approaches to study functional organization of mitochondria and their adaptive and maladaptive network responses to bioenergetic fuels, physiologic demands, environmental challenges and aging. In this review, we consider mitochondria collectively within a multicellular organism as a macroscale "mitochondriome", functioning to organize bioenergetics and metabolism as an organism utilizes environmental resources and protects against environmental threats. We address ...
Source: Free Radical Biology and Medicine - January 6, 2018 Category: Biology Authors: Go YM, Fernandes J, Hu X, Uppal K, Jones DP Tags: Free Radic Biol Med Source Type: research

Nitric oxide synthase 2 enhances the survival of mice during Salmonella Typhimurium infection-induced sepsis by increasing reactive oxygen species, inflammatory cytokines and recruitment of neutrophils to the peritoneal cavity.
This study clearly highlights the NOS2-dependent and -independent responses in this mouse model of peritonitis induced sepsis. Importantly, pre-treatment of Nos2-/- mice with DETA-NO, a NO donor, upon infection, restores neutrophil recruitment, reduces bacterial numbers in the peritoneal cavity, improves liver and cardio-vascular function and enhances survival. Interestingly, DETA-NO treatment does not significantly increase the survival of infected WT mice. The implications of these results and the complex roles of NO as a target molecule during sepsis are discussed. PMID: 29309892 [PubMed - as supplied by publisher]...
Source: Free Radical Biology and Medicine - January 5, 2018 Category: Biology Authors: Yadav S, Pathak S, Sarikhani M, Majumdar S, Ray S, Chandrasekar BS, Adiga V, Sundaresan NR, Nandi D Tags: Free Radic Biol Med Source Type: research

More to NAD+ than meets the eye: a regulator of metabolic pools and gene expression in Arabidopsis.
te;triacq P Abstract Since its discovery more than a century ago, nicotinamide adenine dinucleotide (NAD+) is recognised as a fascinating cornerstone of cellular metabolism. This ubiquitous energy cofactor plays vital roles in metabolic pathways and regulatory processes, a fact emphasised by the essentiality of a balanced NAD+ metabolism for normal plant growth and development. Research on the role of NAD in plants has been predominantly carried out in the model plant Arabidopsis thaliana (Arabidopsis) with emphasis on the redox properties and cellular signalling functions of the metabolite. This review examines t...
Source: Free Radical Biology and Medicine - January 5, 2018 Category: Biology Authors: Gakière B, Fernie AR, Pétriacq P Tags: Free Radic Biol Med Source Type: research

Oxidative Stress and Apoptosis in Benzo[a]pyrene-Induced Neural Tube Defects.
The objectives of this study were to investigate whether there is a direct effect of maternal benzo[α] pyrene (BaP) exposure on the closure of the neural tube in mice, and to examine the underlying mechanisms by combining animal experiments and human subject studies. We found that intraperitoneal injection of BaP from embryonic day 7 at a dose of 250 mg kg-1 induced NTDs (13.3% frequency) in ICR mice. BaP exposure significantly increased expression of genes associated with oxidative stress, Cyp1a1, Sod1 and Sod2, while repressing Gpx1. Elevated apoptosis and higher protein expression of cleaved caspase-3 in the neuro...
Source: Free Radical Biology and Medicine - January 5, 2018 Category: Biology Authors: Lin S, Wang L, Huang Y, Wang Y, Wang C, Greene NDE, Ren A Tags: Free Radic Biol Med Source Type: research

Reactive oxygen species released from astrocytes treated with amyloid beta oligomers elicit neuronal calcium signals that decrease phospho-Ser727-STAT3 nuclear content.
ute;ñez MT Abstract The transcription factor STAT3 has a crucial role in the development and maintenance of the nervous system. In this work, we treated astrocytes with oligomers of the amyloid beta peptide (AβOs), which display potent synaptotoxic activity, and studied the effects of mediators released by AβOs-treated astrocytes on the nuclear location of neuronal serine-727-phosphorylated STAT3 (pSerSTAT3). Treatment of mixed neuron-astrocyte cultures with 0.5µMAβOs induced in neurons a significant decrease of nuclear pSerSTAT3, but not of phosphotyrosine-705 STAT3, the other form of ...
Source: Free Radical Biology and Medicine - January 5, 2018 Category: Biology Authors: Muñoz Y, Paula-Lima AC, Núñez MT Tags: Free Radic Biol Med Source Type: research

Detection of the formyl radical by EPR spin-trapping and mass spectrometry.
Abstract For the first time we here present the unambiguous identification of the formyl radical (●CHO) by EPR (Electron Paramagnetic Resonance) spectroscopy and mass spectrometry (MS) using DMPO (5,5-dimethyl-1-pyrroline N-oxide) as spin trap at ambient temperature without using any catalysator(s). The ●CHO was continuously generated by UV photolysis in closed anoxic environment from pure formaldehyde (HCHO) in aqueous solution. The isotropic hyperfine structure constants of ●CHO were determined as aN = 15.72G and aH = 21.27G. The signals were deconvoluted and split by simulation in their single adduct comp...
Source: Free Radical Biology and Medicine - January 4, 2018 Category: Biology Authors: Bauer NA, Hoque E, Wolf M, Kleigrewe K, Hofmann T Tags: Free Radic Biol Med Source Type: research

Superoxide dismutase protects ribonucleotide reductase from inactivation in yeast.
CC Abstract Ribonucleotide reductase (RNR) catalyses the rate limiting step of DNA synthesis utilising a mechanism that requires a tyrosyl radical. We have previously shown that superoxide can quench protein tyrosyl radicals in vitro, either by oxidative addition, or reduction of the radical to tyrosine. Here, we observe that Saccharomyces cerevisiae strains lacking either copper-zinc SOD (SOD1) or manganese SOD (SOD2) had decreased RNR activity compared to SOD competent yeast. When superoxide production was increased by treatment with paraquat, RNR activity was further decreased, with yeast lacking SOD1 being th...
Source: Free Radical Biology and Medicine - January 3, 2018 Category: Biology Authors: Das AB, Sadowska-Bartosz I, Königstorfer A, Kettle AJ, Winterbourn CC Tags: Free Radic Biol Med Source Type: research

Diabetic nephropathy: is there a role for oxidative stress?
Abstract Oxidative stress has been implicated in the pathophysiology of diabetic nephropathy. Studies in experimental animal models of diabetes strongly implicate oxidant species as a major determinant in the pathophysiology of diabetic kidney disease. The translation, in the clinical setting, of these concepts have been quite disappointing, and new theories have challenged the concepts that oxidative stress per se plays a role in the pathophysiology of diabetic kidney disease. The concept of mitochondrial hormesis has been introduced to explain this apparent disconnect. Hormesis is intended as any cellular proces...
Source: Free Radical Biology and Medicine - January 2, 2018 Category: Biology Authors: Sagoo MK, Gnudi L Tags: Free Radic Biol Med Source Type: research

Five Threads: How U-Shaped Thinking Weaves Together Dogs, Men, Selenium, and Prostate Cancer Risk.
Abstract Prostate cancer is one of the leading causes of cancer-related mortality among men living in developed countries, making the development of safe, practical approaches to prostate cancer risk reduction a high research priority. The relationship between prostate cancer risk and selenium, an essential nutrient required for a number of metabolically important enzymes including glutathione peroxidases, has been investigated, but a satisfactory integration of results has proven elusive. Dogs, like men, naturally develop prostate cancer during aging, providing an appropriate context to study the effects of selen...
Source: Free Radical Biology and Medicine - January 2, 2018 Category: Biology Authors: Waters DJ, Chiang EC Tags: Free Radic Biol Med Source Type: research

Evaluation of the p53 and Thioredoxin reductase in sperm from asthenozoospermic males in comparison to normozoospermic males.
Abstract Thioredoxin (Trx) system has a defensive role against the harmful effect of oxidative stress in sperm. p53 is an important regulator of apoptosis and normal process of spermatogenesis. Regulation of p53 by redox state of the cell and Thioredoxin system has been reported. The aim of this study was to evaluate the ROS level, Thioredoxin reductase (TrxR) activity and p53 protein levels in sperm of asthenozoospermic and normozoospermic males. Semen samples from 80 donors were divided into asthenozoospermic (n=40) and normozoospermic (n=40) groups using the WHO criteria. DNA fragmentation (TUNEL assay) of sper...
Source: Free Radical Biology and Medicine - January 2, 2018 Category: Biology Authors: Moradi MN, Karimi J, Khodadadi I, Amiri I, Karami M, Saidijam M, Vatannejad A, Tavilani H Tags: Free Radic Biol Med Source Type: research

NQO1 downregulation potentiates menadione-induced endothelial-mesenchymal transition during rosette formation in Fuchs endothelial corneal dystrophy.
This study provides first line evidence that MN-induced oxidative stress leads to EMT in corneal endothelial cells, and the effect of which is further potentiated when redox cycling activity of MN is enhanced by the absence of NQO1. Given that NAC inhibits Snail-mediated EMT, this may be a potential therapeutic intervention for FECD. PMID: 29294389 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - December 30, 2017 Category: Biology Authors: Katikireddy KR, White TL, Miyajima T, Vasanth S, Raoof D, Chen Y, Price MO, Price FW, Jurkunas UV Tags: Free Radic Biol Med Source Type: research

Thermal tolerance and thermal sensitivity of heart mitochondria: Mitochondrial integrity and ROS production.
er PU Abstract Cardiac mitochondrial metabolism provides 90% of the ATP necessary for the contractile exertion of the heart muscle. Mitochondria are therefore assumed to play a pivotal role in heart failure (HF), cardiovascular disease and ageing. Heat stress increases energy metabolism and oxygen demand in tissues throughout the body and imposes a major challenge on the heart, which is suspected of being the first organ to fail during heat stress. The underlying mechanisms inducing heart failure are still unclear. To pinpoint the processes implicated in HF during heat stress, we measured mitochondrial respiration...
Source: Free Radical Biology and Medicine - December 30, 2017 Category: Biology Authors: Christen F, Desrosiers V, Dupont-Cyr BA, Vandenberg GW, Le François NR, Tardif JC, Dufresne F, Lamarre SG, Blier PU Tags: Free Radic Biol Med Source Type: research

Molecular imaging of tumor photoimmunotherapy: Evidence of photosensitized tumor necrosis and hemodynamic changes.
Abstract Near-infrared photoimmunotherapy (NIR PIT) employs the photoabsorbing dye IR700 conjugated to antibodies specific for cell surface epidermal growth factor receptor (EGFR). NIR PIT has shown highly selective cytotoxicity in vitro and in vivo. Cell necrosis is thought to be the main mode of cytotoxicity based mainly on in vitro studies. To better understand the acute effects of NIR PIT, molecular imaging studies were performed to assess its cellular and vascular effects. In addition to in vitro studies for cytotoxicity of NIR PIT, the in vivo tumoricidal effects and hemodynamic changes induced by NIR PIT we...
Source: Free Radical Biology and Medicine - December 28, 2017 Category: Biology Authors: Kishimoto S, Oshima N, Yamamoto K, Munasinghe J, Ardenkjaer-Larsen JH, Mitchell JB, Choyke PL, Krishna MC Tags: Free Radic Biol Med Source Type: research

An engineered cell line lacking OGG1 and MUTYH glycosylases implicates the accumulation of genomic 8-oxoguanine as the basis for paraquat mutagenicity.
Abstract Paraquat (1,1'-dimethyl, 4,4'-bipyridinium dichloride; PQ), a widely used herbicide, is toxic to mammals through ingestion, inhalation and skin contact. Epidemiological data suggest that PQ is also mutagenic and carcinogenic, especially in high doses. The toxic and mutagenic properties of PQ are attributed to the ability of the molecule to redox-cycle, which generates reactive oxygen species (ROS) and subsequent oxidative stress. ROS also cause oxidative DNA damage such as 8-oxoguanine (8OG), a mutagenic base that, when replicated, causes G to T transversion mutations. The present study employed the CHO-d...
Source: Free Radical Biology and Medicine - December 28, 2017 Category: Biology Authors: Tajai P, Fedeles BI, Suriyo T, Navasumrit P, Kanitwithayanun J, Essigmann JM, Satayavivad J Tags: Free Radic Biol Med Source Type: research

Corrigendum to "Combined NADPH and the NOX inhibitor apocynin provides greater anti-inflammatory and neuroprotective effects in a mouse model of stroke" [Free Radic. Biol. Med. 104 (2017) 333-345].
Corrigendum to "Combined NADPH and the NOX inhibitor apocynin provides greater anti-inflammatory and neuroprotective effects in a mouse model of stroke" [Free Radic. Biol. Med. 104 (2017) 333-345]. Free Radic Biol Med. 2017 Dec 27;: Authors: Qin YY, Li M, Feng X, Wang J, Cao L, Shen XK, Chen J, Sun M, Sheng R, Han F, Qin ZH PMID: 29289409 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - December 27, 2017 Category: Biology Authors: Qin YY, Li M, Feng X, Wang J, Cao L, Shen XK, Chen J, Sun M, Sheng R, Han F, Qin ZH Tags: Free Radic Biol Med Source Type: research

Redox Clocks: Time to Rethink Redox Interventions.
Abstract Redox interventions have been controversial in the management of chronic disease. The key reason is believed to be a lack of clarity in our understanding of how endogenous dynamics unfold in biochemical redox mechanisms in live cells. Time-resolved, quantitative research strategies combined with high throughput analysis tools may result in realistic characterisation of related in vivo processes. Here we review new evidence about redox dynamics in live cells. We discuss a potential of this line of research to establish new and affordable ways of redox interventions which may efficiently decrease mortality ...
Source: Free Radical Biology and Medicine - December 26, 2017 Category: Biology Authors: Nagy AD, Reddy AB Tags: Free Radic Biol Med Source Type: research

The Potential Therapeutic Effects of Ergothioneine in Pre-eclampsia.
Abstract Ergothioneine (ERG), is a water-soluble amino acid that is derived entirely from dietary sources. It has received much attention as a therapeutic agent due to its anti-oxidant properties, and there are claims of preferential accumulation within high oxidative stress organs. Pre-eclampsia, a condition accompanied by increased oxidative stress, is one of the leading causes of maternal morbidity and mortality. Despite intense research efforts, its aetiologies remain somewhat unclear and there are still no effective treatment options. Clinical trials of the anti-oxidants vitamin C and vitamin E have proven la...
Source: Free Radical Biology and Medicine - December 25, 2017 Category: Biology Authors: Kerley RN, McCarthy C, Kell DB, Kenny LC Tags: Free Radic Biol Med Source Type: research

Interaction between p22phox and Nox4 in the endoplasmic reticulum SUGGESTS A UNIQUE mechanism of NADPH oxidase complex formation.
, Morand S, Leto TL, Geiszt M Abstract The p22phox protein is an essential component of the phagocytic- and inner ear NADPH oxidases but its relationship to other Nox proteins is less clear. We have studied the role of p22phox in the TGF-β1-stimulated H2O2 production of primary human and murine fibroblasts. TGF-β1 induced H2O2 release of the examined cells, and the response was dependent on the expression of both Nox4 and p22phox. Interestingly, the p22phox protein was present in the absence of any detectable Nox/Duox expression, and the p22phox level was unaffected by TGF-β1. On the other hand, Nox...
Source: Free Radical Biology and Medicine - December 23, 2017 Category: Biology Authors: Zana M, Péterfi Z, Kovács HA, Tóth ZE, Enyedi B, Morel F, Paclet MH, Donkó Á, Morand S, Leto TL, Geiszt M Tags: Free Radic Biol Med Source Type: research

The A to Z of Modulated Cell Patterning by Mammalian Thioredoxin Reductases.
r ESJ Abstract Mammalian thioredoxin reductases (TrxRs) are selenocysteine-containing proteins (selenoproteins) that propel a large number of functions through reduction of several substrates including the active site disulfide of thioredoxins (Trxs). Well-known enzymatic systems that in turn are supported by Trxs and TrxRs include deoxyribonucleotide synthesis through ribonucleotide reductase, antioxidant defense through peroxiredoxins and methionine sulfoxide reductases, and redox modulation of a number of transcription factors. Although these functions may be essential for cells due to crucial roles in maintena...
Source: Free Radical Biology and Medicine - December 23, 2017 Category: Biology Authors: Dagnell M, Schmidt EE, Arnér ESJ Tags: Free Radic Biol Med Source Type: research

Priming plant resistance by activation of redox-sensitive genes.
sch C Abstract Priming by natural compounds is an interesting alternative for sustainable agriculture, which also contributes to explore the molecular mechanisms associated with stress tolerance. Although hosts and stress types eventually determine the mode of action of plant-priming agents, it highlights that many of them act on redox signalling. These include vitamins thiamine, riboflavin and quercetin; organic acids like pipecolic, azelaic and hexanoic; volatile organic compounds such as methyl jasmonate; cell wall components like chitosans and oligogalacturonides; H2O2, etc. This review provides data on how pr...
Source: Free Radical Biology and Medicine - December 22, 2017 Category: Biology Authors: González-Bosch C Tags: Free Radic Biol Med Source Type: research

Entrainment of the mouse circadian clock: Effects of stress, exercise, and nutrition.
Abstract The circadian clock system in mammals plays a fundamental role in maintaining homeostasis. Entrainment is an important characteristic of the internal clock, by which appropriate timing is maintained according to external daily stimuli, such as light, stress, exercise, and/or food. Disorganized entrainment or a misaligned clock time, such as jet lag, increases health disturbances. The central clock in the suprachiasmatic nuclei, located in the hypothalamus, receives information about arousal stimuli, such as physical stress or exercise, and changes the clock time by modifying neural activity or the express...
Source: Free Radical Biology and Medicine - December 22, 2017 Category: Biology Authors: Tahara Y, Shibata S Tags: Free Radic Biol Med Source Type: research

Development of a Reactive Oxygen Species-Sensitive Nitric Oxide Synthase Inhibitor for the Treatment of Ischemic Stroke.
In this study, the nitrone 5was designed such that its decomposition product is a NOS inhibitor, 6, effectively leading to NOS inhibition specifically at the site of ROS production. The ability of 5to spin-trap radicals and decompose to 6 was observed using EPR and LC-MS/MS. The pro-drug concept was tested in vitro by measuring cell viability and 6 formation in SH-SY5Y cells subjected to oxygen glucose deprivation (OGD). 5 was found to be more efficacious and more potent than PBN, and was able to increase phospho-Akt while reducing nitrotyrosine and cleaved caspase-3 levels. 6 treatment, but not 5, was found to decrease NO...
Source: Free Radical Biology and Medicine - December 21, 2017 Category: Biology Authors: Nash KM, Schiefer IT, Shah ZA Tags: Free Radic Biol Med Source Type: research

The NOX1 isoform of NADPH oxidase is involved in dysfunction of liver sinusoids in nonalcoholic fatty liver disease.
Abstract The increased production of reactive oxygen species (ROS) has been postulated to play a key role in the progression of nonalcoholic fatty liver disease (NAFLD). However, the source of ROS and mechanisms underlying the development of NAFLD have yet to be established. We observed a significant up-regulation of a minor isoform of NADPH oxidase, NOX1, in the liver of nonalcoholic steatohepatitis (NASH) patients as well as of mice fed a high-fat and high-cholesterol (HFC) diet for 8 weeks. In mice deficient in Nox1 (Nox1KO), increased levels of serum alanine aminotransferase and hepatic cleaved caspase-3 demon...
Source: Free Radical Biology and Medicine - December 20, 2017 Category: Biology Authors: Matsumoto M, Zhang J, Zhang X, Liu J, Jiang JX, Yamaguchi K, Taruno A, Katsuyama M, Iwata K, Ibi M, Cui W, Matsuno K, Marunaka Y, Itoh Y, Torok NJ, Yabe-Nishimura C Tags: Free Radic Biol Med Source Type: research

Redox and the circadian clock in plant immunity: A balancing act.
Abstract Plants' reliance on sunlight for energy makes their light-driven circadian clock a critical regulator in balancing the energy needs for vital activities such as growth and defense. Recent studies show that the circadian clock acts as a strategic planner to prime active defense responses towards the morning or daytime when plants are more vulnerable to attackers due to favorable conditions, such as the opening of stomata required for photosynthesis. Execution of the defense response, on the other hand, is determined according to the cellular redox state and is regulated in part by the production of reactiv...
Source: Free Radical Biology and Medicine - December 19, 2017 Category: Biology Authors: Karapetyan S, Dong X Tags: Free Radic Biol Med Source Type: research

PKC δ-dependent p47phox activation mediates methamphetamine-induced dopaminergic neurotoxicity.
PKCδ-dependent p47phox activation mediates methamphetamine-induced dopaminergic neurotoxicity. Free Radic Biol Med. 2017 Dec 18;: Authors: Dang DK, Shin EJ, Kim DJ, Tran HQ, Jeong JH, Jang CG, Ottersen OP, Nah SY, Hong JS, Nabeshima T, Kim HC Abstract Protein kinase C (PKC) has been recognized to activate NADPH oxidase (PHOX). However, the interaction between PKC and PHOX in vivo remains elusive. Treatment with methamphetamine (MA) resulted in a selective increase in PKCδ expression out of PKC isoforms. PKCδ co-immunoprecipitated with p47phox, and facilitated phosphorylation and memb...
Source: Free Radical Biology and Medicine - December 18, 2017 Category: Biology Authors: Dang DK, Shin EJ, Kim DJ, Tran HQ, Jeong JH, Jang CG, Ottersen OP, Nah SY, Hong JS, Nabeshima T, Kim HC Tags: Free Radic Biol Med Source Type: research

NADPH Oxidase 4 and Endothelial Nitric Oxide Synthase Contribute to Endothelial Dysfunction Mediated by Histone Methylations in Metabolic Memory.
In this study, we demonstrated that vascular ROS was continuously activated in endothelium induced by transient high glucose, as well as sustained vascular endothelial dysfunction. The Nox4 and uncoupled eNOS are the major sources of ROS, while inhibition of Nox4 and eNOS significantly attenuated oxidative stress and almost recovered the endothelial function in metabolic memory. Furthermore, the aberrant histone methylation (H3K4me1, H3K9me2, and H3K9me3) at promoters of Nox4 and eNOS are the main causes for the persistent up-regulation of these two genes. Modifying the histone methylation could reduce the expression level...
Source: Free Radical Biology and Medicine - December 18, 2017 Category: Biology Authors: Liao Y, Gou L, Chen L, Zhong X, Zhang D, Zhu H, Lu X, Zeng T, Deng X, Li Y Tags: Free Radic Biol Med Source Type: research

Methylglyoxal displays colorectal cancer-promoting properties in the murine models of azoxymethane and CT26 isografts.
In conclusion, it is conceivable that MG-induced carbonyl stress may be the pivotal promoter involved in colon cancer progression. PMID: 29269310 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - December 18, 2017 Category: Biology Authors: Lin JA, Wu CH, Yen GC Tags: Free Radic Biol Med Source Type: research

Markers of oxidative damage to lipids, nucleic acids and proteins and antioxidant enzymes activities in Alzheimer's disease brain: a meta-analysis in human pathological specimens.
The objective of this study was to define the pattern of changes in oxidative-stress related markers by brain region in human Alzheimer's disease and mild cognitive impairment brain tissue. Observational case-control studies were identified from systematic queries of PubMed, ISI Web of Science and Scopus databases and studies were evaluated with appropriate quality measures. The data was used to construct a region-by-region meta-analysis of malondialdehyde, 4-hydroxynonenal, protein carbonylation, 8-hydroxyguanine levels and superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase activities. We als...
Source: Free Radical Biology and Medicine - December 15, 2017 Category: Biology Authors: Zabel M, Nackenoff A, Kirsch WM, Harrison F, Perry G, Schrag M Tags: Free Radic Biol Med Source Type: research

WDR26/MIP2 interacts with VDAC1 and regulates VDAC1 expression levels in H9c2 cells.
Abstract MIP2, one of WDR26 isoform, encodes a 498 amino acid protein with an amino-terminal CTLH domain and five carboxyl-terminal WD40 motifs. MIP2 is localized to the mitochondria and protects cardiomyocytes against oxidative stress; however, nothing is known about how MIP2 confers its cytoprotection. Using co-immunoprecipitation (co-IP) method to isolate MIP2-protein complex from Sprague -Dawley rat heart, followed by mass spectrometry analysis, we have identified VDAC1, a protein located at mitochondria, as a novel MIP2-interacting protein in the myocardium of rat hearts as well as H9c2 cells. This interactio...
Source: Free Radical Biology and Medicine - December 15, 2017 Category: Biology Authors: Jiang L, Wang H, Chen G, Feng Y, Zou J, Liu M, Liu K, Wang N, Zhang H, Wang K, Xiao X Tags: Free Radic Biol Med Source Type: research

CKIP-1 affects the polyubiquitination of Nrf2 and Keap1 via mediating Smurf1 to resist HG-induced renal fibrosis in GMCs and diabetic mice kidneys.
Abstract Our previous study indicated that Casein kinase 2 interacting protein-1 (CKIP-1) could promote the activation of the nuclear factor E2-related factor 2 (Nrf2)/ antioxidant response element (ARE) pathway, playing a significant role in inhibiting the fibrosis of diabetic nephropathy (DN). However, the underlying mechanism is still unknown. Here, we investigated whether CKIP-1 affects the polyubiquitination of Nrf2 and its cytosolic inhibitor kelch like ECH-associated protein 1 (Keap1) via mediating Smad ubiquitylation regulatory factor-1 (Smurf1) to promote the activation of the Nrf2/ARE signaling and resis...
Source: Free Radical Biology and Medicine - December 14, 2017 Category: Biology Authors: Gong W, Chen Z, Zou Y, Zhang L, Huang J, Liu P, Huang H Tags: Free Radic Biol Med Source Type: research

The 3-phenylcoumarin derivative 6,7-dihydroxy-3-[3',4'-methylenedioxyphenyl]-coumarin downmodulates the Fc γR- and CR-mediated oxidative metabolism and elastase release in human neutrophils: possible mechanisms underlying inhibition of the formation and release of neutrophil extracellular traps.
In this study, we report the ability of a set of eight 3-phenylcoumarin derivatives bearing 6,7- or 5,7-dihydroxyl groups, free or acetylated, bound to the benzopyrone moiety, to modulate the effector functions of human neutrophils. In general, (i) 6,7-disubstituted compounds (5, 6, 19, 20) downmodulated the Fcγ receptor-mediated neutrophil oxidative metabolism more strongly than 5,7-disubstituted compounds (21, 22, 23, 24), and (ii) hydroxylated compounds (5, 19, 21, 23) downmodulated this neutrophil function more effectively than their acetylated counterparts (6, 20, 22, 24, respectively). Compounds 5 (6,7-dihydrox...
Source: Free Radical Biology and Medicine - December 14, 2017 Category: Biology Authors: Andrade MF, Kabeya LM, Bortot LO, Dos Santos GB, Santos EOL, Albiero LR, Figueiredo-Rinhel ASG, Carvalho CA, Azzolini AECS, Caliri A, Pupo MT, Emery FS, Lucisano-Valim YM Tags: Free Radic Biol Med Source Type: research

Crosstalk between Nrf2 and YAP contributes to maintaining the antioxidant potential and chemoresistance in bladder cancer.
Abstract Redox adaptation plays an important role in cancer cells drug resistance. The antioxidant response is principally mediated by the transcription factor Nrf2, that induces the transcriptional activation of several genes involved in GSH synthesis, chemoresistance, and cytoprotection. YAP is emerging as a key mediator of chemoresistance in a variety of cancers, but its role in controlling the antioxidant status of the cells is yet elusive. Here, we show that impairing YAP protein expression reduced GSH content and Nrf2 protein and mRNA expression in bladder cancer cells. Moreover, in YAP- knockdown cells the ...
Source: Free Radical Biology and Medicine - December 14, 2017 Category: Biology Authors: Ciamporcero E, Daga M, Pizzimenti S, Roetto A, Dianzani C, Compagnone A, Palmieri A, Ullio C, Cangemi L, Pili R, Barrera G Tags: Free Radic Biol Med Source Type: research

Iodine prevents the increase of testosterone-induced oxidative stress in a model of rat prostatic hyperplasia.
M, Aceves C, Anguiano B Abstract Oxidative stress and inflammation are involved in the development and/or progression of benign prostatic hyperplasia (BPH). Molecular iodine (I2) induces antiproliferative and apoptotic effects in prostate cancer cells, but it is unknown if I2 regulates oxidative stress in the normal and/or tumoral prostate. The purpose of this study was to analyze the effects of I2 and celecoxib (Cxb) on oxidative stress and inflammation in a model of prostatic hyperplasia. Cxb was used as positive control of cyclooxygenase-2 (COX-2) inhibition. Prostatic hyperplasia was induced in male Wistar rat...
Source: Free Radical Biology and Medicine - December 14, 2017 Category: Biology Authors: Quintero-García M, Delgado-González E, Sánchez-Tusie A, Vázquez M, Aceves C, Anguiano B Tags: Free Radic Biol Med Source Type: research

Caffeic Acid and Resveratrol Ameliorate Cellular Damage in Cell and Drosophila Models of Spinocerebellar Ataxia Type 3 through Upregulation of Nrf2 Pathway.
Abstract Polyglutamine (polyQ)-expanded mutant ataxin-3 protein, which is prone to misfolding and aggregation, leads to cerebellar neurotoxicity in spinocerebellar ataxia type 3 (SCA3), an inherited PolyQ neurodegenerative disease. Although the exact mechanism is unknown, the pathogenic effects of mutant ataxin-3 are associated with dysregulation of transcription, protein degradation, mitochondrial function, apoptosis, and antioxidant potency. In the present study we explored the protective role and possible mechanism of caffeic acid (CA) and resveratrol (Res) in cells and Drosophila expressing mutant ataxin-3. Tr...
Source: Free Radical Biology and Medicine - December 13, 2017 Category: Biology Authors: Wu YL, Chang JC, Lin WY, Li CC, Hsieh M, Chen HW, Wang TS, Wu WT, Liu CS, Liu KL Tags: Free Radic Biol Med Source Type: research

Corrigendum to "Deletion of NADH oxidase in Listeria monocytogenes promotes the bacterial infection of brain" [Free Radic. Biol. Med. 112 (2017) 608-615].
Corrigendum to "Deletion of NADH oxidase in Listeria monocytogenes promotes the bacterial infection of brain" [Free Radic. Biol. Med. 112 (2017) 608-615]. Free Radic Biol Med. 2017 Dec 12;: Authors: Li S, Yu W, Guan X, Luo Z, Chen G, Liu W, Zhang J PMID: 29242002 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - December 12, 2017 Category: Biology Authors: Li S, Yu W, Guan X, Luo Z, Chen G, Liu W, Zhang J Tags: Free Radic Biol Med Source Type: research

Mkp-1 Protects Mice Against Toxin-Induced Liver Damage by Promoting the Nrf2 Cytoprotective Response.
Abstract The present study was undertaken to investigate the possible protective effect of mitogen-activated protein kinase phosphatase 1 (Mkp-1) on toxin-induced hepatic injury. Here, we uncovered a positive feedback loop between Mkp-1, a dual threonine/tyrosine phosphatase, and nuclear factor erythroid 2-related factor 2 (Nrf2), a crucial regulator of the defense system in the liver. Mkp-1-/- mice exhibited decreased protein levels of Nrf2, phase II gene products, and reduced glutathione (GSH) in the liver. Induction of detoxifying enzymes by the Nrf2 activator butylated hydroxyanisole (BHA) or sulforaphane, was...
Source: Free Radical Biology and Medicine - December 11, 2017 Category: Biology Authors: Luo L, Chen Y, Wang H, Wang S, Liu K, Li X, Wang XJ, Tang X Tags: Free Radic Biol Med Source Type: research

N-acetylcysteine supplementation increases exercise performance and reduces oxidative stress only in individuals with low levels of glutathione.
In conclusion, individuals with low glutathione levels were linked with decreased physical performance, increased oxidative stress and impaired redox metabolism of erythrocytes. NAC supplementation restored both performance and redox homeostasis. PMID: 29233792 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - December 9, 2017 Category: Biology Authors: Paschalis V, Theodorou AA, Margaritelis NV, Kyparos A, Nikolaidis MG Tags: Free Radic Biol Med Source Type: research

Licochalcone A activates Keap1-Nrf2 signaling to suppresses arthritis via phosphorylation of p62 at serine 349.
Abstract Licochalcone A (LCA) is derived from glycyrrhizae radix with antimicrobial, antitumor and anti-inflammatory activities. However, the anti-arthritic function of LCA and underlying mechanism has not been yet explored. The current study investigated the anti-arthritic effect of LCA and elucidated the underlying mechanism. The results showed that LCA significantly suppressed arthritis via the activation of QSTM1 (p62)/nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling in the collage-induced arthritis (CIA) model of DBA mice. In coincided with the results, this anti-arthritic effect of LCA was remark...
Source: Free Radical Biology and Medicine - December 9, 2017 Category: Biology Authors: Su X, Li T, Liu Z, Huang Q, Liao K, Ren R, Lu L, Qi X, Wang M, Chen J, Zhou H, Leung EL, Pan H, Liu J, Wang H, Huang L, Liu L Tags: Free Radic Biol Med Source Type: research

Relevance of 4-F4t-neuroprostane and 10-F4t-neuroprostane to neurological diseases.
Abstract F4-neuroprostanes (F4-NeuroPs) are non-enzymatic oxidized products derived from docosahexaenoic acid (DHA) and are suggested to be oxidative damage biomarkers of neurological diseases. However, 128 isomers can be formed from DHA oxidation and among them, 4(RS)-4-F4t-NeuroP (4-F4t-NeuroP) and 10(RS)-10-F4t-NeuroP (10-F4t-NeuroP) are the most studied. Here, we report the identification and the clinical relevance of 4-F4t-NeuroP and 10-F4t-NeuroP in plasma of four different neurological diseases, including multiple sclerosis (MS), autism spectrum disorders, (ASD) Rett syndrome (RTT), and Down syndrome (DS). ...
Source: Free Radical Biology and Medicine - December 9, 2017 Category: Biology Authors: Signorini C, De Felice C, Durand T, Galano JM, Oger C, Leoncini S, Ciccoli L, Carone M, Ulivelli M, Manna C, Cortelazzo A, Lee JC, Hayek J Tags: Free Radic Biol Med Source Type: research

Cardiovascular disease risk factors and oxidative stress among premenopausal women.
Abstract Oxidative stress is one hypothesized mechanism linking anthropometric, behavioral, and medical risk factors with cardiovascular disease (CVD). We evaluated cross-sectional associations between CVD risk factors and biomarkers of oxidative stress, and investigated these biomarkers as predictors of incident diabetes and hypertension among premenopausal women. F2-isoprostane (F2-IsoP) and metabolite (15-F2t-IsoP-M), reliable biomarkers of oxidative stress, were measured in urine samples collected at enrollment from 897 premenopausal women (ages 35-54) enrolled in the Sister Study cohort without a CVD history....
Source: Free Radical Biology and Medicine - December 8, 2017 Category: Biology Authors: Anderson C, Milne GL, Park YM, Sandler DP, Nichols HB Tags: Free Radic Biol Med Source Type: research