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Sulfiredoxin-1 Enhances Cardiac Progenitor Cell Survival against Oxidative Stress via the Upregulation of the ERK/NRF2 Signal Pathway.
Abstract Cardiac stem/progenitor cells (CPCs) have recently emerged as a potentially transformative regenerative medicine to repair the infarcted heart. However, the limited survival of donor cells is one of the major challenges for CPC therapy. Our recent research effort on preconditioning human CPCs (hCPCs) with cobalt protoporphyrin (CoPP) indicated that sulfiredoxin-1 (SRXN1) is upregulated upon preconditioning aldehyde dehydrogenase bright hCPCs (ALDHbr-hCPCs) with CoPP. Further studies demonstrated that overexpressing SRXN1 enhanced the survival capacity for ALDHbr-hCPCs. This was associated with the up-regu...
Source: Free Radical Biology and Medicine - May 14, 2018 Category: Biology Authors: Li X, He P, Wang X, Zhang S, Devejian N, Bennett E, Cai C Tags: Free Radic Biol Med Source Type: research

AMPK α2 deficiency exacerbates long-term PM2.5 exposure-induced lung injury and cardiac dysfunction.
In this study, we exposed wild-type (WT) and AMPKα2-/- mice to either airborne PM2.5 (mean daily concentration ~64µg/m3) or filtered air for 6 months through a whole-body exposure system. After exposure, AMPKα2-/- mice developed severe lung injury and left ventricular dysfunction. In the PM2.5-exposed lungs and hearts, loss of AMPKα2 resulted in higher levels of fibrotic genes, more collagen deposition, lower levels of peroxiredoxin 5 (Prdx5), and greater induction of oxidative stress and inflammation than observed in the lungs and hearts of WT mice. In PM2.5-exposed BEAS-2B and H9C2 cells, inhibiti...
Source: Free Radical Biology and Medicine - May 9, 2018 Category: Biology Authors: Wang H, Shen X, Tian G, Shi X, Huang W, Wu Y, Sun L, Peng C, Liu S, Huang Y, Chen X, Zhang F, Chen Y, Ding W, Lu Z Tags: Free Radic Biol Med Source Type: research

Glycine Transporter-1 and Glycine Receptor Mediate the Antioxidant Effect of Glycine in Diabetic Rat Islets and INS-1 Cells.
Abstract Oxidative stress is the main inducer of β-cell damage, which underlies the pathogenesis of diabetes. Evidence suggests that glycine, a recognized antioxidant, may improve β-cell function; however, its mechanism in protecting diabetic β-cells against oxidative stress has not been directly investigated. Using a streptozotocin-induced diabetic rat model and INS-1 pancreatic β-cells, we evaluated whether glycine can attenuate diabetic β-cell damage induced by oxidative stress. In diabetic rats, glycine stimulated insulin secretion; enhanced plasma glutathione (GSH), catalase and super...
Source: Free Radical Biology and Medicine - May 9, 2018 Category: Biology Authors: Chen L, Zhang J, Li C, Wang Z, Li J, Zhao D, Wang S, Zhang H, Huang Y, Guo X Tags: Free Radic Biol Med Source Type: research

Kinetic and stoichiometric constraints determine the pathway of H2O2 consumption by red blood cells.
n L Abstract Red blood cells (RBC) are considered as a circulating sink of H2O2, but a significant debate remains over the role of the different intraerythocyte peroxidases. Herein we examined the kinetic of decomposition of exogenous H2O2 by human RBC at different cell densities, using fluorescent and oxymetric methods, contrasting the results against a mathematical model. Fluorescent measurements as well as oxygen production experiments showed that catalase was responsible for most of the decomposition of H2O2 at cell densities suitable for both experimental settings (0.1-10 × 1010 cell L-1), since sodium ...
Source: Free Radical Biology and Medicine - May 9, 2018 Category: Biology Authors: Orrico F, Möller MN, Cassina A, Denicola A, Thomson L Tags: Free Radic Biol Med Source Type: research

Organic selenium compounds as potential chemotherapeutic agents for improved cancer treatment.
Abstract Selenium(Se)-containing compounds have attracted a growing interest as anticancer agents over recent decades, with mounting reports demonstrating their high efficacy and selectivity against cancer cells. Typically, Se compounds exert their cytotoxic effects by acting as pro-oxidants that alter cellular redox homeostasis. However, the precise intracellular targets, signaling pathways affected and mechanisms of cell death engaged following treatment vary with the chemical properties of the selenocompound and its metabolites, as well as the cancer model that is used. Naturally occurring organic Se compounds,...
Source: Free Radical Biology and Medicine - May 7, 2018 Category: Biology Authors: Gandin V, Khalkar P, Braude J, Fernandes AP Tags: Free Radic Biol Med Source Type: research

Insight into ultrasound-mediated reactive oxygen species generation by various metal-porphyrin complexes.
Abstract Ultrasound is used to trigger the cytotoxicity of chemical compounds, known as sonosensitisers, in an approach called sonodynamic therapy (SDT), which is under investigation herein. The generation of reactive oxygen species (ROS) has been proposed as the main biological occurrence that leads to the cytotoxic effects, which are achieved via the synergistic action of two components: the energy-absorbing sonosensitiser and ultrasound (US), which are both harmless per se. Despite some promising results, a lack of investigation into the mechanisms behind US sonosensitiser-mediated ROS generation has prevented ...
Source: Free Radical Biology and Medicine - May 5, 2018 Category: Biology Authors: Giuntini F, Foglietta F, Marucco AM, Troia A, Dezhkunov NV, Pozzoli A, Durando G, Fenoglio I, Serpe L, Canaparo R Tags: Free Radic Biol Med Source Type: research

Histone variant H2A.Z antagonizes the positive effect of the transcriptional activator CPC1 to regulate catalase-3 expression under normal and oxidative stress conditions.
Abstract In eukaryotes, deposition of the histone variant H2A.Z into nucleosomes through the chromatin remodeling complex, SWR1, is a crucial step in modulating gene transcription. Recently, H2A.Z has been shown to control the expression of responsive genes, but the underlying mechanism of how H2A.Z responds to physiological stimuli is not well understood. Here, we reveal that, in Neurospora crassa, H2A.Z is a negative regulator of catalase-3 gene, which is responsible for resistance to oxidative stress. H2A.Z represses cat-3 gene expression through direct incorporation at cat-3 locus in a SWR1 complex dependent p...
Source: Free Radical Biology and Medicine - May 5, 2018 Category: Biology Authors: Dong Q, Wang Y, Qi S, Gai K, He Q, Wang Y Tags: Free Radic Biol Med Source Type: research

C1QTNF1 attenuates angiotensin II-induced cardiac hypertrophy via activation of the AMPKa pathway.
CONCLUSION: Our results demonstrated that C1QTNF1 improves cardiac function and inhibits cardiac hypertrophy and fibrosis by increasing and activating AMPKa, suggesting that C1QTNF1 could be a therapeutic target for cardiac hypertrophy and heart failure. PMID: 29733904 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - May 4, 2018 Category: Biology Authors: Wu L, Gao L, Zhang D, Yao R, Huang Z, Du B, Wang Z, Xiao L, Li P, Li Y, Liang C, Zhang Y Tags: Free Radic Biol Med Source Type: research

Reactive oxygen species are crucial "pro-life "survival signals in plants.
Reactive oxygen species are crucial "pro-life "survival signals in plants. Free Radic Biol Med. 2018 May 03;: Authors: Breusegem FV, Foyer C, Mann G PMID: 29730380 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - May 3, 2018 Category: Biology Authors: Breusegem FV, Foyer C, Mann G Tags: Free Radic Biol Med Source Type: research

Paraoxonase 2 Prevents the Development of Heart Failure.
CONCLUSION: Our study suggests a cardioprotective role for PON2 in both experimental and human heart failure, which may be associated with the ability of PON2 to improve mitochondrial function and diminish ROS generation. PMID: 29729330 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - May 2, 2018 Category: Biology Authors: Li W, Kennedy D, Shao Z, Wang X, Kamdar AK, Weber M, Mislick K, Kiefer K, Morales R, Agatisa-Boyle B, Shih DM, Reddy ST, Moravec CS, Tang WHW Tags: Free Radic Biol Med Source Type: research

The proinflammatory effects of macrophage-derived NADPH oxidase function in autoimmune diabetes.
Abstract Type 1 diabetes (T1D) is an autoimmune disease culminating in the destruction of insulin-producing pancreatic β-cells. While ultimately a T cell-mediated disease, macrophages play an indispensable role in disease initiation and progression. Infiltrating macrophages generate an inflammatory environment by releasing NADPH oxidase-derived superoxide and proinflammatory cytokines. The synthesis of reactive oxygen species (ROS) is acknowledged as putative factors contributing to autoimmunity and β-cell damage in T1D. In addition to direct lysis, free radicals collectively participate in β-cell d...
Source: Free Radical Biology and Medicine - April 30, 2018 Category: Biology Authors: Feduska JM, Tse HM Tags: Free Radic Biol Med Source Type: research

Metal exposure and oxidative stress markers in pregnant Navajo Birth Cohort Study participants.
Abstract Contamination of soil and water by waste from abandoned uranium mines has led to chronic exposures to metal mixtures in Native American communities. Our previous work demonstrated that community exposures to mine waste increase the likelihood of developing cardiovascular disease, as well as the likelihood of developing multiple chronic diseases including diabetes, hypertension and kidney disease. Exposure to various environmental metals is associated with elevated oxidative stress, which is considered a contributor to these and other chronic disease states. The purpose of the current research was to asses...
Source: Free Radical Biology and Medicine - April 30, 2018 Category: Biology Authors: Dashner-Titus EJ, Hoover J, Li L, Lee JH, Du R, Liu KJ, Traber MG, Ho E, Lewis J, Hudson Laurie G Tags: Free Radic Biol Med Source Type: research

The Intricate Role of Selenium and Selenoproteins in Erythropoiesis.
Abstract Selenium (Se) is incorporated as the 21st amino acid selenocysteine (Sec) into the growing polypeptide chain of proteins involved in redox gatekeeper functions. Erythropoiesis presents a particular problem to redox regulation as the presence of iron, heme, and unpaired globin chains lead to high levels of free radical-mediated oxidative stress, which are detrimental to erythroid development and can lead to anemia. Under homeostatic conditions, bone marrow erythropoiesis produces sufficient erythrocytes to maintain homeostasis. In contrast, anemic stress induces an alternative pathway, stress erythropoiesi...
Source: Free Radical Biology and Medicine - April 29, 2018 Category: Biology Authors: Liao C, Carlson BA, Paulson RF, Prabhu KS Tags: Free Radic Biol Med Source Type: research

Anagliptin inhibits neointimal hyperplasia after balloon injury via endothelial cell-specific modulation of SOD-1/RhoA/JNK signaling in the arterial wall.
Abstract Intimal hyperplasia is one of the major complications after stenting, but the underlying mechanisms remain unclear. Our previous study found that the dipeptidyl peptidase IV (DPP-4) inhibitor, Anagliptin, suppresses intimal hyperplasia after balloon injury. Here, we further investigated the effects of Anagliptin on endothelial cell (EC) migration after balloon injury. The results showed that Anagliptin administration significantly reduced intimal hyperplasia by stimulating the migration of endothelial cells, but had no effect on the medial area after balloon injury. Anagliptin elevated the total plasma ac...
Source: Free Radical Biology and Medicine - April 28, 2018 Category: Biology Authors: Li Q, Zhang M, Xuan L, Liu Y, Chen C Tags: Free Radic Biol Med Source Type: research

Posttranslational regulation of CYP2J2 by nitric oxide.
In conclusion, these data suggest that NO regulates CYP2J2 posttranslationally and NO-evoked CYP2J2 degradation undergoes ubiquitin-independent proteasomal degradation pathway unlike CYP2B6. PMID: 29715548 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - April 28, 2018 Category: Biology Authors: Park JW, Lee CM, Cheng JS, Morgan ET Tags: Free Radic Biol Med Source Type: research

Selenophosphate synthetase 1 and its role in redox homeostasis, defense and proliferation.
Abstract Selenophosphate synthetase (SEPHS) synthesizes selenophosphate, the active selenium donor, using ATP and selenide as substrates. SEPHS was initially identified and isolated from bacteria and has been characterized in many eukaryotes and archaea. Two SEPHS paralogues, SEPHS1 and SEPHS2, occur in various eukaryotes, while prokaryotes and archaea have only one form of SEPHS. Between the two isoforms in eukaryotes, only SEPHS2 shows catalytic activity during selenophosphate synthesis. Although SEPHS1 does not contain any significant selenophosphate synthesis activity, it has been reported to play an essential...
Source: Free Radical Biology and Medicine - April 28, 2018 Category: Biology Authors: Na J, Jung J, Bang J, Lu Q, Carlson BA, Guo X, Gladyshev VN, Kim J, Hatfield DL, Lee BJ Tags: Free Radic Biol Med Source Type: research

Berberine exerts antioxidant effects via protection of spiral ganglion cells against cytomegalovirus-induced apoptosis.
This study aims to investigate whether BBR has an anti-apoptosis effect in CMV-induced apoptosis in cultured spiral ganglion cells and explore the possible mechanism. In this study, TUNEL and MTT assays significantly demonstrated that low doses of BBR did not promote cell apoptosis and they also inhibited the CMV-induced cultured spiral ganglion cell apoptosis. Immunofluorescence and Western blot assays indicated that the anti-apoptosis effect of BBR was related to Nox3. Mitochondrial calcium and Western blot assays revealed that NMDAR1 mediated this anti-apoptosis effect. Our results demonstrated that BBR exerted an anti-...
Source: Free Radical Biology and Medicine - April 28, 2018 Category: Biology Authors: Zhuang W, Li T, Wang C, Shi X, Li Y, Zhang S, Zhao Z, Dong H, Qiao Y Tags: Free Radic Biol Med Source Type: research

A Photo-Triggered and Photo-Calibrated Nitric Oxide Donor: Rational Design, Spectral Characterizations, and Biological Applications.
Abstract Nitric oxide (NO) donors are valuable tools to probe the profound implications of NO in health and disease. The elusive nature of NO bio-relevance has largely limited the use of spontaneous NO donors and promoted the development of next generation NO donors, whose NO release is not only stimulated by a trigger, but also readily monitored via a judiciously built-in self-calibration mechanism. Light is without a doubt the most sensitive, versatile and biocompatible method of choice for both triggering and monitoring, for applications in complex biological matrices. Herein, we designed and synthesized an N-n...
Source: Free Radical Biology and Medicine - April 27, 2018 Category: Biology Authors: He H, Liu Y, Zhou Z, Guo C, Wang HY, Wang Z, Wang X, Zhang Z, Wu FG, Wang H, Chen D, Yang D, Liang X, Chen J, Zhou S, Liang X, Qian X, Yang Y Tags: Free Radic Biol Med Source Type: research

Aging attenuates redox adaptive homeostasis and proteostasis in female mice exposed to traffic-derived nanoparticles ('vehicular smog').
This report extends prior findings in male mice by demonstrating the involvement of proteolytic responses to traffic-related air pollution in lung, liver, and heart of female mice, with an age-dependent loss of adaptive homeostasis. PMID: 29709705 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - April 27, 2018 Category: Biology Authors: Pomatto LCD, Cline M, Woodward N, Pakbin P, Sioutas C, Morgan TE, Finch CE, Forman HJ, Davies KJA Tags: Free Radic Biol Med Source Type: research

Argirein alleviates vascular endothelial insulin resistance through suppressing the activation of Nox4-dependent O2- production in diabetic rats.
CONCLUSION: These results suggested that argirein could improve endothelial insulin resistance which was attributed to inhibiting Nox4-dependent redox signaling in RAECs. These studies thus revealed the novel effect of argirein to prevent the vascular complication in T2DM. PMID: 29709706 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - April 27, 2018 Category: Biology Authors: Li Q, Su J, Jin SJ, Wei W, Cong XD, Li XX, Xu M Tags: Free Radic Biol Med Source Type: research

Consequences of mutations and inborn errors of selenoprotein biosynthesis and functions.
Abstract In its 200 years of history, selenium has been defined first as a toxic element and finally as a micronutrient. Selenium is incorporated into selenoproteins as selenocysteine (Sec), the 21st proteinogenic amino acid codified by a stop codon. Specific biosynthetic factors recode UGA stop codon as Sec. The significance of selenoproteins in human health is manifested through the identification of patients with inborn errors in selenoproteins or their biosynthetic factors. Selenoprotein N-related myopathy was the first disease identified due to mutations in a selenoprotein gene. Mutations in GPX4 were linked ...
Source: Free Radical Biology and Medicine - April 27, 2018 Category: Biology Authors: Fradejas-Villar N Tags: Free Radic Biol Med Source Type: research

Mitochondrial targeting of HIF-1 α inhibits hypoxia-induced apoptosis independently of its transcriptional activity.
Mitochondrial targeting of HIF-1α inhibits hypoxia-induced apoptosis independently of its transcriptional activity. Free Radic Biol Med. 2018 Apr 25;: Authors: Li HS, Zhou YN, Li L, Li SF, Long D, Chen XL, Zhang JB, Li YP, Feng L Abstract The transcription factor hypoxia inducible factor-1α (HIF-1α) mediates adaptive responses to hypoxia by nuclear translocation and regulation of gene expression. Mitochondrial changes are critical for the adaptive response to hypoxia. However, the transcriptional and non-transcriptional mechanisms by which HIF-1α regulates mitochondria under hy...
Source: Free Radical Biology and Medicine - April 25, 2018 Category: Biology Authors: Li HS, Zhou YN, Li L, Li SF, Long D, Chen XL, Zhang JB, Li YP, Feng L Tags: Free Radic Biol Med Source Type: research

Electron transfer kinetics of the mitochondrial outer membrane protein mitoNEET.
Abstract Increasing evidence suggests that the mitochondrial outer membrane protein mitoNEET is a key regulator of energy metabolism, iron homeostasis, and production of reactive oxygen species in mitochondria. Previously, we reported that mitoNEET is a redox enzyme that catalyzes electron transfer from the reduced flavin mononucleotide (FMNH2) to oxygen or ubiquinone via its unique [2Fe-2S] clusters. Here, we explore the reduction and oxidation kinetics of the mitoNEET [2Fe-2S] clusters under anaerobic and aerobic conditions. We find that the mitoNEET [2Fe-2S] clusters are rapidly reduced by a catalytic amount of...
Source: Free Radical Biology and Medicine - April 25, 2018 Category: Biology Authors: Li X, Wang Y, Tan G, Lyu J, Ding H Tags: Free Radic Biol Med Source Type: research

Hypothermia augments stress response in mammalian cells.
Abstract Mild hypothermia (32°C) is routinely used in medical practice to alleviate hypoxic ischemic damage, however, the mechanisms that underlie its protective effects remain uncertain. Using a systems approach based on genome-wide expression screens, reporter assays and biochemical studies, we find that cellular hypothermia response is associated with the augmentation of major stress-inducible transcription factors Nrf2 and HIF1Α affecting the antioxidant system and hypoxia response pathways, respectively. At the same time, NF-κB, a transcription factor involved in the control of immune and infl...
Source: Free Radical Biology and Medicine - April 25, 2018 Category: Biology Authors: Eskla KL, Porosk R, Reimets R, Visnapuu T, Vasar E, Hundahl CA, Luuk H Tags: Free Radic Biol Med Source Type: research

Fluorescent probes for the detection of nitroxyl (HNO).
Abstract Nitroxyl (HNO), which according to the IUPAC recommended nomenclature should be named azanone, is the protonated one-electron reduction product of nitric oxide. Recently, it has gained a considerable attention due to the interesting pharmacological effects of its donors. Although there has been great progress in the understanding of HNO chemistry and chemical biology, it still remains the most elusive reactive nitrogen species, and its selective detection is a real challenge. The development of reliable methodologies for the direct detection of azanone is essential for the understanding of important signa...
Source: Free Radical Biology and Medicine - April 25, 2018 Category: Biology Authors: Smulik-Izydorczyk R, Dębowska K, Pięta J, Michalski R, Marcinek A, Sikora A Tags: Free Radic Biol Med Source Type: research

Mapping Three Guanine Oxidation Products along DNA Following Exposure to Three Types of Reactive Oxygen Species.
Abstract Reactive oxygen and nitrogen species generated during respiration, inflammation, and immune response can damage cellular DNA, contributing to aging, cancer, and neurodegeneration. The ability of oxidized DNA bases to interfere with DNA replication and transcription is strongly influenced by their chemical structures and locations with the genome. In the present work, we examined the influence of local DNA sequence context, DNA secondary structure, and oxidant identity on the efficiency and the chemistry of guanine oxidation in the context of the Kras protooncogene. A novel isotope labeling strategy develo...
Source: Free Radical Biology and Medicine - April 24, 2018 Category: Biology Authors: Matter B, Seiler CL, Murphy K, Ming X, Zhao J, Lindgren B, Jones R, Tretyakova N Tags: Free Radic Biol Med Source Type: research

Prevention of 4-hydroxynonenal-induced lipolytic activation by carnosic acid is related to the induction of glutathione S-transferase in 3T3-L1 adipocytes.
In this study, we investigated the effects of carnosic acid (CA) on 4-HNE-induced lipolysis and the inhibition of β-oxidation in 3T3-L1 adipocytes. The results indicated that cells pretreated with CA reduced 4-HNE-mediated free fatty acid (FFA) release. Furthermore, CA reversed the inhibition of phosphorylation of Tyr632 of insulin receptor substrate-1 (IRS-1) and Akt and the phosphorylation of Ser307 of IRS-1. CA inhibited 4-HNE-induced phosphorylation of protein kinase A (PKA) and hormone-sensitive lipase (HSL), and reversed the suppression by 4-HNE of phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (p
Source: Free Radical Biology and Medicine - April 23, 2018 Category: Biology Authors: Liu KL, Kuo WC, Lin CY, Lii CK, Liu YL, Cheng YH, Tsai CW Tags: Free Radic Biol Med Source Type: research

Age and the effect of exercise, nutrition and cognitive training on oxidative stress - the Vienna Active Aging Study (VAAS), a randomized controlled trial.
Abstract The purpose of this study was to investigated the effect of age - over or under life-expectancy (LE) - on six months resistance training alone or combined with a nutritional supplement, and cognitive training by analyzing markers for oxidative stress and antioxidant defense in institutionalized elderly, living in Vienna. Three groups (n=117, age=83.1±6.1 years) - resistance training (RT), RT combined with protein and vitamin supplementation (RTS) or cognitive training (CT) - performed two guided training sessions per week for six months. Oxidative stress, antioxidant defense and DNA strand breaks w...
Source: Free Radical Biology and Medicine - April 23, 2018 Category: Biology Authors: Franzke B, Schober-Halper B, Hofmann M, Oesen S, Tosevska A, Henriksen T, Poulsen HE, Strasser EM, Wessner B, Wagner KH Tags: Free Radic Biol Med Source Type: research

Neurotoxicity of Cytarabine (Ara-C) in Dorsal Root Ganglion Neurons Originates from Impediment of mtDNA Synthesis and Compromise of Mitochondrial Function.
The objective of this work was to elucidate progression of events triggered by antimitotic drugs in postmitotic neurons. For proof of mechanism study, we chose cytarabine (ara-C), an antimetabolite used in treatment of hematological cancers. Ara-C is a cytosine analog that terminates DNA synthesis. To investigate how ara-C affects postmitotic neurons, which replicate mitochondrial but not genomic DNA, we adapted a model of Dorsal Root Ganglion (DRG) neurons. We showed that DNA polymerase γ, which is responsible for mtDNA synthesis, is inhibited by ara-C and that sublethal ara-C exposure of DRG neurons leads to reduct...
Source: Free Radical Biology and Medicine - April 23, 2018 Category: Biology Authors: Zhuo M, Gorgun MF, Englander EW Tags: Free Radic Biol Med Source Type: research

Hyperoxia induces epigenetic changes in newborn mice lungs.
Abstract Supplemental oxygen exposure is a risk factor for the development of bronchopulmonary dysplasia (BPD). Reactive oxygen species may damage lung tissue, but hyperoxia also has the potential to alter genome activity via changes in DNA methylation. Understanding the epigenetic potential of hyperoxia would enable further improvement of the therapeutic strategies for BPD. Here we aimed to identify hyperoxia-related alterations in DNA methylation, which could affect the activity of crucial genetic pathways involved in the development of hyperoxic lung injury. Newborn mice (n = 24) were randomized to hyperoxia (8...
Source: Free Radical Biology and Medicine - April 23, 2018 Category: Biology Authors: Bik-Multanowski M, Revhaug C, Grabowska A, Dobosz A, Madetko-Talowska A, Zasada M, Saugstad OD Tags: Free Radic Biol Med Source Type: research

Evolution, regulation, and function of porcine selenogenome.
In conclusion, expression of porcine selenoproteins was highly responsive to dietary Se and fat intakes, and was involved in body glucose, lipid, and protein metabolism as those of rodents and humans. PMID: 29698745 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - April 23, 2018 Category: Biology Authors: Chen XD, Zhao ZP, Zhou JC, Lei XG Tags: Free Radic Biol Med Source Type: research

NADPH oxidase, oxidative stress and fibrosis in Systemic Sclerosis.
Abstract Systemic sclerosis (SSc) is an autoimmune disease characterized by damage of small vessels, immune abnormalities and exaggerated production of extracellular matrix. The etiology of the disease is unknown and the pathogenesis ill defined. However, there is consistent evidence that oxidative stress contributes to the establishment and progression of the disease. This review examines the most relevant research regarding the involvement of free radicals and of nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidases; NOX) in the pathogenesis of systemic sclerosis. PMID: 29694853 [PubMed - as ...
Source: Free Radical Biology and Medicine - April 22, 2018 Category: Biology Authors: Svegliati S, Spadoni T, Moroncini G, Gabrielli A Tags: Free Radic Biol Med Source Type: research

S-Nitrosoglutathione reductase (GSNOR) inhibitor as an immune modulator in experimental autoimmune encephalomyelitis.
In this study, we evaluated potential of reversible inhibitor of GSNOR (N6022) in comparison with exogenous GSNO in immunopathogenesis of EAE. Daily treatment of EAE mice with N6022 or exogenous GSNO significantly attenuated the clinical disease of EAE, but N6022 treatment showed greater efficacy than GSNO. Both N6022 and exogenous GSNO treatments increased the spleen levels of GSNO, as documented by increased protein-associated S-nitrosothiols, and inhibited polarization and CNS effector function of proinflammatory TH17 cells while inducing the polarization and CNS effector function of anti-inflammatory CD4+ CD25+ FOXP3- ...
Source: Free Radical Biology and Medicine - April 22, 2018 Category: Biology Authors: Saxena N, Won J, Choi S, Singh AK, Singh I Tags: Free Radic Biol Med Source Type: research

Early events in copper-ion catalyzed oxidation of α-synuclein.
In this study, we have examined time-dependent oxidative events related to α-synuclein modification using six different molar ratios of Cu2+/H2O2/protein and Cu2+/H2O2/ascorbate/protein resulting in mild to moderate extents of oxidation. For a Cu2+/H2O2/protein molar ratio of 2.3:7.8:1 only low levels of carbonyls were detected (0.078 carbonyls per protein), whereas a molar ratio of 4.7:15.6:1 gave 0.22 carbonyls per α-synuclein within 15min. With the latter conditions, rapid conversion of 3 out of 4 methionines (Met) to methionine sulfoxide, and 2 out of 4 tyrosines (Tyr) were converted to products including i...
Source: Free Radical Biology and Medicine - April 21, 2018 Category: Biology Authors: Tiwari MK, Leinisch F, Sahin C, Møller IM, Otzen DE, Davies MJ, Bjerrum MJ Tags: Free Radic Biol Med Source Type: research

Multicoloured fluorescent indicators for live-cell and in vivo imaging of inorganic mercury dynamics.
Abstract Engineered fluorescent indicators for visualizing mercury ion (Hg2+) are powerful tools to illustrate the intracellular distribution and serious toxicity of the ion. However, the sensitive and specific detection of Hg2+ in living cells and in vivo is challenging. This paper reported the development of fluorescent indicators for Hg2+ in green or red color by inserting a circularly permuted fluorescent protein into a highly mercury-specific repressor. These sensors provided a rapid, sensitive, specific, and real-time read-out of Hg2+ dynamics in solutions, bacteria, subcellular organelles of mammalian cells...
Source: Free Radical Biology and Medicine - April 20, 2018 Category: Biology Authors: Tao R, Shi M, Zou Y, Cheng D, Wang Q, Liu R, Wang A, Zhu J, Deng L, Hu H, Chen X, Du J, Zhu W, Zhao Y, Yang Y Tags: Free Radic Biol Med Source Type: research

Nrf2 protects against acute lung injury and inflammation by modulating TLR4 and Akt signaling.
Abstract Lung injury, which is associated with systemic inflammatory responses, is a common problem with significant morbidity and mortality. Here, we examined the involvement of toll-like receptor 4 (TLR4) and nuclear factor erythroid 2-related factor 2 (Nrf2) on intestinal ischemia-reperfusion (I/R)-induced lung injury in vivo and in vitro. Analysis of lung tissues in Nrf2-knockout mice by western blotting, immunohistochemistry, and TUNEL assay, and analysis of bronchoalveolar lavage fluid showed that Nrf2 deficiency upregulated TLR4, enhanced I/R-induced lung injury, apoptosis, inflammation, and autophagy, and ...
Source: Free Radical Biology and Medicine - April 17, 2018 Category: Biology Authors: Yan J, Li J, Zhang L, Sun Y, Jiang J, Huang Y, Xu H, Jiang H, Hu R Tags: Free Radic Biol Med Source Type: research

Diffusion of nitric oxide and oxygen in lipoproteins and membranes studied by pyrene fluorescence quenching.
a A Abstract Oxygen and nitric oxide are small hydrophobic molecules that usually need to diffuse a considerable distance to accomplish their biological functions and necessarily need to traverse several lipid membranes. Different methods have been used to study the diffusion of these molecules in membranes and herein we focus in the quenching of fluorescence of pyrenes inserted in the membrane. The pyrene derivatives have long fluorescence lifetimes (around 200 ns) that make them very sensitive to fluorescence quenching by nitric oxide, oxygen and other paramagnetic species. Results show that the apparent diffusi...
Source: Free Radical Biology and Medicine - April 16, 2018 Category: Biology Authors: Möller MN, Denicola A Tags: Free Radic Biol Med Source Type: research

ROS Modifiers and NOX4 Affect the Expression of the Survivin-Associated Radio-Adaptive Response.
Abstract The survivin-associated radio-adaptive response can be induced following exposure to ionizing radiation in the dose range from 5 to 100 mGy, and its magnitude of expression is dependent upon the TP53 mutational status of cells and ROS signaling. The purpose of the study was to investigate the potential role of ROS in the development of the survivin-associated adaptive response. Utilizing human colon carcinoma HCT116 TP53 wild type (WT) and HCT116 isogenic TP53 null mutant (Mut) cell cultures, the roles of inter- and intracellular ROS signaling on expression of the adaptive response as evidenced by changes...
Source: Free Radical Biology and Medicine - April 13, 2018 Category: Biology Authors: Murley JS, Arbiser JL, Weichselbaum RR, Grdina DJ Tags: Free Radic Biol Med Source Type: research

Effect of humidity on photoinduced radicals in human hair.
Abstract EPR spectroscopy was used to monitor formation of free radicals in human hair upon UV irradiation. While the EPR spectra of brown hair were dominated by melanin signal, those of white hair were keratin-derived. The decay of UV induced keratin radicals was enhanced at increased ambient humidity. We argue that at higher humidity the swollen hair provides a more liquid-like environment, and higher molecular mobility in this environment leads to faster radical reactions. This interpretation is consistent with the increased UV-triggered protein damage in hair at high humidity as demonstrated by the protein los...
Source: Free Radical Biology and Medicine - April 13, 2018 Category: Biology Authors: Groves P, Marsh JM, Sun Y, Chaudhary T, Chechik V Tags: Free Radic Biol Med Source Type: research

Activation of GSK3 β/β-TrCP axis via PHLPP1 exacerbates Nrf2 degradation leading to impairment in cell survival pathway during diabetic nephropathy.
Activation of GSK3β/β-TrCP axis via PHLPP1 exacerbates Nrf2 degradation leading to impairment in cell survival pathway during diabetic nephropathy. Free Radic Biol Med. 2018 Apr 12;: Authors: Mathur A, Pandey VK, Kakkar P Abstract NF-E2 p45-related factor 2 (Nrf2), is a major redox sensitive transcription factor that plays an essential role in regulating glucose metabolism. Inactivation of Nrf2 has been associated with diabetic complications however, mechanisms warranting Nrf2 suppression are incompletely understood. We hypothesized that PHLPP1 activates GSK3β to induce β-TrCP medi...
Source: Free Radical Biology and Medicine - April 12, 2018 Category: Biology Authors: Mathur A, Pandey VK, Kakkar P Tags: Free Radic Biol Med Source Type: research

Short-term sleep deprivation with exposure to nocturnal light alters mitochondrial bioenergetics in Drosophila.
Abstract Many studies have shown the effects of sleep deprivation in several aspects of health and disease. However, little is known about how mitochondrial bioenergetics function is affected under this condition. To clarify this, we developed a simple model of short-term sleep deprivation, in which fruit-flies were submitted to a nocturnal light condition and then mitochondrial parameters were assessed by high resolution respirometry (HRR). Exposure of flies to constant light was able to alter sleep patterns, causing locomotor deficits, increasing ROS production and lipid peroxidation, affecting mitochondrial act...
Source: Free Radical Biology and Medicine - April 12, 2018 Category: Biology Authors: Rodrigues NR, Macedo GE, Martins IK, Gomes KK, de Carvalho NR, Posser T, Franco JL Tags: Free Radic Biol Med Source Type: research

Spatio-temporal monitoring of lipid peroxyl radicals in live cell studies combining fluorogenic antioxidants and fluorescence microscopy methods.
Abstract Lipid peroxidation of polyunsaturated fatty acids in cells may occur via their catalytic autoxidation through peroxyl radicals under oxidative stress conditions. Lipid peroxidation is related to a number of pathologies, and may be invoked in new forms of regulated cell death, yet it may also have beneficial roles in cell signaling cascades. Antioxidants are a natural line of defense against lipid peroxidation, and may accordingly impact the biological outcome associated with the redox chemistry of lipid peroxidation. Critical to unraveling the physiological and pathological role of lipid peroxidation is t...
Source: Free Radical Biology and Medicine - April 9, 2018 Category: Biology Authors: Greene LE, Lincoln R, Cosa G Tags: Free Radic Biol Med Source Type: research

Nrf2 signaling and autophagy are complementary in protecting breast cancer cells during glucose deprivation.
In this study, we explored protective mechanisms in breast cancer cells in the setting of glucose deprivation. While breast cancer cells (MCF7 and T47D) survive in glucose-free medium for three days or more, autophagy is induced in this setting. Blocking autophagy pharmacologically with chloroquine or by knock-out of an essential autophagy gene, such as Beclin 1 or ATG7, markedly reduces the ability of cells to survive during glucose deprivation. Autophagy previously was shown to degrade p62, a protein that sequesters KEAP1, and KEAP1 in turn sequesters Nrf2, a master regulator of the antioxidant response. Hence, we invest...
Source: Free Radical Biology and Medicine - April 9, 2018 Category: Biology Authors: Walker A, Singh A, Tully E, Woo J, Le A, Nguyen T, Biswal S, Sharma D, Gabrielson E Tags: Free Radic Biol Med Source Type: research

Honokiol alleviates the degeneration of intervertebral disc via suppressing the activation of TXNIP-NLRP3 inflammasome signal pathway.
Abstract Intervertebral disc degeneration (IVDD) is a multifactorial disease and responsible for many spine related disorders, causes disability in the workforce and heavy social costs all over the world. Honokiol, a low molecular weight natural product, could penetrate into and distribute in IVDs to achieve therapeutic effect in a rat tail model. Therefore, the present study was undertaken to examine the antiinflammatory, antioxidation and chondroprotective effect of honokiol using nucleus pulposus cells and investigate its mechanisms to provide a new basis for future clinical treatment of IVDD. In the current st...
Source: Free Radical Biology and Medicine - April 9, 2018 Category: Biology Authors: Tang P, Gu JM, Xie ZA, Gu Y, Jie ZW, Huang KM, Wang JY, Fan SW, Jiang XS, Hu ZJ Tags: Free Radic Biol Med Source Type: research

The cysteine residue of glial fibrillary acidic protein is a critical target for lipoxidation and required for efficient network organization.
;rez-Sala D Abstract The type III intermediate filament protein glial fibrillary acidic protein (GFAP) contributes to the homeostasis of astrocytes, where it co-polymerizes with vimentin. Conversely, alterations in GFAP assembly or degradation cause intracellular aggregates linked to astrocyte dysfunction and neurological disease. Moreover, injury and inflammation elicit extensive GFAP organization and expression changes, which underline reactive gliosis. Here we have studied GFAP as a target for modification by electrophilic inflammatory mediators. We show that the GFAP cysteine, C294, is targeted by lipoxidation...
Source: Free Radical Biology and Medicine - April 7, 2018 Category: Biology Authors: Viedma-Poyatos Á, de Pablo Y, Pekny M, Pérez-Sala D Tags: Free Radic Biol Med Source Type: research

Redox biosensors in a context of multiparameter imaging.
Abstract A wide variety of genetically encoded fluorescent biosensors are available to date. Some of them have already contributed significantly to our understanding of biological processes occurring at cellular and organismal levels. Using such an approach, outstanding success has been achieved in the field of redox biology. The probes allowed researchers to observe, for the first time, the dynamics of important redox parameters in vivo during embryogenesis, aging, the inflammatory response, the pathogenesis of various diseases, and many other processes. Given the differences in the readout and spectra of the pro...
Source: Free Radical Biology and Medicine - April 6, 2018 Category: Biology Authors: Kostyuk AI, Panova AS, Bilan DS, Belousov VV Tags: Free Radic Biol Med Source Type: research

Fluorescent in vivo imaging of reactive oxygen species and redox potential in plants.
Á, Hernández LE Abstract Reactive oxygen species (ROS) are by-products of aerobic metabolism, and excessive production can result in oxidative stress and cell damage. In addition, ROS function as cellular messengers, working as redox regulators in a multitude of biological processes. Understanding ROS signalling and stress responses requires methods for precise imaging and quantification to monitor local, subcellular and global ROS dynamics with high selectivity, sensitivity and spatiotemporal resolution. In this review, we summarize the present knowledge for in vivo plant ROS imaging and detection, ...
Source: Free Radical Biology and Medicine - April 5, 2018 Category: Biology Authors: Ortega-Villasante C, Burén S, Blázquez-Castro A, Barón-Sola Á, Hernández LE Tags: Free Radic Biol Med Source Type: research

Hepatocyte-specific deletion of LASS2 protects against diet-induced hepatic steatosis and insulin resistance.
Abstract Homo sapienslongevity assurance homolog 2 of yeast LAG1 (LASS2) is expressed mostly in human liver. Here, we explored roles of LASS2 in pathogenesis of hepatic steatosis. Hepatocyte-specific LASS2 knockout (LASS2-/-) mice were generated using Cre-LoxP system. LASS2-/- and wild-type (WT) mice were fed with chow or high-fat diet (HFD). We found LASS2-/- mice were resistant to HFD-induced hepatic steatosis and insulin resistance. In HFD-fed mice, LASS2 deficiency significantly inhibited p38 MAPK and ERK1/ERK2 signaling in mouse liver. This effect was mediated by a significant increase of V-ATPase activity an...
Source: Free Radical Biology and Medicine - April 4, 2018 Category: Biology Authors: Fan S, Wang Y, Wang C, Jin H, Wu Z, Lu J, Zhang Z, Sun C, Shan Q, Wu D, Zhuang J, Sheng N, Xie Y, Li M, Hu B, Fang J, Zheng Y, Qin W Tags: Free Radic Biol Med Source Type: research

Oxidant-Specific Biomarkers of Oxidative Stress. Association with Atherosclerosis and Implication for Antioxidant Effects.
Abstract The unregulated oxidative modification of lipids, proteins, and nucleic acids induced by multiple oxidants has been implicated in the pathogenesis of many diseases. Antioxidants with diverse functions exert their roles either directly or indirectly in the physiological defense network to inhibit such deleterious oxidative modification of biological molecules and resulting damage. The efficacy of antioxidants depends on the nature of oxidants. Therefore, it is important to identify the oxidants which are responsible for modification of biological molecules. Some oxidation products produced selectively by s...
Source: Free Radical Biology and Medicine - April 3, 2018 Category: Biology Authors: Niki E Tags: Free Radic Biol Med Source Type: research

Brain mitochondrial iron accumulates in Huntington's disease, mediates mitochondrial dysfunction, and can be removed pharmacologically.
Abstract Mitochondrial bioenergetic dysfunction is involved in neurodegeneration in Huntington's disease (HD). Iron is critical for normal mitochondrial bioenergetics but can also contribute to pathogenic oxidation. The accumulation of iron in the brain occurs in mouse models and in human HD. Yet the role of mitochondria-related iron dysregulation as a contributor to bioenergetic pathophysiology in HD is unclear. We demonstrate here that human HD and mouse model HD (12-week R6/2 and 12-month YAC128) brains accumulated mitochondrial iron and showed increased expression of iron uptake protein mitoferrin 2 and decrea...
Source: Free Radical Biology and Medicine - April 3, 2018 Category: Biology Authors: Agrawal S, Fox J, Thyagarajan B, Fox J Tags: Free Radic Biol Med Source Type: research