for Journals by Title or ISSN
for Articles by Keywords
help
Followed Journals
Journal you Follow: 0
 
Sign Up to follow journals, search in your chosen journals and, optionally, receive Email Alerts when new issues of your Followed Jurnals are published.
Already have an account? Sign In to see the journals you follow.
Journal Cover   Redox Biology
  [1 followers]  Follow
    
  This is an Open Access Journal Open Access journal
   ISSN (Online) 2213-2317
   Published by Elsevier Homepage  [2812 journals]
  • The redox biology network in cancer pathophysiology and therapeutics

    • Abstract: Publication date: August 2015
      Source:Redox Biology, Volume 5
      Author(s): Gina Manda , Gheorghita Isvoranu , Maria Victoria Comanescu , Adrian Manea , Bilge Debelec Butuner , Kemal Sami Korkmaz
      The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1) and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic), greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular heterogeneity and the hypoxia map in the tumor niche, along with the adjoining and systemic effects of oxidative stress-based therapies.
      Graphical abstract image

      PubDate: 2015-06-29T14:37:17Z
       
  • Autophagy in neonatal hypoxia ischemic brain is associated with oxidative
           stress

    • Abstract: Publication date: Available online 27 June 2015
      Source:Redox Biology
      Author(s): Qing Lu , Valerie A. Harris , Sanjv Kumar , Heidi M Mansour , Stephen M. Black
      Autophagy is activated when the neonatal brain exposed to hypoxia ischemia (HI), but the mechanisms underlying its activation and its role in the neuronal cell death associated with HI is unclear. We have previously shown that reactive oxygen species (ROS) derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase play an important role in HI-mediated neuronal cell death. Thus, the aim of this study was to determine if ROS is involved in the activation of autophagy in HI-mediated neonatal brain injury and to determine if this is a protective or deleterious pathway. Initial electron microscopy data demonstrated that autophagosome formation is elevated in P7 hippocampal slice cultures exposed to oxygen-glucose deprivation (OGD). This corresponded with increased levels of LC3II mRNA and protein. The autophagy inhibitor, 3-Methyladenine (3-MA) effectively reduced LC3II levels and autophagsome formation in hippocampal slice cultures exposed to OGD. Neuronal cell death was significantly attenuated. Finally, we found that the pharmacologic inhibition of NADPH oxidase using apocynin or gp91ds-tat decreased autophagy in hippocampal slice cultures and the rat brain respectively. Thus, our results suggest that an activation of autophagy contributes to neonatal HI brain injury this is oxidative stress dependent.
      Graphical abstract image

      PubDate: 2015-06-29T14:37:17Z
       
  • Borane-protected Phosphines are redox-active radioprotective Agents for
           endothelial Cells

    • Abstract: Publication date: Available online 26 June 2015
      Source:Redox Biology
      Author(s): Megan E. Crowe , Christopher J. Lieven , Alex F. Thompson , Nader Sheibani , Leonard A. Levin
      Exposure to radiation can damage endothelial cells in the irradiated area via the production of reactive oxygen species. We synthesized phosphine-borane complexes that reduce disulfide bonds and had previously been shown to interfere with redox-mediated signaling of cell death. We hypothesized that this class of drugs could interfere with the downstream effects of oxidative stress after irradiation and rescue endothelial cells from radiation damage. Cultured bovine aortic endothelial cells were plated for clonogenic assay prior to exposure to varying doses of irradiation from a 137Cs irradiator and treated with various concentrations of bis(3-propionic acid methyl ester)phenylphosphine borane complex (PB1) at different time points. The clone-forming ability of the irradiated cells was assessed seven days after irradiation. We compared the radioprotective effects of PB1 with the aminothiol radioprotectant WR1065 and known superoxide scavengers. PB1 significantly protected bovine aortic endothelial cells from radiation damage, particularly when treated both before and after radiation. The radioprotection with 1µM PB1 corresponded to a dose-reduction factor of 1.24. Radioprotection by PB1 was comparable to the aminothiol WR1065, but was significantly less toxic and required much lower concentrations of drug (1µM vs. 4mM, respectively). Superoxide scavengers were not radioprotective in this paradigm, indicating the mechanisms for both loss of clonogenicity and PB1 radioprotection are independent of superoxide signaling. These data demonstrate that PB1 is an effective redox-active radioprotectant for endothelial cells in vitro, and is radioprotective at a concentration approximately 4 orders of magnitude lower than the aminothiol WR1065 with less toxicity.
      Graphical abstract image

      PubDate: 2015-06-29T14:37:17Z
       
  • Quantitative combination of natural anti-oxidants prevents metabolic
           syndrome by reducing oxidative stress

    • Abstract: Publication date: Available online 26 June 2015
      Source:Redox Biology
      Author(s): Mingjing Gao , Zhen Zhao , Pengyu Lv , YuFang Li , Juntao Gao , Michael Zhang , Baolu Zhao
      Insulin resistance and abdominal obesity are present in the majority of people with the metabolic syndrome. Antioxidant therapy might be a useful strategy for type 2 diabetes and other insulin-resistant states. The combination of vitamin C (Vc) and vitamin E has synthetic scavenging effect on free radicals and inhibition effect on lipid peroxidation. However, there are few studies about how to define the best combination of more than three anti-oxidants as it is difficult or impossible to test the anti-oxidant effect of the combination of every concentration of each ingredient experimentally. Here we present a math model, which is based on the classical Hill equation to determine the best combination, called Fixed Dose Combination (FDC), of several natural anti-oxidants, including Vc, green tea polyphenols (GTP) and grape seed extract proanthocyanidin (GSEP). Then we investigated the effects of FDC on oxidative stress, blood glucose and serum lipid levels in cultured 3T3-L1 adipocytes, high fat diet (HFD)-fed rats which serve as obesity model, and KK-ay mice as diabetic model. The level of serum malondialdehyde (MDA) in the treated rats was studied and Hematoxylin-Eosin (HE) staining or Oil red slices of liver and adipose tissue in the rats were examined as well. FDC shows excellent antioxidant and anti-glycation activity by attenuating lipid peroxidation. FDC determined in this investigation can become a potential solution to reduce obesity, to improve insulin sensitivity and be beneficial for the treatment of fat and diabetic patients. It is the first time to use the math model to determine the best ratio of three anti-oxidants, which can save much more time and chemical materials than traditional experimental method. This quantitative method represents a potentially new and useful strategy to screen all possible combinations of many natural anti-oxidants, therefore may help develop novel therapeutics with the potential to ameliorate the worldwide metabolic abnormalities.


      PubDate: 2015-06-29T14:37:17Z
       
  • Effect of High glucose concentrations on Human erythrocytes in vitro

    • Abstract: Publication date: Available online 25 June 2015
      Source:Redox Biology
      Author(s): Jana Viskupicova , Dusan Blaskovic , Sabina Galiniak , Mirosław Soszyński , Grzegorz Bartosz , Lubica Horakova , Izabela Sadowska-Bartosz
      Exposure to high glucose concentrations in vitro is often employed as a model for understanding erythrocyte modifications in diabetes. However, effects of such experiments may be affected by glucose consumption during prolonged incubation and changes of cellular parameters conditioned by impaired energy balance. The aim of this study was to compare alterations in various red cell parameters in this type of experiment to differentiate between those affected by glycoxidation and those affected by energy imbalance. Erythrocytes were incubated with 5, 45 or 100mM glucose for up to 72h. High glucose concentrations intensified lipid peroxidation and loss of activities of erythrocyte enzyme (glutathione S-transferase and glutathione reductase). On the other hand, hemolysis, eryptosis, calcium accumulation, loss of glutathione and increase in the GSSG/GSH ratio were attenuated by high glucose apparently due to maintenance of energy supply to the cells. Loss of plasma membrane Ca2+-ATPase activity and decrease in superoxide production were not affected by glucose concentration, being seemingly determined by processes independent of both glycoxidation and energy depletion. These results point to the necessity of careful interpretation of data obtained in experiments, in which erythrocytes are subject to treatment with high glucose concentrations in vitro.
      Graphical abstract image

      PubDate: 2015-06-29T14:37:17Z
       
  • Regulation of NOx enzymes expression in vascular pathophysiology: Focusing
           on transcription factors and epigenetic mechanisms

    • Abstract: Publication date: Available online 25 June 2015
      Source:Redox Biology
      Author(s): Simona-Adriana Manea , Alina Constantin , Gina Manda , Shlomo Sasson , Adrian Manea
      NADPH oxidases (Nox) represent a family of hetero-oligomeric enzymes whose exclusive biological function is the generation of reactive oxygen species (ROS). Nox-derived ROS are essential modulators of signal transduction pathways that control key physiological activities such as cell growth, proliferation, migration, differentiation, and apoptosis, immune responses, and biochemical pathways. Enhanced formation of Nox-derived ROS, which is generally associated with the up-regulation of different Nox subtypes, has been established in various pathologies, namely cardiovascular diseases, diabetes, obesity, cancer, and neurodegeneration. The detrimental effects of Nox-derived ROS are related to alterations in cell signalling and/or direct irreversible oxidative damage of nucleic acids, proteins, carbohydrates, and lipids. Thus, understanding of transcriptional regulation mechanisms of Nox enzymes have been extensively investigated in an attempt to find ways to counteract the excessive formation of Nox-derived ROS in various pathological states. Despite the numerous existing data, the molecular pathways responsible for Nox up-regulation are not completely understood. This review article summarizes some of the recent advances and concepts related to the regulation of Nox expression in the vascular pathophysiology. It highlights the role of transcription factors and epigenetic mechanisms in this process. Identification of the signalling molecules involved in Nox up-regulation, which is associated with the onset and development of cardiovascular dysfunction may contribute to the development of novel strategies for the treatment of cardiovascular diseases.
      Graphical abstract image

      PubDate: 2015-06-29T14:37:17Z
       
  • Redox-modulating agents target NOX2-dependent IKKε oncogenic kinase
           expression and proliferation in human breast cancer cell lines

    • Abstract: Publication date: Available online 23 June 2015
      Source:Redox Biology
      Author(s): Espérance Mukawera , Stefany Chartier , Virginie Williams , Patrick J. Pagano , Réjean Lapointe , Nathalie Grandvaux
      Oxidative stress is considered a causative factor in carcinogenesis, but also in the development of resistance to current chemotherapies. The appropriate usage of redox-modulating compounds is limited by the lack of knowledge of their impact on specific molecular pathways. Increased levels of the IKKε kinase, as a result of gene amplification or aberrant expression, are observed in a substantial number of breast carcinomas. IKKε not only plays a key role in cell transformation and invasiveness, but also in the development to resistance to tamoxifen. Here, we studied the effect of in vitro treatment with the redox-modulating triphenylmethane dyes, Gentian Violet and Brilliant Green, and nitroxide Tempol on IKKε expression and cell proliferation in the human breast cancer epithelial cell lines exhibiting amplification of IKKε, MCF-7 and ZR75.1. We show that Gentian Violet, Brilliant Green and Tempol significantly decrease intracellular superoxide anion levels and inhibit IKKε expression and cell viability. Treatment with Gentian Violet and Brilliant Green was associated with a reduced cyclin D1 expression and activation of caspase 3 and/or 7. Tempol decreased cyclin D1 expression in both cell lines, while activation of caspase 7 was only observed in MCF-7 cells. Silencing of the superoxide-generating NOX2 NADPH oxidase expressed in breast cancer cells resulted in the significant reduction of IKKε expression. Taken together, our results suggest that redox-modulating compounds targeting NOX2 could present a particular therapeutic interest in combination therapy against breast carcinomas exhibiting IKKε amplification.
      Graphical abstract image

      PubDate: 2015-06-24T14:34:33Z
       
  • Dexamethasone acts as a radiosensitizer in three astrocytoma cell lines
           via oxidative stress

    • Abstract: Publication date: Available online 23 June 2015
      Source:Redox Biology
      Author(s): Sylvia Ortega-Martínez
      Glucocorticoids (GCs), which act on stress pathways, are well-established in the co-treatment of different kinds of tumors; however, the underlying mechanisms by which GCs act are not yet well elucidated. As such, this work investigates the role of glucocorticoids, specifically dexamethasone (DEXA), in the processes referred to as DNA damage and DNA damage response (DDR), establishing a new approach in three astrocytomas cell lines (CT2A, APP.PS1 L.1 and APP.PS1 L.3). The results show that DEXA administration increased the basal levels of gamma-H2AX foci, keeping them higher 4 hours after irradiation (IR) of the cells, compared to untreated cells. This means that DEXA might cause increased radiosensitivity in this cell line. On the other hand, DEXA did not have an apparent effect on the formation and disappearance of the 53BP1 foci. Furthermore, it was found that DEXA administered 2 hours before IR led to a radical change in DNA repair kinetics, even DEXA does not affect cell cycle. It is important to highlight that DEXA produced cell death in these cell lines compared to untreated cells. Finally and most important, the high levels of gamma-H2AX could be reversed by administration of ascorbic Acid, a potent blocker of reactive oxygen species, suggesting that DEXA acts by causing DNA damage via oxidative stress. These exiting findings suggest that DEX might promote radiosensitivity in brain tumors, specifically in astrocytoma-like tumors.
      Graphical abstract image

      PubDate: 2015-06-24T14:34:33Z
       
  • Consistent antioxidant and antihypertensive effects of oral sodium nitrite
           in DOCA-salt hypertension

    • Abstract: Publication date: Available online 23 June 2015
      Source:Redox Biology
      Author(s): Jefferson H. Amaral , Graziele C. Ferreira , Lucas C. Pinheiro , Marcelo F. Montenegro , Jose E. Tanus-Santos
      Hypertension is a common disease that includes oxidative stress as a major feature, and oxidative stress impairs physiological nitric oxide (NO) activity promoting cardiovascular pathophysiological mechanisms. While inorganic nitrite and nitrate are now recognized as relevant sources of NO after their bioactivation by enzymatic and non-enzymatic pathways, thus lowering blood pressure, mounting evidence suggests that sodium nitrite also exerts antioxidant effects. Here we show for the first time that sodium nitrite exerts consistent systemic and vascular antioxidant and antihypertensive effects in the deoxycorticosterone-salt (DOCA-salt) hypertension model. This is particularly important because increased oxidative stress plays a major role in the DOCA-salt hypertension model, which is less dependent on activation of the renin-angiotensin system than other hypertension models. Indeed, antihypertensive effects of oral nitrite were associated with increased plasma nitrite and nitrate concentrations, and completely blunted hypertension-induced increases in plasma 8-isoprostane and lipid peroxide levels, in vascular reactive oxygen species, in vascular NADPH oxidase activity, and in vascular xanthine oxidoreductase activity. Together, these findings provide evidence that the oral administration of sodium nitrite consistently decreases the blood pressure in association with major antioxidant effects in experimental hypertension.
      Graphical abstract image

      PubDate: 2015-06-24T14:34:33Z
       
  • Disruption of thioredoxin metabolism enhances the toxicity of transforming
           growth factor β-activated kinase 1 (TAK1) inhibition in KRAS-mutated
           colon cancer cells

    • Abstract: Publication date: August 2015
      Source:Redox Biology, Volume 5
      Author(s): Jennifer E. Hrabe , Brianne R. O’Leary , Melissa A. Fath , Samuel N. Rodman , Anna M. Button , Frederick E. Domann , Douglas R. Spitz , James J. Mezhir
      Transforming growth factor β-activated kinase 1 (TAK1) is critical for survival of many KRAS mutated colorectal cancer cells, and TAK1 inhibition with 5Z-7-oxozeaenol has been associated with oxidative stress leading to tumor cell killing. When SW 620 and HCT 116 human colon cancer cells were treated with 5µM 5Z-7-oxozeaenol, cell viability, growth, and clonogenic survival were significantly decreased. Consistent with TAK1 inhibition being causally related to thiol-mediated oxidative stress, 10mM N-acetylcysteine (NAC) partially reversed the growth inhibitory effects of 5Z-7-oxozeaenol. In addition, 5Z-7-oxozeaenol also increased steady-state levels of H2DCFDA oxidation as well as increased levels of total glutathione (GSH) and glutathione disulfide (GSSG). Interestingly, depletion of GSH using buthionine sulfoximine did not significantly potentiate 5Z-7-oxozeaenol toxicity in either cell line. In contrast, pre-treatment of cells with auranofin (Au) to inhibit thioredoxin reductase activity significantly increased levels of oxidized thioredoxin as well as sensitized cells to 5Z-7-oxozeaenol-induced growth inhibition and clonogenic cell killing. These results were confirmed in SW 620 murine xenografts, where treatment with 5Z-7-oxozeaenol or with Au plus 5Z-7-oxozeaenol significantly inhibited growth, with Au plus 5Z-7-oxozeaenol trending toward greater growth inhibition compared to 5Z-7-oxozeaenol alone. These results support the hypothesis that thiol-mediated oxidative stress is causally related to TAK1-induced colon cancer cell killing. In addition, these results support the hypothesis that thioredoxin metabolism is a critical target for enhancing colon cancer cell killing via TAK1 inhibition and could represent an effective therapeutic strategy in patients with these highly resistant tumors.
      Graphical abstract image

      PubDate: 2015-06-24T14:34:33Z
       
  • Nitric oxide induces hypoxia ischemic injury in the neonatal Brian via the
           disruption of neuronal iron metabolism

    • Abstract: Publication date: Available online 23 June 2015
      Source:Redox Biology
      Author(s): Qing Lu , Valerie A. Harris , Ruslan Rafikov , Xutong Sun , Sanjiv Kumar , Stephen M. Black
      We have recently shown that increased hydrogen peroxide (H2O2) generation is involved in hypoxia-ischemia (HI)-mediated neonatal brain injury. H2O2 can react with free iron to form the hydroxyl radical, through Fenton Chemistry. Thus, the objective of this study was to determine if there was a role for the hydroxyl radical in neonatal HI brain injury and to elucidate the underlying mechanisms. Our data demonstrate that HI increases the deposition of free iron and hydroxyl radical formation, in both P7 hippocampal slice cultures exposed to oxygen-glucose deprivation (OGD), and the neonatal rat exposed to HI. Both these processes were found to be nitric oxide (NO) dependent. Further analysis demonstrated that the NO-dependent increase in iron deposition was mediated through increased transferrin receptor expression and a decrease in ferritin expression. This was correlated with a reduction in aconitase activity. Both NO inhibition and iron scavenging, using deferoxamine administration, reduced hydroxyl radical levels and neuronal cell death. In conclusion, our results suggest that increased NO generation leads to neuronal cell death during neonatal HI, at least in part, by altering iron homeostasis and hydroxyl radical generation.
      Graphical abstract image

      PubDate: 2015-06-24T14:34:33Z
       
  • Determination of protein carbonyls in plasma, cell extracts, tissue
           homogenates, isolated proteins: focus on sample preparation and
           derivatization conditions

    • Abstract: Publication date: Available online 18 June 2015
      Source:Redox Biology
      Author(s): Daniela Weber , Michael J. Davies , Tilman Grune
      Protein oxidation is involved in regulatory physiological events as well as in damage to tissues and is thought to play a key role in the pathophysiology of diseases and in the aging process. Protein-bound carbonyls represent a marker of global protein oxidation, as they are generated by multiple different reactive oxygen species in blood, tissues and cells. Sample preparation and stabilization are key steps in the accurate quantification of oxidation-related products and examination of physiological/pathological processes. This review therefore focuses on the sample preparation processes used in the most relevant methods to detect protein carbonyls after derivatization with 2,4-dinitrophenylhydrazine with an emphasis on measurement in plasma, cells, organ homogenates, isolated proteins and organelles. Sample preparation, derivatization conditions and protein handling are presented for the spectrophotometric and HPLC method as well as for immunoblotting and ELISA. An extensive overview covering these methods in previously published articles is given for researchers who plan to measure protein carbonyls in different samples.
      Graphical abstract image

      PubDate: 2015-06-24T14:34:33Z
       
  • Diet affects the redox system in developing Atlantic cod (Gadus morhua)
           larvae

    • Abstract: Publication date: Available online 12 June 2015
      Source:Redox Biology
      Author(s): Samuel Penglase , Rolf B. Edvardsen , Tomasz Furmanek , Ivar Rønnestad , Ørjan Karlsen , Terje van der Meeren , Kristin Hamre
      The growth and development of marine fish larvae fed copepods is superior to those fed rotifers, but the underlying molecular reasons for this are unclear. In the following study we compared the effects of such diets on redox regulation pathways during development of Atlantic cod (Gadus morhua) larvae. Cod larvae were fed a control diet of copepods or the typical rotifer/Artaemia diet commonly used in commercial marine fish hatcheries, from first feeding until after metamorphosis. The oxidised and reduced glutathione levels, the redox potential, and the mRNA expression of 100 genes in redox system pathways were then compared between treatments during larval development. We found that rotifer/Artaemia-fed cod larvae had lower levels of oxidised glutathione, a more reduced redox potential, and altered expression of approximately half of the redox system genes when compared to copepod-fed larvae. This rotifer/Artaemia diet-induced differential regulation of the redox system was greatest during periods of suboptimal growth. Upregulation of the oxidative stress response transcription factor, nrf2, and NRF2 target genes in rotifer/Artaemia fed larvae suggest this diet induced an NRF2-mediated oxidative stress response. Overall, the data demonstrate that nutritional intake plays a role in regulating the redox system in developing fish larvae. This may be a factor in dietary-induced differences observed in larval growth.
      Graphical abstract image

      PubDate: 2015-06-18T14:10:08Z
       
  • Sch9 regulates intracellular protein ubiquitination by controlling stress
           responses

    • Abstract: Publication date: Available online 9 June 2015
      Source:Redox Biology
      Author(s): Beibei Qie , Zhou Lyu , Lei Lyu , Jun Liu , Xuejie Gao , Yanyan Liu , Wei Duan , Nianhui Zhang , Linfang Du , Ke Liu
      Protein ubiquitination and the subsequent degradation are important means by which aberrant proteins are removed from cells, a key requirement for long-term survival. In this study, we found that the overall level of ubiquitinated proteins dramatically decreased as yeast cell grew from log to stationary phase. Deletion of SCH9, a gene encoding a key protein kinase for longevity control, decreased the level of ubiquitinated proteins in log phase and this effect could be reversed by restoring Sch9 function. We demonstrate here that the decrease of ubiquitinated proteins in sch9Δ cells in log phase is not caused by changes in ubiquitin expression, proteasome activity, or autophagy, but by enhanced expression of stress response factors and a decreased level of oxidative stress. Our results revealed for the first time how Sch9 regulates the level of ubiquitinated proteins and provides new insight into how Sch9 controls longevity.


      PubDate: 2015-06-11T13:34:59Z
       
  • The correlations of glycated hemoglobin and carbohydrate metabolism
           parameters with heart rate variability in apparently healthy sedentary
           young male subjects

    • Abstract: Publication date: Available online 3 June 2015
      Source:Redox Biology
      Author(s): Andriy Cherkas , Orest Abrahamovych , Sergii Golota , Armen Nersesyan , Christoph Pichler , Victoria Serhiyenko , Siegfried Knasmüller , Neven Zarkovic , Peter Eckl
      Sedentary lifestyle is a major risk factor for diabetes, cardiovascular and many other age-related diseases. Heart rate variability (HRV) reflects the function of regulatory systems of internal organs and may sensitively indicate early metabolic disturbances. We hypothesize that quantitative and qualitative changes of HRV in young subjects may reflect early metabolic derangements responsible for further development of clinically significant disease.
      Graphical abstract image

      PubDate: 2015-06-07T14:03:51Z
       
  • Ovotoxicants 4-vinylcyclohexene 1,2-monoepoxide and 4-vinylcyclohexene
           diepoxide disrupt redox status and modify different electrophile sensitive
           target enzymes and genes in Drosophila melanogaster

    • Abstract: Publication date: Available online 4 June 2015
      Source:Redox Biology
      Author(s): Amos O. Abolaji , Jean P. Kamdem , Thiago H. Lugokenski , Ebenezer O. Farombi , Diogo Souza , Élgion L. da Silva Loreto , João B.T. Rocha
      The compounds 4-vinylcyclohexene 1,2-monoepoxide (VCM) and 4-Vinylcyclohexene diepoxide (VCD) are the two downstream metabolites of 4-vinylcyclohexene (VCH), an ovotoxic agent in mammals. In addition, VCM and VCD may be found as by-products of VCH oxidation in the environment. Recently, we reported the involvement of oxidative stress in the toxicity of VCH in Drosophila melanogaster. However, it was not possible to determine the individual contributions of VCM and VCD in VCH toxicity. Hence, we investigated the toxicity of VCM and VCD (10–1000 µM) in flies after 5 days of exposure via the diet. Our results indicated impairments in climbing behaviour and disruptions in antioxidant balance and redox status evidenced by an increase in DCFH oxidation, decreases in total thiol content and glutathione-S-transferase (GST) activity in the flies exposed to VCM and VCD (p < 0.05). These effects were accompanied by disruptions in the transcription of the genes encoding the proteins superoxide dismutase (SOD1), kelch-like erythroid-derived cap-n-collar (CNC) homology (ECH)-associated protein 1 (Keap-1), mitogen activated protein kinase 2 (MAPK-2), catalase, Cyp18a1, JAFRAC 1 (thioredoxin peroxidase 1) and thioredoxin reductase 1 (TrxR−1) (p < 0.05). VCM and VCD inhibited acetylcholinesterase (AChE) and delta aminolevulinic acid dehydratase (δ-ALA D) activities in the flies (p < 0.05). Indeed, here, we demonstrated that different target enzymes and genes were modified by the electrophiles VCM and VCD in the flies. Thus, D. melanogaster has provided further lessons on the toxicity of VCM and VCD which suggest that the reported toxicity of VCH may be mediated by its transformation to VCM and VCD.
      Graphical abstract image

      PubDate: 2015-06-07T14:03:51Z
       
  • Oxidative proteome alterations during skeletal muscle ageing

    • Abstract: Publication date: Available online 3 June 2015
      Source:Redox Biology
      Author(s): Sofia Lourenço dos Santos , Martin A. Baraibar , Staffan Lundberg , Orvar Eeg-Olofsson , Lars Larsson , Bertrand Friguet
      Sarcopenia corresponds to the degenerative loss of skeletal muscle mass, quality, and strength associated with ageing and leads to a progressive impairment of mobility and quality of life. However, the cellular and molecular mechanisms involved in this process are not completely understood. A hallmark of cellular and tissular ageing is the accumulation of oxidatively modified (carbonylated) proteins, leading to a decreased quality of the cellular proteome that could directly impact on normal cellular functions. Although increased oxidative stress has been reported during skeletal muscle ageing, the oxidized protein targets, also referred as to the ‘oxi-proteome’ or ‘carbonylome’, have not been characterized yet. To better understand the mechanisms by which these damaged proteins build up and potentially affect muscular function, proteins targeted by these modifications have been identified in human rectus abdominis muscle obtained from young and old healthy donors using a bi-dimensional gel electrophoresis-based proteomic approach coupled with immunodetection of carbonylated proteins. Among evidenced protein spots, 17 were found as increased carbonylated in biopsies from old donors comparing to young counterparts. These proteins are involved in key cellular functions such as cellular morphology and transport, muscle contraction and energy metabolism. Importantly, impairment of these pathways has been described in skeletal muscle during ageing. Functional decline of these proteins due to irreversible oxidation may therefore impact directly on the above-mentioned pathways, hence contributing to the generation of the sarcopenic phenotype.
      Graphical abstract image

      PubDate: 2015-06-07T14:03:51Z
       
  • Redox regulation of genome stability by effects on gene expression,
           epigenetic pathways and DNA damage/repair

    • Abstract: Publication date: Available online 3 June 2015
      Source:Redox Biology
      Author(s): Yuliya Mikhed , Agnes Görlach , Ulla Knaus , Andreas Daiber
      Reactive oxygen and nitrogen species (e.g. H2O2, nitric oxide) confer redox regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. In addition, classical regulation of gene expression or activity, including gene transcription to RNA followed by translation to the protein level, by transcription factors (e.g. NF-κB, HIF-1α) and mRNA binding proteins (e.g. GAPDH, HuR) is subject to redox regulation. This review will give an update of recent discoveries in this field, and specifically highlight the impact of reactive oxygen and nitrogen species on DNA repair systems that contribute to genomic stability. Emphasis will be placed on the emerging role of redox mechanisms regulating epigenetic pathways (e.g. miRNA, DNA methylation and histone modifications). By providing clinical correlations we discuss how oxidative stress can impact on gene regulation/activity and vice versa, how epigenetic processes, other gene regulatory mechanisms and DNA repair can influence the cellular redox state and contribute or prevent development or progression of disease.
      Graphical abstract image

      PubDate: 2015-06-07T14:03:51Z
       
  • Effects of long-term dietary nitrate supplementation in mice

    • Abstract: Publication date: Available online 29 May 2015
      Source:Redox Biology
      Author(s): Michael P. Hezel , Ming Liu , Tomas A. Schiffer , Filip J. Larsen , Antonio Checa , Craig E. Wheelock , Mattias Carlström , Jon O. Lundberg , Eddie Weitzberg
      Background Inorganic nitrate (NO3 −) is a precursor of nitric oxide (NO) in the body and a large number of short-term studies with dietary nitrate supplementation in animals and humans show beneficial effects on cardiovascular health, exercise efficiency, host defense and ischemia reperfusion injury. In contrast, there is a long withstanding concern regarding the putative adverse effects of chronic nitrate exposure related to cancer and adverse hormonal effects. To address these concerns we performed in mice, a physiological and biochemical multi-analysis on the effects of long-term dietary nitrate supplementation. Design 7 week-old C57BL/6 mice were put on a low-nitrate chow and at 20 weeks-old were treated with NaNO3 (1 mmol/L) or NaCl (1 mmol/L, control) in the drinking water. The groups were monitored for weight gain, food and water consumption, blood pressure, glucose metabolism, body composition and oxygen consumption until one group was reduced to eight animals due to death or illness. At that point remaining animals were sacrificed and blood and tissues were analyzed with respect to metabolism, cardiovascular function, inflammation, and oxidative stress. Results Animals were supplemented for 17 months before final sacrifice. Body composition, oxygen consumption, blood pressure, glucose tolerance were measured during the experiment, and vascular reactivity and muscle mitochondrial efficiency measured at the end of the experiment with no differences identified between groups. Nitrate supplementation was associated with improved insulin response, decreased plasma IL-10 and a trend towards improved survival. Conclusions Long term dietary nitrate in mice, at levels similar to the upper intake range in the western society, is not detrimental.
      Graphical abstract image

      PubDate: 2015-06-01T13:21:35Z
       
  • Norepinephrine-induced apoptotic and hypertrophic responses in H9c2
           cardiac myoblasts are characterized by different repertoire of reactive
           oxygen species generation

    • Abstract: Publication date: Available online 29 May 2015
      Source:Redox Biology
      Author(s): Anita Thakur , Md. Jahangir Alam , M.R. Ajayakumar , Saroj Ghaskadbi , Manish Sharma , Shyamal K. Goswami
      Despite recent advances, the role of ROS in mediating hypertrophic and apoptotic responses in cardiac myocytes elicited by norepinephrine (NE) is rather poorly understood. We demonstrate through our experiments that H9c2 cardiac myoblasts treated with 2 µM NE (hypertrophic dose) generate DCFH-DA positive ROS only for 2 hrs; while those treated with 100 µM NE (apoptotic dose) sustains generation for 48 hrs, followed by apoptosis. Though the levels of DCFH fluorescence were comparable at early time points in the two treatment sets, its quenching by DPI, catalase and MnTmPyP suggested the existence of a different repertoire of ROS. Both doses of NE also induced moderate levels of H2O2 but with different kinetics. Sustained but intermittent generation of highly reactive species detectable by HPF was seen in both treatment sets but no peroxynitrite was generated in either conditions. Sustained generation of hydroxyl radicals with no appreciable differences were noticed in both treatment sets. Nevertheless, despite similar profile of ROS generation between the two conditions, extensive DNA damage as evident from the increase in 8-OH-dG content, formation of γ-H2AX and PARP cleavage was seen only in cells treated with the higher dose of NE. We therefore conclude that hypertrophic and apoptotic doses of NE generate distinct but comparable repertoire of ROS/RNS leading to two very distinct downstream responses.
      Graphical abstract image

      PubDate: 2015-06-01T13:21:35Z
       
  • Breathing new life into nitric oxide signaling; a brief overview of the
           interplay between oxygen and nitric oxide

    • Abstract: Publication date: Available online 22 May 2015
      Source:Redox Biology
      Author(s): Douglas D. Thomas
      Nitric oxide (•NO, nitrogen monoxide) is one of the most unique biological signaling molecules associated with a multitude of physiologic and pathological conditions. In order to fully appreciate its numerous roles, it is essential to understand its basic biochemical properties. Most signaling effector molecules such as steroids or proteins have a significant life-span and function through classical receptor-ligand interactions. •NO, however, is a short-lived free-radical gas that only reacts with two types of molecules under biological conditions; metals and other free radicals. These simple interactions can lead to a myriad of complex intermediates which in turn have their own phenotypic effects. For these reasons, responses to •NO often appear to be random or contradictory when outcomes are compared across various experimental settings. This article will serve as a brief overview of the chemical, biological, and microenvironmental factors that dictate •NO signaling with an emphasis on •NO metabolism. The prominent role that oxygen (dioxygen, O2) plays in •NO metabolism and how it influences the biological effects of •NO will be highlighted. This information and these concepts are intended to help students and investigators think about the interpretation of data from experiments where biological effects of •NO are being elucidated.
      Graphical abstract image

      PubDate: 2015-05-27T12:54:47Z
       
  • Protein lipoxidation: detection strategies and challenges

    • Abstract: Publication date: Available online 21 May 2015
      Source:Redox Biology
      Author(s): Giancarlo Aldini , M. Rosário Domingues , Corinne M. Spickett , Pedro Domingues , Alessandra Altomare , Francisco J. Sánchez-Gómez , Clara L. Oeste , Dolores Pérez-Sala
      Enzymatic and non-enzymatic lipid metabolism can give rise to reactive species that may covalently modify cellular or plasma proteins through a process known as lipoxidation. Under basal conditions, protein lipoxidation can contribute to normal cell homeostasis and participate in signaling or adaptive mechanisms, as exemplified by lipoxidation of Ras proteins or of the cytoskeletal protein vimentin, both of which behave as sensors of electrophilic species. Nevertheless, increased lipoxidation under pathological conditions may lead to deleterious effects on protein structure or aggregation. This can result in impaired degradation and accumulation of abnormally folded proteins contributing to pathophysiology, as may occur in neurodegenerative diseases. Identification of the protein targets of lipoxidation and its functional consequences under pathophysiological situations can unveil the modification patterns associated with the various outcomes, as well as preventive strategies or potential therapeutic targets. Given the wide structural variability of lipid moieties involved in lipoxidation, highly sensitive and specific methods for its detection are required. Derivatization of reactive carbonyl species is instrumental in the detection of adducts retaining carbonyl groups. In addition, use of tagged derivatives of electrophilic lipids enables enrichment of lipoxidized proteins or peptides. Ultimate confirmation of lipoxidation requires high resolution mass spectrometry approaches to unequivocally identify the adduct and the targeted residue. Moreover, rigorous validation of the targets identified and assessment of the functional consequences of these modifications are essential. Here we present an update on methods to approach the complex field of lipoxidation along with validation strategies and functional assays illustrated with well-studied lipoxidation targets.
      Graphical abstract image

      PubDate: 2015-05-22T12:14:54Z
       
  • Can nitric oxide synthase activity be unequivocally measured in red blood
           cells and platelets' If yes, by which assay'

    • Abstract: Publication date: August 2015
      Source:Redox Biology, Volume 5
      Author(s): Dimitrios Tsikas



      PubDate: 2015-05-22T12:14:54Z
       
  • Response to commentary

    • Abstract: Publication date: August 2015
      Source:Redox Biology, Volume 5
      Author(s): Miriam M. Cortese-Krott , Malte Kelm



      PubDate: 2015-05-22T12:14:54Z
       
  • Editors' Forum Discussion of controversies in the measurement of
           nitric oxide metabolites in biological matrices

    • Abstract: Publication date: August 2015
      Source:Redox Biology, Volume 5
      Author(s): Santiago Lamas



      PubDate: 2015-05-22T12:14:54Z
       
  • Thiol redox homeostasis in neurodegenerative disease

    • Abstract: Publication date: August 2015
      Source:Redox Biology, Volume 5
      Author(s): Gethin J. McBean , Mutay Aslan , Helen R. Griffiths , Rita C. Torrão
      This review provides an overview of the biochemistry of thiol redox couples and the significance of thiol redox homeostasis in neurodegenerative disease. The discussion is centred on cysteine/cystine redox balance, the significance of the xc − cystine–glutamate exchanger and the association between protein thiol redox balance and neurodegeneration, with particular reference to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and glaucoma. The role of thiol disulphide oxidoreductases in providing neuroprotection is also discussed.
      Graphical abstract image

      PubDate: 2015-05-17T11:42:38Z
       
  • Fetal–maternal interface impedance parallels local NADPH oxidase
           related superoxide production

    • Abstract: Publication date: August 2015
      Source:Redox Biology, Volume 5
      Author(s): L. Guedes-Martins , E. Silva , A.R. Gaio , J. Saraiva , A.I. Soares , J. Afonso , F. Macedo , H. Almeida
      Blood flow assessment employing Doppler techniques is a useful procedure in pregnancy evaluation, as it may predict pregnancy disorders coursing with increased uterine vascular impedance, as pre-eclampsia. While the local causes are unknown, emphasis has been put on reactive oxygen species (ROS) excessive production. As NADPH oxidase (NOX) is a ROS generator, it is hypothesized that combining Doppler assessment with NOX activity might provide useful knowledge on placental bed disorders underlying mechanisms. A prospective longitudinal study was performed in 19 normal course, singleton pregnancies. Fetal aortic isthmus (AoI) and maternal uterine arteries (UtA) pulsatility index (PI) were recorded at two time points: 20–22 and 40–41 weeks, just before elective Cesarean section. In addition, placenta and placental bed biopsies were performed immediately after fetal extraction. NOX activity was evaluated using a dihydroethidium-based fluorescence method and associations to PI values were studied with Spearman correlations. A clustering of pregnancies coursing with higher and lower PI values was shown, which correlated strongly with placental bed NOX activity, but less consistently with placental tissue. The study provides evidence favoring that placental bed NOX activity parallels UtA PI enhancement and suggests that an excess in oxidation underlies the development of pregnancy disorders coursing with enhanced UtA impedance.
      Graphical abstract image

      PubDate: 2015-05-17T11:42:38Z
       
  • Standardization and quality control in quantifying non-enzymatic oxidative
           protein modifications in relation to ageing and disease: Why is it
           important and why is it hard?

    • Abstract: Publication date: August 2015
      Source:Redox Biology, Volume 5
      Author(s): Olgica Nedić , Adelina Rogowska-Wrzesinska , Suresh I.S. Rattan
      Post-translational modifications (PTM) of proteins determine the activity, stability, specificity, transportability and lifespan of a protein. Some PTM are highly specific and regulated involving various enzymatic pathways, but there are other non-enzymatic PTM (nePTM), which occur stochastically, depend on the ternary structure of proteins and can be damaging. It is often observed that inactive and abnormal proteins accumulate in old cells and tissues. The nature, site and extent of nePTM give rise to a population of that specific protein with alterations in structure and function ranging from being fully active to totally inactive molecules. Determination of the type and the amount (abundance) of nePTM is essential for establishing connection between specific protein structure and specific biological role. This article summarizes analytical demands for reliable quantification of nePTM, including requirements for the assay performance, standardization and quality control, and points to the difficulties, uncertainties and un-resolved issues.
      Graphical abstract image

      PubDate: 2015-05-17T11:42:38Z
       
  • Neuron specific reduction in CuZnSOD is not sufficient to initiate a full
           sarcopenia phenotype

    • Abstract: Publication date: August 2015
      Source:Redox Biology, Volume 5
      Author(s): Kavithalakshmi Sataranatarajan , Rizwan Qaisar , Carol Davis , Giorgos K. Sakellariou , Aphrodite Vasilaki , Yiqiang Zhang , Yuhong Liu , Shylesh Bhaskaran , Anne McArdle , Malcolm Jackson , Susan V. Brooks , Arlan Richardson , Holly Van Remmen
      Our previous studies showed that adult (8 month) mice lacking CuZn-superoxide dismutase (CuZnSOD, Sod1KO mice) have neuromuscular changes resulting in dramatic accelerated muscle atrophy and weakness that mimics age-related sarcopenia. We have further shown that loss of CuZnSOD targeted to skeletal muscle alone results in only mild weakness and no muscle atrophy. In this study, we targeted deletion of CuZnSOD specifically to neurons (nSod1KO mice) and determined the effect on muscle mass and weakness. The nSod1KO mice show a significant loss of CuZnSOD activity and protein level in brain and spinal cord but not in muscle tissue. The masses of the gastrocnemius, tibialis anterior and extensor digitorum longus (EDL) muscles were not reduced in nSod1KO compared to wild type mice, even at 20 months of age, although the quadriceps and soleus muscles showed small but statistically significant reductions in mass in the nSod1KO mice. Maximum isometric specific force was reduced by 8–10% in the gastrocnemius and EDL muscle of nSod1KO mice, while soleus was not affected. Muscle mitochondrial ROS generation and oxidative stress measured by levels of reactive oxygen/nitrogen species (RONS) regulatory enzymes, protein nitration and F2-isoprostane levels were not increased in muscle from the nSod1KO mice. Although we did not find evidence of denervation in the nSod1KO mice, neuromuscular junction morphology was altered and the expression of genes associated with denervation acetylcholine receptor subunit alpha (AChRα), the transcription factor, Runx1 and GADD45α) was increased, supporting a role for neuronal loss of CuZnSOD initiating alterations at the neuromuscular junction. These results and our previous studies support the concept that CuZnSOD deficits in either the motor neuron or muscle alone are not sufficient to initiate a full sarcopenic phenotype and that deficits in both tissues are required to recapitulate the loss of muscle observed in Sod1KO mice.
      Graphical abstract image

      PubDate: 2015-05-17T11:42:38Z
       
  • Oxidative stress triggered by naturally occurring flavone apigenin results
           in senescence and chemotherapeutic effect in human colorectal cancer cells
           

    • Abstract: Publication date: August 2015
      Source:Redox Biology, Volume 5
      Author(s): Kacoli Banerjee , Mahitosh Mandal
      Recent studies involving phytochemical polyphenolic compounds have suggested flavones often exert pro-oxidative effect in vitro against wide array of cancer cell lines. The aim of this study was to evaluate the in-vitro pro-oxidative activity of apigenin, a plant based flavone against colorectal cancer cell lines and investigate cumulative effect on long term exposure. In the present study, treatment of colorectal cell lines HT-29 and HCT-15 with apigenin resulted in anti-proliferative and apoptotic effects characterized by biochemical and morphological changes, including loss of mitochondrial membrane potential which aided in reversing the impaired apoptotic machinery leading to negative implications in cancer pathogenesis. Apigenin induces rapid free radical species production and the level of oxidative damage was assessed by qualitative and quantitative estimation of biochemical markers of oxidative stress. Increased level of mitochondrial superoxide suggested dose dependent mitochondrial oxidative damage which was generated by disruption in anti-apoptotic and pro-apoptotic protein balance. Continuous and persistent oxidative stress induced by apigenin at growth suppressive doses over extended treatment time period was observed to induce senescence which is a natural cellular mechanism to attenuate tumor formation. Senescence phenotype inducted by apigenin was attributed to changes in key molecules involved in p16-Rb and p53 independent p21 signaling pathways. Phosphorylation of retinoblastoma was inhibited and significant up-regulation of p21 led to simultaneous suppression of cyclins D1 and E which indicated the onset of senescence. Pro-oxidative stress induced premature senescence mediated by apigenin makes this treatment regimen a potential chemopreventive strategy and an in vitro model for aging research.
      Graphical abstract image

      PubDate: 2015-05-17T11:42:38Z
       
  • Protection against renal ischemia–reperfusion injury in vivo by the
           mitochondria targeted antioxidant MitoQ

    • Abstract: Publication date: August 2015
      Source:Redox Biology, Volume 5
      Author(s): Anna J. Dare , Eleanor A. Bolton , Gavin J. Pettigrew , J. Andrew Bradley , Kourosh Saeb-Parsy , Michael P. Murphy
      Ischemia–reperfusion (IR) injury to the kidney occurs in a range of clinically important scenarios including hypotension, sepsis and in surgical procedures such as cardiac bypass surgery and kidney transplantation, leading to acute kidney injury (AKI). Mitochondrial oxidative damage is a significant contributor to the early phases of IR injury and may initiate a damaging inflammatory response. Here we assessed whether the mitochondria targeted antioxidant MitoQ could decrease oxidative damage during IR injury and thereby protect kidney function. To do this we exposed kidneys in mice to in vivo ischemia by bilaterally occluding the renal vessels followed by reperfusion for up to 24h. This caused renal dysfunction, measured by decreased creatinine clearance, and increased markers of oxidative damage. Administering MitoQ to the mice intravenously 15min prior to ischemia protected the kidney from damage and dysfunction. These data indicate that mitochondrial oxidative damage contributes to kidney IR injury and that mitochondria targeted antioxidants such as MitoQ are potential therapies for renal dysfunction due to IR injury.


      PubDate: 2015-05-17T11:42:38Z
       
  • Dimethyl fumarate modulates antioxidant and lipid metabolism in
           oligodendrocytes

    • Abstract: Publication date: August 2015
      Source:Redox Biology, Volume 5
      Author(s): He Huang , Alexandra Taraboletti , Leah P. Shriver
      Oxidative stress contributes to pathology associated with inflammatory brain disorders and therapies that upregulate antioxidant pathways may be neuroprotective in diseases such as multiple sclerosis. Dimethyl fumarate, a small molecule therapeutic for multiple sclerosis, activates cellular antioxidant signaling pathways and may promote myelin preservation. However, it is still unclear what mechanisms may underlie this neuroprotection and whether dimethyl fumarate affects oligodendrocyte responses to oxidative stress. Here, we examine metabolic alterations in oligodendrocytes treated with dimethyl fumarate by using a global metabolomic platform that employs both hydrophilic interaction liquid chromatography–mass spectrometry and shotgun lipidomics. Prolonged treatment of oligodendrocytes with dimethyl fumarate induces changes in citric acid cycle intermediates, glutathione, and lipids, indicating that this compound can directly impact oligodendrocyte metabolism. These metabolic alterations are also associated with protection from oxidant challenge. This study provides insight into the mechanisms by which dimethyl fumarate could preserve myelin integrity in patients with multiple sclerosis.
      Graphical abstract image

      PubDate: 2015-05-17T11:42:38Z
       
  • Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction

    • Abstract: Publication date: August 2015
      Source:Redox Biology, Volume 5
      Author(s): Emily A. Resseguie , Rhonda J. Staversky , Paul S. Brookes , Michael A. O’Reilly
      High levels of oxygen (hyperoxia) are often used to treat individuals with respiratory distress, yet prolonged hyperoxia causes mitochondrial dysfunction and excessive reactive oxygen species (ROS) that can damage molecules such as DNA. Ataxia telangiectasia mutated (ATM) kinase is activated by nuclear DNA double strand breaks and delays hyperoxia-induced cell death through downstream targets p53 and p21. Evidence for its role in regulating mitochondrial function is emerging, yet it has not been determined if mitochondrial dysfunction or ROS activates ATM. Because ATM maintains mitochondrial homeostasis, we hypothesized that hyperoxia induces both mitochondrial dysfunction and ROS that activate ATM. In A549 lung epithelial cells, hyperoxia decreased mitochondrial respiratory reserve capacity at 12h and basal respiration by 48h. ROS were significantly increased at 24h, yet mitochondrial DNA double strand breaks were not detected. ATM was not required for activating p53 when mitochondrial respiration was inhibited by chronic exposure to antimycin A. Also, ATM was not further activated by mitochondrial ROS, which were enhanced by depleting manganese superoxide dismutase (SOD2). In contrast, ATM dampened the accumulation of mitochondrial ROS during exposure to hyperoxia. Our findings suggest that hyperoxia-induced mitochondrial dysfunction and ROS do not activate ATM. ATM more likely carries out its canonical response to nuclear DNA damage and may function to attenuate mitochondrial ROS that contribute to oxygen toxicity.
      Graphical abstract image

      PubDate: 2015-05-17T11:42:38Z
       
  • Fluorescence labeling of carbonylated lipids and proteins in cells using
           coumarin-hydrazide

    • Abstract: Publication date: August 2015
      Source:Redox Biology, Volume 5
      Author(s): Venukumar Vemula , Zhixu Ni , Maria Fedorova
      Carbonylation is a generic term which refers to reactive carbonyl groups present in biomolecules due to oxidative reactions induced by reactive oxygen species. Carbonylated proteins, lipids and nucleic acids have been intensively studied and often associated with onset or progression of oxidative stress related disorders. In order to reveal underlying carbonylation pathways and biological relevance, it is crucial to study their intracellular formation and spatial distribution. Carbonylated species are usually identified and quantified in cell lysates and body fluids after derivatization using specific chemical probes. However, spatial cellular and tissue distribution have been less often investigated. Here, we report coumarin-hydrazide, a fluorescent chemical probe for time- and cost-efficient labeling of cellular carbonyls followed by fluorescence microscopy to evaluate their intracellular formation both in time and space. The specificity of coumarin-hydrazide was confirmed in time- and dose-dependent experiments using human primary fibroblasts stressed with paraquat and compared with conventional DNPH-based immunocytochemistry. Both techniques stained carbonylated species accumulated in cytoplasm with strong perinuclear clustering. Using a complimentary array of analytical methods specificity of coumarin-hydrazide probe towards both protein- and lipid-bound carbonyls has been shown. Additionally, co-distribution of carbonylated species and oxidized phospholipids was demonstrated.
      Graphical abstract image

      PubDate: 2015-05-17T11:42:38Z
       
  • Hexapeptide-11 is a novel modulator of the proteostasis network in human
           diploid fibroblasts

    • Abstract: Publication date: August 2015
      Source:Redox Biology, Volume 5
      Author(s): Aimilia D. Sklirou , Marianna Ralli , Maria Dominguez , Issidora Papassideri , Alexios-Leandros Skaltsounis , Ioannis P. Trougakos
      Despite the fact that several natural products (e.g. crude extracts or purified compounds) have been found to activate cell antioxidant responses and/or delay cellular senescence the effect(s) of small peptides on cell viability and/or modulation of protective mechanisms (e.g. the proteostasis network) remain largely elusive. We have thus studied a hexapeptide (Hexapeptide-11) of structure Phe–Val–Ala–Pro–Phe–Pro (FVAPFP) originally isolated from yeast extracts and later synthesized by solid state synthesis to high purity. We show herein that Hexapeptide-11 exhibits no significant toxicity in normal human diploid lung or skin fibroblasts. Exposure of fibroblasts to Hexapeptide-11 promoted dose and time-dependent activation of proteasome, autophagy, chaperones and antioxidant responses related genes. Moreover, it promoted increased nuclear accumulation of Nrf2; higher expression levels of proteasomal protein subunits and increased proteasome peptidase activities. In line with these findings we noted that Hexapeptide-11 conferred significant protection in fibroblasts against oxidative-stress-mediated premature cellular senescence, while at in vivo skin deformation assays in human subjects it improved skin elasticity. Finally, Hexapeptide-11 was found to induce the activity of extracellular MMPs and it also suppressed cell migration. Our presented findings indicate that Hexapeptide-11 is a promising anti-ageing agent.
      Graphical abstract image

      PubDate: 2015-05-17T11:42:38Z
       
  • Differentiating between apparent and actual rates of H2O2 metabolism by
           isolated rat muscle mitochondria to test a simple model of mitochondria as
           regulators of H2O2 concentration

    • Abstract: Publication date: Available online 7 May 2015
      Source:Redox Biology
      Author(s): Jason R. Treberg , Daniel Munro , Sheena Banh , Pamela Zacharias , Emianka Sotiri
      Mitochondria are often regarded as a major source of reactive oxygen species (ROS) in animal cells, with H2O2 being the predominant ROS released from mitochondria; however, it has been recently demonstrated that energized brain mitochondria may act as stabilizers of H2O2 concentration (Starkov et al. [1]) based on the balance between production and the consumption of H2O2, the later of which is a function of [H2O2] and follows first order kinetics. Here we test the hypothesis that isolated skeletal muscle mitochondria, from the rat, are able to modulate [H2O2] based upon the interaction between the production of ROS, as superoxide/H2O2, and the H2O2 decomposition capacity. The compartmentalization of detection systems for H2O2 and the intramitochondrial metabolism of H2O2 leads to spacial separation between these two components of the assay system. This results in an underestimation of rates when relying solely on extramitochondrial H2O2 detection. We find that differentiating between these apparent rates found when using extramitochondrial H2O2 detection and the actual rates of metabolism is important to determining the rate constant for H2O2 consumption by mitochondria in kinetic experiments. Using the high rate of ROS production by mitochondria respiring on succinate, we demonstrate that net H2O2 metabolism by mitochondria can approach a stable steady-state of extramitochondrial [H2O2]. Importantly, the rate constant determined by extrapolation of kinetic experiments is similar to the rate constant determined as the [H2O2] approaches a steady state.
      Graphical abstract image

      PubDate: 2015-05-17T11:42:38Z
       
  • Oxygen in human health from life to death – an approach to teaching
           redox biology and signaling to graduate and medical students

    • Abstract: Publication date: Available online 11 April 2015
      Source:Redox Biology
      Author(s): Margaret M. Briehl
      In the absence of oxygen human life is measured in minutes. In the presence of oxygen, normal metabolism generates reactive species (ROS) that have the potential to cause cell injury contributing to human aging and disease. Between these extremes, organisms have developed means for sensing oxygen and ROS and regulating their cellular processes in response. Redox signaling contributes to the control of cell proliferation and death. Aberrant redox signaling underlies many human diseases. The attributes acquired by altered redox homeostasis in cancer cells illustrate this particularly well. This teaching review and the accompanying illustrations provide an introduction to redox biology and signaling aimed at instructors of graduate and medical students.
      Graphical abstract image

      PubDate: 2015-04-12T23:48:00Z
       
  • A potential role for endogenous proteins as sacrificial sunscreens and
           antioxidants in human tissues

    • Abstract: Publication date: Available online 11 April 2015
      Source:Redox Biology
      Author(s): Sarah A. Hibbert , Rachel E.B. Watson , Neil K. Gibbs , Patrick Costello , Clair Baldock , Anthony S. Weiss , Christopher E.M. Griffiths , Michael J. Sherratt
      Excessive ultraviolet radiation (UVR) exposure of the skin is associated with adverse clinical outcomes. Although both exogenous sunscreens and endogenous tissue components (including melanins and tryptophan-derived compounds) reduce UVR penetration, the role of endogenous proteins in absorbing environmental UV wavelengths is poorly defined. Having previously demonstrated that proteins which are rich in UVR-absorbing amino acid residues are readily degraded by broadband UVB-radiation (which contains UVA, UVB and UVC wavelengths) here we hypothesised that UV chromophore (Cys, Trp and Tyr) content can predict the susceptibility of structural proteins in skin and the eye to damage by physiologically relevant doses (up to 15.4 J/cm2) of solar UVR (95% UVA, 5% UVB). We show that: i) purified suspensions of UV-chromophore-rich fibronectin dimers, fibrillin microfibrils and β- and γ-lens crystallins undergo solar simulated radiation (SSR)-induced aggregation and/or decomposition and ii) exposure to identical doses of SSR has minimal effect on the size or ultrastructure of UV chromophore-poor tropoelastin, collagen I, collagen VI microfibrils and α-crystallin. If UV chromophore content is a factor in determining protein stability in vivo, we would expect that the tissue distribution of Cys, Trp and Tyr-rich proteins would correlate with regional UVR exposure. From bioinformatic analysis of 244 key structural proteins we identified several biochemically distinct, yet UV chromophore-rich, protein families. The majority of these putative UV-absorbing proteins (including the late cornified envelope proteins, keratin associated proteins, elastic fibre-associated components and β- and γ-crystallins) are localised and/or particularly abundant in tissues that are exposed to the highest doses of environmental UVR, specifically the stratum corneum, hair, papillary dermis and lens. We therefore propose that UV chromophore-rich proteins are localised in regions of high UVR exposure as a consequence of an evolutionary pressure to express sacrificial protein sunscreens which reduce UVR penetration and hence mitigate tissue damage.
      Graphical abstract image

      PubDate: 2015-04-12T23:48:00Z
       
  • Redox theory of aging

    • Abstract: Publication date: August 2015
      Source:Redox Biology, Volume 5
      Author(s): Dean P. Jones
      Metazoan genomes encode exposure memory systems to enhance survival and reproductive potential by providing mechanisms for an individual to adjust during lifespan to environmental resources and challenges. These systems are inherently redox networks, arising during evolution of complex systems with O2 as a major determinant of bioenergetics, metabolic and structural organization, defense, and reproduction. The network structure decreases flexibility from conception onward due to differentiation and cumulative responses to environment (exposome). The redox theory of aging is that aging is a decline in plasticity of genome–exposome interaction that occurs as a consequence of execution of differentiation and exposure memory systems. This includes compromised mitochondrial and bioenergetic flexibility, impaired food utilization and metabolic homeostasis, decreased barrier and defense capabilities and loss of reproductive fidelity and fecundity. This theory accounts for hallmarks of aging, including failure to maintain oxidative or xenobiotic defenses, mitochondrial integrity, proteostasis, barrier structures, DNA repair, telomeres, immune function, metabolic regulation and regenerative capacity.
      Graphical abstract image

      PubDate: 2015-04-03T23:03:31Z
       
  • High glucose, glucose fluctuation and carbonyl stress enhance brain
           microvascular endothelial barrier dysfunction: Implications for diabetic
           cerebral microvasculature

    • Abstract: Publication date: Available online 2 April 2015
      Source:Redox Biology
      Author(s): Wei Li , Ronald E. Maloney , Tak Yee Aw
      We previously demonstrated that in normal glucose (5 mM), methylglyoxal (MG, a model of carbonyl stress) induced brain microvascular endothelial cell (IHEC) dysfunction that was associated with occludin glycation and prevented by N-acetylcysteine (NAC). Herein, we investigated the impact of high glucose and low GSH, conditions that mimicked the diabetic state, on MG-induced IHEC dysfunction. MG-induced loss of transendothelial electrical resistance (TEER) was potentiated in IHECs cultured for 7 or 12 days in 25 mM glucose (hyperglycemia); moreover, barrier function remained disrupted 6 h after cell transfer to normal glucose media (acute glycemic fluctuation). Notably, basal occludin glycation was elevated under these glycemic states. TEER loss was exaggerated by inhibition of glutathione (GSH) synthesis and abrogated by NAC, which corresponded to GSH decreases and increases, respectively. Significantly, glyoxalase II activity was attenuated in hyperglycemic cells. Moreover, hyperglycemia and GSH inhibition increased MG accumulation, consistent with a compromised capacity for MG elimination. α-oxoaldehydes (MG plus glyoxal) levels were elevated in streptozotocin-induced diabetic rat plasma. Immunohistochemistry revealed a prevalence of MG-positive, but fewer occludin-positive microvessels in the diabetic brain in vivo, and western analysis confirmed an increase in MG-occludin adducts. These results provide the first evidence that hyperglycemia and acute glucose fluctuation promote MG-occludin formation and exacerbate brain microvascular endothelial dysfunction. Low occludin expression and high glycated-occludin contents in diabetic brain in vivo are factors that would contribute to the dysfunction of the cerebral microvasculature during diabetes.
      Graphical abstract image

      PubDate: 2015-04-03T23:03:31Z
       
  • Lyme: inflammation, oxidative stress, and mitochondrial dysfunction

    • Abstract: Publication date: Available online 16 March 2015
      Source:Redox Biology
      Author(s): Brandon N. Peacock , Teshome B. Gherezghiher , Jennifer D. Hilario , Gottfried H. Kellermann
      Lyme borreliosis is transmitted through the bite of a tick that is infected by the bacterial spirochete Borrelia burgdorferi. Clinical manifestation of the disease can lead to heart conditions, neurological disorders, and inflammatory disorders. Oxidative stress has been implicated in the pathogenesis of many human diseases. The aim of this study was to investigate the mechanisms of oxidative stress and intracellular communication in Lyme borreliosis patients. Mitochondrial superoxide and cytosolic ionized calcium was measured in peripheral blood mononuclear cells (PBMCs) of Lyme borreliosis patients and healthy controls. Mitochondrial superoxide levels were significantly higher (p < 0.0001) in Lyme borreliosis patients (n = 32) as compared to healthy controls (n = 30). Significantly low (p < 0.0001) levels of cytosolic ionized calcium were also observed in Lyme borreliosis patients (n = 11) when compared to healthy controls (n = 11). These results indicate that there is an imbalance of reactive oxygen species and cytosolic calcium in Lyme borreliosis patients. The results further suggest that oxidative stress and interrupted intracellular communication may ultimately contribute to a condition of mitochondrial dysfunction in the immune cells of Lyme borreliosis patients.
      Graphical abstract image

      PubDate: 2015-03-18T21:42:16Z
       
  • Expression of xCT and activity of system xc− are regulated by NRF2
           in human breast cancer cells in response to oxidative stress

    • Abstract: Publication date: Available online 18 March 2015
      Source:Redox Biology
      Author(s): Eric Habib , Katja Linher-Melville , Han-Xin Lin , Gurmit Singh
      Cancer cells adapt to high levels of oxidative stress in order to survive and proliferate by activating key transcription factors. One such master regulator, the redox sensitive transcription factor NF E2 Related Factor 2 (NRF2), controls the expression of cellular defense genes including those encoding intracellular redox-balancing proteins involved in glutathione (GSH) synthesis. Under basal conditions, Kelch-like ECH-associated protein 1 (KEAP1) targets NRF2 for ubiquitination. In response to oxidative stress, NRF2 dissociates from KEAP1, entering the nucleus and binding to the antioxidant response element (ARE) in the promoter of its target genes. Elevated reactive oxygen species (ROS) production may deplete GSH levels within cancer cells. System xc −, an antiporter that exports glutamate while importing cystine to be converted into cysteine for GSH synthesis, is upregulated in cancer cells in response to oxidative stress. Here, we provided evidence that the expression of xCT, the light chain subunit of system xc −, is regulated by NRF2 in representative human breast cancer cells. Hydrogen peroxide (H2O2) treatment increased nuclear translocation of NRF2, also increasing levels of xCT mRNA and protein and extracellular glutamate release. Overexpression of NRF2 up-regulated the activity of the xCT promoter, which contains a proximal ARE. In contrast, overexpression of KEAP1 repressed promoter activity and decreased xCT protein levels, while siRNA knockdown of KEAP1 up-regulated xCT protein levels and transporter activity. These results demonstrate the importance of the KEAP1/NRF2 pathway in balancing oxidative stress in breast cancer cells through system xc −. We have previously shown that xCT is upregulated in various cancer cell lines under oxidative stress. In the current investigation, we focused on MCF-7 cells as a model for mechanistic studies.
      Graphical abstract image

      PubDate: 2015-03-18T21:42:16Z
       
  • Persistent oxidative stress in human neural stem cells exposed to low
           fluences of charged particles

    • Abstract: Publication date: Available online 11 March 2015
      Source:Redox Biology
      Author(s): Janet E. Baulch , Brianna M. Craver , Katherine K. Tran , Liping Yu , Nicole Chmielewski , Barrett D. Allen , Charles L. Limoli
      Exposure to the space radiation environment poses risks for a range of deleterious health effects due to the unique types of radiation encountered. Galactic cosmic rays are comprised of a spectrum of highly energetic nuclei that deposit densely ionizing tracks of damage along the particle trajectory. These tracks are distinct from those generated by the more sparsely ionizing terrestrial radiations, and elicit complex cellular damage when charged particles traverse the tissues of the body. The exquisite radiosensitivity of multipotent neural stem and progenitor cells found within the neurogenic regions of the brain predispose the central nervous system to elevated risks for radiation induced sequelae. Here we show that human neural stem cells (hNSC) exposed to different charged particles at space relevant fluences exhibit significant and persistent oxidative stress. Radiation induced oxidative stress was found to be most dependent on total dose rather than on the linear energy transfer of the incident particle. The use of redox sensitive fluorogenic dyes possessing relative specificity for hydroxyl radicals, peroxynitrite, nitric oxide (NO) and mitochondrial superoxide confirmed that most irradiation paradigms elevated reactive oxygen and nitrogen species (ROS and RNS, respectively) in hNSC over a 1 week interval following exposure. Nitric oxide synthase (NOS) was not the major source of elevated nitric oxides, as the use of NOS inhibitors had little effect on NO dependent fluorescence. Our data provide extensive evidence for the capability of low doses of charged particles to elicit marked changes in the metabolic profile of irradiated hNSC. Radiation induced changes in redox state may render the brain more susceptible to the development of neurocognitive deficits that could affect an astronaut’s ability to perform complex tasks during extended missions in deep space.
      Graphical abstract image

      PubDate: 2015-03-14T21:25:22Z
       
  • Advancing age increases sperm chromatin damage and impairs fertility in
           peroxiredoxin 6 null mice

    • Abstract: Publication date: Available online 25 February 2015
      Source:Redox Biology
      Author(s): Burak Ozkosem , Sheldon I. Feinstein , Aron B. Fisher , Cristian O’Flaherty
      Due to socioeconomic factors, more couples are choosing to delay conception than ever. Increasing average maternal and paternal age in developed countries over the past 40 years has raised the question of how aging affects reproductive success of males and females. Since oxidative stress in the male reproductive tract increases with age, we investigated the impact of advanced paternal age on the integrity of sperm nucleus and reproductive success of males by using a Prdx6−/− mouse model. We compared sperm motility, cytoplasmic droplet retention sperm chromatin quality and reproductive outcomes of young (2-month-old), adult (8-month-old), and old (20-month-old) Prdx6−/− males with their age-matched wild type (WT) controls. Absence of PRDX6 caused age-dependent impairment of sperm motility and sperm maturation and increased sperm DNA fragmentation and oxidation as well as decreased sperm DNA compaction and protamination. Litter size, total number of litters and total number of pups per male were significantly lower in Prdx6−/− males compared to WT controls. These abnormal reproductive outcomes were severely affected by age in Prdx6−/− males. In conclusion, the advanced paternal age affects sperm chromatin integrity and fertility more severely in the absence of PRDX6, suggesting a protective role of PRDX6 in age-associated decline in the sperm quality and fertility in mice.
      Graphical abstract image

      PubDate: 2015-02-27T22:52:43Z
       
  • An educational overview of the chemistry, biochemistry and therapeutic
           aspects of Mn porphyrins – from superoxide dismutation to
           H2O2-driven pathways

    • Abstract: Publication date: Available online 7 February 2015
      Source:Redox Biology
      Author(s): Ines Batinic-Haberle , Artak Tovmasyan , Ivan Spasojevic
      SOD mimics thus far developed belong to the classes of Mn-(MnPs) and Fe porphyrins(FePs), Mn(III) salens, Mn(II) cyclic polyamines and metal salts. Due to their remarkable stability we have predominantly explored Mn porphyrins, aiming initially at mimicking kinetics and thermodynamics of the catalysis of O2 . dismutation by SOD enzymes. Several MnPs are of potency similar to SOD enzymes. The in vivo bioavailability and toxicity of MnPs have been addressed also. Numerous in vitro and in vivo studies indicate their impressive therapeutic efficacy. Increasing insight into complex cellular redox biology has been accompanied by increasing awareness of complex redox chemistry of MnPs. During O2 •− dismutation process, the most powerful Mn porphyrin-based SOD mimics reduce and oxidize O2 •− with close to identical rate constants. Therefore MnPs reduce and oxidize other reactive species also (none of them appear specific to MnPs), acting as reductants (antioxidant) and pro-oxidants. Distinction must be made between the type of reactions of MnPs and the favorable therapeutic effects, we observe, which may be of either anti- or pro-oxidative nature. H2O2/MnP mediated oxidation of protein thiols and its impact on cellular transcription seems to dominate redox biology of MnPs. It has been thus far demonstrated that the ability of MnPs to catalyze O2 •− dismutation parallels all other reactivities (such as ONOO−) and in turn their therapeutic efficacies. Assuming safely that all diseases have in common the perturbation of cellular redox environment, developing SOD mimics still seems to be the most appropriate strategy for the design of potent redox-active therapeutics.
      Graphical abstract image

      PubDate: 2015-02-23T05:01:51Z
       
  • Redox signaling in acute pancreatitis

    • Abstract: Publication date: Available online 27 January 2015
      Source:Redox Biology
      Author(s): Salvador Pérez , Javier Pereda , Luis Sabater , Juan Sastre
      Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling modulator in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF-VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis.


      PubDate: 2015-01-29T15:32:56Z
       
  • Border between natural product and drug: comparison of the related
           benzoquinones idebenone and coenzyme Q10

    • Abstract: Publication date: Available online 14 January 2015
      Source:Redox Biology
      Author(s): Nuri Gueven , Krystel Woolley , Jason Smith
      CoenzymeQ10 is a ubiquitous component of cellular membranes and belongs to the class of benzoquinones that mainly differ with regards to the length and composition of their hydrophobic tail. The characteristic quinone group can accept electrons from various biological sources and is converted by a one electron transfer to the unstable semiquinone or by a two electron transfer to the more stable hydroquinone. This feature makes CoQ10 the bona fide cellular electron transfer molecule within the mitochondrial respiratory chain and also makes it a potent cellular antioxidant. These activities serve as justification for its popular use as food supplement. Another quinone with similarities to the naturally occurring CoQ10 is the idebenone, which shares its quinone moiety with CoQ10, but at the same time differs from CoQ10 by the presence of a much shorter, less lipophilic tail. However, despite its similarity to CoQ10, idebenone cannot be isolated from any natural sources but instead was synthesized and selected as a pharmacologically active compound in the 1980s by Takeda Pharmaceuticals purely based on its pharmacological properties. Several recent clinical trials demonstrated some therapeutic efficacy of idebenone in different indications and as a consequence, many practitioners question if the freely available CoQ10 could not be used instead. Here, we describe the molecular and pharmacological features of both molecules that arise from their structural differences to answer the question if idebenone is merely a CoQ10 analogue as frequently perpetuated in the literature or a pharmaceutical drug with entirely different features.
      Graphical abstract image

      PubDate: 2015-01-16T14:31:29Z
       
  • Role of lipid peroxidation derived 4-hydroxynonenal (4-HNE) in cancer:
           focusing on mitochondria

    • Abstract: Publication date: Available online 29 December 2014
      Source:Redox Biology
      Author(s): Huiqin Zhong , Huiyong Yin
      Oxidative stress − induced lipid peroxidation has been associated with human physiology and diseases including cancer. Overwhelming data suggest that reactive lipid mediators generated from this process, such as 4-hydroxynonenal (4-HNE), are biomarkers for oxidative stress and important players for mediating a number of signaling pathways. The biological effects of 4-HNE are primarily due to covalent modification of important biomolecules including proteins, DNA, and phospholipids containing amino group. In this review, we summarize recent progress on the role of 4-HNE in pathogenesis of cancer and focus on the involvement of mitochondria: generation of 4-HNE from oxidation of mitochondria-specific phospholipid cardiolipin; covalent modification of mitochondrial proteins, lipids, and DNA; potential therapeutic strategies for targeting mitochondrial ROS generation, lipid peroxidation, and 4-HNE.


      PubDate: 2015-01-02T11:17:18Z
       
 
 
JournalTOCs
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Email: journaltocs@hw.ac.uk
Tel: +00 44 (0)131 4513762
Fax: +00 44 (0)131 4513327
 
About JournalTOCs
API
Help
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-2015