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Angiotensin converting enzyme inhibitors enhance the hypotensive effects of propofol by increasing nitric oxide production.
In this study we evaluated 65 patients, divided into three groups: hypertensive patients chronically treated with ACEi (HT-ACEi; n=21), hypertensive patients treated with other antihypertensive drugs instead of ACEi, such as angiotensin II receptor blockers, β-blockers or diuretics (HT; n=21) and healthy normotensive subjects (NT; n=23). Venous blood samples were collected at baseline and after 10minutes of anesthesia with propofol2 mg/kg administrated intravenously by bolus injection. Hemodynamic parameters were recorded at each blood sample collection. Nitrite levels were determined by using an ozone-based chemilumi...
Source: Free Radical Biology and Medicine - November 11, 2017 Category: Biology Authors: Oliveira-Paula GH, Pinheiro LC, Ferreira GC, Garcia WNP, Lacchini R, Garcia LV, Tanus-Santos JE Tags: Free Radic Biol Med Source Type: research

Anti-tumor effects of cold atmospheric pressure plasma on vestibular schwannoma demonstrate its feasibility as an intra-operative adjuvant treatment.
Abstract Vestibular schwannoma (VS), although a benign intracranial tumor, causes morbidities by brainstem compression. Since chemotherapy is not very effective in most Nf2-negative schwannomas, surgical removal or radiation therapy is required. However, depending on the size and site of the tumor, these approaches may cause loss of auditory or vestibular functions, and severely decrease the post-surgical wellbeing. Here, we examined the feasibility of cold atmospheric pressure plasma (CAP) as an intra-operative adjuvant treatment for VS after surgery. Cell death was efficiently induced in both human HEI-193 and m...
Source: Free Radical Biology and Medicine - November 11, 2017 Category: Biology Authors: Yoon YJ, Suh MJ, Lee HY, Lee HJ, Choi EH, Moon IS, Song K Tags: Free Radic Biol Med Source Type: research

Mutual influence of sleep and circadian clocks on physiology and cognition.
Abstract The 24-hour sleep-wake cycle is one of the most prominent outputs of the circadian clock system. At the same time, changes in sleep-wake behavior feedback on behavioral and physiological circadian rhythms, thus altering the coordination of the body's clock network. Sleep and circadian rhythm disruption have similar physiological endpoints including metabolic, cognitive, and immunologic impairments. This raises the question to which extent these phenomena are causally linked. In this review, we summarize different physiologic outcomes of sleep deprivation and mistimed sleep and discuss the experimental evi...
Source: Free Radical Biology and Medicine - November 10, 2017 Category: Biology Authors: Heyde I, Kiehn JT, Oster H Tags: Free Radic Biol Med Source Type: research

Topical electrophilic nitro-fatty acids potentiate cutaneous inflammation.
Abstract Endogenous electrophilic fatty acids mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction and gene expression. Nitro-fatty acids and other electrophilic fatty acids may thus be useful for the prevention and treatment of immune-mediated diseases, including inflammatory skin disorders. In this regard, subcutaneous (SC) injections of nitro oleic acid (OA-NO2), an exemplary nitro-fatty acid, inhibit skin inflammation in a model of allergic contact dermatitis (ACD). Given the nitration of unsaturated fatty acids during metabolic and inflammatory processes and the gro...
Source: Free Radical Biology and Medicine - November 10, 2017 Category: Biology Authors: Mathers AR, Carey CD, Killeen ME, Salvatore SR, Ferris LK, Freeman BA, Schopfer FJ, Falo LD Tags: Free Radic Biol Med Source Type: research

SIRT6 protects against hepatic ischemia/reperfusion injury by inhibiting apoptosis and autophagy related cell death.
In this study, we explored whether SIRT6 is protective against hepatic I/R injury and elucidated the underlying mechanisms. The expression of SIRT6 was significantly decreased during reperfusion compared with the control group. SIRT6-LKO mice exhibited significantly aggravated oxidative stress, mitochondrial dysfunction, inflammatory responses, mitogen-activated protein kinase (MAPK) signaling activation, and apoptosis and autophagy related hepatocyte death compared with control mice. In vitro studies in SIRT6-KO hepatocytes exhibited similar results. In contrast, SIRT6 upregulation alleviated liver damage during hepatic I...
Source: Free Radical Biology and Medicine - November 9, 2017 Category: Biology Authors: Zhang S, Jiang S, Wang H, Di W, Deng C, Jin Z, Yi W, Xiao X, Nie Y, Yang Y Tags: Free Radic Biol Med Source Type: research

F2-isoprostanes can mediate bleomycin-induced lung fibrosis.
In this study, we have investigated the potential key role of F2-IsoPs as markers and mediators of bleomycin (BLM)-induced pulmonary fibrosis in rats. During the in vivo study, plasma F2-IsoPs showed a peak at 7 days and remained elevated for the entire experimental period. Lung F2-IsoP content nearly tripled 7 days following the intratracheal instillation of BLM, and by 28 days, the value increased about fivefold compared to the controls. Collagen deposition correlated with F2-IsoP content in the lung. Furthermore, from day 21 onwards, lung sections from BLM-treated animals showed α-smooth muscle actin (α-SMA)...
Source: Free Radical Biology and Medicine - November 9, 2017 Category: Biology Authors: Arezzini B, Vecchio D, Signorini C, Stringa B, Gardi C Tags: Free Radic Biol Med Source Type: research

Sod2 gene polymorphism may modulate some biochemical responses to a 12-week swimming training.
SOD2 GENE POLYMORPHISM MAY MODULATE SOME BIOCHEMICAL RESPONSES TO A 12-WEEK SWIMMING TRAINING. Free Radic Biol Med. 2017 Nov 03;: Authors: Jówko E, Gromisz W, Sadowski J, Cieśliński I, Kotowska J Abstract The aim of the study was to analyze the effect of SOD2 Val16Ala polymorphism on blood biochemical response to chronic swimming training. Healthy men (students of physical education) participated in a swimming training program (ST group) or served as a control group (CON group). The swimming training program lasted 12 weeks (1.5h per day; 4 days per week). Fasting blood samples were obtained ...
Source: Free Radical Biology and Medicine - November 3, 2017 Category: Biology Authors: Jówko E, Gromisz W, Sadowski J, Cieśliński I, Kotowska J Tags: Free Radic Biol Med Source Type: research

Nitration-mediated deficiency of cystathionine β-synthase activity accelerates the progression of hyperhomocysteinemia.
Nitration-mediated deficiency of cystathionine β-synthase activity accelerates the progression of hyperhomocysteinemia. Free Radic Biol Med. 2017 Nov 03;113:519-529 Authors: Wang H, Sun Q, Zhou Y, Zhang H, Luo C, Xu J, Dong Y, Wu Y, Liu H, Wang W Abstract Deficiency of cystathionine β-synthase (CBS) activity is the most common cause of increased homocysteine (Hcy). However, until now the underlying mechanisms why CBS activity decreased still remain unresolved. The goal of this study was to explore the contribution of nitrative stress to deficiency of CBS activity, and further identify the po...
Source: Free Radical Biology and Medicine - November 3, 2017 Category: Biology Authors: Wang H, Sun Q, Zhou Y, Zhang H, Luo C, Xu J, Dong Y, Wu Y, Liu H, Wang W Tags: Free Radic Biol Med Source Type: research

Derangement of intestinal epithelial cell monolayer by dietary cholesterol oxidation products.
DERANGEMENT OF INTESTINAL EPITHELIAL CELL MONOLAYER BY DIETARY CHOLESTEROL OXIDATION PRODUCTS. Free Radic Biol Med. 2017 Nov 01;: Authors: Deiana M, Calfapietra S, Incani A, Atzeri A, Rossin D, Loi R, Sottero B, Iaia N, Poli G, Biasi F Abstract The emerging role of the diet in the incidence of intestinal inflammatory diseases has stimulated research on the influence of eating habits with pro-inflammatory properties in inducing epithelial barrier disturbance. Cholesterol oxidation products, namely oxysterols, have been shown to promote and sustain oxidative/inflammatory reactions in human digestive tra...
Source: Free Radical Biology and Medicine - November 1, 2017 Category: Biology Authors: Deiana M, Calfapietra S, Incani A, Atzeri A, Rossin D, Loi R, Sottero B, Iaia N, Poli G, Biasi F Tags: Free Radic Biol Med Source Type: research

Mitochondrial Catalase Induces Cells Transformation Through Nucleolin-dependent Cox-2 mRNA Stabilization.
Abstract It's well documented that over-production of reactive oxygen species (ROS) causes detrimental damages to cells. While a low level of ROS, such as H2O2, functions as signaling transducer and motivates cell proliferation in both cancer and non-transformed stem cells. As a double-edged sword, the direct evidence for demonstrating the function of H2O2 in the cause of tumor is barely characterized in intact cells. In our current study, we found that targeted expression of mitochondrial catalase (mCAT), but not catalase, could significantly reduce the accumulation of H2O2 in mouse epithelial JB6 Cl41 cells, con...
Source: Free Radical Biology and Medicine - October 30, 2017 Category: Biology Authors: Liao X, Huang C, Zhang D, Wang J, Li J, Jin H, Huang C Tags: Free Radic Biol Med Source Type: research

Mechanisms of myeloperoxidase catalyzed oxidation of H2S by H2O2 or O2 to produce potent protein Cys-polysulfide-inducing species.
J, Obinger CC, Nagy P Abstract The interaction of heme proteins with hydrogen sulfide is gaining attention as an important element in sulfide-mediated protection against oxidative stress and in regulation of redox signaling. In our previous study we reported the efficient reversible inhibition of myeloperoxidase (MPO) activity by sulfide and the kinetics of the reactions of sulfide with ferric MPO, Compound I and Compound II. Here we provide several lines of evidence that a central intermediate species in the turnover of MPO by sulfide is the Compound III state. Compound III is formed in the reactions of sulfide w...
Source: Free Radical Biology and Medicine - October 30, 2017 Category: Biology Authors: Garai D, Ríos-González BB, Furtmüller PG, Fukuto JM, Xian M, López-Garriga J, Obinger CC, Nagy P Tags: Free Radic Biol Med Source Type: research

Redox Regulation of Circadian Molecular Clock in Chronic Airway Diseases.
Abstract At the cellular level, circadian timing is maintained by the molecular clock, a family of interacting clock gene transcription factors, nuclear receptors and kinases called clock genes. Daily rhythms in pulmonary function are dictated by the circadian timing system, including rhythmic susceptibility to the harmful effects of air born pollutants, exacerbations in patients with chronic airway disease and the immune-inflammatory response to infection. Further, evidence strongly suggests that the circadian molecular clock has a robust reciprocal interaction with redox signaling and plays a considerable role i...
Source: Free Radical Biology and Medicine - October 30, 2017 Category: Biology Authors: Sundar IK, Sellix MT, Rahman I Tags: Free Radic Biol Med Source Type: research

Mitochondrial targeted curcumin exhibits anticancer effects through disruption of mitochondrial redox and modulation of TrxR2 activity.
This study also demonstrates the role of TrxR2 and mitochondrial DNA damage in mitocurcumin mediated killing of cancer cells. PMID: 29080841 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - October 25, 2017 Category: Biology Authors: Jayakumar S, Patwardhan RS, Pal D, Singh B, Sharma D, Kutala VK, Kumar Sandur S Tags: Free Radic Biol Med Source Type: research

Enhanced B-Raf-mediated NRF2 gene transcription and HATs-mediated NRF2 protein acetylation contributes to ABCC1-mediated chemoresistance and glutathione-mediated survival in acquired topoisomerase II poison-resistant cancer cells.
Abstract Nuclear factor erythroid-2-related factor 2 (NRF2) mainly regulates transcriptional activation through antioxidant-responsive elements (AREs) present in the promoters of NRF2 target genes. Recently, we found that NRF2 was overexpressed in a KB-derived drug-resistant cancer cell panel. In this panel, KB-7D cells, which show acquired resistance to topoisomerase II (Top II) poisons, exhibited the highest NRF2 activation. To investigate whether NRF2 directly contributed to acquired resistance against Top II poisons, we manipulated NRF2 by genetic and pharmacological approaches. The result demonstrated that si...
Source: Free Radical Biology and Medicine - October 25, 2017 Category: Biology Authors: Chen HH, Chang HH, Chang JY, Tang YC, Cheng YC, Lin LM, Cheng SY, Huang CH, Sun MW, Chen CT, Kuo CC Tags: Free Radic Biol Med Source Type: research

Aging and parkinson's disease: inflammaging, neuroinflammation and biological remodelling as key factors in pathogenesis.
AGING AND PARKINSON'S DISEASE: INFLAMMAGING, NEUROINFLAMMATION AND BIOLOGICAL REMODELLING AS KEY FACTORS IN PATHOGENESIS. Free Radic Biol Med. 2017 Oct 25;: Authors: Calabrese V, Santoro A, Monti D, Crupi R, Paola RD, Latteri S, Cuzzocrea S, Zappia M, Giordano J, Calabrese EJ, Franceschi C Abstract In order to better understand the pathogenesis of Parkinson's Disease (PD) it is important to consider possible contributory factors inherent to the aging process, as age-related changes in a number of physiological systems (perhaps incurred within particular environments) appear to influence the onset and ...
Source: Free Radical Biology and Medicine - October 25, 2017 Category: Biology Authors: Calabrese V, Santoro A, Monti D, Crupi R, Paola RD, Latteri S, Cuzzocrea S, Zappia M, Giordano J, Calabrese EJ, Franceschi C Tags: Free Radic Biol Med Source Type: research

Conversion of NOX2 into a constitutive enzyme in vitro and in living cells, after its binding with a chimera of the regulatory subunits.
Abstract During the phagocytosis of pathogens by phagocyte cells, the NADPH oxidase complex is activated to produce superoxide anion, a precursor of microbial oxidants. The activated NADPH oxidase complex from phagocytes consists in two transmembrane proteins (Nox2 and p22(phox)) and four cytosolic proteins (p40(phox), p47(phox), p67(phox) and Rac1-2). In the resting state of the cells, these proteins are dispersed in the cytosol, the membrane of granules and the plasma membrane. In order to synchronize the assembly of the cytosolic subunits on the membrane components of the oxidase, a fusion of the cytosolic prot...
Source: Free Radical Biology and Medicine - October 24, 2017 Category: Biology Authors: Masoud R, Serfaty X, Erard M, Machillot P, Karimi G, Hudik E, Wien F, Baciou L, Levin CH, Bizouarn T Tags: Free Radic Biol Med Source Type: research

Synergistic Enhancement of Topotecan-Induced Cell Death by Ascorbic Acid in Human Breast MCF-7 Tumor Cells.
In this report we describe the formation of a topotecan radical, catalyzed by a peroxidase-hydrogen peroxide system. While this topotecan radical did not undergo oxidation-reduction with molecular O2, it rapidly reacted with reduced glutathione and cysteine, regenerating topotecan and forming the corresponding glutathiyl and cysteiniyl radicals. Ascorbic acid, which produces hydrogen peroxide in tumor cells, significantly increased topotecan cytotoxicity in MCF-7 tumor cells. The presence of ascorbic acid also increased both topoisomerase I-dependent topotecan-induced DNA cleavage complex formation and topotecan-induced DN...
Source: Free Radical Biology and Medicine - October 24, 2017 Category: Biology Authors: Sinha BK, van 't Erve TJ, Kumar A, Bortner CD, Motten AG, Mason RP Tags: Free Radic Biol Med Source Type: research

Down Syndrome: From Development to Adult Life to Alzheimer Disease.
PMID: 29079527 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - October 24, 2017 Category: Biology Authors: Butterfield DA, Perluigi M Tags: Free Radic Biol Med Source Type: research

Increased Serotransferrin and Ceruloplasmin Turnover in Diet-Controlled Patients with Type 2 Diabetes.
In this study, shotgun proteomics and (2)H2O-based metabolic labeling were used to characterize post-translational modifications and assess the kinetics of Trf and Cp in T2DM patients and matched controls in vivo. Six early lysine (Amadori) and one advanced arginine glycation were detected in Trf. No glycations, but five asparagine deamidations, were found in Cp. T2DM patients had increased fractional catabolic rates of both Trf and Cp that correlated with HbA1c (p
Source: Free Radical Biology and Medicine - October 24, 2017 Category: Biology Authors: Golizeh M, Lee K, Ilchenko S, Ösme A, Bena J, Sadygov R, Kashyap S, Kasumov T Tags: Free Radic Biol Med Source Type: research

Ergothioneine stands out from hercynine in the reaction with singlet oxygen: resistance to glutathione and TRIS in the generation of specific products indicates high reactivity.
l;ndemann D Abstract The candidate vitamin ergothioneine (ET), an imidazole-2-thione derivative of histidine betaine, is generally considered an antioxidant. However, the precise physiological role of ET is still unresolved. Here, we investigated in vitro the hypothesis that ET serves specifically to eradicate noxious singlet oxygen ((1)O2). Pure (1)O2 was generated by thermolysis at 37°C of N,N'-di(2,3-dihydroxypropyl)-1,4-naphthalenedipropanamide 1,4-endoperoxide (DHPNO2). Assays of DHPNO2 with ET or hercynine (= ET minus sulfur) at pH 7.4 were analyzed by LC-MS in full scan mode to detect products. Based on...
Source: Free Radical Biology and Medicine - October 23, 2017 Category: Biology Authors: Stoffels C, Oumari M, Perrou A, Termath A, Schlundt W, Schmalz HG, Schäfer M, Wewer V, Metzger S, Schömig E, Gründemann D Tags: Free Radic Biol Med Source Type: research

Neutrophil granule proteins generate bactericidal ammonia chloramine on reaction with hydrogen peroxide.
Abstract The neutrophil enzyme, myeloperoxidase, by converting hydrogen peroxide (H2O2) and chloride to hypochlorous acid (HOCl), provides important defense against ingested micro-organisms. However, there is debate about how efficiently HOCl is produced within the phagosome and whether its reactions with phagosomal constituents influence the killing mechanism. The phagosome is a small space surrounding the ingested organism, into which superoxide, H2O2 and high concentrations of proteins from cytoplasmic granules are released. Previous studies imply that HOCl is produced in the phagosome, but a large proportion s...
Source: Free Radical Biology and Medicine - October 18, 2017 Category: Biology Authors: Green JN, Chapman ALP, Bishop CJ, Winterbourn CC, Kettle AJ Tags: Free Radic Biol Med Source Type: research

Selenium-containing indolyl compounds: kinetics of reaction with inflammation-associated oxidants and protective effect against oxidation of extracellular matrix proteins.
es MJ Abstract Activated white blood cells generate multiple oxidants in response to invading pathogens. Thus, hypochlorous acid (HOCl) is generated via the reaction of myeloperoxidase (from neutrophils and monocytes) with hydrogen peroxide, and peroxynitrous acid (ONOOH), a potent oxidizing and nitrating agent is formed from superoxide radicals and nitric oxide, generated by stimulated macrophages. Excessive or misplaced production of these oxidants has been linked to multiple human pathologies, including cardiovascular disease. Atherosclerosis is characterized by chronic inflammation and the presence of oxidized...
Source: Free Radical Biology and Medicine - October 18, 2017 Category: Biology Authors: Casaril AM, Ignasiak MT, Chuang CY, Vieira B, Padilha NB, Carroll L, Lenardão EJ, Savegnago L, Davies MJ Tags: Free Radic Biol Med Source Type: research

Analysis of endogenous H2S and H2Sn in mouse brain by high-performance liquid chromatography with fluorescence and tandem mass spectrometric detection.
Abstract Previous studies indicated that bound sulfur species (BSS), including hydrogen polysulfide (H2Sn), have various physiological functions in mammalian cells. Although H2Sn molecules have been considered as secondary metabolites derived from hydrogen sulfide (H2S) based on in vitro studies or predetermined reaction formula, the physiological form of BSS and their endogenous concentration remain unclear. In the present study, we aimed to improve the usual method using monobromobimane (mBB) followed by high performance liquid chromatographic (HPLC) analysis for HS(-) for simultaneous determination of H2S, H2...
Source: Free Radical Biology and Medicine - October 18, 2017 Category: Biology Authors: Koike S, Kawamura K, Kimura Y, Shibuya N, Kimura H, Ogasawara Y Tags: Free Radic Biol Med Source Type: research

CHAC2 is essential for self-renewal and Glutathione maintenance in human embryonic stem cells.
Abstract Glutathione (GSH), the major non-enzymatic antioxidant, plays a critical role in cellular reactive oxygen species (ROS) neutralization. Moreover, GSH is required for the self-renewal maintenance of human embryonic stem cells (hESCs), and is highly accumulated in undifferentiated cells. Among 8 GSH biosynthesis-related enzymes, we found CHAC2 is highly enriched in undifferentiated hESCs. CHAC2 downregulation in hESCs efficiently decreased the levels of GSH and blocked self-renewal. The self-renewal of sh-CHAC2 cells can be rescued by GSH supplement. CHAC2 downregulation promoted mesoderm differentiation an...
Source: Free Radical Biology and Medicine - October 17, 2017 Category: Biology Authors: Wang CK, Yang SC, Hsu SC, Chang FP, Lin YT, Chen SF, Cheng CL, Hsiao M, Lu FL, Lu J Tags: Free Radic Biol Med Source Type: research

Melatonin reduces oxidative damage and upregulates heat shock protein 90 expression in cryopreserved human semen.
In this study, we added melatonin to cryoprotectant to examine its effect on frozen-thawed human sperm. We found that adding 0.1mM melatonin to cryoprotectant significantly increased sperm viability (24.80 ± 0.46% vs. 20.97 ± 1.27%, P
Source: Free Radical Biology and Medicine - October 16, 2017 Category: Biology Authors: Deng SL, Sun TC, Yu K, Wang ZP, Zhang BL, Zhang Y, Wang XX, Lian ZX, Liu YX Tags: Free Radic Biol Med Source Type: research

Limitations of Oxygen Delivery to Cells in Culture: An Underappreciated Problem in Basic and Translational Research.
Abstract Molecular oxygen is one of the most important variables in modern cell culture systems. Fluctuations in its concentration can affect cell growth, differentiation, signaling, and free radical production. In order to maintain culture viability, experimental validity, and reproducibility, it is imperative that oxygen levels be consistently maintained within physiological "normoxic" limits. Use of the term normoxia, however, is not consistent among scientists who experiment in cell culture. It is typically used to describe the atmospheric conditions of a standard incubator, not the true microenviron...
Source: Free Radical Biology and Medicine - October 12, 2017 Category: Biology Authors: Place TL, Domann FE, Case AJ Tags: Free Radic Biol Med Source Type: research

Dysregulation of Neurotrophin Signaling in the Pathogenesis of Alzheimer Disease and of Alzheimer Disease in Down Syndrome.
Abstract Neurotrophic factors, including the members of the neurotrophin family, play important roles in the development and maintenance of the nervous system. Trophic factor signals must be transmitted over long distances from axons and dendrites to the cell bodies of neurons. A mode of signaling well suited to the challenge of robust long distance signaling is the signaling endosome. We review the biology of signaling endosomes and the "signaling endosome hypothesis". Evidence for disruption of signaling endosome function in disorders of the nervous system is also reviewed. Changes in endosome structur...
Source: Free Radical Biology and Medicine - October 11, 2017 Category: Biology Authors: Chen XQ, Sawa M, Mobley WC Tags: Free Radic Biol Med Source Type: research

Metabolomic analysis of oxidative stress: Superoxide dismutase mutation and paraquat induced stress in Drosophila melanogaster.
Abstract Oxidative stress results in substantial biochemical and physiological perturbations in essentially all organisms. To determine the broad metabolic effects of oxidative stress, we have quantified the response in Drosophila melanogaster to both genetically and environmentally derived oxidative stress. Flies were challenged with loss of Superoxide dismutase activity or chronic or acute exposure to the oxidizing chemical paraquat. Metabolic changes were then quantified using a recently developed chemical isotope labelling (CIL) liquid chromatography - mass spectrometry (LC-MS) platform that targets the carbox...
Source: Free Radical Biology and Medicine - October 11, 2017 Category: Biology Authors: Doran ML, Knee JM, Wang N, Rzezniczak TZ, Parkes TL, Li L, Merritt TJS Tags: Free Radic Biol Med Source Type: research

Dimerization and oxidation of tryptophan in UV-A photolysis sensitized by kynurenic acid.
Abstract Photoinduced generation of radicals in the eye lens may play an important role in the modification of proteins, leading to their coloration, aggregation, and insolubilization. The radicals can be formed via the reactions of photoexcited endogenous chromophores of the human lens with lens proteins, in particular with tryptophan residues. In the present work we studied the reactions induced by UV-A (315-400nm) light between kynurenic acid (KNA), an effective photosensitizer present in the lens, and N-acetyl-L-tryptophan (NTrpH) under aerobic and anaerobic conditions. Our results show that the reaction mecha...
Source: Free Radical Biology and Medicine - October 9, 2017 Category: Biology Authors: Sormacheva ED, Sherin PS, Tsentalovich YP Tags: Free Radic Biol Med Source Type: research

Reactive oxygen species enhance mitochondrial function, insulin sensitivity and glucose uptake in skeletal muscle of senescence accelerated prone mice SAMP8.
Abstract Whereas reactive oxygen species (ROS) can have opposite impacts on insulin signaling, they have mainly been associated with mitochondrial dysfunction in skeletal muscle. We analyzed the relationship between these three features in skeletal muscle of senescence accelerated mice (SAM) prone (P8), which are characterized by enhanced oxidative stress compared to SAM resistant (R1). Oxidative stress, ROS production, antioxidant system, mitochondrial content and functioning, as well as in vitro and in vivo insulin signaling were investigated in gastrocnemius and quadriceps muscles. In SAMP8 compared to SAMR1, m...
Source: Free Radical Biology and Medicine - October 9, 2017 Category: Biology Authors: Barquissau V, Capel F, Dardevet D, Feillet-Coudray C, Gallinier A, Chauvin MA, Rieusset J, Morio B Tags: Free Radic Biol Med Source Type: research

Administration of 5-methoxyindole-2-carboxylic acid that potentially targets mitochondrial dihydrolipoamide dehydrogenase confers cerebral preconditioning against ischemic stroke injury.
The objective of this study was to investigate a possible role of mitochondrial dihydrolipoamide dehydrogenase (DLDH) as a chemical preconditioning target for neuroprotection against ischemic injury. We used 5-methoxyindole-2-carboxylic acid (MICA), a reportedly reversible DLDH inhibitor, as the preconditioning agent and administered MICA to rats mainly via dietary intake. Upon completion of 4 week's MICA treatment, rats underwent 1h transient ischemia and 24h reperfusion followed by tissue collection. Our results show that MICA protected the brain against ischemic stroke injury as the infarction volume of the brain from t...
Source: Free Radical Biology and Medicine - October 7, 2017 Category: Biology Authors: Wu J, Li R, Li W, Ren M, Thangthaeng N, Sumien N, Liu R, Yang S, Simpkins JW, Forster MJ, Yan LJ Tags: Free Radic Biol Med Source Type: research

Dysfunction of Autophagy and Endosomal-lysosomal Pathways: Roles in Pathogenesis of Down Syndrome and Alzheimer's Disease.
Abstract Individuals with Down syndrome (DS) have an increased risk of early-onset Alzheimer's Disease (AD), largely owing to a triplication of the APP gene, located on chromosome 21. In DS and AD, defects in endocytosis and lysosomal function appear at the earliest stages of disease development and progress to widespread failure of intraneuronal waste clearance, neuritic dystrophy and neuronal cell death. The same genetic factors that cause or increase AD risk are also direct causes of endosomal-lysosomal dysfunction, underscoring the essential partnership between this dysfunction and APP metabolites in AD pathog...
Source: Free Radical Biology and Medicine - October 6, 2017 Category: Biology Authors: Colacurcio DJ, Pensalfini A, Jiang Y, Nixon RA Tags: Free Radic Biol Med Source Type: research

Hydrogen peroxide resistance in Strigomonas culicis: effects on mitochondrial functionality and Aedes aegypti interaction.
o RFS Abstract Reactive oxygen species (ROS) are toxic molecules involved in several biological processes such as cellular signaling, proliferation, differentiation and cell death. Adaptations to oxidative environments are crucial for the success of the colonization of insects by protozoa. Strigomonas culicis is a monoxenic trypanosomatid found in the midgut of mosquitoes and presenting a life cycle restricted to the epimastigote form. Among S. culicis peculiarities, there is an endosymbiotic bacterium in the cytoplasm, which completes essential biosynthetic routes of the host cell and may represent an intermediar...
Source: Free Radical Biology and Medicine - October 6, 2017 Category: Biology Authors: Bombaça ACS, Dias FA, Ennes-Vidal V, Garcia-Gomes ADS, Sorgine MHF, d'Avila-Levy CM, Menna-Barreto RFS Tags: Free Radic Biol Med Source Type: research

Reduced silent information regulator 1 signaling exacerbates sepsis-induced myocardial injury and mitigates the protective effect of a liver X receptor agonist.
This study was designed to determine the role of LXR activation in the septic heart with a focus on SIRT1 (silent information regulator 1) signaling. Male cardiac-specific SIRT1 knockout mice (SIRT1-/-) and their wild-type littermates were subjected to sepsis by cecal ligation and puncture (CLP) in the presence or absence of LXR agonist T0901317. The survival rate of mice was recorded during the 7-day period post CLP. Our results demonstrated that SIRT1-/- mice suffered from exacerbated mortality and myocardial injury in comparison with their wild-type littermates. Meanwhile, T0901317 treatment improved mice survival, acco...
Source: Free Radical Biology and Medicine - October 6, 2017 Category: Biology Authors: Han D, Li X, Li S, Su T, Fan WS, Qiao HY, Chen JW, Fan MM, Li XJ, Wang YB, Ma S, Qiu Y, Tian ZH, Cao F Tags: Free Radic Biol Med Source Type: research

Temporal changes in glutathione biosynthesis during the lipopolysaccharide-induced inflammatory response of THP-1 macrophages.
In this study, we investigated the temporal changes in the intracellular glutathione (GSH), the master antioxidant, and the expression of glutamate cysteine ligase (GCL), the rate-limiting enzyme for GSH biosynthesis, in the inflammatory response of human macrophages (THP1 cells) to lipopolysaccharide. Intracellular GSH concentration was decreased significantly in the early phase (~6h) of LPS exposure, and then gradually went back to the basal level in the late phase (9~24h). The expression level of the catalytic subunit of GCL (GCLC) followed a similar pattern of change as GSH: its mRNA and protein levels were reduced in ...
Source: Free Radical Biology and Medicine - October 6, 2017 Category: Biology Authors: Zhang H, Liu H, Zhou L, Yuen J, Forman HJ Tags: Free Radic Biol Med Source Type: research

GABAergic over-inhibition, a promising hypothesis for cognitive deficits in Down syndrome.
Abstract Down syndrome (DS), also known as trisomy 21, is the most common genetic cause of intellectual disability. It is also a model human disease for exploring consequences of gene dosage imbalance on complex phenotypes. Learning and memory impairments linked to intellectual disabilities in DS could result from synaptic plasticity deficits and excitatory-inhibitory alterations leading to changes in neuronal circuitry in the brain of affected individuals. Increasing number of studies in mouse and cellular models converge towards the assumption that excitatory-inhibitory imbalance occurs in DS, likely early durin...
Source: Free Radical Biology and Medicine - October 6, 2017 Category: Biology Authors: de San Martin JZ, Delabar JM, Bacci A, Potier MC Tags: Free Radic Biol Med Source Type: research

Acute mental stress induces mitochondrial bioenergetic crisis and hyper-fission along with aberrant mitophagy in the gut mucosa in rodent model of stress-related mucosal disease.
We report that in rat-SRMD model, cold restraint-stress severely damaged gut mitochondrial functions to generate superoxide anion (O2(•-)), depletion of ATP and shifted mitochondrial fission-fusion dynamics towards enhanced fission to induce mucosal injury. Activation of mitophagy to clear damaged, fragmented mitochondria was evident from mitochondrial translocation of Parkin and PINK1 along with enhanced mitochondrial proteome ubiquitination, depletion of mitochondrial DNA copy number and TOM 20. However, excess and sustained accumulation of O2(•-)-generating defective mitochondria overpowered the mitophagic mac...
Source: Free Radical Biology and Medicine - October 6, 2017 Category: Biology Authors: De R, Mazumder S, Sarkar S, Debsharma S, Siddiqui AA, Saha SJ, Banerjee C, Nag S, Saha D, Bandyopadhyay U Tags: Free Radic Biol Med Source Type: research

Differential carbonylation of proteins in end-stage human fatty and nonfatty NASH.
CONCLUSIONS: These results indicate that cellular factors regulating mechanisms of protein carbonylation may be different depending on pathological diagnosis of NASH. Furthermore these studies are the first to use LC-MS/MS analysis of carbonylated proteins in human NAFLD and explore possible mechanistic links with end stage cirrhosis due to fatty liver disease and the generation of reactive aldehydes. PMID: 28988798 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - October 5, 2017 Category: Biology Authors: Shearn CT, Saba LM, Roede JR, Orlicky DJ, Shearn AH, Petersen DR Tags: Free Radic Biol Med Source Type: research

Muscle-derived extracellular superoxide dismutase inhibits endothelial activation and protects against multiple organ dysfunction syndrome in mice.
Abstract Multiple organ dysfunction syndrome (MODS) is a detrimental clinical complication in critically ill patients with high mortality. Emerging evidence suggests that oxidative stress and endothelial activation (induced expression of adhesion molecules) of vital organ vasculatures are key, early steps in the pathogenesis. We aimed to ascertain the role and mechanism(s) of enhanced extracellular superoxide dismutase (EcSOD) expression in skeletal muscle in protection against MODS induced by endotoxemia. We showed that EcSOD overexpressed in skeletal muscle-specific transgenic mice (TG) redistributes to other pe...
Source: Free Radical Biology and Medicine - October 2, 2017 Category: Biology Authors: Call JA, Donet J, Martin KS, Sharma AK, Chen X, Zhang J, Cai J, Galarreta CA, Okutsu M, Du Z, Lira VA, Zhang M, Mehrad B, Annex BH, Klibanov AL, Bowler RP, Laubach VE, Peirce SM, Yan Z Tags: Free Radic Biol Med Source Type: research

Oxidative stress in early cystic fibrosis lung disease is exacerbated by airway glutathione deficiency.
Abstract Neutrophil-derived myeloperoxidase (MPO) is recognized as a major source of oxidative stress at the airway surface of a cystic fibrosis (CF) lung where, despite limited evidence, the antioxidant glutathione is widely considered to be low. The aims of this study were to establish whether oxidative stress or glutathione status are associated with bronchiectasis and whether glutathione deficiency is inherently linked to CF or a consequence of oxidative stress. MPO was measured by ELISA in 577 bronchoalveolar lavage samples from 205 clinically-phenotyped infants and children with CF and 58 children without CF...
Source: Free Radical Biology and Medicine - October 2, 2017 Category: Biology Authors: Dickerhof N, Pearson JF, Hoskin TS, Berry LJ, Turner R, Sly PD, Kettle AJ, AREST CF Tags: Free Radic Biol Med Source Type: research

Synergistic toxicity of epigallocatechin-3-gallate and diethyldithiocarbamate, a lethal encounter involving redox-active copper.
Abstract Dithiocarbamates (DTC) are widely used in agricultural, industrial and therapeutic domains. There are ample opportunities for human exposure to DTC. Green tea extracts, with epigallocatechin-3-gallate (EGCG) being the most abundant constituent, have been used as dietary supplements for body weight reduction. Our hypothesis is that DTC can act as a copper ionophore to increase hepatic levels of redox-active copper which promotes EGCG auto-oxidation to produce oxidative stress and toxicity. The results of the present study in a mouse model is consistent with this hypothesis, showing that co-administration o...
Source: Free Radical Biology and Medicine - September 30, 2017 Category: Biology Authors: Zhang K, Dong R, Sun K, Wang X, Wang J, Yang CS, Zhang J Tags: Free Radic Biol Med Source Type: research

Structural requirements of flavonoids to induce heme oxygenase-1 expression.
We reported previously that the flavonoid quercetin protects arteries from oxidant-induced endothelial dysfunction and attenuates atherosclerosis in apolipoprotein E gene knockout mice, with induction of heme oxygenase-1 (Hmox1) playing a critical role. The present study investigated the structural requirements of flavonoids to induce Hmox1 in human aortic endothelial cells (HAEC). We identified ortho-dihydroxyl groups and an α,β-unsaturated system attached to a catechol as the key structural requirements for Hmox1 induction. Active but not inactive flavonoids had a low oxidation potential and prevented ascorbat...
Source: Free Radical Biology and Medicine - September 29, 2017 Category: Biology Authors: Croft KD, Zhang D, Jiang R, Ayer A, Shengule S, Payne RJ, Ward NC, Stocker R Tags: Free Radic Biol Med Source Type: research

nNOS uncoupling by oxidized LDL: implications in atherosclerosis.
PMID: 28970060 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - September 29, 2017 Category: Biology Authors: Navia-Pelaez JM, Campos-Mota GP, Araujo de Souza JC, Aguilar EC, Stergiopulos N, Alvarez-Leite JI, Aggum Capettini LS Tags: Free Radic Biol Med Source Type: research

Dendritic spine pathology and thrombospondin-1 deficits in Down syndrome.
Abstract Abnormal dendritic spine structure and function is one of the most prominent features associated with neurodevelopmental disorders including Down syndrome (DS). Defects in both spine morphology and spine density may underlie alterations in neuronal and synaptic plasticity, ultimately affecting cognitive ability. Here we briefly examine the role of astrocytes in spine alterations and more specifically the involvement of astrocyte-secreted thrombospondin 1 (TSP-1) deficits in spine and synaptic pathology in DS. PMID: 28965914 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - September 28, 2017 Category: Biology Authors: Torres MD, Garcia O, Tang C, Busciglio J Tags: Free Radic Biol Med Source Type: research

Portacaval shunting causes differential mitochondrial superoxide production in brain regions.
Abstract The portacaval shunting (PCS) prevents portal hypertension and recurrent bleeding of esophageal varices. On the other hand, it can induce chronic hyperammonemia and is considered to be the best model of mild hepatic encephalopathy (HE). Pathogenic mechanisms of HE and dysfunction of the brain in hyperammonemia are not fully elucidated, but it was originally suggested that the pathogenetic defect causes destruction of antioxidant defense which leads to an increase in the production of reactive oxygen species (ROS) and the occurrence of oxidative stress. In order to gain insight into the pathogenic mechanis...
Source: Free Radical Biology and Medicine - September 27, 2017 Category: Biology Authors: Kosenko EA, Tikhonova LA, Alilova GA, Montoliu C, Barreto GE, Aliev G, Kaminsky YG Tags: Free Radic Biol Med Source Type: research

Redox imbalance due to the loss of mitochondrial NAD(P)-transhydrogenase markedly aggravates high fat diet-induced fatty liver disease in mice.
si AE Abstract The mechanisms by which a high fat diet (HFD) promotes non-alcoholic fatty liver disease (NAFLD) appear to involve liver mitochondrial dysfunctions and redox imbalance. We hypothesized that a HFD would increase mitochondrial reliance on NAD(P)-transhydrogenase (NNT) as the source of NADPH for antioxidant systems that counteract NAFLD development. Therefore, we studied HFD-induced liver mitochondrial dysfunctions and NAFLD in C57Unib.B6 congenic mice with (Nnt(+/+)) or without (Nnt(-/-)) NNT activity; the spontaneously mutated allele (Nnt(-/-)) was inherited from the C57BL/6J mouse substrain. After 2...
Source: Free Radical Biology and Medicine - September 27, 2017 Category: Biology Authors: Navarro CDC, Figueira TR, Francisco A, Dal'Bó GA, Ronchi JA, Rovani JC, Escanhoela CAF, Oliveira HCF, Castilho RF, Vercesi AE Tags: Free Radic Biol Med Source Type: research

UCP2 inhibition induces ROS/Akt/mTOR axis: role of GAPDH nuclear translocation in genipin/everolimus anticancer synergism.
Abstract Several studies indicate that mitochondrial uncoupling protein 2 (UCP2) plays a pivotal role in cancer development by decreasing reactive oxygen species (ROS) produced by mitochondrial metabolism and by sustaining chemoresistance to a plethora of anticancer drugs. Here, we demonstrate that inhibition of UCP2 triggers Akt/mTOR pathway in a ROS-dependent mechanism in pancreatic adenocarcinoma cells. This event reduces the antiproliferative outcome of UCP2 inhibition by genipin, creating the conditions for the synergistic counteraction of cancer cell growth with the mTOR inhibitor everolimus. Inhibition of p...
Source: Free Radical Biology and Medicine - September 26, 2017 Category: Biology Authors: Dando I, Pacchiana R, Pozza ED, Cataldo I, Bruno S, Conti P, Cordani M, Grimaldi A, Butera G, Caraglia M, Scarpa A, Palmieri M, Donadelli M Tags: Free Radic Biol Med Source Type: research

Arctic Ground Squirrel resist peroxynitrite-mediated cell death in response to oxygen glucose deprivation.
Abstract Cerebral ischemia-reperfusion (I/R) injury initiate a cascade of events, generating nitric oxide (NO) and superoxide(O2(•-)) to form peroxynitrite (ONOO(-)), a potent oxidant. Arctic ground squirrel (AGS; Urocitellus parryii) show high tolerance to I/R injury. However, the underlying mechanism remains elusive. We hypothesize that tolerance to I/R modeled in an acute hippocampal slice preparation in AGS is modulated by reduced oxidative and nitrative stress. Hippocampal slices (400 μm) from rat and AGS were subjected to oxygen glucose deprivation (OGD) using a novel microperfusion technique. Slices...
Source: Free Radical Biology and Medicine - September 26, 2017 Category: Biology Authors: Bhowmick S, Drew KL Tags: Free Radic Biol Med Source Type: research

Formation and detection of oxidant-generated tryptophan dimers in peptides and proteins.
In this study, second-order rate constants were determined for Trp(●) dimerization in Trp-containing peptides to be 2-6 × 10(8)M(-1) s(-1) by pulse radiolysis. Peptide charge and molecular mass correlated negatively with these rate constants. Exposure of Trp-containing peptides to steady-state radiolysis in the presence of NaN3 resulted in consumption of the parent peptide, and detection by LC-MS of up to 4 different isomeric Trp-Trp cross-links. Similar species were detected with other oxidants, including CO3(●-) (from the HCO3(-) -dependent peroxidase activity of bovine superoxide dismutase) and peroxynitrous a...
Source: Free Radical Biology and Medicine - September 26, 2017 Category: Biology Authors: Carroll L, Pattison DI, Davies JB, Anderson RF, Lopez-Alarcon C, Davies MJ Tags: Free Radic Biol Med Source Type: research

Increased levels of inflammatory plasma markers and obesity risk in a mouse model of Down syndrome.
Abstract Down syndrome (DS) is caused by the trisomy of human chromosome 21 and is the most common genetic cause of intellectual disability. In addition to the intellectual deficiencies and physical anomalies, DS individuals present a higher prevalence of obesity and subsequent metabolic disorders than healthy adults. There is increasing evidence from both clinical and experimental studies indicating the association of visceral obesity with a pro-inflammatory status and recent studies have reported that obese people with DS suffer from low-grade systemic inflammation. However, the link between adiposity and inflam...
Source: Free Radical Biology and Medicine - September 25, 2017 Category: Biology Authors: Fructuoso M, Rachdi L, Philippe E, Denis RG, Magnan C, Le Stunff H, Janel N, Dierssen M Tags: Free Radic Biol Med Source Type: research