Antioxidants

15 pages, 803 KiB

Open AccessReview

Reactive Oxygen Species and the Redox-Regulatory Network in Cold Stress Acclimation

by Anna Dreyer and Karl-Josef Dietz

Antioxidants 2018, 7(11), 169; https://doi.org/10.3390/antiox7110169 - 21 Nov 2018

Cited by 98 | Viewed by 6484

Cold temperatures restrict plant growth, geographical extension of plant species, and agricultural practices. This review deals with cold stress above freezing temperatures often defined as chilling stress. It focuses on the redox regulatory network of the cell under cold temperature conditions. Reactive oxygen [...] Read more.

Cold temperatures restrict plant growth, geographical extension of plant species, and agricultural practices. This review deals with cold stress above freezing temperatures often defined as chilling stress. It focuses on the redox regulatory network of the cell under cold temperature conditions. Reactive oxygen species (ROS) function as the final electron sink in this network which consists of redox input elements, transmitters, targets, and sensors. Following an introduction to the critical network components which include nicotinamide adenine dinucleotide phosphate (NADPH)-dependent thioredoxin reductases, thioredoxins, and peroxiredoxins, typical laboratory experiments for cold stress investigations will be described. Short term transcriptome and metabolome analyses allow for dissecting the early responses of network components and complement the vast data sets dealing with changes in the antioxidant system and ROS. This review gives examples of how such information may be integrated to advance our knowledge on the response and function of the redox regulatory network in cold stress acclimation. It will be exemplarily shown that targeting the redox network might be beneficial and supportive to improve cold stress acclimation and plant yield in cold climate. Full article

(This article belongs to the Special Issue Thioredoxin and Glutaredoxin Systems)

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34 pages, 1709 KiB

Open AccessReview

The Plasma Membrane: A Platform for Intra- and Intercellular Redox Signaling

by Daniela E. Nordzieke and Iria Medraño-Fernandez

Antioxidants 2018, 7(11), 168; https://doi.org/10.3390/antiox7110168 - 20 Nov 2018

Cited by 63 | Viewed by 8219

Abstract

Membranes are of outmost importance to allow for specific signal transduction due to their ability to localize, amplify, and direct signals. However, due to the double-edged nature of reactive oxygen species (ROS)—toxic at high concentrations but essential signal molecules—subcellular localization of ROS-producing systems [...] Read more.

Membranes are of outmost importance to allow for specific signal transduction due to their ability to localize, amplify, and direct signals. However, due to the double-edged nature of reactive oxygen species (ROS)—toxic at high concentrations but essential signal molecules—subcellular localization of ROS-producing systems to the plasma membrane has been traditionally regarded as a protective strategy to defend cells from unwanted side-effects. Nevertheless, specialized regions, such as lipid rafts and caveolae, house and regulate the activated/inhibited states of important ROS-producing systems and concentrate redox targets, demonstrating that plasma membrane functions may go beyond acting as a securing lipid barrier. This is nicely evinced by nicotinamide adenine dinucleotide phosphate (NADPH)-oxidases (NOX), enzymes whose primary function is to generate ROS and which have been shown to reside in specific lipid compartments. In addition, membrane-inserted bidirectional H₂O₂-transporters modulate their conductance precisely during the passage of the molecules through the lipid bilayer, ensuring time-scaled delivery of the signal. This review aims to summarize current evidence supporting the role of the plasma membrane as an organizing center that serves as a platform for redox signal transmission, particularly NOX-driven, providing specificity at the same time that limits undesirable oxidative damage in case of malfunction. As an example of malfunction, we explore several pathological situations in which an inflammatory component is present, such as inflammatory bowel disease and neurodegenerative disorders, to illustrate how dysregulation of plasma-membrane-localized redox signaling impacts normal cell physiology. Full article

(This article belongs to the Special Issue Thiol Redox Systems in Health and Disease)

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8 pages, 18515 KiB

Open AccessArticle

GPX1 Localizes to the Nucleus in Prostate Epithelium and its Levels are not Associated with Prostate Cancer Recurrence

by Dede N. Ekoue, Emmanuel Ansong, Lenny K. Hong, Larisa Nonn, Virgilia Macias, Ryan Deaton, Rawan Rupnow, Peter H. Gann, Andre Kajdacsy-Balla and Alan M. Diamond

Antioxidants 2018, 7(11), 167; https://doi.org/10.3390/antiox7110167 - 18 Nov 2018

Cited by 5 | Viewed by 3533

Abstract

Glutathione peroxidase 1 (GPX1) is an extensively studied selenium-dependent protein that reduces hydrogen and lipid peroxides to water. Because of its antioxidant function and its responsiveness to dietary intakes of selenium, an essential trace element whose levels are inversely associated with prostate cancer [...] Read more.

Glutathione peroxidase 1 (GPX1) is an extensively studied selenium-dependent protein that reduces hydrogen and lipid peroxides to water. Because of its antioxidant function and its responsiveness to dietary intakes of selenium, an essential trace element whose levels are inversely associated with prostate cancer risk, GPX1 levels were assessed in a prostate cancer tissue microarray, comparing cases of recurrent prostate cancer following prostatectomy to non-recurrent controls. While GPX1 is generally considered as a protein that resides in both the cytoplasm and mitochondria, we detected strong nuclear staining by immunofluorescence using GPX1-specific antibodies. Nuclear localization of GPX1 was also observed in both primary prostate epithelial cells and the immortalized prostate-derived cell line RWPE-1, but not in LNCaP or PC3 prostate tumor-derived cell lines. Quantification of GPX1 levels in the entire cell, the cytoplasm, and the nucleus did not indicate any association of either its levels or subcellular distribution with prostate cancer recurrence. While GPX1 levels may not have an impact on survival among men with prostate cancer, the data indicates that this extensively characterized protein may have a novel function in the nucleus of prostate epithelial cells. Full article

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11 pages, 2603 KiB

Open AccessArticle

Crystal Structure of the Apo-Form of NADPH-Dependent Thioredoxin Reductase from a Methane-Producing Archaeon

by Rubén M. Buey, Ruth A. Schmitz, Bob B. Buchanan and Monica Balsera

Antioxidants 2018, 7(11), 166; https://doi.org/10.3390/antiox7110166 - 17 Nov 2018

Cited by 6 | Viewed by 4259

Abstract

The redox regulation of proteins via reversible dithiol/disulfide exchange reactions involves the thioredoxin system, which is composed of a reductant, a thioredoxin reductase (TR), and thioredoxin (Trx). In the pyridine nucleotide-dependent Trx reduction pathway, reducing equivalents, typically from reduced nicotinamide adenine dinucleotide phosphate [...] Read more.

The redox regulation of proteins via reversible dithiol/disulfide exchange reactions involves the thioredoxin system, which is composed of a reductant, a thioredoxin reductase (TR), and thioredoxin (Trx). In the pyridine nucleotide-dependent Trx reduction pathway, reducing equivalents, typically from reduced nicotinamide adenine dinucleotide phosphate (NADPH), are transferred from NADPH-TR (NTR) to Trx and, in turn, to target proteins, thus resulting in the reversible modification of the structural and functional properties of the targets. NTR enzymes contain three functional sites: an NADPH binding pocket, a non-covalently bound flavin cofactor, and a redox-active disulfide in the form of CxxC. With the aim of increasing our knowledge of the thioredoxin system in archaea, we here report the high-resolution crystal structure of NTR from the methane-generating organism Methanosarcina mazei strain Gö1 (MmNTR) at 2.6 Å resolution. Based on the crystals presently described, MmNTR assumes an overall fold that is nearly identical to the archetypal fold of authentic NTRs; however, surprisingly, we observed no electron density for flavin adenine dinucleotide (FAD) despite the well-defined and conserved FAD-binding cavity in the folded module. Remarkably, the dimers of the apo-protein within the crystal were different from those observed by small angle X-ray scattering (SAXS) for the holo-protein, suggesting that the binding of the flavin cofactor does not require major protein structural rearrangements. Rather, binding results in the stabilization of essential parts of the structure, such as those involved in dimer stabilization. Altogether, this structure represents the example of an apo-form of an NTR that yields important insight into the effects of the cofactor on protein folding. Full article

(This article belongs to the Special Issue Thioredoxin and Glutaredoxin Systems)

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19 pages, 1106 KiB

Open AccessReview

Structural/Functional Matches and Divergences of Phytoprostanes and Phytofurans with Bioactive Human Oxylipins

by Sonia Medina, Ángel Gil-Izquierdo, Thierry Durand, Federico Ferreres and Raúl Domínguez-Perles

Antioxidants 2018, 7(11), 165; https://doi.org/10.3390/antiox7110165 - 16 Nov 2018

Cited by 29 | Viewed by 4108

Abstract

Structure-activity relationship (SAR) constitutes a crucial topic to discover new bioactive molecules. This approach initiates with the comparison of a target candidate with a molecule or a collection of molecules and their attributed biological functions to shed some light in the details of [...] Read more.

Structure-activity relationship (SAR) constitutes a crucial topic to discover new bioactive molecules. This approach initiates with the comparison of a target candidate with a molecule or a collection of molecules and their attributed biological functions to shed some light in the details of one or more SARs and subsequently using that information to outline valuable application of the newly identified compounds. Thus, while the empiric knowledge of medicinal chemistry is critical to these tasks, the results retrieved upon dedicated experimental demonstration retrieved resorting to modern high throughput analytical approaches and techniques allow to overwhelm the constraints adduced so far to the successful accomplishment of such tasks. Therefore, the present work reviews critically the evidences reported to date on the occurrence of phytoprostanes and phytofurans in plant foods, and the information available on their bioavailability and biological activity, shedding some light on the expectation waken up due to their structural similarities with prostanoids and isoprostanes. Full article

(This article belongs to the Special Issue Lipid Peroxidation: Analysis and Applications in Biological Systems)

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15 pages, 2250 KiB

Open AccessArticle

Characterization of TrxC, an Atypical Thioredoxin Exclusively Present in Cyanobacteria

by Luis López-Maury, Luis G. Heredia-Martínez and Francisco J. Florencio

Antioxidants 2018, 7(11), 164; https://doi.org/10.3390/antiox7110164 - 13 Nov 2018

Cited by 8 | Viewed by 4394

Abstract

Cyanobacteria form a diverse group of oxygenic photosynthetic prokaryotes considered to be the antecessor of plant chloroplast. They contain four different thioredoxins isoforms, three of them corresponding to m, x and y type present in plant chloroplast, while the fourth one (named [...] Read more.

Cyanobacteria form a diverse group of oxygenic photosynthetic prokaryotes considered to be the antecessor of plant chloroplast. They contain four different thioredoxins isoforms, three of them corresponding to m, x and y type present in plant chloroplast, while the fourth one (named TrxC) is exclusively found in cyanobacteria. TrxC has a modified active site (WCGLC) instead of the canonical (WCGPC) present in most thioredoxins. We have purified it and assayed its activity but surprisingly TrxC lacked all the classical activities, such as insulin precipitation or activation of the fructose-1,6-bisphosphatase. Mutants lacking trxC or over-expressing it were generated in the model cyanobacterium Synechocystis sp. PCC 6803 and their phenotypes have been analyzed. The ΔtrxC mutant grew at similar rates to WT in all conditions tested although it showed an increased carotenoid content especially under low carbon conditions. Overexpression strains showed reduced growth under the same conditions and accumulated lower amounts of carotenoids. They also showed lower oxygen evolution rates at high light but higher Fv’/Fm’ and Non-photochemical-quenching (NPQ) in dark adapted cells, suggesting a more oxidized plastoquinone pool. All these data suggest that TrxC might have a role in regulating photosynthetic adaptation to low carbon and/or high light conditions. Full article

(This article belongs to the Special Issue Thioredoxin and Glutaredoxin Systems)

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10 pages, 246 KiB

Open AccessArticle

Production of a Novel Functional Fruit Beverage Consisting of Cornelian Cherry Juice and Probiotic Bacteria

by Ioanna Mantzourani, Chryssa Nouska, Antonia Terpou, Athanasios Alexopoulos, Eugenia Bezirtzoglou, Mihalis I. Panayiotidis, Alexis Galanis and Stavros Plessas

Antioxidants 2018, 7(11), 163; https://doi.org/10.3390/antiox7110163 - 12 Nov 2018

Cited by 63 | Viewed by 5852

Abstract

The present study describes the development of a novel functional beverage through the application of probiotic Lactobacillus plantarum ATCC (American Type Culture Collection) 14917 in Cornelian cherry juice fermentation. The probiotic was employed in free and immobilized in a delignified wheat bran carrier [...] Read more.

The present study describes the development of a novel functional beverage through the application of probiotic Lactobacillus plantarum ATCC (American Type Culture Collection) 14917 in Cornelian cherry juice fermentation. The probiotic was employed in free and immobilized in a delignified wheat bran carrier (DWB) form. Cornelian cherry juice was fermented for 24 h and then it was stored at 4 °C for 4 weeks. Several parameters were evaluated such as residual sugar, organic acid and alcohol levels, total phenolics content, and cell viability as well as consumers acceptance. Regarding sugar and organic acids analyses, it was proved that the probiotic free or immobilized biocatalyst was effective. The concentration of ethanol was maintained at low levels (0.3–0.9% v/v). The total phenolic content of fermented Cornelian cherry juice with immobilized cells was recorded in higher levels (214–264 mg GAE/100 mL) for all the cold storage time compared to fermented juice with free cells (165–199 mg GAE/100 mL) and non-fermented juice (135–169 mg GAE/100 mL). Immobilized cells retained their viability in higher levels (9.95 log cfu/mL at the 4th week) compared to free cells (7.36 log cfu/mL at the 4th week). No significant sensory differences were observed among the fermented and the non-fermented samples. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

9 pages, 721 KiB

Open AccessArticle

Exercise and Redox Status Responses Following Alpha-Lipoic Acid Supplementation in G6PD Deficient Individuals

by Kalliopi Georgakouli, Ioannis G. Fatouros, Apostolos Fragkos, Theofanis Tzatzakis, Chariklia K. Deli, Konstantinos Papanikolaou, Yiannis Koutedakis and Athanasios Z. Jamurtas

Antioxidants 2018, 7(11), 162; https://doi.org/10.3390/antiox7110162 - 12 Nov 2018

Cited by 6 | Viewed by 4504

Abstract

G6PD deficiency renders cells more susceptible to oxidative insults, while antioxidant dietary supplementation could restore redox balance and ameliorate exercise-induced oxidative stress. To examine the effects of alpha-lipoic acid (ALA) supplementation on redox status indices in G6PD deficient individuals, eight male adults with [...] Read more.

G6PD deficiency renders cells more susceptible to oxidative insults, while antioxidant dietary supplementation could restore redox balance and ameliorate exercise-induced oxidative stress. To examine the effects of alpha-lipoic acid (ALA) supplementation on redox status indices in G6PD deficient individuals, eight male adults with G6PD deficiency (D) participated in this randomized double-blind placebo-controlled crossover trial. Participants were randomly assigned to receive ALA (600 mg/day) or placebo for 4 weeks separated by a 4-week washout period. Before and at the end of each treatment period, participants exercised following an exhaustive treadmill exercise protocol. Blood samples were obtained before (at rest), immediately after and 1h after exercise for later analysis of total antioxidant capacity (TAC), uric acid, bilirubin, thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PC). ALA resulted in significantly increased resting TAC and bilirubin concentrations. Moreover, TAC increased immediately and 1h after exercise following both treatment periods, whereas bilirubin increased immediately after and 1h after exercise following only ALA. No significant change in uric acid, TBARS or PC was observed at any time point. ALA supplementation for 4 weeks may enhance antioxidant status in G6PD individuals; however, it does not affect redox responses to acute exercise until exhaustion or exercise performance. Full article

(This article belongs to the Special Issue Exercise and Inflammation)

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10 pages, 940 KiB

Open AccessReview

Cancer-Associated Function of 2-Cys Peroxiredoxin Subtypes as a Survival Gatekeeper

by Sang Won Kang, Sunmi Lee and Joanna H. S. Lee

Antioxidants 2018, 7(11), 161; https://doi.org/10.3390/antiox7110161 - 11 Nov 2018

Cited by 12 | Viewed by 4180

Abstract

Cancer cells are abnormal cells that do not comply with tissue homeostasis but undergo uncontrolled proliferation. Such abnormality is driven mostly by somatic mutations on oncogenes and tumor suppressors. Cancerous mutations show intra-tumoral heterogeneity across cancer types and eventually converge into the self-activation [...] Read more.

Cancer cells are abnormal cells that do not comply with tissue homeostasis but undergo uncontrolled proliferation. Such abnormality is driven mostly by somatic mutations on oncogenes and tumor suppressors. Cancerous mutations show intra-tumoral heterogeneity across cancer types and eventually converge into the self-activation of proliferative signaling. While transient production of intracellular reactive oxygen species (ROS) is essential for cell signaling, its persistent production is cytotoxic. Thus, cancer cells require increased levels of intracellular ROS for continuous proliferation, but overexpress cellular peroxidase enzymes, such as 2-Cys peroxiredoxins, to maintain ROS homeostasis. However, suppression of 2-Cys peroxiredoxins has also been reported in some metastatic cancers. Hence, the cancer-associated functions of 2-Cys peroxiredoxins must be illuminated in the cellular context. In this review, we describe the distinctive signaling roles of 2-Cys peroxiredoxins beyond their intrinsic ROS-scavenging role in relation to cancer cell death and survival. Full article

(This article belongs to the Special Issue The Role of Peroxiredoxins in Cancer)

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20 pages, 11594 KiB

Open AccessArticle

Comparative Effects of Coenzyme Q10 or n-3 Polyunsaturated Fatty Acid Supplementation on Retinal Angiogenesis in a Rat Model of Oxygen-Induced Retinopathy

by Kay D. Beharry, Charles L. Cai, Faisal Siddiqui, Sara Chowdhury, Christina D’Agrosa, Gloria B. Valencia and Jacob V. Aranda

Antioxidants 2018, 7(11), 160; https://doi.org/10.3390/antiox7110160 - 9 Nov 2018

Cited by 19 | Viewed by 4174

Abstract

Neonatal intermittent hypoxia (IH) or apnea afflicts 70% to 90% of all preterm infants <28 weeks gestation, and is associated with severe retinopathy of prematurity (ROP). We tested the hypotheses that coenzyme Q10 (CoQ10) or omega-3 polyunsaturated fatty acids (n-3 PUFAs) [...] Read more.

Neonatal intermittent hypoxia (IH) or apnea afflicts 70% to 90% of all preterm infants <28 weeks gestation, and is associated with severe retinopathy of prematurity (ROP). We tested the hypotheses that coenzyme Q10 (CoQ10) or omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation during neonatal IH reduces the severity of oxygen-induced retinopathy (OIR). Newborn rats were exposed to two IH paradigms: (1) 50% O₂ with brief hypoxia (12% O₂); or (2) 21% O₂ with brief hypoxia, until postnatal day 14 (P14), during which they received daily oral CoQ10 in olive oil, n-3 PUFAs in fish oil, or olive oil only and compared to room air (RA) treated groups. Pups were examined at P14, or placed in RA until P21. Retinal angiogenesis, histopathology, and morphometry were determined. Both IH paradigms produced severe OIR, but these were worsened with 50/12% O₂ IH. CoQ10 and n-3 PUFAs reduced the severity of OIR, as well as ocular growth factors in both IH paradigms, but CoQ10 was more effective in 50/12% O₂ IH. Supplementation with either CoQ10 or n-3 PUFAs targeting IH-induced retinal injury is individually effective for ameliorating specific characteristics consistent with ROP. Given the complexity of ROP, further studies are needed to determine whether combined CoQ10 and n-3 PUFAs supplementation would optimize their efficacy and result in a better outcome. Full article

(This article belongs to the Special Issue Antioxidants and Retinal Disease)

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23 pages, 2665 KiB

Open AccessReview

Hydrogen Peroxide and Redox Regulation of Developments

by Christine Rampon, Michel Volovitch, Alain Joliot and Sophie Vriz

Antioxidants 2018, 7(11), 159; https://doi.org/10.3390/antiox7110159 - 6 Nov 2018

Cited by 64 | Viewed by 7560

Abstract

Reactive oxygen species (ROS), which were originally classified as exclusively deleterious compounds, have gained increasing interest in the recent years given their action as bona fide signalling molecules. The main target of ROS action is the reversible oxidation of cysteines, leading to the [...] Read more.

Reactive oxygen species (ROS), which were originally classified as exclusively deleterious compounds, have gained increasing interest in the recent years given their action as bona fide signalling molecules. The main target of ROS action is the reversible oxidation of cysteines, leading to the formation of disulfide bonds, which modulate protein conformation and activity. ROS, endowed with signalling properties, are mainly produced by NADPH oxidases (NOXs) at the plasma membrane, but their action also involves a complex machinery of multiple redox-sensitive protein families that differ in their subcellular localization and their activity. Given that the levels and distribution of ROS are highly dynamic, in part due to their limited stability, the development of various fluorescent ROS sensors, some of which are quantitative (ratiometric), represents a clear breakthrough in the field and have been adapted to both ex vivo and in vivo applications. The physiological implication of ROS signalling will be presented mainly in the frame of morphogenetic processes, embryogenesis, regeneration, and stem cell differentiation. Gain and loss of function, as well as pharmacological strategies, have demonstrated the wide but specific requirement of ROS signalling at multiple stages of these processes and its intricate relationship with other well-known signalling pathways. Full article

(This article belongs to the Special Issue Thioredoxin and Glutaredoxin Systems)

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4 pages, 147 KiB

Open AccessEditorial

Antioxidants and Second Messengers of Free Radicals

by Neven Zarkovic

Antioxidants 2018, 7(11), 158; https://doi.org/10.3390/antiox7110158 - 6 Nov 2018

Cited by 17 | Viewed by 3246

Abstract

In the recent years, numerous research on the pathology of oxidative stress has been completed by intense studies on redox signaling implementing various experimental models and clinical trials. [...] Full article

(This article belongs to the Special Issue Antioxidants and Second Messengers of Free Radicals)

12 pages, 1717 KiB

Open AccessArticle

Oxygen and Glucose Levels in Cell Culture Media Determine Resveratrol’s Effects on Growth, Hydrogen Peroxide Production, and Mitochondrial Dynamics

by Joao Fonseca, Fereshteh Moradi, Andrew J. F. Valente and Jeffrey A. Stuart

Antioxidants 2018, 7(11), 157; https://doi.org/10.3390/antiox7110157 - 5 Nov 2018

Cited by 21 | Viewed by 4958

Abstract

Resveratrol is a plant-derived polyphenol that has been widely studied for its putative health promoting effects. Many of those studies have been conducted in cell culture, in supra-physiological levels of oxygen and glucose. Resveratrol interacts with reactive oxygen species (ROS) as an antioxidant [...] Read more.

Resveratrol is a plant-derived polyphenol that has been widely studied for its putative health promoting effects. Many of those studies have been conducted in cell culture, in supra-physiological levels of oxygen and glucose. Resveratrol interacts with reactive oxygen species (ROS) as an antioxidant or pro-oxidant. Resveratrol affects the expression and activities of ROS-producing enzymes and organelles. It is therefore important to consider how cell culture conditions might determine the effects of resveratrol on cultured cells. We determined the effects of resveratrol on cell growth, hydrogen peroxide production, and mitochondrial network characteristics in C2C12 mouse myoblasts and PC3 human prostate cancer cells under conditions of physiological (5%) and supra-physiological (18%) oxygen, and normo- (5 mM) and hyper-glycemia (25 mM). Interestingly, most effects of resveratrol on the parameters measured here were dependent upon prevailing oxygen and glucose levels during the experiment. Many of the effects of resveratrol on cell growth, hydrogen peroxide production, and mitochondrial network characteristics that were seen in 25 mM glucose and/or 18% oxygen were absent under the physiologically relevant conditions of 5 mM glucose with 5% oxygen. These findings emphasize the importance of using physiologically meaningful starting conditions for cell-culture experiments with resveratrol and indeed any manipulation affecting ROS metabolism and mitochondria. Full article

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3 pages, 171 KiB

Open AccessEditorial

Superoxide Dismutases (SODs) and SOD Mimetics

by Gloria E. O. Borgstahl and Rebecca E. Oberley-Deegan

Antioxidants 2018, 7(11), 156; https://doi.org/10.3390/antiox7110156 - 2 Nov 2018

Cited by 87 | Viewed by 6621

Abstract

Superoxide dismutase (SOD) is the only known enzyme to directly scavenge a free radical. [...] Full article

(This article belongs to the Special Issue Superoxide Dismutase (SOD) Enzymes, Mimetics and Oxygen Radicals)

18 pages, 3542 KiB

Open AccessArticle

In Vivo Effects of Methionine Sulfoxide Reductase Deficiency in Drosophila melanogaster

by Lindsay Bruce, Diana Singkornrat, Kelsey Wilson, William Hausman, Kelli Robbins, Lingxi Huang, Katie Foss and David Binninger

Antioxidants 2018, 7(11), 155; https://doi.org/10.3390/antiox7110155 - 1 Nov 2018

Cited by 6 | Viewed by 4006

Abstract

The deleterious alteration of protein structure and function due to the oxidation of methionine residues has been studied extensively in age-associated neurodegenerative disorders such as Alzheimer’s and Parkinson’s Disease. Methionine sulfoxide reductases (MSR) have three well-characterized biological functions. The most commonly studied function [...] Read more.

The deleterious alteration of protein structure and function due to the oxidation of methionine residues has been studied extensively in age-associated neurodegenerative disorders such as Alzheimer’s and Parkinson’s Disease. Methionine sulfoxide reductases (MSR) have three well-characterized biological functions. The most commonly studied function is the reduction of oxidized methionine residues back into functional methionine thus, often restoring biological function to proteins. Previous studies have successfully overexpressed and silenced MSR activity in numerous model organisms correlating its activity to longevity and oxidative stress. In the present study, we have characterized in vivo effects of MSR deficiency in Drosophila. Interestingly, we found no significant phenotype in animals lacking either methionine sulfoxide reductase A (MSRA) or methionine sulfoxide reductase B (MSRB). However, Drosophila lacking any known MSR activity exhibited a prolonged larval third instar development and a shortened lifespan. These data suggest an essential role of MSR in key biological processes. Full article

(This article belongs to the Special Issue Methionine Sulfoxide Reductases and Oxidative Damage)

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14 pages, 669 KiB

Open AccessArticle

Antioxidant Activities of Dialium indum L. Fruit and Gas Chromatography-Mass Spectrometry (GC-MS) of the Active Fractions

by Muhamad Faris Osman, Norazian Mohd Hassan, Alfi Khatib and Siti Marponga Tolos

Antioxidants 2018, 7(11), 154; https://doi.org/10.3390/antiox7110154 - 1 Nov 2018

Cited by 8 | Viewed by 5762

Abstract

The fruit of Dialium indum L. (Fabaceae) is one of the edible wild fruits native to Southeast Asia. The mesocarp is consumed as sweets while the exocarp and seed are regarded as waste. This study aimed to evaluate the antioxidant activities of the [...] Read more.

The fruit of Dialium indum L. (Fabaceae) is one of the edible wild fruits native to Southeast Asia. The mesocarp is consumed as sweets while the exocarp and seed are regarded as waste. This study aimed to evaluate the antioxidant activities of the fruit by using four assays, which measure its capabilities in reducing phosphomolybdic-phosphotungstic acid reagents, neocuproine, 2,2-diphenyl-picrylhydrazyl (DPPH), and inhibiting linoleic acid peroxidation. The active fractions were then analyzed by gas chromatography-mass spectrometry (GC-MS). The results showed that the seed methanol fraction (SMF) exhibited the strongest antioxidant activity with significantly higher (p < 0.05) gallic acid equivalence (GAE), total antioxidant capacity (TAC), and DPPH radical scavenging activity (IC₅₀ 31.71; 0.88 µg/mL) than the other fractions. The exocarp dichloromethane fraction (EDF) was the discriminating fraction by having remarkable linoleic acid peroxidation inhibition (IC₅₀ 121.43; 2.97 µg/mL). A total of thirty-eight metabolites were detected in derivatized EDF and SMF with distinctive classes of phenolics and amino acids, respectively. Bioautography-guided fractionation of EDF afforded five antioxidant-enriched subfractions with four other detected phenolics. The results revealed the antioxidant properties of D. indum fruit, which has potential benefits in pharmaceutical, nutraceutical, and cosmeceutical applications. Full article

(This article belongs to the Special Issue Antioxidant Activity of Polyphenolic Plant Extracts)

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8 pages, 1538 KiB

Open AccessArticle

Determining the Rate-Limiting Step for Light-Responsive Redox Regulation in Chloroplasts

by Keisuke Yoshida and Toru Hisabori

Antioxidants 2018, 7(11), 153; https://doi.org/10.3390/antiox7110153 - 31 Oct 2018

Cited by 23 | Viewed by 4305

Abstract

Thiol-based redox regulation ensures light-responsive control of chloroplast functions. Light-derived signal is transferred in the form of reducing power from the photosynthetic electron transport chain to several redox-sensitive target proteins. Two types of protein, ferredoxin-thioredoxin reductase (FTR) and thioredoxin (Trx), are well recognized [...] Read more.

Thiol-based redox regulation ensures light-responsive control of chloroplast functions. Light-derived signal is transferred in the form of reducing power from the photosynthetic electron transport chain to several redox-sensitive target proteins. Two types of protein, ferredoxin-thioredoxin reductase (FTR) and thioredoxin (Trx), are well recognized as the mediators of reducing power. However, it remains unclear which step in a series of redox-relay reactions is the critical bottleneck for determining the rate of target protein reduction. To address this, the redox behaviors of FTR, Trx, and target proteins were extensively characterized in vitro and in vivo. The FTR/Trx redox cascade was reconstituted in vitro using recombinant proteins from Arabidopsis. On the basis of this assay, we found that the FTR catalytic subunit and f-type Trx are rapidly reduced after the drive of reducing power transfer, irrespective of the presence or absence of their downstream target proteins. By contrast, three target proteins, fructose 1,6-bisphosphatase (FBPase), sedoheptulose 1,7-bisphosphatase (SBPase), and Rubisco activase (RCA) showed different reduction patterns; in particular, SBPase was reduced at a low rate. The in vivo study using Arabidopsis plants showed that the Trx family is commonly and rapidly reduced upon high light irradiation, whereas FBPase, SBPase, and RCA are differentially and slowly reduced. Both of these biochemical and physiological findings suggest that reducing power transfer from Trx to its target proteins is a rate-limiting step for chloroplast redox regulation, conferring distinct light-responsive redox behaviors on each of the targets. Full article

(This article belongs to the Special Issue Thioredoxin and Glutaredoxin Systems)

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14 pages, 6368 KiB

Open AccessArticle

Towards Initial Indications for a Thiol-Based Redox Control of Arabidopsis 5-Aminolevulinic Acid Dehydratase

by Daniel Wittmann, Sigri Kløve, Peng Wang and Bernhard Grimm

Antioxidants 2018, 7(11), 152; https://doi.org/10.3390/antiox7110152 - 31 Oct 2018

Cited by 9 | Viewed by 4362

Abstract

Thiol-based redox control is one of the important posttranslational mechanisms of the tetrapyrrole biosynthesis pathway. Many enzymes of the pathway have been shown to interact with thioredoxin (TRX) and Nicotinamide adenine dinucleotide phosphate (NADPH)-dependent thioredoxin reductase C (NTRC). We examined the redox-dependency of [...] Read more.

Thiol-based redox control is one of the important posttranslational mechanisms of the tetrapyrrole biosynthesis pathway. Many enzymes of the pathway have been shown to interact with thioredoxin (TRX) and Nicotinamide adenine dinucleotide phosphate (NADPH)-dependent thioredoxin reductase C (NTRC). We examined the redox-dependency of 5-aminolevulinic acid dehydratase (ALAD), which catalyzed the conjugation of two 5-aminolevulinic acid (ALA) molecules to porphobilinogen. ALAD interacted with TRX f, TRX m and NTRC in chloroplasts. Consequently, less ALAD protein accumulated in the trx f1, ntrc and trx f1/ntrc mutants compared to wild-type control resulting in decreased ALAD activity. In a polyacrylamide gel under non-reducing conditions, ALAD monomers turned out to be present in reduced and two oxidized forms. The reduced and oxidized forms of ALAD differed in their catalytic activity. The addition of TRX stimulated ALAD activity. From our results it was concluded that (i) deficiency of the reducing power mainly affected the in planta stability of ALAD; and (ii) the reduced form of ALAD displayed increased enzymatic activity. Full article

(This article belongs to the Special Issue Thioredoxin and Glutaredoxin Systems)

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16 pages, 2234 KiB

Open AccessArticle

Hmox1 Upregulation Is a Mutual Marker in Human Tumor Cells Exposed to Physical Plasma-Derived Oxidants

by Sander Bekeschus, Eric Freund, Kristian Wende, Rajesh Kumar Gandhirajan and Anke Schmidt

Antioxidants 2018, 7(11), 151; https://doi.org/10.3390/antiox7110151 - 27 Oct 2018

Cited by 28 | Viewed by 4091

Abstract

Increasing numbers of cancer deaths worldwide demand for new treatment avenues. Cold physical plasma is a partially ionized gas expelling a variety of reactive oxygen and nitrogen species, which can be harnesses therapeutically. Plasmas and plasma-treated liquids have antitumor properties in vitro and [...] Read more.

Increasing numbers of cancer deaths worldwide demand for new treatment avenues. Cold physical plasma is a partially ionized gas expelling a variety of reactive oxygen and nitrogen species, which can be harnesses therapeutically. Plasmas and plasma-treated liquids have antitumor properties in vitro and in vivo. Yet, global response signatures to plasma treatment have not yet been identified. To this end, we screened eight human cancer cell lines to investigate effects of low-dose, tumor-static plasma-treated medium (PTM) on cellular activity, immune-modulatory properties, and transcriptional levels of 22 redox-related genes. With PTM, a moderate reduction of metabolic activity and modest modulation of chemokine/cytokine pattern and markers of immunogenic cell death was observed. Strikingly, the Nuclear factor (erythroid-derived 2)-like 2 (nrf2) target heme oxygenase 1 (hmox1) was upregulated in all cell lines 4 h post PTM-treatment. nrf2 was not changed, but its baseline expression inversely and significantly correlated with hmox1 expression after exposure to PTM. Besides awarding hmox1 a central role with plasma-derived oxidants, we present a transcriptional redox map of 22 targets and chemokine/cytokine secretion map of 13 targets across eight different human tumor cell lines of four tumor entities at baseline activity that are useful for future studies in this field. Full article

(This article belongs to the Special Issue Nrf2 in Dermatological Pathologies)

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10 pages, 1215 KiB

Open AccessArticle

Effects of Bcl-2/Bcl-x_L Inhibitors on Pulmonary Artery Smooth Muscle Cells

by Vladyslava Rybka, Yuichiro J. Suzuki and Nataliia V. Shults

Antioxidants 2018, 7(11), 150; https://doi.org/10.3390/antiox7110150 - 26 Oct 2018

Cited by 15 | Viewed by 3883

Abstract

Pulmonary arterial hypertension (PAH) is a fatal disease without satisfactory therapeutic options. By the time patients are diagnosed with this disease, the remodeling of pulmonary arteries has already developed due to the abnormal growth of pulmonary vascular cells. Therefore, agents that reduce excess [...] Read more.

Pulmonary arterial hypertension (PAH) is a fatal disease without satisfactory therapeutic options. By the time patients are diagnosed with this disease, the remodeling of pulmonary arteries has already developed due to the abnormal growth of pulmonary vascular cells. Therefore, agents that reduce excess pulmonary vascular cells have therapeutic potential. Bcl-2 is known to function in an antioxidant pathway to prevent apoptosis. The present study examined the effects of inhibitors of the anti-apoptotic proteins Bcl-2 and Bcl-x_L. ABT-263 (Navitoclax), ABT-199 (Venetoclax), ABT-737, and Obatoclax, which all promoted the death of cultured human pulmonary artery smooth muscle cells. Further examinations using ABT-263 showed that Bcl-2/Bcl-x_L inhibition indeed promoted apoptotic programmed cell death. ABT-263-induced cell death was inhibited by antioxidants. ABT-263 also promoted autophagy; however, the inhibition of autophagy did not suppress ABT-263-induced cell death. This is in contrast to other previously studied drugs, including anthracyclines and proteasome inhibitors, which were found to mediate autophagy to induce cell death. The administration of ABT-263 to rats with PAH in vivo resulted in the reversal of pulmonary vascular remodeling. Thus, promoting apoptosis by inhibiting anti-apoptotic Bcl-2 and Bcl-x_L effectively kills pulmonary vascular smooth muscle cells and reverses pulmonary vascular remodeling. Full article

(This article belongs to the Special Issue Novel Aspects of Redox, Antioxidant and Mitochondrial Signaling)

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18 pages, 845 KiB

Open AccessReview

Heat Sepsis Precedes Heat Toxicity in the Pathophysiology of Heat Stroke—A New Paradigm on an Ancient Disease

by Chin Leong Lim

Antioxidants 2018, 7(11), 149; https://doi.org/10.3390/antiox7110149 - 25 Oct 2018

Cited by 66 | Viewed by 15104

Abstract

Heat stroke (HS) is an ancient illness dating back more than 2000 years and continues to be a health threat and to cause fatality during physical exertion, especially in military personnel, fire-fighters, athletes, and outdoor laborers. The current paradigm in the pathophysiology and [...] Read more.

Heat stroke (HS) is an ancient illness dating back more than 2000 years and continues to be a health threat and to cause fatality during physical exertion, especially in military personnel, fire-fighters, athletes, and outdoor laborers. The current paradigm in the pathophysiology and prevention of HS focuses predominantly on heat as the primary trigger and driver of HS, which has not changed significantly for centuries. However, pathological and clinical reports from HS victims and research evidence from animal and human studies support the notion that heat alone does not fully explain the pathophysiology of HS and that HS may also be triggered and driven by heat- and exercise-induced endotoxemia. Exposure to heat and exercise stresses independently promote the translocation of lipopolysaccharides (LPS) from gram-negative bacteria in the gut to blood in the circulatory system. Blood concentration of LPS can increase to a threshold that triggers the systemic inflammatory response, leading to the downstream ramifications of cellular and organ damage with sepsis as the end point i.e., heat sepsis. The dual pathway model (DPM) of HS proposed that HS is triggered by two independent pathways sequentially along the core temperature continuum of >40 °C. HS is triggered by heat sepsis at Tc < 42 °C and by the heat toxicity at Tc > 42 °C, where the direct effects of heat alone can cause cellular and organ damage. Therefore, heat sepsis precedes heat toxicity in the pathophysiology of HS. Full article

(This article belongs to the Special Issue Exercise and Inflammation)

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Antioxidants, Volume 7, Issue 11 (November 2018) – 21 articles

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