Effects of Iron Excess on Nicotiana plumbaginifolia Plants (Implications to Oxidative Stress)

Fe excess is believed to generate oxidative stress. To contribute to the understanding of Fe metabolism, Fe excess was induced in Nicotiana plumbaginifolia grown in hydroponic culture upon root cutting. Toxicity symptoms leading to brown spots covering the leaf surface became visible after 6 h. Photosynthesis was greatly affected within 12 h; the photosynthetic rate was decreased by 40%. Inhibition of photosynthesis was accompanied by photoinhibition, increased reduction of photosystem II, and higher thylakoid energization. Fe excess seemed to stimulate photorespiration because catalase activity doubled. To cope with cellular damage, respiration rate increased and cytosolic glucose-6-phosphate dehydrogenase activity more than doubled. Simultaneously, the content of free hexoses was reduced. Indicative of generation of oxidative stress was doubling of ascorbate peroxidase activity within 12 h. Contents of the antioxidants ascorbate and glutathione were reduced by 30%, resulting in equivalent increases of dehydroascorbate and oxidized glutathione. Taken together, moderate changes in leaf Fe content have a dramatic effect on plant metabolism. This indicates that cellular Fe concentrations must be finely regulated to avoid cellular damage most probably because of oxidative stress induced by Fe.     

Oxidative Burst and Hypoosmotic Stress in Tobacco Cell Suspensions

Oxidative burst constitutes an early response in plant defense reactions toward pathogens, but active oxygen production may also be induced by other stimuli. The oxidative response of suspension-cultured tobacco (Nicotiana tabacum cv Xanthi) cells to hypoosmotic and mechanical stresses was characterized. The oxidase involved in the hypoosmotic stress response showed similarities by its NADPH dependence and its inhibition by iodonium diphenyl with the neutrophil NADPH oxidase. Activation of the oxidative response by hypoosmotic stress needed protein phosphorylation and anion effluxes, as well as opening of Ca²⁺ channels. Inhibition of the oxidative response impaired Cl⁻ efflux, K⁺ efflux, and extracellular alkalinization, suggesting that the oxidative burst may play a role in ionic flux regulation. Active oxygen species also induced the cross-linking of a cell wall protein, homologous to a soybean (Glycine max L.) extensin, that may act as part of cell volume and turgor regulation through modification of the physical properties of the cell wall.     

A Cyanobacterium Lacking Iron Superoxide Dismutase Is Sensitized to Oxidative Stress Induced with Methyl Viologen but Is Not Sensitized to Oxidative Stress Induced with Norflurazon

A strain of Synechococcus sp. strain PCC 7942 with no functional Fe superoxide dismutase (SOD), designated sodB⁻, was characterized by its growth rate, photosynthetic pigments, and cyclic photosynthetic electron transport activity when treated with methyl viologen or norflurazon (NF). In their unstressed conditions, both the sodB⁻ and wild-type strains had similar chlorophyll and carotenoid contents and catalase activity, but the wild type had a faster growth rate and higher cyclic electron transport activity. The sodB⁻ was very sensitive to methyl viologen, indicating a specific role for the FeSOD in protection against superoxide generated in the cytosol. In contrast, the sodB⁻ mutant was less sensitive than the wild type to oxidative stress imposed with NF. This suggests that the FeSOD does not protect the cell from excited singlet-state oxygen generated within the thylakoid membrane. Another up-regulated antioxidant, possibly the MnSOD, may confer protection against NF in the sodB⁻ strain. These results support the hypothesis that different SODs have specific protective functions within the cell.     

Focus: The Science of Stress: Oxidative Stress and Inflammation in Cardiovascular Diseases and Cancer: Role of Non-coding RNAs

High oxidative stress, Th1/Th17 immune response, M1 macrophage inflammation, and cell death are associated with cardiovascular diseases. Controlled oxidative stress, Th2/Treg anti-tumor immune response, M2 macrophage inflammation, and survival are associated with cancer. MiR-21 protects against cardiovascular diseases but may induce tumor growth by retaining the anti-inflammatory M2 macrophage and Treg phenotypes and inhibiting apoptosis. Down-regulation of let-7, miR-1, miR-9, miR-16, miR-20a, miR-22a, miR-23a, miR-24a, miR-26a, miR-29, miR-30a, miR-34a, miR-124, miR-128, miR-130a, miR-133, miR-140, miR-143-145, miR-150, miR-153, miR-181a, miR-378, and miR-383 may aid cancer cells to escape from stresses. Upregulation of miR-146 and miR-223 may reduce anti-tumor immune response together with miR-21 that also protects against apoptosis. MiR-155 and silencing of let-7e, miR-125, and miR-126 increase anti-tumor immune response. MiR expression depends on oxidative stress, cytokines, MYC, and TGF-β, and expression of silencing lncRNAs and circ-RNAs. However, one lncRNA or circ-RNA may have opposite effects by targeting several miRs. For example, PVT1 induces apoptosis by targeting miR-16a and miR-30a but inhibits apoptosis by silencing miR-17. In addition, levels of a non-coding RNA in a cell type depend not only on expression in that cell type but also on an exchange of microvesicles between cell types and tumors. Although we got more insight into the function of a growing number of individual non-coding RNAs, overall, we do not know enough how several of them interact in functional networks and how their expression changes at different stages of disease progression.     

Oxidative Stress Alters Syndecan-1 Distribution in Lungs with Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by severe, progressive fibrosis. Roles for inflammation and oxidative stress have recently been demonstrated, but despite advances in understanding the pathogenesis, there are still no effective therapies for IPF. This study investigates how extracellular superoxide dismutase (EC-SOD), a syndecan-binding antioxidant enzyme, inhibits inflammation and lung fibrosis. We hypothesize that EC-SOD protects the lung from oxidant damage by preventing syndecan fragmentation/shedding. Wild-type or EC-SOD-null mice were exposed to an intratracheal instillation of asbestos or bleomycin. Western blot was used to detect syndecans in the bronchoalveolar lavage fluid and lung. Human lung samples (normal and IPF) were also analyzed. Immunohistochemistry for syndecan-1 and EC-SOD was performed on human and mouse lungs. In vitro, alveolar epithelial cells were exposed to oxidative stress and EC-SOD. Cell supernatants were analyzed for shed syndecan-1 by Western blot. Syndecan-1 ectodomain was assessed in wound healing and neutrophil chemotaxis. Increases in human syndecan-1 are detected in lung homogenates and lavage fluid of IPF lungs. Syndecan-1 is also significantly elevated in the lavage fluid of EC-SOD-null mice after asbestos and bleomycin exposure. On IHC, syndecan-1 staining increases within fibrotic areas of human and mouse lungs. In vitro, EC-SOD inhibits oxidant-induced loss of syndecan-1 from A549 cells. Shed and exogenous syndecan-1 ectodomain induce neutrophil chemotaxis, inhibit alveolar epithelial wound healing, and promote fibrogenesis. Oxidative shedding of syndecan-1 is an underlying cause of neutrophil chemotaxis and aberrant wound healing that may contribute to pulmonary fibrosis.Idiopathic pulmonary fibrosis (IPF)² is an interstitial lung disease characterized by severe and progressive fibrosis. IPF patients have a mean survival of 3–5 years (1, 2) and no effective therapies (3, 4), other than orthotopic lung transplantation, have proven to improve survival. The pathogenesis of IPF is poorly understood; however, inflammation and oxidant/antioxidant imbalances in the lung are thought to play important roles (5–7). A better understanding of the molecular mechanisms involved in oxidative injury and fibrosis could lead to the development of novel therapeutic targets.Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme bound to heparan sulfate in the lung extracellular matrix (8–10), which can inhibit inflammation (11, 12) and prevent subsequent development of fibrosis (13–16). Despite its beneficial role, the mechanisms through which EC-SOD protects the lung remain unknown.The extracellular matrix (ECM) is essential for tissue homeostasis and changes in the ECM microenvironment can be detrimental to cell function during inflammation and wound healing. Heparan sulfate proteoglycans (HSPG) contain a membrane-bound core protein and extracellular carbohydrate side chains. Syndecans are the most abundant HSPG in humans; there are 4 isoforms with variable cell expression (17, 18). Both syndecan-1 and -4 are expressed in the lung, with epithelial cell and ubiquitous expression, respectively (19). Syndecans are essential for ECM homeostasis by binding cytokines and growth factors, acting as co-receptors and soluble effectors. They also have potential roles in inflammation (18, 20, 21), fibrosis (22, 23), and wound healing (24–26). Syndecans are shed under physiological and pathological conditions but the function of shed syndecans is poorly understood (22). Reactive oxygen species (ROS) are capable of fragmenting HSPG (27) and other ECM components. Notably, EC-SOD has been shown to prevent oxidative damage to many ECM components (23, 28, 29). Within the lung, EC-SOD binds to syndecan-1 on the cell surface via a heparin-binding domain (8, 30). Because of the known functions of syndecans and its close interaction with EC-SOD, syndecan-1 is a key target that may contribute to the anti-inflammatory and anti-fibrotic effects of EC-SOD in the lung and in the pulmonary fibrosis.This study was conducted to determine the role of EC-SOD in protecting the ECM from oxidative stress and to investigate our hypothesis that EC-SOD protects the lung from inflammation and fibrosis by inhibiting oxidant-induced shedding of syndecan-1. Our findings suggest that a loss of EC-SOD in the lung leaves syndecan-1 vulnerable to oxidative stress and that oxidatively shed syndecan-1 ectodomain induces neutrophil chemotaxis, impairs epithelial wound healing, and promotes fibrogenesis. The discovery that oxidative stress alters the distribution of syndecan-1 in the lung microenvironment is a novel finding in the context of pulmonary fibrosis. These findings advance the understanding of the pathogenesis of idiopathic pulmonary fibrosis and provide a potential new therapeutic target for intervention in IPF.     

Androgen Excess Produces Systemic Oxidative Stress and Predisposes to β-Cell Failure in Female Mice

In women, excess production of the male hormone, testosterone (T), is accompanied by insulin resistance. However, hyperandrogenemia is also associated with β-cell dysfunction and type 2 diabetes raising the possibility that androgen receptor (AR) activation predisposes to β-cell failure. Here, we tested the hypothesis that excess AR activation produces systemic oxidative stress thereby contributing to β-cell failure. We used normal female mice (CF) and mice with androgen resistance by testicular feminization (Tfm). These mice were exposed to androgen excess and a β-cell stress induced by streptozotocin (STZ). We find that following exposure to T, or the selective AR-agonist dehydrotestosterone (DHT), CF mice challenged with STZ, which are normally protected, are prone to β-cell failure and insulin-deficient diabetes. Conversely, T-induced predisposition to β-cell failure is abolished in Tfm mice. We do not observe any proapoptotic effect of DHT alone or in the presence of H₂O₂ in cultured mouse and human islets. However, we observe that exposure of CF mice to T or DHT provokes systemic oxidative stress, which is eliminated in Tfm mice. This work has significance for hyperandrogenic women; excess activation of AR by testosterone may provoke systemic oxidative stress. In the presence of a prior β-cell stress, this may predispose to β-cell failure.     

Excess Dietary Sodium Selenite Alters Apoptotic Population and Oxidative Stress Markers of Spleens in Broilers

Three hundred 1-day-old avian broilers were fed on a basic diet (0.2 mg/kg selenium) or the same diet amended to contain 1, 5, 10, and 15 mg/kg selenium supplied as sodium selenite (n = 60/group). In comparison with those of 0.2 mg/kg selenium group, the percentages of annexin V-positive splenocytes were increased in 5, 10, and 15 mg/kg selenium groups. TUNEL assay revealed that apoptotic cells with brown-stained nuclei distributed within the red pulp and white pulp of the spleens with increased frequency of occurrence in 10 and 15 mg/kg selenium groups in comparison with that of 0.2 mg/kg Se group. Sodium selenite-induced oxidative stress in spleens of chickens was evidenced by decrease in glutathione peroxidase, superoxide dismutase, and catalase activities and increase in malondialdehyde contents. The results indicate that excess dietary selenium in the range of 5–15 mg/kg of feed causes oxidative stress, which may be mainly responsible for the increased apoptosis of splenocytes in chickens.     

A Comparative Study on the Effects of Excess Iodine and Herbs with Excess Iodine on Thyroid Oxidative Stress in Iodine-Deficient Rats

This study aimed to compare the effect of excess iodine and herbs with excess iodine on treating iodine deficiency-induced goiter from the perspective of oxidative stress and to measure selenium values in Chinese herbs. One hundred twenty 4-week-old Wistar rats were selected and randomly divided into four groups after inducing iodine-deficiency goiter: normal control group (NC), model control group (MC), iodine excess group (IE), and herbs with iodine excess group (HIE). The activities of oxidative enzymes and levels of oxidative products were measured using biochemical tests. The expression of 4-hydroxynonenal (4-HNE) in the thyroid was detected by immunohistochemistry and the expression of peroxiredoxin 5 (PRDX5) by the Western blot and immunohistochemistry. Selenium values in iodine-excessive herbs were measured by hydride generation-atomic fluorescence spectrometry. The herbs with iodine excess were tested to contain rich selenium. The activities of superoxide dismutase (SOD) and PRDX5 increased markedly, and the values of malondialdehyde (MDA) and 4-HNE decreased significantly in the HIE group. In conclusion, compared with excess iodine, herbs with excess iodine damaged thyroid follicular cells less, which may be related to the increase of antioxidant capacity and rich selenium values in iodine-excessive herbs.     

Ferrous Ions Detected in Iron-Overloaded Cord Blood Plasma From Preterm and Term Babies: Implications for Oxidative Stress

Redox active iron chelatable to bleomycin is often present in the plasma of cord blood samples taken from preterm and term babies. The low caeruloplasmin and high ascorbate levels in plasma at birth may allow this iron to exist in the reduced ferrous state. In support of this postulate thirteen cord blood samples showing the presence of low molecular mass iron were able to degrade DNA in the presence of bleomycin and plasma.     

Ferrous Ions Detected in Iron-Overloaded Cord Blood Plasma From Preterm and Term Babies: Implications for Oxidative Stress

Redox active iron chelatable to bleomycin is often present in the plasma of cord blood samples taken from preterm and term babies. The low caeruloplasmin and high ascorbate levels in plasma at birth may allow this iron to exist in the reduced ferrous state. In support of this postulate thirteen cord blood samples showing the presence of low molecular mass iron were able to degrade DNA in the presence of bleomycin and plasma.     

Oxidative Stress in Synaptosomal Proteins from Mutant Presenilin-1 Knock-in Mice: Implications for Familial Alzheimer's Disease

Presenilin-1 (PS-1) is a transmembrane protein that may be involved in the processing of amyloid precursor protein (APP). Mutations in PS-1 are the major cause of familial Alzheimer's disease (AD). AD brain is under significant oxidative stress, including protein oxidation. In the present study, protein oxidation was compared in synaptosomes from knock-in mice expressing mutant human PS-1 (M146V mutation) and from wild-type mice expressing non-mutant human PS-1. Synaptosomal membrane protein conformational alterations associated with oxidative stress were measured using electron paramagnetic resonance (EPR) in conjunction with a protein-specific spin-label. Direct synaptosomal protein oxidation was assessed by a carbonyl detection assay. Synaptosomal proteins from PS-1 mutant mice displayed increased oxidative stress as measured by both techniques, compared with synaptosomal proteins from wild type mice. These data suggest that PS-1 mutations cause oxidative alterations in synaptosomal membrane protein structure and oxidative modification of synaptosomal proteins. Our findings suggest that familial AD may be associated with oxidative stress that may play a pivotal role in neuronal dysfunction and death.     

Excess Success for Psychology Articles in the Journal Science

This article describes a systematic analysis of the relationship between empirical data and theoretical conclusions for a set of experimental psychology articles published in the journal Science between 2005–2012. When the success rate of a set of empirical studies is much higher than would be expected relative to the experiments'' reported effects and sample sizes, it suggests that null findings have been suppressed, that the experiments or analyses were inappropriate, or that the theory does not properly follow from the data. The analyses herein indicate such excess success for 83% (15 out of 18) of the articles in Science that report four or more studies and contain sufficient information for the analysis. This result suggests a systematic pattern of excess success among psychology articles in the journal Science.