Special Issue "Redox Signaling in Biology and Patho-Biology"
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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry, Molecular Biology and Biophysics".
Deadline for manuscript submissions: 30 December 2013
Special Issue Editor
Guest Editor
Dr. Gregor Drummen
Guest Editor for MDPI, Switzerland
E-Mail: drummen@mdpi.com
Phone: +49 211 40 51 810
Fax: +49 211 47 45 476
Interests: quantum dots; bionanotechnology; two-photon fluorescence imaging; cellular imaging; fluorescence microscopy; nucleic acids; DNA damage; cancer; cell signaling; radiation biology; oxidative stress; lipids and biomembranes; lipid peroxidation
Special Issue Information
Dear Colleagues,
Molecular oxygen is one of those fundamental and essential elements to ensure life and survival of most organisms on the third rock from the sun. Through this molecule, efficient formation of the energy molecule and genetic building block ATP is possible and thus allows the organism to perform work (the thermodynamical definition thereof). However, it is the same molecular oxygen that threatens aerobic life on this planet, because of its potential for radical formation (it is a biradical, although Pauli restricted). From molecular oxygen derived species, Reactive Oxygen Species (ROS), have long been implicated in a multitude of diseases, but not until the discovery that nitric oxide is an essential signaling molecule has the view of the all destructive ROS changed to include normal biological function. Redox signaling has become an important field of research in the biological and biomedical sciences. The importance of these mechanisms that influence genes and thus cell function, but might also involve epigenetic modifications, is clear; the mechanisms themselves are still largely intangible.
This special issue calls for contributions, original research, mini and full reviews, commentaries, educational papers, and perspectives that address the progress and current standing in redox signaling biology. These include, but are not limited to:
- molecular aspects of reactive species involved in redox signaling
- antioxidants, and other redox-dependent processes
- redox-based therapeutics and impact on health care
Other aspects of oxidative stress, please submit to the separate issue on Oxidative Stress and Ageing in IJMS
Dr. Gregor Drummen
Guest Editor
Submission
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed Open Access monthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs).
Published Papers (19 papers)
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Received: 2 August 2012; in revised form: 4 October 2012 / Accepted: 9 October 2012 / Published: 12 October 2012
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Abstract: When cellular reducing enzymes fail to shield the cell from increased amounts of reactive oxygen species (ROS), oxidative stress arises. The redox state is misbalanced, DNA and proteins are damaged and cellular transcription networks are activated. This condition can lead to the initiation and/or to the progression of atherosclerosis, tumors or pulmonary hypertension; diseases that are decisively furthered by the presence of oxidizing agents. Redox sensitive genes, like the zinc finger transcription factor early growth response 1 (Egr-1), play a pivotal role in the pathophysiology of these diseases. Apart from inducing apoptosis, signaling partners like the MEK/ERK pathway or the protein kinase C (PKC) can activate salvage programs such as cell proliferation that do not ameliorate, but rather worsen their outcome. Here, we review the currently available data on Egr-1 related signal transduction cascades in response to oxidative stress in the progression of epidemiologically significant diseases. Knowing the molecular pathways behind the pathology will greatly enhance our ability to identify possible targets for the development of new therapeutic strategies.
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Received: 21 December 2012; in revised form: 21 January 2013 / Accepted: 23 January 2013 / Published: 30 January 2013
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Abstract: Oxidative folding in the mitochondrial intermembrane space (IMS) is a key cellular event associated with the folding and import of a large and still undetermined number of proteins. This process is catalyzed by an oxidoreductase, Mia40 that is able to recognize substrates with apparently little or no homology. Following substrate oxidation, Mia40 is reduced and must be reoxidized by Erv1/Alr1 that consequently transfers the electrons to the mitochondrial respiratory chain. Although our understanding of the physiological relevance of this process is still limited, an increasing number of pathologies are being associated with the impairment of this pathway; especially because oxidative folding is fundamental for several of the proteins involved in defense against oxidative stress. Here we review these aspects and discuss recent findings suggesting that oxidative folding in the IMS is modulated by the redox state of the cell.
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Received: 24 December 2012; in revised form: 23 January 2013 / Accepted: 31 January 2013 / Published: 6 February 2013
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Abstract: Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis.
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Received: 6 January 2013; in revised form: 30 January 2013 / Accepted: 31 January 2013 / Published: 7 February 2013
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Abstract: Hydrogen peroxide (H2O2) is an important second messenger in cellular signal transduction. H2O2-dependent signalling regulates many cellular processes, such as proliferation, differentiation, migration and apoptosis. Nevertheless, H2O2 is an oxidant and a major contributor to DNA damage, protein oxidation and lipid peroxidation, which can ultimately result in cell death and/or tumourigenesis. For this reason, cells have developed complex antioxidant systems to scavenge ROS. Recently, our laboratory identified the protein, annexin A2, as a novel cellular redox regulatory protein. Annexin A2 possesses a reactive cysteine residue (Cys-8) that is readily oxidized by H2O2 and subsequently reduced by the thioredoxin system, thereby enabling annexin A2 to participate in multiple redox cycles. Thus, a single molecule of annexin A2 can inactivate several molecules of H2O2. In this report, we will review the studies detailing the reactivity of annexin A2 thiols and the importance of these reactive cysteine(s) in regulating annexin A2 structure and function. We will also focus on the recent reports that establish novel functions for annexin A2, namely as a protein reductase and as a cellular redox regulatory protein. We will further discuss the importance of annexin A2 redox regulatory function in disease, with a particular focus on tumour progression.
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Received: 24 December 2012; in revised form: 28 January 2013 / Accepted: 31 January 2013 / Published: 7 February 2013
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Abstract: The outdated idea that reactive oxygen species (ROS) are only dangerous products of cellular metabolism, causing toxic and mutagenic effects on cellular components, is being replaced by the view that ROS have several important functions in cell signaling. In aerobic organisms, ROS can be generated from different sources, including the mitochondrial electron transport chain, xanthine oxidase, myeloperoxidase, and lipoxygenase, but the only enzyme family that produces ROS as its main product is the NADPH oxidase family (NOX enzymes). These transfer electrons from NADPH (converting it to NADP−) to oxygen to make O2•−. Due to their stability, the products of NADPH oxidase, hydrogen peroxide, and superoxide are considered the most favorable ROS to act as signaling molecules. Transcription factors that regulate gene expression involved in carcinogenesis are modulated by NADPH oxidase, and it has emerged as a promising target for cancer therapies. The present review discusses the mechanisms by which NADPH oxidase regulates signal transduction pathways in view of tyrosine kinase receptors, which are pivotal to regulating the hallmarks of cancer, and how ROS mediate the cytotoxicity of several cancer drugs employed in clinical practice.
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Received: 27 December 2012; in revised form: 4 February 2013 / Accepted: 6 February 2013 / Published: 19 February 2013
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Abstract: Cadmium (Cd) is a toxic heavy metal that is considered an environmental contaminant. Several sources of human exposure to Cd, including employment in primary metal industries, production of certain batteries, foods, soil and cigarette smoke, are known. Its inhalation has been related to different respiratory diseases and toxic effects, among which alterations of the physiological redox state in individuals exposed to the metal have been described. Host-cell redox changes characteristic of oxidative stress facilitate the progression of viral infection through different mechanisms. In this paper, we have demonstrated that pre-treatment with CdCl2 of MDCK cells increased influenza virus replication in a dose-dependent manner. This phenomenon was related to increased viral protein expression (about 40% compared with untreated cells). The concentration of CdCl2, able to raise the virus titer, also induced oxidative stress. The addition of two antioxidants, a glutathione (GSH) derivative or the GSH precursor, N-acetyl-L-cysteine, to Cd pre-treated and infected cells restored the intracellular redox state and significantly inhibited viral replication. In conclusion, our data demonstrate that Cd-induced oxidative stress directly increases the ability of influenza virus to replicate in the host-cell, thus suggesting that exposure to heavy metals, such as this, could be a risk factor for individuals exposed to a greater extent to the contaminant, resulting in increased severity of virus-induced respiratory diseases.
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Received: 5 January 2013; in revised form: 24 January 2013 / Accepted: 29 January 2013 / Published: 19 February 2013
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Abstract: Repurposing approved and abandoned non-oncological drugs is an alternative developmental strategy for the identification of anticancer therapeutics that has recently attracted considerable attention. Due to the essential role of the cellular heat shock response in cytoprotection through the maintenance of proteostasis and suppression of apoptosis, small molecule heat shock response antagonists can be harnessed for targeted induction of cytotoxic effects in cancer cells. Guided by gene expression array analysis and a phenotypic screen interrogating a collection of 3,7-diamino-phenothiazinium derivatives, we have identified the redox-drug methylene blue (MB), used clinically for the infusional treatment of methemoglobinemia, as a negative modulator of heat shock response gene expression in human metastatic melanoma cells. MB-treatment blocked thermal (43 °C) and pharmacological (celastrol, geldanamycin) induction of heat shock response gene expression, suppressing Hsp70 (HSPA1A) and Hsp27 (HSPB1) upregulation at the mRNA and protein level. MB sensitized melanoma cells to the apoptogenic activity of geldanamycin, an Hsp90 antagonist known to induce the counter-regulatory upregulation of Hsp70 expression underlying cancer cell resistance to geldanamycin chemotherapy. Similarly, MB-cotreatment sensitized melanoma cells to other chemotherapeutics (etoposide, doxorubicin). Taken together, these data suggest feasibility of repurposing the non-oncological redox drug MB as a therapeutic heat shock response antagonist for cancer cell chemosensitization.
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Received: 31 December 2012; in revised form: 12 February 2013 / Accepted: 17 February 2013 / Published: 21 February 2013
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Abstract: In the pulmonary vasculature, mechanical forces such as cyclic stretch induce changes in vascular signaling, tone and remodeling. Nitric oxide is a potent regulator of soluble guanylate cyclase (sGC), which drives cGMP production, causing vasorelaxation. Pulmonary artery smooth muscle cells (PASMCs) express inducible nitric oxide synthase (iNOS), and while iNOS expression increases during late gestation, little is known about how cyclic stretch impacts this pathway. In this study, PASMC were subjected to cyclic stretch of 20% amplitude and frequency of 1 Hz for 24 h and compared to control cells maintained under static conditions. Cyclic stretch significantly increased cytosolic oxidative stress as compared to static cells (62.9 ± 5.9% vs. 33.3 ± 5.7% maximal oxidation), as measured by the intracellular redox sensor roGFP. Cyclic stretch also increased sGCβ protein expression (2.5 ± 0.9-fold), sGC activity (1.5 ± 0.2-fold) and cGMP levels (1.8 ± 0.2-fold), as well as iNOS mRNA and protein expression (3.0 ± 0.9 and 2.6 ± 0.7-fold, respectively) relative to control cells. An antioxidant, recombinant human superoxide dismutase (rhSOD), significantly decreased stretch-induced cytosolic oxidative stress, but did not block stretch-induced sGC activity. Inhibition of iNOS with 1400 W or an iNOS-specific siRNA inhibited stretch-induced sGC activity by 30% and 68% respectively vs. static controls. In conclusion, cyclic stretch increases sGC expression and activity in an iNOS-dependent manner in PASMC from fetal lambs. The mechanism that produces iNOS and sGC upregulation is not yet known, but we speculate these effects represent an early compensatory mechanism to counteract the effects of stretch-induced oxidative stress. A better understanding of the interplay between these two distinct pathways could provide key insights into future avenues to treat infants with pulmonary hypertension.
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Received: 17 January 2013; in revised form: 13 February 2013 / Accepted: 17 February 2013 / Published: 26 February 2013
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Abstract: Hepatitis C virus (HCV) infects approximately 3% of the world’s population. Currently licensed treatment of HCV chronic infection with pegylated-interferon-α and ribavirin, is not fully effective against all HCV genotypes and is associated to severe side effects. Thus, development of novel therapeutics and identification of new targets for treatment of HCV infection is necessary. Current opinion is orienting to target antiviral drug discovery to the host cell pathways on which the virus relies, instead of against viral structures. Many intracellular signaling pathways manipulated by HCV for its own replication are finely regulated by the oxido-reductive (redox) state of the host cell. At the same time, HCV induces oxidative stress that has been found to affect both virus replication as well as progression and severity of HCV infection. A dual role, positive or negative, for the host cell oxidized conditions on HCV replication has been reported so far. This review examines current information about the effect of oxidative stress on HCV life cycle and the main redox-regulated intracellular pathways activated during HCV infection and involved in its replication.
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Received: 19 December 2012; in revised form: 22 February 2013 / Accepted: 28 February 2013 / Published: 11 March 2013
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Abstract: The NAD+-dependent deacetylases Sirt1 and Sirt2 mediate cellular stress responses and are highly expressed in vascular endothelial cells. In contrast to the well-documented protective actions of Sirt1, the role of endothelial Sirt2 remains unknown. Using cDNA microarray and PCR validation, we examined global gene expression changes in response to Sirt2 knock down in primary human umbilical vein endothelial cells under oxidative stress. We found that Sirt2 knock down changed expression of 340 genes, which are mainly involved in cellular processes including actin binding, cellular amino acid metabolic process, transmembrane receptor protein serine/threonine kinase signaling, ferrous iron transport, protein transport and localization, cell morphogenesis, and functions associated with endosome membrane and the trans-Golgi network. These genes and associated functions were largely non-overlapping with those altered by Sirt1 knock down. Moreover, we showed that pharmacological inhibition of Sirt2 attenuated oxidant-induced cell toxicity in endothelial cells. These suggest that Sirt2 is functionally important in endothelial cells under oxidative stress, and may have a primarily distinct role as compared to Sirt1. Our results may provide a basis for future studies aiming to dissect the specific signaling pathway(s) that mediates specific Sirt2 functions in endothelial cells.
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Received: 14 January 2013; in revised form: 14 February 2013 / Accepted: 20 February 2013 / Published: 15 March 2013
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Abstract: Free radicals are chemical particles containing one or more unpaired electrons, which may be part of the molecule. They cause the molecule to become highly reactive. The free radicals are also known to play a dual role in biological systems, as they can be either beneficial or harmful for living systems. It is clear that there are numerous mechanisms participating on the protection of a cell against free radicals. In this review, our attention is paid to metallothioneins (MTs) as small, cysteine-rich and heavy metal-binding proteins, which participate in an array of protective stress responses. The mechanism of the reaction of metallothioneins with oxidants and electrophilic compounds is discussed. Numerous reports indicate that MT protects cells from exposure to oxidants and electrophiles, which react readily with sulfhydryl groups. Moreover, MT plays a key role in regulation of zinc levels and distribution in the intracellular space. The connections between zinc, MT and cancer are highlighted.
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Received: 31 December 2012; in revised form: 5 March 2013 / Accepted: 7 March 2013 / Published: 18 March 2013
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Abstract: Five antioxidant and two oxidative stress assays were applied to serum samples of 43 healthy males. The antioxidant tests showed different inter-assay correlations. A very good correlation of 0.807 was observed between the ferric reducing ability of plasma (FRAP) and total antioxidant status (TAS) assay and also a fair correlation of 0.501 between the biological antioxidant potential (BAP) and TAS assay. There was no statistically significant correlation between the BAP and FRAP assay. The anti-oxidant assays have a high correlation with uric acid, especially the TAS (0.922) and FRAP assay (0.869). The BAP assay has a much lower and no statistically significant correlation with uric acid (0.302), which makes BAP more suitable for the antioxidant status. The total thiol assay showed no statistically significant correlation with uric acid (0.114). The total thiol assay, which is based on a completely different principle, showed a good and statistically significant correlation with the BAP assay (0.510) and also to the TAS assay, but to a lower and not significant extent (0.279) and not with the FRAP assay (−0.008). The oxy-adsorbent test (OXY) assay has no correlation with any of the other assays tested. The oxidative stress assays, reactive oxygen metabolites (ROM) and total oxidant status (TOS), based on a different principle, do not show a statistically significant correlation with the serum samples in this study. Both assays showed a negative, but not significant, correlation with the antioxidant assays. In conclusion, the ROM, TOS, BAP and TTP assays are based on different principles and will have an additional value when a combination of these assays will be applied in large-scale population studies.
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Received: 24 December 2012; in revised form: 4 February 2013 / Accepted: 20 February 2013 / Published: 18 March 2013
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Abstract: Over the years, anthropogenic factors have led to cadmium (Cd) accumulation in the environment causing various health problems in humans. Although Cd is not a Fenton-like metal, it induces oxidative stress in various animal models via indirect mechanisms. The degree of Cd-induced oxidative stress depends on the dose, duration and frequency of Cd exposure. Also the presence or absence of serum in experimental conditions, type of cells and their antioxidant capacity, as well as the speciation of Cd are important determinants. At the cellular level, the Cd-induced oxidative stress either leads to oxidative damage or activates signal transduction pathways to initiate defence responses. This balance is important on how different organ systems respond to Cd stress and ultimately define the pathological outcome. In this review, we highlight the Cd-induced oxidant/antioxidant status as well as the damage versus signalling scenario in relation to Cd toxicity. Emphasis is addressed to Cd-induced pathologies of major target organs, including a section on cell proliferation and carcinogenesis. Furthermore, attention is paid to Cd-induced oxidative stress in undifferentiated stem cells, which can provide information for future therapies in preventing Cd-induced pathologies.
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Received: 10 January 2013; in revised form: 8 March 2013 / Accepted: 11 March 2013 / Published: 19 March 2013
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Abstract: The air that we breathe contains nearly 21% oxygen, most of which is utilized by mitochondria during respiration. While we cannot live without it, it was perceived as a bane to aerobic organisms due to the generation of reactive oxygen and nitrogen metabolites by mitochondria and other cellular compartments. However, this dogma was challenged when these species were demonstrated to modulate cellular responses through altering signaling pathways. In fact, since this discovery of a dichotomous role of reactive species in immune function and signal transduction, research in this field grew at an exponential pace and the pursuit for mechanisms involved began. Due to a significant number of review articles present on the reactive species mediated cell death, we have focused on emerging novel pathways such as autophagy, signaling and maintenance of the mitochondrial network. Despite its role in several processes, increased reactive species generation has been associated with the origin and pathogenesis of a plethora of diseases. While it is tempting to speculate that anti-oxidant therapy would protect against these disorders, growing evidence suggests that this may not be true. This further supports our belief that these reactive species play a fundamental role in maintenance of cellular and tissue homeostasis.
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Andreas Daiber, Steffen Daub, Markus Bachschmid, Stefan Schildknecht, Matthias Oelze, Sebastian Steven, Patrick Schmidt, Alexandra Megner, Masayuki Wada, Tadashi Tanabe, Thomas Münzel, Serge Bottari and Volker Ullrich
Received: 31 December 2012; in revised form: 11 March 2013 / Accepted: 18 March 2013 / Published: 8 April 2013
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Abstract: The reaction product of nitric oxide and superoxide, peroxynitrite, is a potent biological oxidant. The most important oxidative protein modifications described for peroxynitrite are cysteine-thiol oxidation and tyrosine nitration. We have previously demonstrated that intrinsic heme-thiolate (P450)-dependent enzymatic catalysis increases the nitration of tyrosine 430 in prostacyclin synthase and results in loss of activity which contributes to endothelial dysfunction. We here report the sensitive peroxynitrite-dependent nitration of an over-expressed and partially purified human prostacyclin synthase (3.3 μM) with an EC50 value of 5 μM. Microsomal thiols in these preparations effectively compete for peroxynitrite and block the nitration of other proteins up to 50 μM peroxynitrite. Purified, recombinant PGIS showed a half-maximal nitration by 10 μM 3-morpholino sydnonimine (Sin-1) which increased in the presence of bicarbonate, and was only marginally induced by freely diffusing NO2-radicals generated by a peroxidase/nitrite/hydrogen peroxide system. Based on these observations, we would like to emphasize that prostacyclin synthase is among the most efficiently and sensitively nitrated proteins investigated by us so far. In the second part of the study, we identified two classes of peroxynitrite scavengers, blocking either peroxynitrite anion-mediated thiol oxidations or phenol/tyrosine nitrations by free radical mechanisms. Dithiopurines and dithiopyrimidines were highly effective in inhibiting both reaction types which could make this class of compounds interesting therapeutic tools. In the present work, we highlighted the impact of experimental conditions on the outcome of peroxynitrite-mediated nitrations. The limitations identified in this work need to be considered in the assessment of experimental data involving peroxynitrite.
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Received: 1 March 2013; in revised form: 29 March 2013 / Accepted: 2 April 2013 / Published: 10 April 2013
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Abstract: Oxidative stress has been implicated in the pathogenesis of Friedreich’s Ataxia (FRDA), a neurodegenerative disease caused by the decreased expression of frataxin, a mitochondrial protein responsible of iron homeostasis. Under conditions of oxidative stress, the activation of the transcription factor NF-E2-related factor (Nrf2) triggers the antioxidant cellular response by inducing antioxidant response element (ARE) driven genes. Increasing evidence supports a role for the Nrf2-ARE pathway in neurodegenerative diseases. In this study, we analyzed the expression and the distribution of Nrf2 in silenced neurons for frataxin gene. Decreased Nrf2 mRNA content and a defective activation after treatment with pro-oxidants have been evidenced in frataxin-silenced neurons by RT-PCR and confocal microscopy. The loss of Nrf2 in FRDA may greatly enhance the cellular susceptibility to oxidative stress and make FRDA neurons more vulnerable to injury. Our findings may help to focus on this promising target, especially in its emerging role in the neuroprotective response.
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Received: 10 January 2013; in revised form: 2 March 2013 / Accepted: 7 March 2013 / Published: 12 April 2013
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Abstract: Adaptation to aerobic life leads organisms to sense reactive oxygen species and use the signal for coordination of the entire metabolism. Glycolysis in plants is a particular network where specific steps, like oxidation of glyceraldehydes-3-phosphate (Ga3P), are critical in order for it to function. The triose-phosphate can be converted into 3-phosphoglycerate through the phosphorylating Ga3P dehydrogenase (Ga3PDHase, EC 1.2.1.12) producing ATP and NADH, or via the non-phosphorylating enzyme (np-Ga3PDHase; EC 1.2.1.9) generating NADPH. In this work we found redox regulation to be a posttranslational mechanism allowing the fine-tuning of the triose-phosphate fate. Both enzymes were inactivated after oxidation by reactive oxygen and nitrogen species. Kinetic studies determined that Ga3PDHase is marked (63-fold) more sensitive to oxidants than np-Ga3PDHase. Thioredoxin-h reverted the oxidation of both enzymes (although with differences between them), suggesting a physiological redox regulation. The results support a metabolic scenario where the cytosolic triose-phosphate dehydrogenases are regulated under changeable redox conditions. This would allow coordinate production of NADPH or ATP through glycolysis, with oxidative signals triggering reducing power synthesis in the cytosol. The NADPH increment would favor antioxidant responses to cope with the oxidative situation, while the thioredoxin system would positively feedback NADPH production by maintaining np-Ga3PDHase at its reduced active state.
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Received: 1 March 2013; in revised form: 10 April 2013 / Accepted: 16 April 2013 / Published: 26 April 2013
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Abstract: Reactive oxygen species (ROS) can be both beneficial and deleterious. Under normal physiological conditions, ROS production is tightly regulated, and ROS participate in both pathogen defense and cellular signaling. However, insufficient ROS detoxification or ROS overproduction generates oxidative stress, resulting in cellular damage. Oxidative stress has been linked to various inflammatory diseases. Inflammation is an essential response in the protection against injurious insults and thus important at the onset of wound healing. However, hampered resolution of inflammation can result in a chronic, exaggerated response with additional tissue damage. In the pathogenesis of several inflammatory skin conditions, e.g., sunburn and psoriasis, inflammatory-mediated tissue damage is central. The prolonged release of excess ROS in the skin can aggravate inflammatory injury and promote chronic inflammation. The cellular redox balance is therefore tightly regulated by several (enzymatic) antioxidants and pro-oxidants; however, in case of chronic inflammation, the antioxidant system may be depleted, and prolonged oxidative stress occurs. Due to the central role of ROS in inflammatory pathologies, restoring the redox balance forms an innovative therapeutic target in the development of new strategies for treating inflammatory skin conditions. Nevertheless, the clinical use of antioxidant-related therapies is still in its infancy.
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Received: 16 February 2013; in revised form: 18 April 2013 / Accepted: 6 May 2013 / Published: 21 May 2013
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Abstract: Obesity represents a major risk factor for a plethora of severe diseases, including diabetes, cardiovascular disease, non-alcoholic fatty liver disease, and cancer. It is often accompanied by an increased risk of mortality and, in the case of non-fatal health problems, the quality of life is impaired because of associated conditions, including sleep apnea, respiratory problems, osteoarthritis, and infertility. Recent evidence suggests that oxidative stress may be the mechanistic link between obesity and related complications. In obese patients, antioxidant defenses are lower than normal weight counterparts and their levels inversely correlate with central adiposity; obesity is also characterized by enhanced levels of reactive oxygen or nitrogen species. Inadequacy of antioxidant defenses probably relies on different factors: obese individuals may have a lower intake of antioxidant- and phytochemical-rich foods, such as fruits, vegetables, and legumes; otherwise, consumption of antioxidant nutrients is normal, but obese individuals may have an increased utilization of these molecules, likewise to that reported in diabetic patients and smokers. Also inadequate physical activity may account for a decreased antioxidant state. In this review, we describe current concepts in the meaning of obesity as a state of chronic oxidative stress and the potential interventions to improve redox balance.
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Last update: 18 May 2012
