Recently published articles in
Free Radical Biology and Medicine

Mouse brain plasmalogens are targets for hypochlorous acid-mediated modification in vitro and in vivo

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 31 August 2010

Andreas, Üllen , Günter, Fauler , Harald, Köfeler , Sabine, Waltl , Christoph, Nusshold , ...

Plasmalogens, 1-O-alk-1?-enyl-2-acyl-sn-glycerophospholipids are significant constituents of cellular membranes and are essential for normal brain development. Plasmalogens, which contain a vinyl ether bond at the sn-1 position, are preferential targets for hypochlorous acid (HOCl), generated by myeloperoxidase (MPO) from H2O2 and chloride ions. Since MPO is implicated in neurodegeneration, the present study pursued two aims: i) to investigate the reactivity of mouse brain plasmalogens towards HOCl in vitro, and ii) to obtain in vivo evidence for MPO-mediated brain plasmalogen modification. Liquid chromatography coupled to hybrid linear ion trap - Fourier transform - ion cyclotron resonance mass spectrometry revealed plasmalogen modification in...


Thu, 02 Sep 2010 12:09

An oxidative environment promotes growth of Mycobacterium abscessus

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 31 August 2010

Rebecca E., Oberley-deegan , Brittany W., Rebits , Michael R., Weaver , Angela K., Tollefson , Xiyuan, Bai , ...

Mycobacterium abscessus (M. abscessus) infections, particularly those causing chronic lung diseases, are becoming more prevalent worldwide. M. abscessus infections are difficult to treat due to antibiotic resistance. Thus, new treatment options are urgently needed. M. abscessus are intracellular pathogens that primarily infect macrophages and fibroblasts. Because this bacterium has only recently been identified as a separate species, very little is known about M. abscessus-host interactions and how M. abscessus growth is regulated. Oxidative stress has long been shown to inhibit growth of bacterial organisms. However, some intracellular bacteria, such as Mycobacterium tuberculosis, grow well in oxidizing environments. In the present...


Thu, 02 Sep 2010 12:09

Editorial Board

Publication year: 2010
Source: Free Radical Biology and Medicine, Volume 49, Issue 7, 15 October 2010, Page IFC

[No author name available]


Fri, 27 Aug 2010 03:08

Invitation to Submit Critical Methods Articles

Publication year: 2010
Source: Free Radical Biology and Medicine, Volume 49, Issue 7, 15 October 2010, Page v

[No author name available]


Fri, 27 Aug 2010 03:08

Announcements and Calendar

Publication year: 2010
Source: Free Radical Biology and Medicine, Volume 49, Issue 7, 15 October 2010, Page 1254

[No author name available]


Fri, 27 Aug 2010 03:08

Ferricytochrome c protects mitochondrial cytochrome c oxidase against hydrogen peroxide-induced oxidative damage

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 27 August 2010

Erik, Sedlák , Marian, Fabian , Neal C., Robinson , Andrej, Musatov

Excess of ferricytochrome c protects purified mitochondrial cytochrome c oxidase and bound cardiolipin from hydrogen peroxide-induced oxidative modification. All of the peroxide-induced changes within cytochrome c oxidase, such as oxidation of Trp19,IV and Trp48,VIIc, partial dissociation of subunits VIa and VIIa, and generation of cardiolipin hydroperoxide, no longer take place in the presence of ferricytochrome c. Furthermore, ferricytochrome c suppresses the yield of H2O2-induced free radical detectable by electron paramagnetic resonance spectroscopy within cytochrome c oxidase. These protective effects are based on two mechanisms. The first involves the peroxidase/catalase-like activity of ferricytochrome c, which results in the decomposition of H2O2,...


Fri, 27 Aug 2010 03:08

A reinvestigation of the reaction of coumarins with superoxide in the liposomal bilayer: Correlation between depth and reactivity

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 27 August 2010

Sharona, Shachan-Tov , Michal, Afri , Aryeh A., Frimer

Afri et al. reported in this Journal (Free Rad. Biol. Med. 32:605-618; 2002) that a direct relationship exists between the depth of alkanoylcoumarins 1 within the liposomal lipid-bilayer and the rate the latter undergo superoxide mediated saponification. These results were based on a correlation between the 13C NMR chemical shift of polarizable carbonyl carbons and the ET(30) polarity they sense. Subsequent studies challenged these results, however, demonstrating that, in conjugated ketones and aldehydes, charge separation influences the ET(30) polarity measured. To elucidate whether this was true for conjugated esters such as coumarins as well, the non-conjugated analogs, 3,4-dihydrocoumarins 11 and...


Fri, 27 Aug 2010 03:08

H2O2-induced mitochondrial fragmentation in C2C12 myocytes

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 27 August 2010

Xiying, Fan , Rajaa, Hussien , George A., Brooks

In skeletal muscle and many other cell types, mitochondria exist as an elaborate and dynamic network in which ?individual? mitochondria exist only transiently even under non-stimulated conditions. The balance of continuous mitochondrial fission and fusion defines the morphology of the mitochondrial reticulum. Environmental stimuli, such as oxidative stress, can influence fusion and fission rates, resulting in a transformation of the network's connectivity. Using confocal laser scanning microscopy of C2C12 mouse myocytes, we show that acute exposure to the reactive oxygen species (ROS) hydrogen peroxide (H2O2) induces a slow fragmentation of the mitochondrial reticulum that is reversible over 24hours. Although H2O2...


Fri, 27 Aug 2010 03:08

Advanced age-related denervation and fiber type grouping in skeletal muscle of SOD1 knockout mice

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 26 August 2010

Tatiana Y., Kostrominova

In this study skeletal muscle from 1.5-month-old and 10-month-old Cu/Zn superoxide dismutase (SOD1) homozygous knockout (JLSod1-/-) mice obtained from the Jackson Laboratory (C57Bl6/129SvEv background) were compared with muscles from age- and sex-matched heterozygous (JLSod1-/+) littermates. The results of the current study were compared with previously published data on two different strains of Sod1-/- mice: one from Dr. Epstein's Laboratory (ELSod1-/-; C57Bl6 background) and the other from Cephalon Inc. (CSod1-/- ; 129/CD-1 background). Grouping of succinate dehydrogenase-positive fibers characterized muscles of Sod1-/- mice from all three strains. 10-month-old Sod1-/- mice from C and JL displayed pronounced denervation of GTN muscle, while...


Thu, 26 Aug 2010 03:08

Candida albicans heme oxygenase and its product CO contribute to pathogenesis of candidemia and alter systemic chemokine and cytokine expression

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 25 August 2010

Dhammika H.M.L.P., Navarathna , David D., Roberts

Mammalian heme oxygenases play important roles in immune regulation by producing immunosuppressive CO. The pathogenic yeast Candida albicans encodes a heme oxygenase, Hmx1, that is specifically induced by the host protein hemoglobin, suggesting a role in the pathogenesis of disseminated bloodstream infections. We show that exposing mice to therapeutic levels of CO increases C. albicans virulence, whereas a HMX1 null strain has decreased virulence in murine disseminated candidiasis. Levels of several regulatory cytokines and chemokines are decreased in mice infected with the null strain, and initial lesions in the kidney are more rapidly cleared following PMN infiltration. Reconstitution of one...


Wed, 25 Aug 2010 03:08

Carbon monoxide (CO)-releasing molecule CORM-3 suppresses vascular endothelial cell SOD-1/-2 activity while up-regulating the cell surface levels of SOD-3 in heparin-dependent manner

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 24 August 2010

Shinjiro, Mizuguchi , Alfredo, Capretta , Shigefumi, Suehiro , Noritoshi, Nishiyama , Patrick, Luke , ...

The role of CO in modulation of anti-oxidant enzyme function has not been investigated, yet.In this study we assessed the effects and potential mechanisms of ruthenium-based water-soluble CO-releasing molecule, CORM-3, in modulation of superoxide dismutase (SOD) activity/binding in vascular endothelial cells (HUVEC). To this end, HUVEC were treated with CORM-3 (100?M) and assessed for total SOD activity in cell lysates (cell-associated SOD activity) and cell culture supernatants (soluble-SOD). In parallel, release/binding of extracellular-SOD (SOD-3) in the absence or presence of heparin (1-10IU/ml), a key factor regulating SOD-3-cell surface binding, was investigated. In addition, the effects of CORM-3 on modulation of...


Tue, 24 Aug 2010 03:08

Cytoprotective effect of vitamin E homologues against glutamate-induced cell death in immature primary cortical neuron cultures: Tocopherols and tocotrienols exert similar effects by antioxidant function

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 22 August 2010

Yoshiro, Saito , Keiko, Nishio , Yoko Ogawa, Akazawa , Kazunori, Yamanaka , Akiko, Miyama , ...

Glutamate plays a critical role in pathological cell death within the nervous system. Vitamin E is known to protect cells from glutamate cytotoxicity, either by direct antioxidant action or by indirect non-antioxidant action. Further, ?-tocotrienol (?-T3) has been reported to be more effective against glutamate-induced cytotoxicity than ?-tocopherol (?-T). In order to shed more light on the function of vitamin E against glutamate toxicity, the protective effects of eight vitamin E homologues and related compounds, 2,2,5,7,8-pentamethyl-6-chromanol (PMC) and 2-carboxy-2,5,7,8-pentamethyl-6-chromanol (Trolox), against glutamate induced cytotoxicity on immature primary cortical neurons were examined by using different protocols. Glutamate induced depletion of glutathione...


Sun, 22 Aug 2010 03:08

SOD1 and MitoTEMPO partially prevent MPTP, necrosis and mitochondrial apoptosis following ATP depletion-recovery

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 22 August 2010

Huan Ling, Liang , Filip, Sedlic , Zeljko, Bosnjak , Vani, Nilakantan

Generation of excessive reactive oxygen species (ROS) leads to mitochondrial dysfunction, apoptosis and necrosis in renal ischemia-reperfusion (IR) injury. Previously we showed that lentiviral vector mediated over-expression of superoxide dismutase-1 (SOD1) in proximal tubular epithelial cells (LLC-PK1) reduced cytotoxicity in an in vitro model of IR injury. Here, we examined the effects of SOD1 over-expression on mitochondrial signaling following ATP depletion-recovery (ATP-DR). To examine the role of mitochondrial ROS, a subset of cells were treated with the mitochondrial antioxidant, MitoTEMPO. ATP-DR-mediated increases in mitochondrial calcium ([Ca2+]m), loss of mitochondrial membrane potential (??m) and increase in mitochondrial permeability transition pore (MPTP)...


Sun, 22 Aug 2010 03:08

Paul Hochstein 1926-2010

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Uncorrected Proof, Available online 21 August 2010

Kelvin J.A., Davies


Sun, 22 Aug 2010 03:08

Multiple roles of Microsomal Glutathione Transferase 1 in cellular protection, a mechanistic study

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 19 August 2010

Katarina, Johansson , Julia, Järvliden , Vladimir, Gogvadze , Ralf, Morgenstern

The aim of this study was to investigate the involvement of membrane bound Microsomal glutathione transferase 1 (MGST1) in cellular resistance against oxidative stress as well as mechanism of protection. Microsomal GST1 is ubiquitously expressed and predominantly located in the endoplasmic reticulum and outer mitochondrial membrane. Utilising MCF7 cells overexpressing MGST1 we show significant protection against agents that are known to induce lipid peroxidation (e.g cumene hydroperoxide and tert-butyl hydroperoxide), and an end-product of lipid peroxidation (e.g 4-hydroxy-2-nonenal). Furthermore, our results demonstrate that MGST1 protection can be enhanced by vitamin E when toxicity depends on oxidative stress, but not when...


Thu, 19 Aug 2010 03:08

Carbonyl reductase 1 protects pancreatic ß-cells against oxidative stress-induced apoptosis in glucotoxicity and glucolipotoxicity

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 19 August 2010

M.A., Rashid , Seonmin, Lee , Eunyoung, Tak , Jisun, Lee , Tae Gyu, Choi , ...

Carbonyl reductase 1 (CBR1) plays an important role in detoxification of reactive lipid aldehydes. Oxidative stress has been implicated in pathogenesis of pancreatic ß-cell failure. However, the functional roles of CBR1 in pancreatic ß-cell failure have not been studied yet. Therefore, we investigated the role of CBR1 in pancreatic ß-cell failure under glucotoxic and glucolipotoxic conditions. Under both the conditions, knockdown of CBR1 by specific siRNA increased ß-cell apoptosis, expression of the lipogenic enzymes (such as ACC, FAS and ABCA1), intracellular lipid accumulation, oxidative stress, ER stress, and nuclear SREBP1c, but decreased GSIS. In contrast, overexpression of CBR1 showed the...


Thu, 19 Aug 2010 03:08

Corrigendum to ?Puerarin attenuates high-glucose-and diabetes-induced vascular smooth muscle cell proliferation by blocking PKC?2/Rac1-dependent signaling? [Free Radic. Biol. Med. 48 (2010) 471?482]

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Uncorrected Proof, Available online 19 August 2010

Li-Hua, Zhu , Lang, Wang , Dong, Wang , Hong, Jiang , Qi-Zhu, Tang , ...


Thu, 19 Aug 2010 03:08

Corrigendum to ?Impaired dephosphorylation renders G6PD-knockdown HepG2 cells more susceptible to H2O2-induced apoptosis? [Free Radic. Biol. Med. 49 (2010) 361?373]

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Uncorrected Proof, Available online 19 August 2010

Chang-Jun, Lin , Hung-Yao, Ho , Mei-Ling, Cheng , Tsai-Hong, You , Jau-Song, Yu , ...


Thu, 19 Aug 2010 03:08

New hypotheses on the pathways of formation of malondialdehyde and isofurans

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 17 August 2010

Arnold N., Onyango , Naomichi, Baba

Malondialdehyde (MDA) is a mutagenic compound which has been widely used as a biomarker of oxidative stress. However, the nonenzymatic mechanisms of its formation are not well understood. Some lipid oxidation products were previously suggested to be MDA precursors and found to afford MDA heterolytically under acidic conditions. We predict that some of these compounds are not important MDA sources under the autoxidative conditions in which the bulk of MDA should be formed in vivo, and that others require further oxidative modifications to generate MDA homolytically. Thus, we outline the likely important pathways of MDA formation in vivo. All these...


Wed, 18 Aug 2010 03:08

Hydrogen peroxide mediates EGCG-induced antioxidant protection in human keratinocytes

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 12 August 2010

Leonilla, Elbling , Irene, Herbacek , Rosa-Maria, Weiss , Christian, Jantschitsch , Michael, Micksche , ...

Health beneficial effects of (-)-epigallocatechin-3-gallate (EGCG), the main catechin of green tea, have been attributed to complex interactions with a focus on antioxidative properties. Susceptibility to auto-oxidation and production of cytotoxic reactive oxygen species (ROS), mostly H2O2, has been suggested to occur in vitro but also in vivo [1]. In this study, we address whether auto-oxidation-derived H2O2 may be involved in the cytoprotective effects of EGCG. To that end we investigated keratinocyte-derived HaCat and Hl-60 promyelocytic leukaemia cells with significantly different sensitivities against H2O2 (IC50 117.3 versus 58.3?M, respectively) and EGCG (134.1 versus 84.1?M). HaCat significantly resisted cytotoxicity and DNA...


Sat, 14 Aug 2010 03:08

Acetyl-L-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 12 August 2010

Travis J., Rump , P.M. Abdul, Muneer , Adam, Szlachetka , Allyson, Lamb , Catherine, Haorei , ...

The studies presented here demonstrate the protective effect of acetyl-L-carnitine (ALC) from alcohol-induced oxidative neuroinflammation, neuronal degeneration, and impaired neurotransmission. Our findings revealed the cellular and biochemical mechanisms of alcohol-induced oxidative damage in different types of brain cells. Chronic ethanol administration to mice caused an increase in inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (3-NT) adduct formation in frontal cortical neurons but not in astrocytes from brains of these animals. Interestingly, alcohol administration caused a rather selective activation of NADPH oxidase (NOX), which, in turn, enhanced levels of reactive oxygen species (ROS) and 4-hydroxynonenal (4-HNE) but these were predominantly localized...


Sat, 14 Aug 2010 03:08

Cellular effects of photo-generated oxidants and long-lived, reactive, hydroperoxide photoproducts

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 12 August 2010

Aldwin Suryo, Rahmanto , Philip E., Morgan , Clare L., Hawkins , Michael J., Davies

Reaction of radicals and singlet oxygen (1O2) with proteins results in both direct damage, and the formation of long-lived reactive hydroperoxides. Elevated levels of protein hydroperoxide-derived products have been detected in multiple human pathologies, suggesting that these secondary oxidants contribute to tissue damage. Previous studies have provided evidence for protein hydroperoxide-mediated inhibition of thiol-dependent enzymes, and modulation of signalling processes in isolated systems. In this study 1O2 and hydroperoxides have been generated in J774A.1 macrophage-like cells using visible light and the photosensitizer Rose Bengal, with the consequences of oxidant formation examined both immediately and after subsequent (dark phase) incubation. Significant...


Sat, 14 Aug 2010 03:08

Peroxynitrite mediates right-ventricular dysfunction in nitric oxide-exposed juvenile rats

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 12 August 2010

Robert P., Jankov , Patricia, Lewis , Crystal, Kantores , Julijana, Ivanovska , Emily Z., Xu , ...

Chronic pulmonary hypertension in infancy and childhood frequently culminates in right-ventricular (RV) failure and early death. Current management may include prolonged treatment with inhaled nitric oxide (iNO). Our objective was to examine the effects of iNO on established chronic hypoxic pulmonary hypertension in juvenile rats, a model of chronic neonatal pulmonary hypertension characterized by increased pulmonary vascular resistance, vascular remodeling (RV hypertrophy and arterial medial wall thickening) and significant RV dysfunction. Pups were exposed to air or hypoxia (13% O2) from postnatal days 1-21 while receiving iNO (20ppm) from days 14-21. In hypoxia-exposed animals, treatment with iNO decreased pulmonary vascular...


Sat, 14 Aug 2010 03:08

Editorial Board

Publication year: 2010
Source: Free Radical Biology and Medicine, Volume 49, Issue 6, 15 September 2010, Page IFC

[No author name available]


Wed, 11 Aug 2010 03:08

Open Invitation for Submission of Critical Methods Articles

Publication year: 2010
Source: Free Radical Biology and Medicine, Volume 49, Issue 6, 15 September 2010, Page v

[No author name available]


Wed, 11 Aug 2010 03:08

Announcements and Calendar

Publication year: 2010
Source: Free Radical Biology and Medicine, Volume 49, Issue 6, 15 September 2010, Page 1146

[No author name available]


Wed, 11 Aug 2010 03:08

Dysfunctional Nrf2-Keap1 redox signalling in skeletal muscle of sedentary old

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 11 August 2010

Adeel, Safdar , Justin, deBeer , Mark A., Tarnopolsky

The role of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) and kelch-like ECH-associated protein 1 (Keap1) redox signalling has not been characterized in human skeletal muscle despite an extensive delineation of oxidative stress in the aetiology of aging and sarcopenia. We assessed if the age-associated decline in antioxidant response is due, at least in part, to dysfunction in Nrf2-Keap1 redox signalling. We also evaluated if an active lifestyle can conserve skeletal muscle cellular redox status via activation of Nrf2-Keap1 signalling. Here we show that a recreationally active lifestyle is associated with the activation of up-stream modulators that induce Nrf2-mediated antioxidant...


Wed, 11 Aug 2010 03:08

Modulation of doxorubicin-induced cardiac dysfunction in dominant negative p38? mitogen-activated protein kinase mice

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 10 August 2010

Rajarajan A., Thandavarayan , Kenichi, Watanabe , Flori R., Sari , Meilei, Ma , Arun Prasath, Lakshmanan , ...

Doxorubicin (Dox) is a widely used antitumor drug, but its application is limited because of its cardiotoxic side effects. Increased expression of p38? mitogen-activated protein kinase (MAPK) promotes cardiomyocytes apoptosis and associated with cardiac dysfunction induced by prolonged-agonist stimulation. However, the role of p38? MAPK is not clear in Dox-induced cardiac injury. Cardiac dysfunction was induced by a single injection of Dox into wild-type (WT) mice and transgenic mice with cardiac-specific expression of a dominant-negative mutant form of p38? MAPK (TG). Left ventricular (LV) fractional shortening and ejection fraction were higher and the expression of phospho-p38 MAPK and phospho-MAPK activated...


Wed, 11 Aug 2010 03:08

Molecular characterization, expression analysis and role of aldh3b1 in the cellular protection against oxidative stress

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 8 August 2010

Satori A., Marchitti , Chad, Brocker , David J., Orlicky , Vasilis, Vasiliou

Aldehyde dehydrogenase (ALDH) enzymes are critical in the detoxification of aldehydes. The human genome contains 19 ALDH genes, mutations in which are the basis of several diseases. The expression, subcellular localization, enzyme kinetics and role of ALDH3B1 against aldehyde- and oxidant-induced cytotoxicity were investigated. ALDH3B1 was purified from Sf9 cells using chromatographic methods and enzyme kinetics were determined spectrophotometrically. ALDH3B1 demonstrated high affinity for hexanal (Km 62?M), octanal (Km 8?M), 4-hydroxy-2-nonenal (4HNE) (Km 52?M) and benzaldehyde (Km 46?M). Low affinity was seen towards acetaldehyde (Km 23.3mM), malondialdehyde (Km 152mM) and the ester p-nitrophenylacetate (Km 3.6mM). ALDH3B1 mRNA was abundant in...


Wed, 11 Aug 2010 03:08

Editorial Board

Publication year: 2010
Source: Free Radical Biology and Medicine, Volume 49, Issue 6, 15 September 2010, Page IFC

[No author name available]


Tue, 10 Aug 2010 04:08

Open Invitation for Submission of Critical Methods Articles

Publication year: 2010
Source: Free Radical Biology and Medicine, Volume 49, Issue 6, 15 September 2010, Page v

[No author name available]


Tue, 10 Aug 2010 04:08

Announcements and Calendar

Publication year: 2010
Source: Free Radical Biology and Medicine, Volume 49, Issue 6, 15 September 2010, Page 1146

[No author name available]


Tue, 10 Aug 2010 04:08

Molecular characterization, expression analysis and role of aldh3b1 in the cellular protection against oxidative stress

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 8 August 2010

Satori A., Marchitti , Chad, Brocker , David J., Orlicky , Vasilis, Vasiliou

Aldehyde dehydrogenase (ALDH) enzymes are critical in the detoxification of aldehydes. The human genome contains 19 ALDH genes, mutations in which are the basis of several diseases. The expression, subcellular localization, enzyme kinetics and role of ALDH3B1 against aldehyde- and oxidant-induced cytotoxicity were investigated. ALDH3B1 was purified from Sf9 cells using chromatographic methods and enzyme kinetics were determined spectrophotometrically. ALDH3B1 demonstrated high affinity for hexanal (Km 62?M), octanal (Km 8?M), 4-hydroxy-2-nonenal (4HNE) (Km 52?M) and benzaldehyde (Km 46?M). Low affinity was seen towards acetaldehyde (Km 23.3mM), malondialdehyde (Km 152mM) and the ester p-nitrophenylacetate (Km 3.6mM). ALDH3B1 mRNA was abundant in...


Tue, 10 Aug 2010 04:08

Role of dioxins and heavy metals in cancer and neurological diseases by ROS-mediated mechanisms

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 7 August 2010

José M., Matés , Juan A., Segura , Francisco J., Alonso , Javier, Márquez

Oxidants have critical functions inside healthy and unhealthy cells. Deregulated cell cycle and apoptosis, both regulated by oxidative stress, have been described as hallmarks in mitotic (cancer) and post-mitotic (neuronal) cells. This review will provide an updated revision of the oxidant effects of some environmental contaminants like dioxins and the heavy metals cadmium, cobalt, and copper. Dioxins exert their toxic action acting on phase I and phase II enzymes, such as cytochromes P450, superoxide dismutase, and glutathione peroxidase, promoting cell proliferation, growth arrest, and apoptosis, affecting cancer homeostasis and neuronal function. Heavy metals manifest cytotoxic effects in different cells and...


Sun, 08 Aug 2010 03:08

Nox enzymes from fungus to fly to fish and what they tell us about Nox function in mammals

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 7 August 2010

Jesús, Aguirre , J. David, Lambeth

The production of reactive oxygen species (ROS) in a highly regulated fashion is a hallmark of members of the NADPH oxidase (Nox) family of enzymes. Nox enzymes are present in most eukaryotic groups such as the amebozoid, fungi, algae and plants, and animals, where they are involved in seemingly diverse biological processes. However, a comprehensive survey of Nox functions throughout biology reveals common functional themes. Noxes are often activated in response to stressful conditions such as nutrient starvation, physical damage or pathogen attack. Although the end result varies depending on the organism and tissue, Nox-produced ROS mediates the response to...


Sun, 08 Aug 2010 03:08

Thioredoxin interacting protein inhibits hypoxia-inducible factor transcriptional activity

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 6 August 2010

Michael R., Farrell , Lynette K., Rogers , Yusen, Liu , Stephen E., Welty , Trent E., Tipple

Vascular endothelial growth factor (VEGF) is required for proper lung development and is transcriptionally regulated in alveolar epithelial cells by hypoxia inducible factor (HIF). Previous findings in a newborn mouse model of bronchopulmonary dysplasia (BPD) suggest that thioredoxin interacting protein (Txnip) is a novel regulator of VEGF expression. The present studies were designed to test the hypothesis that Txnip negatively regulates VEGF through effects on HIF-mediated gene expression. To test this hypothesis, we first examined the levels of VEGF and Txnip protein in the lungs of 1day-old newborn and E19 embryos and detected a significant inverse correlation. To elucidate the...


Sat, 07 Aug 2010 03:08

A radiation induced adaptive response prolongs the survival of prion infected mice

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 6 August 2010

Margot, Plews , Sharon L.R., Simon , Douglas R., Boreham , Debra, Parchaliuk , Heather, Wyatt , ...

Previously, it has been demonstrated that an "adaptive response" that includes the prevention, repair and removal of oxidative damage can be evoked by radiation doses and dose rates substantially lower than those at which risks have been observed. The exact pathogenic mechanism of prion diseases is unknown, but circumstantial evidence suggests that oxidative stress plays a central role. The exposure of the prion infected mice to four 500mGy/fraction doses of 60Co-? radiation administered every other day at a low dose rate (0.5mGy/min) starting at either 2days prior to infection, 7days post infection (dpi) or 50 dpi significantly prolonged the survival...


Sat, 07 Aug 2010 03:08

Proapoptotic effects of long chain vitamin E metabolites in HepG2 cells are mediated by oxidative stress

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 6 August 2010

Marc, Birringer , Dennis, Lington , Silvia, Vertuani , Stefano, Manfredini , Daniel, Scharlau , ...

While the metabolism of vitamin E has been extensively studied in cell culture, animals and humans, biochemical analyses of intermediate metabolites are scarce. We here describe synthesis and pro-apoptotic properties of long-chain metabolites of alpha- and delta-tocopherol. Several long-chain vitamin E metabolites, namely 13?-hydroxy- and 13?-carboxychromanols, were synthesized from garcinoic acid, a delta-tocotrienol derivative extracted from the African bitter nut Garcinia kola. Both alpha- and delta-13?-carboxychromanol induced cell death in HepG2 cells at EC50 of 13.5 and 6.5?M, respectively. Apoptosis was quantified by Annexin-V/7-AAD staining and flow cytometry analysis. By immunoblot analyses, we observed activation of both caspase-3 and -9...


Sat, 07 Aug 2010 03:08

Chronic Alcohol-Induced Liver Injury and Oxidant Stress is Decreased in Cytochrome P4502E1 Knockout Mice and Restored in Humanized Cytochrome P4502E1 Knockin Mice

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 6 August 2010

Yongke, Lu , Defeng, Wu , Xiaodong, Wang , Stephen C., Ward , Arthur I., Cederbaum

A major pathway for chronic ethanol-induced liver injury is ethanol-induced oxidant stress. Several pathways contribute to mechanisms by which ethanol induces oxidant stress. While some studies support a role for cytochrome P450 2E1 (CYP2E1), others do not. Most previous studies were conducted in the intragastric infusion model of ethanol administration. There is a need to develop oral models of significant liver injury and to evaluate the possible role of CYP2E1 in ethanol actions in such models. We evaluated chronic ethanol-induced liver injury, steatosis and oxidant stress in wild type (WT) mice, CYP2E1 knockout (KO) mice and in humanized CYP2E1 knockin...


Sat, 07 Aug 2010 03:08

Malondialdehyde/Acetaldehyde Adduct (MAA) is the Dominant Epitope Following MDA Modification of Proteins in Atherosclerosis?

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 6 August 2010

Michael J., Duryee , Lynell W., Klassen , Courtney S., Schaffert , Dean J., Tuma , Carlos D., Hunter , ...

Antibodies to malondialdehyde (MDA) modified macromolecules (adducts) have been detected in the serum of patients with atherosclerosis and correlate with the progression of this disease. However, the epitope and its formation have not been characterized. Studies have shown that excess MDA can be degraded to acetaldehyde which combines with proteins to from a stable dihydropyridine adduct. To investigate, mice were immunized with (MDA) adducts in the absence of adjuvant and showed an increase in antibodies to MDA adducts and the carrier protein as the concentration of MDA was increased. In fact, a number of the commercially available antibodies to MDA...


Sat, 07 Aug 2010 03:08

Determinants of oxidant stress in extremely low birth weight premature infants

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 5 August 2010

Philippe, Chessex , Carla, Watson , Gregor W., Kaczala , Thérèse, Rouleau , Marie-Eve, Lavoie , ...

Early in life, premature neonates are at risk of oxidant stress. They often require total parenteral nutrition (TPN) that is however contaminated with oxidation products. Co-administration of parenteral multivitamins (MVP) with the lipid emulsion (LIP) prevents lipid peroxidation. We hypothesized that LIP+MVP induces a lower oxidant load compared to preparations where MVP is administered with the amino acid solution (AA+MVP). The aim was to compare markers of oxidant stress in premature neonates receiving LIP+MVP either exposed to or protected from light or AA+MVP. Antioxidant vitamins, the redox potential of glutathione, isoprostane and di-tyrosine were measured in urine or blood sampled...


Thu, 05 Aug 2010 03:08

Knockout of the transcription factor Nrf2 disrupts spermatogenesis in an age-dependent manner

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 5 August 2010

Brooke N., Nakamura , Gregory, Lawson , Jefferson Y., Chan , Jésus, Banuelos , Mabel M., Cortés , ...

Oxidative stress occurs when generation of reactive oxygen species (ROS) overwhelms antioxidant defenses. Oxidative stress has been associated with male infertility. The transcription factor Nuclear Factor-Erythroid 2-Related Factor 2 (NRF2) regulates basal and inducible transcription of genes encoding enzymes important for protection against ROS. We hypothesized that deletion of the Nrf2 gene causes testicular and epididymal oxidative stress, which disrupts spermatogenesis. Our results show that male Nrf2-/- mice have decreased fertility compared to wild type and heterozygous littermates, due to accumulating seminiferous tubule damage with increasing age. Testicular sperm head counts, epididymal sperm counts, and epididymal sperm motility in 2month...


Thu, 05 Aug 2010 03:08

Role of quinones on the ascorbate reduction rates of S-nitrosogluthathione

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 5 August 2010

Pedro, Sanchez-Cruz , Carmelo, Garcia , Antonio E., Alegria

Quinones are one of the largest class of antitumor agents approved for clinical use and several antitumor quinones are in different stages of clinical and preclinical development. Many of these are metabolites of, or are, environmental toxins. Due to their chemical structure these are known to enhance electron transfer processes such as ascorbate oxidation and NO reduction. The paraquinones 2,6-dimethyl-1,4-benzoquinone (DMBQ), 1,4-benzoquinone (BQ), methyl-1,4-benzoquinone (MBQ), 2,6-dimethoxy-1,4-benzoquinone (DMOBQ), 2-hydroxymethyl-6-methoxy-1,4-benzoquinone (HMOBQ), trimethyl-1,4-benzoquinone (TMQ), tetramethyl-1,4-benzoquinone (DQ), 2,3-dimethoxy-5-methyl-1,4-benzoquinone (UBQ-0), the paranaphthoquinones 1,4-naphthoquinone (NQ), menadione (MNQ), 1,4-naphthoquinone-2-sulfonate (NQ2S), juglone (JQ) and phenanthroquinone (PHQ) all enhance the anaerobic rate of ascorbate reduction of GSNO to produce...


Thu, 05 Aug 2010 03:08

Role of oxidative stress in high glucose and diabetes -induced increased expression of Gq/11? proteins and associated signaling in vascular smooth muscle cells

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 5 August 2010

Magda, Descorbeth , Madhu B., Anand-Srivastava

We have recently shown that aortic vascular smooth muscle cells (VSMC) from streptozotocin (STZ)-induced diabetic rats and A10 VSMCs exposed to high glucose exhibited increased levels of Gq? and PLC? proteins. In the present study, we investigated if the enhanced oxidative stress in hyperglycemia/diabetes contributes to the increased expression of the Gq/11?, PLC? proteins and associated signaling in VSMCs by using antioxidants. The levels of Gq/11? and PLC?1/2 proteins, as determined by western blotting, were significantly increased in A10 VSMCs exposed to high glucose and in aortic VSMC from STZ-diabetic rats compared with control cells and were restored to control...


Thu, 05 Aug 2010 03:08

Arecoline, a major alkaloid of areca nut, causes neurotoxicity through enhancement of oxidative stress and suppression of antioxidant protective system

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 4 August 2010

Yu-Tzu, Shih , Po See, Chen , Chi-Han, Wu , Yu-Ting, Tseng , Yang-Chang, Wu , ...

Arecoline, an areca nut alkaloid, has been noted for its potential cognitive enhancing effects in patients with Alzheimer's dementia. However, it has been confirmed that areca nut use is associated with oral and pharyngeal cancers. In addition, arecoline is genotoxic and cytotoxic both in vitro and in vivo through oxidative stress dependent mechanisms. The aim of this study was to investigate whether arecoline would interfere with the antioxidant defense system and induce cytotoxicity in rat primary cortical neurons. Results indicated arecoline (50-200 ?M) induced neuronal cell death, and catalase, NADPH oxidase inhibitors (diphenyleneiodonium chloride (DPI) and apocynin) and caspase inhibitor...


Wed, 04 Aug 2010 03:08

Selective vulnerability of neurons to acute toxicity following proteasome inhibitor treatment: Implications for oxidative stress and insolubility of newly synthesized proteins

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 3 August 2010

Kalavathi, Dasuri , Philip J., Ebenezer , Le, Zhang , Sun Ok, Fernandez-Kim , Romina M., Uranga , ...

Maintaining protein homeostasis is vital to cell viability, with numerous studies demonstrating a role for proteasome inhibition occurring during the aging of a variety of tissues, and presumably contributing to the disruption of cellular homeostasis during aging. In the present study we sought to elucidate the differences between neurons and astrocytes in regards to basal levels of protein synthesis, proteasome-mediated protein degradation, and sensitivity to cytoxicity following proteasome inhibitor treatment. In these studies we demonstrate that neurons have an increased vulnerability, as compared to astrocyte cultures, to proteasome inhibitor-induced cytotoxicity. No significant difference was observed between these two cell types...


Tue, 03 Aug 2010 03:08

Cardiac Overexpression of Insulin-Like Growth Factor I (IGF-1) Attenuates Chronic Alcohol Intake-Induced Myocardial Contractile Dysfunction But Not Hypertrophy: Role of Akt, mTOR, GSK3? and PTEN

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 3 August 2010

Bingfang, Zhang , Subat, Turdi , Quan, Li , Faye L., Lopez , Anna R., Eason , ...

Chronic alcohol intake leads to the development of alcoholic cardiomyopathy manifested by cardiac hypertrophy and contractile dysfunction. This study was designed to examine the effect of transgenic overexpression of insulin-like growth factor I (IGF-1) on alcohol-induced cardiac contractile dysfunction. Wild-type FVB and cardiac-specific IGF-1 mice were placed on a 4% alcohol or control diet for 16 weeks. Cardiac geometry and mechanical function were evaluated by echocardiography, cardiomyocyte and intracellular Ca2+ properties. Histological analyses for cardiac fibrosis and apoptosis were evaluated by Masson trichrome staining and TUNEL assay, respectively. Expression and/or phosphorylation of Cu/Zn superoxide dismutase (SOD1), Ca2+ handling proteins, key...


Tue, 03 Aug 2010 03:08

Pulmonary vascular and cardiac effects of peroxynitrite decomposition in newborn rats

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 2 August 2010

Jaques, Belik , Danielle, Stevens , Jingyi, Pan , Brendan A.S., McIntyre , Crystal, Kantores , ...

Evidence implicates oxidative stress as playing a prominent role in the pathogenesis of pulmonary hypertension, to which peroxynitrite anion (ONOO-) may make a major contribution. Hypothesizing that removal of ONOO- would attenuate chronic neonatal pulmonary hypertension, we examined the effects of a ONOO- decomposition catalyst (FeTPPS) on pulmonary arteries in vitro, primary cultured pulmonary artery smooth muscle cell (PASMC) and cardiomyocyte survival and growth, as well as central hemodynamics in rat pups exposed to hypoxia (13% O2) for 7 days from birth. Daily FeTPPS (30 mg/kg ip) reduced lung nitrotyrosine content, attenuated vascular remodeling and normalized pulmonary vascular resistance in...


Mon, 02 Aug 2010 04:08

Cytotoxic potency of H2O2 in cell cultures: Impact of cell concentration and exposure time

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 29 July 2010

Michael, Gülden , Anne, Jess , Julia, Kammann , Edmund, Maser , Hasso, Seibert

Using C6 glioma cells in this study it was investigated in detail how exposure time and cell concentration affect the cytotoxic potency of H2O2 in vitro. Median cytotoxic concentrations (EC50) decreased from 500 ?M to 30 ?M with increasing incubation time from 1 to 24 hours. 24 hours proved to be sufficient to determine incipient cytotoxic concentrations of H2O2. The incipient EC50 values were linearly related to the cell concentration. A cell concentration-independent median cytotoxic cell dose (ED50) of 430 nmoles/mg cell protein or 860 nmoles/107 cells was derived. Median cytotoxic H2O2 concentrations were completely eliminated from the culture medium...


Thu, 29 Jul 2010 03:07

Nrf2 and DJ1 are consistently upregulated in inflammatory multiple sclerosis lesions

Publication year: 2010
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 29 July 2010

Jack, van Horssen , Joost A.R., Drexhage , Thomas, Flor , Wouter, Gerritsen , Paul van, der Valk , ...

Oxidative stress plays a major role in multiple sclerosis (MS), a chronic inflammatory central nervous system (CNS) disease. Invading leukocytes contribute to cell damage and demyelination by the production of excessive amounts of cytotoxic mediators, including reactive oxygen species (ROS). To counteract the damaging effects of ROS the CNS is endowed with a repertoire of endogenous antioxidant enzymes, which are regulated by the transcription factor NF-E2-related factor 2 (Nrf2). Upon exposure to ROS, Nrf2 translocates to the nucleus allowing transcriptional activation of various antioxidant enzymes. DJ1 is a protein that is involved in the stabilization of Nrf2 and hence acts...


Thu, 29 Jul 2010 03:07