Induction Of Antioxidant Defenses Research Articles

Effect of salinity, nitrogen and phosphorus stresses on growth and photosynthetic activity of the marine microalga Dunaliella parva

The growth of the marine green alga Dunaliella parva was studied and optimized under different salinity levels of NaCl (0.5, 1, 2, 2.5, and 3.5 M). The growth was monitored by cell number pigment content (Chl. a, Chl. b, and carotenoids). The grown alga, under the optimal conditions, was exposed to different stresses (nitrogen, phosphorus starvation, and salinity either singly or combined. Under nitrogen and phosphorus starvation, either singly or combined, the growth rate and the metabolic activities were decreased. Under salt stress (2.5 M NaCl) combined with N starvation and heavy metals stress, glycerol production increased, while glycerol synthesis decreased under salt stress of 1 M NaCl and P starvation. Also, free radicals (total antioxidant, reducing power, DPPH, and Lipid peroxidation), pigment content, and activity of antioxidant enzymes were recorded. D. parva grown under salinity level (2.5 M NaCl) combined with nutrient starvation correlated with more efficient enzymatic antioxidant activity accumulation. This study strongly suggested that the induction of antioxidant defense was one component of the tolerance mechanism of D. parva to salinity, as evidenced by its growth behavior.

Mammalian target of rapamycin inhibition protects glioma cells from temozolomide-induced cell death

Glioblastoma is an incurable brain tumor with a median survival below two years. Trials investigating targeted therapy with inhibitors of the kinase mTOR have produced ambiguous results. Especially combination of mTOR inhibition with standard temozolomide radiochemotherapy has resulted in reduced survival in a phase II clinical trial. To date, this phenomenon is only poorly understood. To recreate the therapeutic setting in vitro, we exposed glioblastoma cell lines to co-treatment with rapamycin and temozolomide and assessed cell viability, DNA damage and reactive oxygen species. Additionally, we employed a novel translatomic based mass spectrometry approach (“mePROD”) to analyze acute changes in translated proteins. mTOR inhibition with rapamycin protected glioblastoma cells from temozolomide toxicity. Following co-treatment of temozolomide with rapamycin, an increased translation of reactive oxygen species (ROS)-detoxifying proteins was detected by mass spectrometry. This was accompanied by improved ROS-homeostasis and reduced DNA damage. Additionally, rapamycin induced the expression of the DNA repair enzyme O-6-methylguanine-DNA methyltransferase (MGMT) in glioblastoma cells with an unmethylated MGMT gene promotor. Inhibition of mTOR antagonized the cytotoxic effects of temozolomide in vitro. The induction of antioxidant defences and MGMT are two underlying candidate mechanisms. Further functional experiments in vitro and in vivo are warranted to characterize this effect that appears relevant for combinatorial therapeutic strategies.

Evaluation of heat stress induced plant metabolites in Fagopyrum esculentum Moench. by exogenous application of plant growth promoters

Global warming has a direct relation with high temperature and management of heat stress in field crops is important for sustainable agriculture. Common buckwheat ( Fagorpyrum esculentum Moench.) is an emerging pseudocereal and alternative food crop but shows sensitivity to heat stress. This two years (2017 and 2018) research was conducted to explore the physiological and biochemical mechanism of improving heat stress tolerance in buckwheat with foliar spray of different plant growth promoters (PGPs). The preoptimized levels of moringa leaf extract (MLE) of fresh (MFLE, 3%) and dried leaves (MDLE, 10%), ascorbic acid (AsA, 0.5 mM), a vitamin biosynthesized in plants and thiourea (TU, 10 mM), a synthetic growth bioregulator were foliar sprayed. Results revealed that growth attributes including shoot (34.61%) and root length (27.62%), dry weight (641.94% and 40.23%, respectively), stem diameter (52.05%), no. of roots per plant (27.27%), leaf area (24.86%), and no. of internodes per plant (16.17%) were impaired by heat stress. Similarly, antioxidants including leaf and root superoxide dismutase (17.11% and 21.43%), peroxidase (16.81% and 8.40%) and catalase (6.51% and 6.54%), respectively, were significantly affected by heat stress. PGPs spray alleviated heat damage by reducing the biosynthesis of leaf and root MDA and H2O2, and preferential induction of enzymatic antioxidants. PCA-biplot analysis showed that, amongst PGPs, MDLE was greatly effective in inducing antioxidant defense under heat stress. PCA and correlation matrix revealed that PGPs prompted induction of antioxidants was effective more in roots than leaves under heat stress. Conclusively, the induction of antioxidant defense with the PGPs especially with MLEs spray is the main mechanism, with great implications for heat tolerance in common buckwheat.

Induction of antioxidant defenses by a low-dose cadmium priming alleviates heat stress in pigeon pea

Global warming has a devastating effect on the growth and productivity of plants. Pigeon pea, the second most important legume crop with high nutritional value, is at high risk due to high temperature exposure. Priming is an innovative agronomical application that can be used as a strategy to minimize the detrimental effects of any kind of stresses. In this study, we investigated how low dose of cadmium priming alleviates heat stress (HS) in pigeon pea seedlings. The results demonstrated that low dose of cadmium priming induced the expression of antioxidant systems and maintain a redox homeostasis. An enhanced level of antioxidant glutathione, and antioxidative enzymes (SOD, APX, and GR) were observed in Cd+HS leaf (40 μM Cd priming followed by exposure to HS, 42°C) as compared to the HS leaf. Moreover, a reduction in hydrogen peroxide (H2O2) and oxidized glutathione (GSSG) content was also noticed in Cd+HS leaf. The GSH/GSSG ratio, which was indicative of the redox state in the plant system, was also high in Cd+HS leaf as compared to HS leaf. Thus, the priming of pigeon pea seeds with low dose Cd alleviates HS by elevating antioxidant defenses, ultimately protecting pigeon pea seedlings against HS.

Hypoxia-Mediated ATF4 Induction Promotes Survival in Detached Conditions in Metastatic Murine Mammary Cancer Cells.

Regions of hypoxia are common in solid tumors and drive changes in gene expression that increase risk of cancer metastasis. Tumor cells must respond to the stress of hypoxia by activating genes to modify cell metabolism and antioxidant response to improve survival. The goal of the current study was to determine the effect of hypoxia on cell metabolism and markers of oxidative stress in metastatic (metM-Wntlung) compared with nonmetastatic (M-Wnt) murine mammary cancer cell lines. We show that hypoxia induced a greater suppression of glutamine to glutamate conversion in metastatic cells (13% in metastatic cells compared to 7% in nonmetastatic cells). We also show that hypoxia increased expression of genes involved in antioxidant response in metastatic compared to nonmetastatic cells, including glutamate cysteine ligase catalytic and modifier subunits and malic enzyme 1. Interestingly, hypoxia increased the mRNA level of the transaminase glutamic pyruvic transaminase 2 (Gpt2, 7.7-fold) only in metM-Wntlung cells. The change in Gpt2 expression was accompanied by transcriptional (4.2-fold) and translational (6.5-fold) induction of the integrated stress response effector protein activating transcription factor 4 (ATF4). Genetic depletion ATF4 demonstrated importance of this molecule for survival of hypoxic metastatic cells in detached conditions. These findings indicate that more aggressive, metastatic cancer cells utilize hypoxia for metabolic reprogramming and induction of antioxidant defense, including activation of ATF4, for survival in detached conditions.

Bystander effect of ultraviolet A radiation protects A375 melanoma cells by induction of antioxidant defense

Ultraviolet (UV) irradiated cells release factors that result in varied responses by non-irradiated cells via bystander effects (BE). The UV-BE is dependent on the cell types involved and on the wavelength of the radiation. Using conditioned medium from UVA-irradiated A375 human melanoma cells (UVA-CM), UVA-bystander response was evaluated on the viability of naïve A375 cells. UVA-CM treatment itself did not alter cell viability; however, UVA-CM treated bystander cells were more resistant to the lethal action of UVA, UVB, UVC or H2O2. Effects of UVA-CM on cell proliferation, mechanism of cell death, DNA damage, malondialdehyde formation, generation of reactive oxygen species (ROS) and antioxidant status were studied in A375 cells. We observed that UVA-CM triggered antioxidant defenses to elicit protective responses through elevation of antioxidant enzyme activities in cells, which persisted until 5 h after exposure to UVA-CM. This was possibly responsible for decreased generation of ROS and diminished DNA and membrane damage in cells. These bystander cells were resistant to killing when exposed to different genotoxic agents. Damaged nuclei, induction of apoptosis and autophagic death were also lowered in these cells. The influence of UVA-CM on cancer stem cells side population was assessed. Highlights: UVA radiation induced bystander effects in A375 cells Damage by genotoxicants is suppressed due to lower ROS generation on UVA-CM treatment UVA-CM exposure enhanced higher activities of CAT and GPx Resistance to genotoxic agents in such cells was due to elevated antioxidant defence UVA-bystander phenomenon was a protective response

Abstract 2325: Hypoxia-mediated ATF4 induction promotes survival in detached conditions in metastatic murine mammary cancer cells

Abstract Regions of hypoxia are common in solid tumors and drive changes in gene expression that increase risk of cancer metastasis. Tumor cells must respond to the stress of hypoxia by activating genes to modify cell metabolism and antioxidant response to improve survival. The goal of the current studies was to determine the effect of hypoxia on cell metabolism and markers of oxidative stress in non-metastatic M-Wnt compared to metastatic metM-Wntlung murine mammary cancer cell lines. We show that hypoxia increased expression of genes involved in antioxidant response in metastatic compared to non-metastatic cells, including glutamate cysteine ligase catalytic and modifier subunits and malic enzyme 1. Further, hypoxia induces a greater suppression of glutamine to glutamate conversion in metastatic cells (15% in metastatic cells compared to 9% in non-metastatic cells). Interestingly, hypoxia increased the mRNA level of the transaminase glutamic pyruvic transaminase 2 (Gpt2, 7.7-fold) only in metM-Wntlung cells. The change in Gpt2 expression was accompanied by transcriptional (4.2-fold) and translational (6.5-fold) induction of the integrated stress response effector protein activating transcription factor 4 (ATF4), which mediated survival of hypoxic metastatic cells in detached conditions, as shown by genetic ATF4 depletion. These data indicate that more aggressive, metastatic cancer cells rely on metabolic reprogramming and induction of antioxidant defense, including activation of ATF4, in hypoxia for survival in detached conditions. Citation Format: Violet A. Kiesel, Stephen D. Hursting, Dorothy Teegarden. Hypoxia-mediated ATF4 induction promotes survival in detached conditions in metastatic murine mammary cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2325.

Characterization of mechanisms involved in tolerance and accumulation of Cd in Biscutella auriculata L.

Biscutella auriculata L. is one of the rare species that is able to grow in a very contaminated mining area in Villamayor de Calatrava (Ciudad Real, Spain). In an effort to understand the mechanisms involved in the tolerance of this plant to high metal concentrations, we grew B. auriculata in the presence of 125μM Cd(NO3)2 for 15 days and analysed different parameters associated with plant growth, nitric oxide and reactive oxygen species metabolism, metal uptake and translocation, photosynthesis rate and biothiol (glutathione and phytochelatins) content. Treatment with Cd led to growth inhibition in both the leaves and the roots, as well as a reduction of photosynthetic parameters, transpiration and stomatal conductance. The metal was mainly accumulated in the roots and in the vascular tissue, although most Cd was detected in areas surrounding their epidermal cells, while in the leaves the metal accumulated mainly in spongy mesophyll, stomata and trichrome. Based on the Cd bioaccumulation (5.93) and translocation (0.15) factors, this species denoted enrichment of the metal in the roots and its low translocation to the upper tissues. Biothiol analysis showed a Cd-dependent increase of reduced glutathione (GSH) as well as the phytochelatins (PC2 and PC3) in both roots and leaves. Cd-promoted oxidative damage occurred mainly in the leaves due to disturbances in enzymatic and nonenzymatic antioxidants, while the roots did not show significant damage as a result of induction of antioxidant defences. It can be concluded that B. auriculata is a new Cd-tolerant plant with an ability to activate efficient metal-sequestering mechanisms in the root surface and leaves and to induce PCs, as well as antioxidative defences in roots.

In vivo assessment of silver nanoparticle induced reactive oxygen species reveals tissue specific effects on cellular redox status in the nematode Caenorhabditis elegans

The current study provides an in vivo analysis of the production of reactive oxygen species (ROS) and oxidative stress in the nematode Caenorhabditis elegans following exposure to EU reference silver nanoparticles NM300K and AgNO3. Induction of antioxidant defenses was measured through the application of a SOD-1 reporter, and the HyPer and GRX biosensor strains to monitor changes in the cellular redox state. Both forms of Ag resulted in an increase in sod-1 expression, elevated H2O2 levels and an imbalance in the cellular GSSG/GSH redox status. Microscopy analysis of the strains revealed that AgNO3 induced ROS-related effects in multiple tissues, including the pharynx, intestinal cells and muscle tissues. In contrast, NM300K resulted in localized ROS production and oxidative stress, specifically in tissues surrounding the intestinal lumen. This indicates that Ag from AgNO3 exposure was readily transported across the whole body, while Ag or ROS from NM300K exposure was predominantly confined within the luminal tissues. Concentrations resulting in an increase in ROS production and changes in GSSG/GSH ratio were in line with the levels associated with observed physiological toxic effects. However, sod-1 was not induced at the lowest Ag concentrations, although reprotoxicity was seen at these levels. While both forms of Ag caused oxidative stress, impaired development, and reprotoxicity, the results suggest different involvement of ROS production to the toxic effects of AgNO3versus NM300K.

The Nrf2/HO-1 Axis as Targets for Flavanones: Neuroprotection by Pinocembrin, Naringenin, and Eriodictyol.

Flavanones are a group of flavonoids that derive from their immediate chalcone precursors through the action of chalcone isomerase enzymes. The Aromatic A and B rings, C4-keto group, and the 15-carbon flavonoid skeleton are all evident in flavanones, but a notable absence of C2-C3 double bond and a lack of oxygenation at C-3 position of the C-ring makes them distinctively different from other groups such as flavonols (e.g., quercetin). On the basis of oxygenation level in the B ring, flavanones can vary from each other as exemplified by pinocembrin (no oxygenation), naringenin (4′-hydroxyl), or eriodictyol (3′,4′-dihydroxyl substitution). These groups are generally weaker free radical scavengers as compared to quercetin and derivatives though eriodictyol has a better free radical scavenging profile within the group due to the presence of the catechol functional moiety. In this communication, their antioxidant potential through the induction of antioxidant defenses is scrutinized. These compounds as exemplified by pinocembrin could induce the nuclear factor erythroid 2-related factor 2- (Nrf2-) heme oxygenase-1 (HO-1) axis leading to amelioration of oxidative stress in cellular and animal models. Their neuroprotective effect through such mechanism is discussed.

Plant growth retardants (PGRs) affect growth and secondary metabolite biosynthesis in Stevia rebaudiana Bertoni under drought stress

Beyond the inhibitory action against the gibberellin biosynthesis, some plant growth retardants (PGRs) can play an important role in regulating plant responses to abiotic stress through the induction of different tolerance mechanisms. The aim of the present study was the exploitation of the potential of PGRs in enhancing the resistance to drought stress in Stevia rebaudiana Bert. Therefore, the effects of three PGRs on stevia plants grown under drought stress condition were investigated. Stevia plants were first subjected to water stress and, second, treated with PGRs to detect PGRs effect on biometric, productive and phytochemical characteristics of drought stressed-plants. The control plants were uniformly irrigated at 3-day intervals, while water-stress conditions were imposed by watering the plants at 12-day intervals. Subsequently, the Chlorocholine chloride (CCC, as Copalyl diphosphate synthase inhibitor and Kaurene synthase inhibitor), Paclobutrazol (PBZ, as Kaurene oxidase inhibitor) and Daminozide (DAM, as anti-gibberellins) were applied in drought stressed-plants. The CCC and DAM were sprayed on stevia shoots, while PBZ was drenched. The obtained results showed that leaf dry weight of stevia plants was significantly reduced by drought stress, but this parameter increased as a consequence of CCC and PBZ treatments. Drought stress also caused a significant reduction in total steviol glycoside (SVglys) content. This reduction was more pronounced in drought stressed-plants treated with CCC, while PBZ was able to counteract the SVglys reduction, with SVgly content similar to that observed in the control. Similarly, PBZ was able to increase the soluble sugar production and total antioxidant capacity in the leaves of stressed-stevia plants. These findings suggested that CCC and, in particular, PBZ had a protective effect on stevia growth under drought stress by induction of antioxidant defenses and soluble sugar production. CCC seems to inhibit gibberellin biosynthesis, preventing the SVglys production, while DAM and PBZ, as gibberellin inhibitors, didn't have a negative effect on SVglys production in drought stressed-plants. This observation seems to emphasize their role in limiting the rate of target enzymes of CCC in SVglys biosynthetic pathway. Moreover, the induction of glucose production, as a substrate for SVglys biosynthesis, could be a convincing evidence for SVglys promotion in PBZ treated-plants.

Exposure of Monocytic Cells to Lipopolysaccharide Induces Coordinated Endotoxin Tolerance, Mitochondrial Biogenesis, Mitophagy, and Antioxidant Defenses.

In order to limit the adverse effects of excessive inflammation, anti-inflammatory responses are stimulated at an early stage of an infection, but during sepsis these can lead to deactivation of immune cells including monocytes. In addition, there is emerging evidence that the up-regulation of mitochondrial quality control mechanisms, including mitochondrial biogenesis and mitophagy, is important during the recovery from sepsis and inflammation. We aimed to describe the relationship between the compensatory immune and mitochondrial responses that are triggered following exposure to an inflammatory stimulus in human monocytic cells. Incubation with lipopolysaccharide resulted in a change in the immune phenotype of THP-1 cells consistent with the induction of endotoxin tolerance, similar to that seen in deactivated septic monocytes. After exposure to LPS there was also early evidence of oxidative stress, which resolved in association with the induction of antioxidant defenses and the stimulation of mitochondrial degradation through mitophagy. This was compensated by a parallel up-regulation of mitochondrial biogenesis that resulted in an overall increase in mitochondrial respiratory activity. These observations improve our understanding of the normal homeostatic responses that limit the adverse cellular effects of unregulated inflammation, and which may become ineffective when an infection causes sepsis.

Exogenes Silizium schützt Brassica-napus-Pflanzen vor salzinduziertem oxidativen Stress durch die Modulation des AsA-GSH-Zyklus, thiolabhängiger antioxidativer Enzyme und der Glyoxalase-Systeme

Although silicon (Si) has showed its potential role in mitigating abiotic stress-induced damages in many plant species its role in coordinated induction of antioxidant defense is yet to be elucidated. Therefore, we studied rapeseed (Brassica napus) seedlings applied with exogenous Si for changes occurring in antioxidant defense and glyoxalase systems. Seedlings (12-day-old) grown semi-hydroponically were exposed to Si (silicon dioxide, SiO2; 1 mM) solely and in combination with NaCl (100 and 200 mM) for 48 h. Salinity created oxidative damage by increasing H2O2 and malondialdehyde (MDA) contents resulting in disruption of antioxidant defense system and in arousing methylglyoxal (MG) toxicity by the down-regulation of glyoxalase enzyme activities. Exogenous Si treatment showed reduction of both H2O2 and MDA contents and up-regulation of antioxidant components including the activities of related enzymes (APX, MDHAR, DHAR, GR, GST, GPX and CAT) and the contents of AsA and GSH. Enhanced activities of glyoxalase I (Gly I) and glyoxalase II (Gly II) detoxified the toxic MG. Thus, this study clearly indicates that Si improved plant tolerance to salinity stress through enhancement of both antioxidant defense and glyoxalase systems that led to reduced oxidative damage and MG toxicity.

Evaluating toxicity of copper(II) oxide nanoparticles (CuO-NPs) through waterborne exposure to tilapia (Oreochromis mossambicus) by tissue accumulation, oxidative stress, histopathology, and genotoxicity.

Metal oxide nanoparticles are widely used in industries, and peak level can be confirmed in their surroundings. In the present study, the sub-lethal effects of CuO-NPs from low to high concentration as 0.5 to 1.5mg/L were observed in tilapia (Oreochromis mossambicus). Accumulation of copper from CuO-NPs was increased with the increase in doses, and maximum accumulation was found in the gill than liver and muscles. The increased lipid peroxidation level was observed in the gill as compared to liver, and the similar results were obtained in catalase and glutathione while superoxide dismutase level was higher in the liver than gills. In histological alterations, gill edema, curved tips, fusion of gill lamellae, and thickening of primary and secondary gill lamellae were observed. Necrosis and apoptosis with condensed nuclear bodies and pyknotic nuclei were observed in the liver at the highest dose concentration. In a genotoxic study, the highest value of % tail DNA and olive tail movement was observed with increasing concentrations. Copper oxide nanoparticles has greater potential to accumulate in the soft tissues, which may cause respiratory distress such as oxidative stress, induction of antioxidant defense by raising glutathione, organ pathology, and genotoxicity.

Protective Effect of Flavonoids from Ziziphus jujuba cv. Jinsixiaozao against Acetaminophen-Induced Liver Injury by Inhibiting Oxidative Stress and Inflammation in Mice.

This study was aimed to investigate the chemical composition, antioxidant activities and hepatoprotective effect of flavonoids from Ziziphus jujuba cv. Jinsixiaozao (ZJF). The composition of ZJF was analyzed by high performance liquid chromatography (HPLC) and Liquid chromatography–mass spectrometry (LC–MS), and antioxidant properties were investigated by biological assays in vitro. The hepatoprotective activity of ZJF was evaluated in acetaminophen (APAP)-treated BALB/c mice. Results indicate that ZJF displayed significant antioxidant capacity. Pretreatment with ZJF significantly decreased APAP-elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (TB). Activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were enhanced with ZJF administration, while malondialdehyde (MDA) level and glutathione (GSH) depletion were reduced. Meanwhile, ZJF reversed the suppression of nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, and up-regulated the protein expression of NAD(P)H: quinone oxidoreductase 1(NQO1) in liver damage mice. Furthermore, ZJF attenuated APAP-induced inflammatory mediator production, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β). Expression of p65 showed that ZJF dampened nuclear factor-κB (NF-κB) activation. The results strongly indicate that the hepatoprotective role of ZJF in APAP-induced hepatotoxicity might result from its induction of antioxidant defense via activation of Nrf2 and reduction of inflammation via inhibition of NF-κB.

Antioxidant enzymes in chickpea colonized by Piriformospora indica participate in defense against the pathogen Botrytis cinerea

Piriformospora indica, a root endophytic fungus, promotes growth of the economically important chickpea plant (Cicer arietinum Linn.) and protects it against the pathogenic fungus Botrytis cinerea. Biomass and root development were found to be significantly improved in chickpea plants colonized with P. indica as compared to the plants grown without P. indica as well as from the plants infected with the B. cinerea. Our PCR analyses showed that gradual increase in the colonization of P. indica in the plants result in the inhibition of the colonization of B. cinerea. P. indica colonized plants showed increased antioxidant enzyme activities. Interestingly, there were pronounced decrease in the antioxidant enzyme activities in shoots infected with B. cinerea and colonized with P. indica in alternate and simultaneous mode as compared to plants infected with B. cinerea alone. We conclude that P. indica helps plants to overcome the disease load by enhancing antioxidant enzyme defense system. Our data suggest that, bio-protective action of P. indica might be mediated via systemic induction of antioxidant defense in the host plants.

Single swim sessions in C. elegans induce key features of mammalian exercise

BackgroundExercise exerts remarkably powerful effects on metabolism and health, with anti-disease and anti-aging outcomes. Pharmacological manipulation of exercise benefit circuits might improve the health of the sedentary and the aging populations. Still, how exercised muscle signals to induce system-wide health improvement remains poorly understood. With a long-term interest in interventions that promote animal-wide health improvement, we sought to define exercise options for Caenorhabditis elegans.ResultsHere, we report on the impact of single swim sessions on C. elegans physiology. We used microcalorimetry to show that C. elegans swimming has a greater energy cost than crawling. Animals that swam continuously for 90 min specifically consumed muscle fat supplies and exhibited post-swim locomotory fatigue, with both muscle fat depletion and fatigue indicators recovering within 1 hour of exercise cessation. Quantitative polymerase chain reaction (qPCR) transcript analyses also suggested an increase in fat metabolism during the swim, followed by the downregulation of specific carbohydrate metabolism transcripts in the hours post-exercise. During a 90 min swim, muscle mitochondria matrix environments became more oxidized, as visualized by a localized mitochondrial reduction-oxidation-sensitive green fluorescent protein reporter. qPCR data supported specific transcriptional changes in oxidative stress defense genes during and immediately after a swim. Consistent with potential antioxidant defense induction, we found that a single swim session sufficed to confer protection against juglone-induced oxidative stress inflicted 4 hours post-exercise.ConclusionsIn addition to showing that even a single swim exercise bout confers physiological changes that increase robustness, our data reveal that acute swimming-induced changes share common features with some acute exercise responses reported in humans. Overall, our data validate an easily implemented swim experience as C. elegans exercise, setting the foundation for exploiting the experimental advantages of this model to genetically or pharmacologically identify the exercise-associated molecules and signaling pathways that confer system-wide health benefits.

Short‐term ammonium supply induces cellular defence to prevent oxidative stress inArabidopsisleaves

Plants can assimilate nitrogen from soil pools of both ammonium and nitrate, and the relative levels of these two nitrogen sources are highly variable in soil. Long-term ammonium nutrition is known to cause damage to Arabidopsis that has been linked to mitochondrial oxidative stress. Using hydroponic cultures, we analysed the consequences of rapid shifts between nitrate and ammonium nutrition. This did not induce growth retardation, showing that Arabidopsis can compensate for the changes in redox metabolism associated with the variations in nitrogen redox status. During the first 3 h of ammonium treatment, we observed distinct transient shifts in reactive oxygen species (ROS), low-mass antioxidants, ROS-scavenging enzymes, and mitochondrial alternative electron transport pathways, indicating rapid but temporally separated changes in chloroplastic, mitochondrial and cytosolic ROS metabolism. The fast induction of antioxidant defences significantly lowered intracellular H2 O2 levels, and thus protected Arabidopsis leaves from oxidative stress. On the other hand elevated extracellular ROS production in response to ammonium supply may be involved in signalling. The response pattern displays an intricate plasticity of Arabidopsis redox metabolism to minimise stress in responses to nutrient changes.

YI-03 - Induction of antioxidant defences by Cu(II)ATSM: Role of DJ-1 and Nrf2

YI-03 - Induction of antioxidant defences by Cu(II)ATSM: Role of DJ-1 and Nrf2

Loss of functional OPA1 unbalances redox state: implications in dominant optic atrophy pathogenesis.

Objective OPA1 mutations cause protein haploinsufficiency leading to dominant optic atrophy (DOA), an incurable retinopathy with variable severity. Up to 20% of patients also develop extraocular neurological complications. The mechanisms that cause this optic atrophy or its syndromic forms are still unknown. After identifying oxidative stress in a mouse model of the pathology, we sought to determine the consequences of OPA1 dysfunction on redox homeostasis.MethodsMitochondrial respiration, reactive oxygen species levels, antioxidant defenses, and cell death were characterized by biochemical and in situ approaches in both in vitro and in vivo models of OPA1 haploinsufficiency.ResultsA decrease in aconitase activity suggesting an increase in reactive oxygene species and an induction of antioxidant defenses was observed in cortices of a murine model as well as in OPA1 downregulated cortical neurons. This increase is associated with a decline in mitochondrial respiration in vitro. Upon exogenous oxidative stress, OPA1‐depleted neurons did not further exhibit upregulated antioxidant defenses but were more sensitive to cell death. Finally, low levels of antioxidant enzymes were found in fibroblasts from patients supporting their role as modifier factors.InterpretationOur study suggests that the pro‐oxidative state induced by OPA1 loss may contribute to DOA pathogenesis and that differences in antioxidant defenses can explain the variability in expressivity. Furthermore, antioxidants may be used as therapy as they could prevent or delay DOA symptoms in patients.