Baseline and stress-induced levels of corticosterone in male and female Afrotropical and European temperate stonechats during breeding.

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Apfelbeck, Beate; Helm, Barbara; Illera, Juan Carlos; Mortega, Kim G; Smiddy, Patrick; Evans, Neil P

2017-05-22

Latitudinal variation in avian life histories falls along a slow-fast pace of life continuum: tropical species produce small clutches, but have a high survival probability, while in temperate species the opposite pattern is found. This study investigated whether differential investment into reproduction and survival of tropical and temperate species is paralleled by differences in the secretion of the vertebrate hormone corticosterone (CORT). Depending on circulating concentrations, CORT can both act as a metabolic (low to medium levels) and a stress hormone (high levels) and, thereby, influence reproductive decisions. Baseline and stress-induced CORT was measured across sequential stages of the breeding season in males and females of closely related taxa of stonechats (Saxicola spp) from a wide distribution area. We compared stonechats from 13 sites, representing Canary Islands, European temperate and East African tropical areas. Stonechats are highly seasonal breeders at all these sites, but vary between tropical and temperate regions with regard to reproductive investment and presumably also survival. In accordance with life-history theory, during parental stages, post-capture (baseline) CORT was overall lower in tropical than in temperate stonechats. However, during mating stages, tropical males had elevated post-capture (baseline) CORT concentrations, which did not differ from those of temperate males. Female and male mates of a pair showed correlated levels of post-capture CORT when sampled after simulated territorial intrusions. In contrast to the hypothesis that species with low reproduction and high annual survival should be more risk-sensitive, tropical stonechats had lower stress-induced CORT concentrations than temperate stonechats. We also found relatively high post-capture (baseline) and stress-induced CORT concentrations, in slow-paced Canary Islands stonechats. Our data support and refine the view that baseline CORT facilitates energetically

Genetic variation of drought tolerance in Pinus pinaster at three hierarchical levels: a comparison of induced osmotic stress and field testing.

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Gaspar, Maria João; Velasco, Tania; Feito, Isabel; Alía, Ricardo; Majada, Juan

2013-01-01

Understanding the survival capacity of forest trees to periods of severe water stress could improve knowledge of the adaptive potential of different species under future climatic scenarios. In long lived organisms, like forest trees, the combination of induced osmotic stress treatments and field testing can elucidate the role of drought tolerance during the early stages of establishment, the most critical in the life of the species. We performed a Polyethylene glycol-osmotic induced stress experiment and evaluated two common garden experiments (xeric and mesic sites) to test for survival and growth of a wide range clonal collection of Maritime pine. This study demonstrates the importance of additive vs non additive effects for drought tolerance traits in Pinus pinaster, and shows differences in parameters determining the adaptive trajectories of populations and family and clones within populations. The results show that osmotic adjustment plays an important role in population variation, while biomass allocation and hydric content greatly influence survival at population level. Survival in the induced osmotic stress experiment presented significant correlations with survival in the xeric site, and height growth at the mesic site, at population level, indicating constraints of adaptation for those traits, while at the within population level no significant correlation existed. These results demonstrate that population differentiation and within population genetic variation for drought tolerance follow different patterns.

Genetic variation of drought tolerance in Pinus pinaster at three hierarchical levels: a comparison of induced osmotic stress and field testing.

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Maria João Gaspar

Full Text Available Understanding the survival capacity of forest trees to periods of severe water stress could improve knowledge of the adaptive potential of different species under future climatic scenarios. In long lived organisms, like forest trees, the combination of induced osmotic stress treatments and field testing can elucidate the role of drought tolerance during the early stages of establishment, the most critical in the life of the species. We performed a Polyethylene glycol-osmotic induced stress experiment and evaluated two common garden experiments (xeric and mesic sites to test for survival and growth of a wide range clonal collection of Maritime pine. This study demonstrates the importance of additive vs non additive effects for drought tolerance traits in Pinus pinaster, and shows differences in parameters determining the adaptive trajectories of populations and family and clones within populations. The results show that osmotic adjustment plays an important role in population variation, while biomass allocation and hydric content greatly influence survival at population level. Survival in the induced osmotic stress experiment presented significant correlations with survival in the xeric site, and height growth at the mesic site, at population level, indicating constraints of adaptation for those traits, while at the within population level no significant correlation existed. These results demonstrate that population differentiation and within population genetic variation for drought tolerance follow different patterns.

Induced resistance in tomato by SAR activators during predisposing salinity stress

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Matthew Francis Pye

2013-05-01

Full Text Available Plant activators are chemicals that induce disease resistance. The phytohormone salicylic acid (SA is a crucial signal for systemic acquired resistance (SAR, and SA-mediated resistance is a target of several commercial plant activators, including Actigard (1,2,3-benzothiadiazole-7-thiocarboxylic acid-s-methyl-ester, BTH and Tiadinil (N-(3-chloro-4-methylphenyl-4-methyl-1,2,3-thiadiazole-5-carboxamide, TDL. BTH and TDL were examined for their impact on abscisic acid (ABA-mediated, salt-induced disease predisposition in tomato seedlings. A brief episode of salt stress to roots significantly increased the severity of disease caused by Pseudomonas syringae pv. tomato (Pst and Phytophthora capsici relative to non-stressed plants. Root treatment with TDL induced resistance to Pst in leaves and provided protection in both non-stressed and salt-stressed seedlings in WT and highly susceptible NahG plants. Non-stressed and salt-stressed ABA-deficient sitiens mutants were highly resistant to Pst. Neither TDL nor BTH induced resistance to root infection by P. capsici, nor did they moderate the salt-induced increment in disease severity. Root treatment with these plant activators increased the levels of ABA in roots and shoots similar to levels observed in salt-stressed plants. The results indicate that SAR activators can protect tomato plants from bacterial speck disease under predisposing salt stress, and suggest that some SA-mediated defense responses function sufficiently in plants with elevated levels of ABA.

Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

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Bhattacharya, Sharmila; Hosamani, Ravikumar

2015-01-01

Altered gravity environments can induce increased oxidative stress in biological systems. Microarray data from our previous spaceflight experiment (FIT experiment on STS-121) indicated significant changes in the expression of oxidative stress genes in adult fruit flies after spaceflight. Currently, our lab is focused on elucidating the role of hypergravity-induced oxidative stress and its impact on the nervous system in Drosophila melanogaster. Biochemical, molecular, and genetic approaches were combined to study this effect on the ground. Adult flies (2-3 days old) exposed to acute hypergravity (3g, for 1 hour and 2 hours) showed significantly elevated levels of Reactive Oxygen Species (ROS) in fly brains compared to control samples. This data was supported by significant changes in mRNA expression of specific oxidative stress and antioxidant defense related genes. As anticipated, a stress-resistant mutant line, Indy302, was less vulnerable to hypergravity-induced oxidative stress compared to wild-type flies. Survival curves were generated to study the combined effect of hypergravity and pro-oxidant treatment. Interestingly, many of the oxidative stress changes that were measured in flies showed sex specific differences. Collectively, our data demonstrate that altered gravity significantly induces oxidative stress in Drosophila, and that one of the organs where this effect is evident is the brain.

Thiamine and benfotiamine prevent stress-induced suppression of hippocampal neurogenesis in mice exposed to predation without affecting brain thiamine diphosphate levels.

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Vignisse, Julie; Sambon, Margaux; Gorlova, Anna; Pavlov, Dmitrii; Caron, Nicolas; Malgrange, Brigitte; Shevtsova, Elena; Svistunov, Andrey; Anthony, Daniel C; Markova, Natalyia; Bazhenova, Natalyia; Coumans, Bernard; Lakaye, Bernard; Wins, Pierre; Strekalova, Tatyana; Bettendorff, Lucien

2017-07-01

Thiamine is essential for normal brain function and its deficiency causes metabolic impairment, specific lesions, oxidative damage and reduced adult hippocampal neurogenesis (AHN). Thiamine precursors with increased bioavailability, especially benfotiamine, exert neuroprotective effects not only for thiamine deficiency (TD), but also in mouse models of neurodegeneration. As it is known that AHN is impaired by stress in rodents, we exposed C57BL6/J mice to predator stress for 5 consecutive nights and studied the proliferation (number of Ki67-positive cells) and survival (number of BrdU-positive cells) of newborn immature neurons in the subgranular zone of the dentate gyrus. In stressed mice, the number of Ki67- and BrdU-positive cells was reduced compared to non-stressed animals. This reduction was prevented when the mice were treated (200mg/kg/day in drinking water for 20days) with thiamine or benfotiamine, that were recently found to prevent stress-induced behavioral changes and glycogen synthase kinase-3β (GSK-3β) upregulation in the CNS. Moreover, we show that thiamine and benfotiamine counteract stress-induced bodyweight loss and suppress stress-induced anxiety-like behavior. Both treatments induced a modest increase in the brain content of free thiamine while the level of thiamine diphosphate (ThDP) remained unchanged, suggesting that the beneficial effects observed are not linked to the role of this coenzyme in energy metabolism. Predator stress increased hippocampal protein carbonylation, an indicator of oxidative stress. This effect was antagonized by both thiamine and benfotiamine. Moreover, using cultured mouse neuroblastoma cells, we show that in particular benfotiamine protects against paraquat-induced oxidative stress. We therefore hypothesize that thiamine compounds may act by boosting anti-oxidant cellular defenses, by a mechanism that still remains to be unveiled. Our study demonstrates, for the first time, that thiamine and benfotiamine prevent

Protective effects of carnosol against oxidative stress induced brain damage by chronic stress in rats.

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Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Borji, Abasalt; Samini, Mohammad; Farkhondeh, Tahereh

2017-05-04

Oxidative stress through chronic stress destroys the brain function. There are many documents have shown that carnosol may have a therapeutic effect versus free radical induced diseases. The current research focused the protective effect of carnosol against the brain injury induced by the restraint stress. The restraint stress induced by keeping animals in restrainers for 21 consecutive days. Thereafter, the rats were injected carnosol or vehicle for 21 consecutive days. At the end of experiment, all the rats were subjected to his open field test and forced swimming test. Afterwards, the rats were sacrificed for measuring their oxidative stress parameters. To measure the modifications in the biochemical aspects after the experiment, the activities of malondialdehyde (MDA), reduced glutathione (GSH), as well as superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were evaluated in the whole brain. Our data showed that the animals received chronic stress had a raised immobility time versus the non-stressed animals (p < 0.01). Furthermore, chronic stress diminished the number of crossing in the animals that were subjected to the chronic stress versus the non-stressed rats (p < 0.01). Carnosol ameliorated this alteration versus the non-treated rats (p < 0.05). In the vehicle treated rats that submitted to the stress, the level of MDA levels was significantly increased (P < 0.001), and the levels of GSH and antioxidant enzymes were significantly decreased versus the non-stressed animals (P < 0.001). Carnosol treatment reduced the modifications in the stressed animals as compared with the control groups (P < 0.001). All of these carnosol effects were nearly similar to those observed with fluoxetine. The current research shows that the protective effects of carnosol may be accompanied with enhanced antioxidant defenses and decreased oxidative injury.

Oxidative Stress Induces Senescence in Cultured RPE Cells.

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Aryan, Nona; Betts-Obregon, Brandi S; Perry, George; Tsin, Andrew T

2016-01-01

The aim of this research is to determine whether oxidative stress induces cellular senescence in human retinal pigment epithelial cells. Cultured ARPE19 cells were subjected to different concentrations of hydrogen peroxide to induce oxidative stress. Cells were seeded into 24-well plates with hydrogen peroxide added to cell medium and incubated at 37°C + 5% CO2 for a 90-minute period [at 0, 300, 400 and 800 micromolar (MCM) hydrogen peroxide]. The number of viable ARPE19 cells were recorded using the Trypan Blue Dye Exclusion Method and cell senescence was measured by positive staining for senescence-associated beta-galactosidase (SA-beta-Gal) protein. Without hydrogen peroxide treatment, the number of viable ARPE19 cells increased significantly from 50,000 cells/well to 197,000 within 72 hours. Treatment with hydrogen peroxide reduced this level of cell proliferation significantly (to 52,167 cells at 400 MCM; to 49,263 cells at 800 MCM). Meanwhile, cells with a high level of positive senescence-indicator SA-Beta-Gal-positive staining was induced by hydrogen peroxide treatment (from a baseline level of 12% to 80% at 400 MCM and at 800 MCM). Our data suggests that oxidative stress from hydrogen peroxide treatment inhibited ARPE19 cell proliferation and induced cellular senescence.

Histone deacetylase inhibition abolishes stress-induced spatial memory impairment.

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Vargas-López, Viviana; Lamprea, Marisol R; Múnera, Alejandro

2016-10-01

Acute stress induced before spatial training impairs memory consolidation. Although non-epigenetic underpinning of such effect has been described, the epigenetic mechanisms involved have not yet been studied. Since spatial training and intense stress have opposite effects on histone acetylation balance, it is conceivable that disruption of such balance may underlie acute stress-induced spatial memory consolidation impairment and that inhibiting histone deacetylases prevents such effect. Trichostatin-A (TSA, a histone deacetylase inhibitor) was used to test its effectiveness in preventing stress' deleterious effect on memory. Male Wistar rats were trained in a spatial task in the Barnes maze; 1-h movement restraint was applied to half of them before training. Immediately after training, stressed and non-stressed animals were randomly assigned to receive either TSA (1mg/kg) or vehicle intraperitoneal injection. Twenty-four hours after training, long-term spatial memory was tested; plasma and brain tissue were collected immediately after the memory test to evaluate corticosterone levels and histone H3 acetylation in several brain areas. Stressed animals receiving vehicle displayed memory impairment, increased plasma corticosterone levels and markedly reduced histone H3 acetylation in prelimbic cortex and hippocampus. Such effects did not occur in stressed animals treated with TSA. The aforementioned results support the hypothesis that acute stress induced-memory impairment is related to histone deacetylation. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional role of CCCTC binding factor (CTCF) in stress-induced apoptosis

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Li Tie; Lu Luo

2007-01-01

CTCF, a nuclear transcriptional factor, is a multifunctional protein and involves regulation of growth factor- and cytokine-induced cell proliferation/differentiation. In the present study, we investigated the role of CTCF in protecting stress-induced apoptosis in various human cell types. We found that UV irradiation and hyper-osmotic stress induced human corneal epithelial (HCE) and hematopoietic myeloid cell apoptosis detected by significantly increased caspase 3 activity and decreased cell viability. The stress-induced apoptotic response in these cells requires down-regulation of CTCF at both mRNA and protein levels, suggesting that CTCF may play an important role in downstream events of stress-induced signaling pathways. Inhibition of NFκB activity prevented stress-induced down-regulation of CTCF and increased cell viability against stress-induced apoptosis. The anti-apoptotic effect of CTCF was further studied by manipulating CTCF activities in HCE and hematopoietic cells. Transient transfection of cDNAs encoding full-length human CTCF markedly suppressed stress-induced apoptosis in these cells. In contrast, knocking down of CTCF mRNA using siRNA specific to CTCF significantly promoted stress-induced apoptosis. Thus, our results reveal that CTCF is a down stream target of stress-induced signaling cascades and it plays a significant anti-apoptotic role in regulation of stress-induced cellular responses in HCE and hematopoietic myeloid cells

Acute stress may induce ovulation in women

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Cano Antonio

2010-05-01

Full Text Available Abstract Background This study aims to gather information either supporting or rejecting the hypothesis that acute stress may induce ovulation in women. The formulation of this hypothesis is based on 2 facts: 1 estrogen-primed postmenopausal or ovariectomized women display an adrenal-progesterone-induced ovulatory-like luteinizing hormone (LH surge in response to exogenous adrenocorticotropic hormone (ACTH administration; and 2 women display multiple follicular waves during an interovulatory interval, and likely during pregnancy and lactation. Thus, acute stress may induce ovulation in women displaying appropriate serum levels of estradiol and one or more follicles large enough to respond to a non-midcycle LH surge. Methods A literature search using the PubMed database was performed to identify articles up to January 2010 focusing mainly on women as well as on rats and rhesus monkeys as animal models of interaction between the hypothalamic-pituitary-adrenal (HPA and hypothalamic-pituitary-gonadal (HPG axes. Results Whereas the HPA axis exhibits positive responses in practically all phases of the ovarian cycle, acute-stress-induced release of LH is found under relatively high plasma levels of estradiol. However, there are studies suggesting that several types of acute stress may exert different effects on pituitary LH release and the steroid environment may modulate in a different way (inhibiting or stimulating the pattern of response of the HPG axis elicited by acute stressors. Conclusion Women may be induced to ovulate at any point of the menstrual cycle or even during periods of amenorrhea associated with pregnancy and lactation if exposed to an appropriate acute stressor under a right estradiol environment.

Rnd3 induces stress fibres in endothelial cells through RhoB

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Undine Gottesbühren

2012-12-01

Rnd proteins are atypical Rho family proteins that do not hydrolyse GTP and are instead regulated by expression levels and post-translational modifications. Rnd1 and Rnd3/RhoE induce loss of actin stress fibres and cell rounding in multiple cell types, whereas responses to Rnd2 are more variable. Here we report the responses of endothelial cells to Rnd proteins. Rnd3 induces a very transient decrease in stress fibres but subsequently stimulates a strong increase in stress fibres, in contrast to the reduction observed in other cell types. Rnd2 also increases stress fibres whereas Rnd1 induces a loss of stress fibres and weakening of cell–cell junctions. Rnd3 does not act through any of its known signalling partners and does not need to associate with membranes to increase stress fibres. Instead, it acts by increasing RhoB expression, which is then required for Rnd3-induced stress fibre assembly. Rnd2 also increases RhoB levels. These data indicate that the cytoskeletal response to Rnd3 expression is dependent on cell type and context, and identify regulation of RhoB as a new mechanism for Rnd proteins to affect the actin cytoskeleton.

Characterizing dose response relationships: Chronic gamma radiation in Lemna minor induces oxidative stress and altered polyploidy level.

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Van Hoeck, Arne; Horemans, Nele; Van Hees, May; Nauts, Robin; Knapen, Dries; Vandenhove, Hildegarde; Blust, Ronny

2015-12-01

The biological effects and interactions of different radiation types in plants are still far from understood. Among different radiation types, external gamma radiation treatments have been mostly studied to assess the biological impact of radiation toxicity in organisms. Upon exposure of plants to gamma radiation, ionisation events can cause, either directly or indirectly, severe biological damage to DNA and other biomolecules. However, the biological responses and oxidative stress related mechanisms under chronic radiation conditions are poorly understood in plant systems. In the following study, it was questioned if the Lemna minor growth inhibition test is a suitable approach to also assess the radiotoxicity of this freshwater plant. Therefore, L. minor plants were continuously exposed for seven days to 12 different dose rate levels covering almost six orders of magnitude starting from 80 μGy h(-1) up to 1.5 Gy h(-1). Subsequently, growth, antioxidative defence system and genomic responses of L. minor plants were evaluated. Although L. minor plants could survive the exposure treatment at environmental relevant exposure conditions, higher dose rate levels induced dose dependent growth inhibitions starting from approximately 27 mGy h(-1). A ten-percentage growth inhibition of frond area Effective Dose Rate (EDR10) was estimated at 95 ± 7 mGy h(-1), followed by 153 ± 13 mGy h(-1) and 169 ± 12 mGy h(-1) on fresh weight and frond number, respectively. Up to a dose rate of approximately 5 mGy h(-1), antioxidative enzymes and metabolites remained unaffected in plants. A significant change in catalase enzyme activity was found at 27 mGy h(-1) which was accompanied with significant increases of other antioxidative enzyme activities and shifts in ascorbate and glutathione content at higher dose rate levels, indicating an increase in oxidative stress in plants. Recent plant research hypothesized that environmental genotoxic stress conditions

Early developmental and temporal characteristics of stress-induced secretion of pituitary-adrenal hormones in prenatally stressed rat pups.

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Takahashi, L K; Kalin, N H

1991-08-30

Previous experiments revealed that 14-day-old prenatally stressed rats have significantly elevated concentrations of plasma adrenocorticotrophic hormone (ACTH) and corticosterone suggesting these animals have an overactive hypothalamic-pituitary-adrenal (HPA) system. In these studies, however, stress-induced hormone levels were determined only immediately after exposure to an acute stressor. Therefore, in the current study, we examined in postnatal days 7, 14 and 21 prenatally stressed rats the stress-induced time course of this pituitary-adrenal hormone elevation. Plasma ACTH and corticosterone were measured in the basal state and at 0.0, 0.5, 1.0, 2.0 and 4.0 h after a 10-min exposure period to foot shocks administered in the context of social isolation. Results indicated that at all 3 ages, plasma ACTH in prenatally stressed rats was significantly elevated. Corticosterone concentrations were also significantly higher in prenatally stressed than in control rats, especially in day 14 rats. Analysis of stress-induced hormone fluctuations over time indicated that by 14 days of age, both prenatally stressed than in control and control rats had significant increases in plasma ACTH and corticosterone after exposure to stress. Furthermore, although prenatally stressed rats had significantly higher pituitary-adrenal hormone concentrations than control animals, the post-stress temporal patterns of decline in ACTH and corticosterone levels were similar between groups. Results suggest that throughout the preweaning period, prenatal stress produces an HPA system that functions in a manner similar to that of controls but at an increased level.

5,7-Dimethoxycoumarin prevents chronic mild stress induced depression in rats through increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels

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Wei Yang

2018-02-01

Full Text Available The current study was aimed to investigate the role of 5,7-dimethoxycoumarin in the prevention of chronic mild stress induced depression in rats. The chronic mild stress rat model was prepared using the known protocols. The results from open-field test showed that rats in the chronic mild stress group scored very low in terms of crossings and rearings than those of the normal rats. However, pre-treatment of the rats with 10 mg/kg doses of 5,7-dimethoxycoumarin prevented decline in the locomotor activity by chronic mild stress. The level of monoamine oxidase-A in the chronic mild stress rat hippocampus was markedly higher. Chronic mild stress induced increase in the monoamine oxidase-A level was inhibited by pre-treatment with 10 mg/kg doses of 5,7-dimethoxycoumarin in the rats. Chronic mild stress caused a marked increase in the level of caspase-3 mRNA and proteins in rat hippocampus tissues. The increased level of caspase-3 mRNA and protein level was inhibited by treatment of rats with 5,7-dimethoxycoumarin (10 mg/kg. 5,7-Dimethoxycoumarin administration into the rats caused a marked increase in the levels of heat shock protein-70 mRNA and protein. The levels of heat shock protein-70 were markedly lower both in normal and chronic mild stress groups of rats compared to the 5,7-dimethoxycoumarin treated groups. Thus 5,7-dimethoxycoumarin prevented the chronic mild stress induced depression in rats through an increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels.

5,7-Dimethoxycoumarin prevents chronic mild stress induced depression in rats through increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels.

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Yang, Wei; Wang, Huanlin

2018-02-01

The current study was aimed to investigate the role of 5,7-dimethoxycoumarin in the prevention of chronic mild stress induced depression in rats. The chronic mild stress rat model was prepared using the known protocols. The results from open-field test showed that rats in the chronic mild stress group scored very low in terms of crossings and rearings than those of the normal rats. However, pre-treatment of the rats with 10 mg/kg doses of 5,7-dimethoxycoumarin prevented decline in the locomotor activity by chronic mild stress. The level of monoamine oxidase-A in the chronic mild stress rat hippocampus was markedly higher. Chronic mild stress induced increase in the monoamine oxidase-A level was inhibited by pre-treatment with 10 mg/kg doses of 5,7-dimethoxycoumarin in the rats. Chronic mild stress caused a marked increase in the level of caspase-3 mRNA and proteins in rat hippocampus tissues. The increased level of caspase-3 mRNA and protein level was inhibited by treatment of rats with 5,7-dimethoxycoumarin (10 mg/kg). 5,7-Dimethoxycoumarin administration into the rats caused a marked increase in the levels of heat shock protein-70 mRNA and protein. The levels of heat shock protein-70 were markedly lower both in normal and chronic mild stress groups of rats compared to the 5,7-dimethoxycoumarin treated groups. Thus 5,7-dimethoxycoumarin prevented the chronic mild stress induced depression in rats through an increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels.

Corticosterone levels and behavioral changes induced by simultaneous exposure to chronic social stress and enriched environments in NMRI male mice.

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Mesa-Gresa, Patricia; Ramos-Campos, Marta; Redolat, Rosa

2016-05-01

Environmental enrichment (EE) is an experimental model which is believed to counteract some of the effects induced by stressors, although few studies have exposed rodents simultaneously to EE and stress. Our aim was to compare the short- and long-term effects of different housing conditions in mice submitted to chronic stress. 128 NMRI male mice arrived at our laboratory on postnatal day (PND) 21. During Phase I (PND 28), animals were randomly assigned to four experimental conditions: 1) EE+STRESS: mice housed in EE and submitted to social stress (n=32); 2) EE+NO STRESS: mice housed in EE without stress (n=32); 3) SE+STRESS: mice maintained in standard conditions (SE) and submitted to social stress (n=32); and 4) SE+NO STRESS (n=32). At the end of Phase I (PND 77), one cohort of 32 animals was used for behavioral assessment whereas another cohort of 32 was sacrificed for corticosterone analysis. Results indicated that EE animals showed less body weight, higher water and food intake, diminished anxiety response and decreased motor and exploratory behavior than SE mice. Mice exposed to stress gained less body weight, showed higher food and fluid intake and displayed decreased exploratory behavior than non-stressed mice. Furthermore, EE+STRESS group displayed significantly higher corticosterone levels than EE+NO STRESS group whereas EE+NO STRESS group showed lower levels than SE+NO STRESS. On PND 83, Phase II of the study began. Animals (n=96) were assigned to two different housing conditions: EE (n=48) and SE (n=48). On PND 112, corticosterone analysis (n=32) and behavioral study (n=64) were done. The factor "Housing Phase II" reached statistical significance. Results indicated that EE animals showed lower body weight and higher fluid intake than SE group, as well as decreased anxiety. No clear effects on motor and exploratory behavior or learning were observed. When long-term effects were analyzed, results indicated that "Initial Housing" condition was significant

Stress-induced alterations of left-right electrodermal activity coupling indexed by pointwise transinformation.

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Světlák, M; Bob, P; Roman, R; Ježek, S; Damborská, A; Chládek, J; Shaw, D J; Kukleta, M

2013-01-01

In this study, we tested the hypothesis that experimental stress induces a specific change of left-right electrodermal activity (EDA) coupling pattern, as indexed by pointwise transinformation (PTI). Further, we hypothesized that this change is associated with scores on psychometric measures of the chronic stress-related psychopathology. Ninety-nine university students underwent bilateral measurement of EDA during rest and stress-inducing Stroop test and completed a battery of self-report measures of chronic stress-related psychopathology. A significant decrease in the mean PTI value was the prevalent response to the stress conditions. No association between chronic stress and PTI was found. Raw scores of psychometric measures of stress-related psychopathology had no effect on either the resting levels of PTI or the amount of stress-induced PTI change. In summary, acute stress alters the level of coupling pattern of cortico-autonomic influences on the left and right sympathetic pathways to the palmar sweat glands. Different results obtained using the PTI, EDA laterality coefficient, and skin conductance level also show that the PTI algorithm represents a new analytical approach to EDA asymmetry description.

The obesity-induced transcriptional regulator TRIP-Br2 mediates visceral fat endoplasmic reticulum stress-induced inflammation.

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Qiang, Guifen; Kong, Hyerim Whang; Fang, Difeng; McCann, Maximilian; Yang, Xiuying; Du, Guanhua; Blüher, Matthias; Zhu, Jinfang; Liew, Chong Wee

2016-04-25

The intimate link between location of fat accumulation and metabolic disease risk and depot-specific differences is well established, but how these differences between depots are regulated at the molecular level remains largely unclear. Here we show that TRIP-Br2 mediates endoplasmic reticulum (ER) stress-induced inflammatory responses in visceral fat. Using in vitro, ex vivo and in vivo approaches, we demonstrate that obesity-induced circulating factors upregulate TRIP-Br2 specifically in visceral fat via the ER stress pathway. We find that ablation of TRIP-Br2 ameliorates both chemical and physiological ER stress-induced inflammatory and acute phase response in adipocytes, leading to lower circulating levels of inflammatory cytokines. Using promoter assays, as well as molecular and pharmacological experiments, we show that the transcription factor GATA3 is responsible for the ER stress-induced TRIP-Br2 expression in visceral fat. Taken together, our study identifies molecular regulators of inflammatory response in visceral fat that-given that these pathways are conserved in humans-might serve as potential therapeutic targets in obesity.

Oxidative stress in MeHg-induced neurotoxicity

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Farina, Marcelo, E-mail: farina@ccb.ufsc.br [Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC (Brazil); Aschner, Michael [Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (United States); Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN (United States); Rocha, Joao B.T., E-mail: jbtrocha@yahoo.com.br [Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil)

2011-11-15

Methylmercury (MeHg) is an environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. Although the molecular mechanisms mediating MeHg-induced neurotoxicity are not completely understood, several lines of evidence indicate that oxidative stress represents a critical event related to the neurotoxic effects elicited by this toxicant. The objective of this review is to summarize and discuss data from experimental and epidemiological studies that have been important in clarifying the molecular events which mediate MeHg-induced oxidative damage and, consequently, toxicity. Although unanswered questions remain, the electrophilic properties of MeHg and its ability to oxidize thiols have been reported to play decisive roles to the oxidative consequences observed after MeHg exposure. However, a close examination of the relationship between low levels of MeHg necessary to induce oxidative stress and the high amounts of sulfhydryl-containing antioxidants in mammalian cells (e.g., glutathione) have led to the hypothesis that nucleophilic groups with extremely high affinities for MeHg (e.g., selenols) might represent primary targets in MeHg-induced oxidative stress. Indeed, the inhibition of antioxidant selenoproteins during MeHg poisoning in experimental animals has corroborated this hypothesis. The levels of different reactive species (superoxide anion, hydrogen peroxide and nitric oxide) have been reported to be increased in MeHg-exposed systems, and the mechanisms concerning these increments seem to involve a complex sequence of cascading molecular events, such as mitochondrial dysfunction, excitotoxicity, intracellular calcium dyshomeostasis and decreased antioxidant capacity. This review also discusses potential therapeutic strategies to counteract MeHg-induced toxicity and oxidative stress, emphasizing the use of organic selenocompounds, which generally present higher affinity for MeHg when compared to the classically

Acute stress induces hyperacusis in women with high levels of emotional exhaustion.

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Dan Hasson

Full Text Available BACKGROUND: Hearing problems is one of the top ten public health disorders in the general population and there is a well-established relationship between stress and hearing problems. The aim of the present study was to explore if an acute stress will increase auditory sensitivity (hyperacusis in individuals with high levels of emotional exhaustion (EE. METHODS: Hyperacusis was assessed using uncomfortable loudness levels (ULL in 348 individuals (140 men; 208 women; age 23-71 years. Multivariate analyses (ordered logistic regression, were used to calculate odds ratios, including interacting or confounding effects of age, gender, ear wax and hearing loss (PTA. Two-way ANCOVAs were used to assess possible differences in mean ULLs between EE groups pre- and post-acute stress task (a combination of cold pressor, emotional Stroop and Social stress/video recording. RESULTS: There were no baseline differences in mean ULLs between the three EE groups (one-way ANOVA. However, after the acute stress exposure there were significant differences in ULL means between the EE-groups in women. Post-hoc analyses showed that the differences in mean ULLs were between those with high vs. low EE (range 5.5-6.5 dB. Similar results were found for frequencies 0.5 and 1 kHz. The results demonstrate that women with high EE-levels display hyperacusis after an acute stress task. The odds of having hyperacusis were 2.5 (2 kHz, right ear; left ns and 2.2 (4 kHz, right ear; left ns times higher among those with high EE compared to those with low levels. All these results are adjusted for age, hearing loss and ear wax. CONCLUSION: Women with high levels of emotional exhaustion become more sensitive to sound after an acute stress task. This novel finding highlights the importance of including emotional exhaustion in the diagnosis and treatment of hearing problems.

Acute stress induces hyperacusis in women with high levels of emotional exhaustion.

Science.gov (United States)

Hasson, Dan; Theorell, Töres; Bergquist, Jonas; Canlon, Barbara

2013-01-01

Hearing problems is one of the top ten public health disorders in the general population and there is a well-established relationship between stress and hearing problems. The aim of the present study was to explore if an acute stress will increase auditory sensitivity (hyperacusis) in individuals with high levels of emotional exhaustion (EE). Hyperacusis was assessed using uncomfortable loudness levels (ULL) in 348 individuals (140 men; 208 women; age 23-71 years). Multivariate analyses (ordered logistic regression), were used to calculate odds ratios, including interacting or confounding effects of age, gender, ear wax and hearing loss (PTA). Two-way ANCOVAs were used to assess possible differences in mean ULLs between EE groups pre- and post-acute stress task (a combination of cold pressor, emotional Stroop and Social stress/video recording). There were no baseline differences in mean ULLs between the three EE groups (one-way ANOVA). However, after the acute stress exposure there were significant differences in ULL means between the EE-groups in women. Post-hoc analyses showed that the differences in mean ULLs were between those with high vs. low EE (range 5.5-6.5 dB). Similar results were found for frequencies 0.5 and 1 kHz. The results demonstrate that women with high EE-levels display hyperacusis after an acute stress task. The odds of having hyperacusis were 2.5 (2 kHz, right ear; left ns) and 2.2 (4 kHz, right ear; left ns) times higher among those with high EE compared to those with low levels. All these results are adjusted for age, hearing loss and ear wax. Women with high levels of emotional exhaustion become more sensitive to sound after an acute stress task. This novel finding highlights the importance of including emotional exhaustion in the diagnosis and treatment of hearing problems.

Characterizing dose response relationships: Chronic gamma radiation in Lemna minor induces oxidative stress and altered polyploidy level

International Nuclear Information System (INIS)

Van Hoeck, Arne; Horemans, Nele; Van Hees, May; Nauts, Robin; Knapen, Dries; Vandenhove, Hildegarde; Blust, Ronny

2015-01-01

The biological effects and interactions of different radiation types in plants are still far from understood. Among different radiation types, external gamma radiation treatments have been mostly studied to assess the biological impact of radiation toxicity in organisms. Upon exposure of plants to gamma radiation, ionisation events can cause, either directly or indirectly, severe biological damage to DNA and other biomolecules. However, the biological responses and oxidative stress related mechanisms under chronic radiation conditions are poorly understood in plant systems. In the following study, it was questioned if the Lemna minor growth inhibition test is a suitable approach to also assess the radiotoxicity of this freshwater plant. Therefore, L. minor plants were continuously exposed for seven days to 12 different dose rate levels covering almost six orders of magnitude starting from 80 μGy h"−"1 up to 1.5 Gy h"−"1. Subsequently, growth, antioxidative defence system and genomic responses of L. minor plants were evaluated. Although L. minor plants could survive the exposure treatment at environmental relevant exposure conditions, higher dose rate levels induced dose dependent growth inhibitions starting from approximately 27 mGy h"−"1. A ten-percentage growth inhibition of frond area Effective Dose Rate (EDR_1_0) was estimated at 95 ± 7 mGy h"−"1, followed by 153 ± 13 mGy h"−"1 and 169 ± 12 mGy h"−"1 on fresh weight and frond number, respectively. Up to a dose rate of approximately 5 mGy h"−"1, antioxidative enzymes and metabolites remained unaffected in plants. A significant change in catalase enzyme activity was found at 27 mGy h"−"1 which was accompanied with significant increases of other antioxidative enzyme activities and shifts in ascorbate and glutathione content at higher dose rate levels, indicating an increase in oxidative stress in plants. Recent plant research hypothesized that environmental genotoxic

Hydroxyurea-Induced Replication Stress

Directory of Open Access Journals (Sweden)

Kenza Lahkim Bennani-Belhaj

2010-01-01

Full Text Available Bloom's syndrome (BS displays one of the strongest known correlations between chromosomal instability and a high risk of cancer at an early age. BS cells combine a reduced average fork velocity with constitutive endogenous replication stress. However, the response of BS cells to replication stress induced by hydroxyurea (HU, which strongly slows the progression of replication forks, remains unclear due to publication of conflicting results. Using two different cellular models of BS, we showed that BLM deficiency is not associated with sensitivity to HU, in terms of clonogenic survival, DSB generation, and SCE induction. We suggest that surviving BLM-deficient cells are selected on the basis of their ability to deal with an endogenous replication stress induced by replication fork slowing, resulting in insensitivity to HU-induced replication stress.

Low-level lasers affect Escherichia coli cultures in hyperosmotic stress

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Pinheiro, C. C.; Barboza, L. L.; Paoli, F.; Fonseca, A. S.

2015-08-01

Physical characteristics and practical properties have made lasers of interest for biomedical applications. Effects of low-level lasers on biological tissues could occur or be measurable depending on cell type, presence of a pathologic process or whether the cells are in an adverse environment. The objective of this work was to evaluate the survival, morphology and filamentation of E. coli cells proficient and deficient in the repair of oxidative DNA lesions exposed low-level red and infrared lasers submitted to hyperosmotic stress. Wild type and endonuclease VIII deficient E. coli cells in exponential and stationary growth phase were exposed to red and infrared lasers and submitted to hyperosmotic stress. Cell viability, filamentation phenotype and cell morphology were evaluated. Cell viability was not significantly altered but previous laser exposure induced filamentation and an altered area of stressed cells depending on physiologic condition and presence of the DNA repair. Results suggest that previous exposure to low-level red and infrared lasers could not affect viability but induced morphologic changes in cells submitted to hyperosmotic stress depending on physiologic conditions and repair of oxidative DNA lesions.

Despite higher glucocorticoid levels and stress responses in female rats, both sexes exhibit similar stress-induced changes in hippocampal neurogenesis

NARCIS (Netherlands)

Hulshof, Henriette J.; Novati, Arianna; Luiten, Paul G. M.; den Boer, Johan A.; Meerlo, Peter

2012-01-01

Sex differences in stress reactivity may be one of the factors underlying the increased sensitivity for the development of psychopathologies in women. Particularly, an increased hypothalamic-pituitary-adrenal (HPA) axis reactivity in females may exacerbate stress-induced changes in neuronal

Differential effects of stress-induced cortisol responses on recollection and familiarity-based recognition memory.

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McCullough, Andrew M; Ritchey, Maureen; Ranganath, Charan; Yonelinas, Andrew

2015-09-01

Stress-induced changes in cortisol can impact memory in various ways. However, the precise relationship between cortisol and recognition memory is still poorly understood. For instance, there is reason to believe that stress could differentially affect recollection-based memory, which depends on the hippocampus, and familiarity-based recognition, which can be supported by neocortical areas alone. Accordingly, in the current study we examined the effects of stress-related changes in cortisol on the processes underlying recognition memory. Stress was induced with a cold-pressor test after incidental encoding of emotional and neutral pictures, and recollection and familiarity-based recognition memory were measured one day later. The relationship between stress-induced cortisol responses and recollection was non-monotonic, such that subjects with moderate stress-related increases in cortisol had the highest levels of recollection. In contrast, stress-related cortisol responses were linearly related to increases in familiarity. In addition, measures of cortisol taken at the onset of the experiment showed that individuals with higher levels of pre-learning cortisol had lower levels of both recollection and familiarity. The results are consistent with the proposition that hippocampal-dependent memory processes such as recollection function optimally under moderate levels of stress, whereas more cortically-based processes such as familiarity are enhanced even with higher levels of stress. These results indicate that whether post-encoding stress improves or disrupts recognition memory depends on the specific memory process examined as well as the magnitude of the stress-induced cortisol response. Copyright © 2015 Elsevier Inc. All rights reserved.

Identification of 30 protein species involved in replicative senescence and stress-induced premature senescence

DEFF Research Database (Denmark)

Dierick, Jean François; Kalume, Dário E; Wenders, Frédéric

2002-01-01

Exposure of human proliferative cells to subcytotoxic stress triggers stress-induced premature senescence (SIPS) which is characterized by many biomarkers of replicative senescence. Proteomic comparison of replicative senescence and stress-induced premature senescence indicates that, at the level...

Effects of Uric Acid on Exercise-induced Oxidative Stress

OpenAIRE

平井, 富弘

2001-01-01

We studied effects of uric acid on exercise― induced oxidative stress in humans based on a hypothesis that uric acid acts as an antioxidant to prevent from exercise―induced oxidative stress. Relation between uric acid level in plasma and increase of thiobarbituric acid reactive substance (TBARS)after the cycle ergometer exercise was examined. Thiobarbituricacid reactive substance in plasma increased after the ergometer exercise. High uric acid in plasma did not result in low increase of TBARS...

Stress-induced hyperthermia in translational stress research

NARCIS (Netherlands)

Vinkers, C.H.; Penning, R.; Ebbens, M.M.; Helhammer, J.; Verster, J.C.; Kalkman, C.J.; Olivier, B.

2010-01-01

The stress-induced hyperthermia (SIH) response is the transient change in body temperature in response to acute stress. This body temperature response is part of the autonomic stress response which also results in tachycardia and an increased blood pressure. So far, a SIH response has been found in

Glucocorticoids mediate stress-induced impairment of retrieval of stimulus-response memory.

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Atsak, Piray; Guenzel, Friederike M; Kantar-Gok, Deniz; Zalachoras, Ioannis; Yargicoglu, Piraye; Meijer, Onno C; Quirarte, Gina L; Wolf, Oliver T; Schwabe, Lars; Roozendaal, Benno

2016-05-01

Acute stress and elevated glucocorticoid hormone levels are well known to impair the retrieval of hippocampus-dependent 'declarative' memory. Recent findings suggest that stress might also impair the retrieval of non-hippocampal memories. In particular, stress shortly before retention testing was shown to impair the retrieval of striatal stimulus-response associations in humans. However, the mechanism underlying this stress-induced retrieval impairment of non-hippocampal stimulus-response memory remains elusive. In the present study, we investigated whether an acute elevation in glucocorticoid levels mediates the impairing effects of stress on retrieval of stimulus-response memory. Male Sprague-Dawley rats were trained on a stimulus-response task in an eight-arm radial maze until they learned to associate a stimulus, i.e., cue, with a food reward in one of the arms. Twenty-four hours after successful acquisition, they received a systemic injection of vehicle, corticosterone (1mg/kg), the corticosterone-synthesis inhibitor metyrapone (35mg/kg) or were left untreated 1h before retention testing. We found that the corticosterone injection impaired the retrieval of stimulus-response memory. We further found that the systemic injection procedure per se was stressful as the vehicle administration also increased plasma corticosterone levels and impaired the retrieval of stimulus-response memory. However, memory retrieval was not impaired when rats were tested 2min after the systemic vehicle injection, before any stress-induced elevation in corticosterone levels had occurred. Moreover, metyrapone treatment blocked the effect of injection stress on both plasma corticosterone levels and memory retrieval impairment, indicating that the endogenous corticosterone response mediates the stress-induced memory retrieval impairment. None of the treatments affected rats' locomotor activity or motivation to search for the food reward within the maze. These findings show that stress

Biologically Synthesized Gold Nanoparticles Ameliorate Cold and Heat Stress-Induced Oxidative Stress in Escherichia coli

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Xi-Feng Zhang

2016-06-01

Full Text Available Due to their unique physical, chemical, and optical properties, gold nanoparticles (AuNPs have recently attracted much interest in the field of nanomedicine, especially in the areas of cancer diagnosis and photothermal therapy. Because of the enormous potential of these nanoparticles, various physical, chemical, and biological methods have been adopted for their synthesis. Synthetic antioxidants are dangerous to human health. Thus, the search for effective, nontoxic natural compounds with effective antioxidative properties is essential. Although AuNPs have been studied for use in various biological applications, exploration of AuNPs as antioxidants capable of inhibiting oxidative stress induced by heat and cold stress is still warranted. Therefore, one goal of our study was to produce biocompatible AuNPs using biological methods that are simple, nontoxic, biocompatible, and environmentally friendly. Next, we aimed to assess the antioxidative effect of AuNPs against oxidative stress induced by cold and heat in Escherichia coli, which is a suitable model for stress responses involving AuNPs. The response of aerobically grown E. coli cells to cold and heat stress was found to be similar to the oxidative stress response. Upon exposure to cold and heat stress, the viability and metabolic activity of E. coli was significantly reduced compared to the control. In addition, levels of reactive oxygen species (ROS and malondialdehyde (MDA and leakage of proteins and sugars were significantly elevated, and the levels of lactate dehydrogenase activity (LDH and adenosine triphosphate (ATP significantly lowered compared to in the control. Concomitantly, AuNPs ameliorated cold and heat-induced oxidative stress responses by increasing the expression of antioxidants, including glutathione (GSH, glutathione S-transferase (GST, super oxide dismutase (SOD, and catalase (CAT. These consistent physiology and biochemical data suggest that AuNPs can ameliorate cold and

Similar cold stress induces sex-specific neuroendocrine and working memory responses.

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Solianik, Rima; Skurvydas, Albertas; Urboniene, Daiva; Eimantas, Nerijus; Daniuseviciute, Laura; Brazaitis, Marius

2015-01-01

Men have higher cold-induced neuroendocrine response than women; nevertheless, it is not known whether a different stress hormone rise elicits different effects on cognition during whole body cooling. The objective was to compare the effect of cold-induced neuroendocrine responses on the performance of working memory sensitive tasks between men and women. The cold stress continued until rectal temperature reached 35.5 degree C or for a maximum of 170 min. Working memory performance and stress hormone concentrations were monitored. During cold stress, body temperature variables dropped in all subjects (P < 0.001) and did not differ between sexes. Cold stress raised plasma epinephrine and serum cortisol levels only in men (P < 0.05). Cold stress adversely affected memory performance in men but not in women (P < 0.05). The present study indicated that similar moderate cold stress in men and women induces sex-specific neuroendocrine and working memory responses.

The Yeast Environmental Stress Response Regulates Mutagenesis Induced by Proteotoxic Stress

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Shor, Erika; Fox, Catherine A.; Broach, James R.

2013-01-01

Conditions of chronic stress are associated with genetic instability in many organisms, but the roles of stress responses in mutagenesis have so far been elucidated only in bacteria. Here, we present data demonstrating that the environmental stress response (ESR) in yeast functions in mutagenesis induced by proteotoxic stress. We show that the drug canavanine causes proteotoxic stress, activates the ESR, and induces mutagenesis at several loci in an ESR-dependent manner. Canavanine-induced mutagenesis also involves translesion DNA polymerases Rev1 and Polζ and non-homologous end joining factor Ku. Furthermore, under conditions of chronic sub-lethal canavanine stress, deletions of Rev1, Polζ, and Ku-encoding genes exhibit genetic interactions with ESR mutants indicative of ESR regulating these mutagenic DNA repair processes. Analyses of mutagenesis induced by several different stresses showed that the ESR specifically modulates mutagenesis induced by proteotoxic stress. Together, these results document the first known example of an involvement of a eukaryotic stress response pathway in mutagenesis and have important implications for mechanisms of evolution, carcinogenesis, and emergence of drug-resistant pathogens and chemotherapy-resistant tumors. PMID:23935537

[Prediabetes as a riskmarker for stress-induced hyperglycemia in critically ill adults].

Science.gov (United States)

García-Gallegos, Diego Jesús; Luis-López, Eliseo

2017-01-01

It is not known if patients with prediabetes, a subgroup of non-diabetic patients that usually present hyperinsulinemia, have higher risk to present stress-induced hyperglycemia. The objective was to determine if prediabetes is a risk marker to present stress-induced hyperglycemia. Analytic, observational, prospective cohort study of non-diabetic critically ill patients of a third level hospital. We determined plasmatic glucose and glycated hemoglobin (HbA1c) at admission to diagnose stress-induced hyperglycemia (glucose ≥ 140 mg/dL) and prediabetes (HbA1c between 5.7 and 6.4%), respectively. We examined the proportion of non-prediabetic and prediabetic patients that developed stress hyperglycemia with contingence tables and Fisher's exact test for nominal scales. Of 73 patients studied, we found a proportion of stress-induced hyperglycemia in 6.6% in those without prediabetes and 61.1% in those with prediabetes. The Fisher's exact test value was 22.46 (p Prediabetes is a risk marker for stress-induced hyperglycemia in critically ill adults.

Comparison of stress-induced changes in adults and pups: is aldosterone the main adrenocortical stress hormone during the perinatal period in rats?

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János Varga

Full Text Available Positive developmental impact of low stress-induced glucocorticoid levels in early development has been recognized for a long time, while possible involvement of mineralocorticoids in the stress response during the perinatal period has been neglected. The present study aimed at verifying the hypothesis that balance between stress-induced glucocorticoid and mineralocorticoid levels is changing during postnatal development. Hormone responses to two different stressors (insulin-induced hypoglycaemia and immune challenge induced by bacterial lipopolysaccharid measured in 10-day-old rats were compared to those in adults. In pups corticosterone responses to both stressors were significantly lower than in adults, which corresponded well with the stress hyporesponsive period. Importantly, stress-induced elevations in aldosterone concentration were significantly higher in pups compared both to corticosterone elevations and to those in adulthood with comparable adrenocorticotropin concentrations in the two age groups. Greater importance of mineralocorticoids compared to glucocorticoids in postnatal period is further supported by changes in gene expression and protein levels of gluco- (GR and mineralocorticoid receptors (MR and selected enzymes measured by quantitative PCR and immunohystochemistry in the hypothalamus, hippocampus, prefrontal cortex, liver and kidney. Gene expression of 11beta-hydroxysteroid dehydrogenase 2 (11β-HSD2, an enzyme enabling preferential effects of aldosterone on mineralocorticoid receptors, was higher in 10-day-old pups compared to adult animals. On the contrary, the expression and protein levels of GR, MR and 11β-HSD1 were decreased. Presented results clearly show higher stress-induced release of aldosterone in pups compared to adults and strongly suggest greater importance of mineralocorticoids compared to glucocorticoids in stress during the postnatal period.

ATF4 is involved in the regulation of simulated microgravity induced integrated stress response

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Li, Yingxian; Li, Qi; Wang, Xiaogang; Sun, Qiao; Wan, Yumin; Li, Yinghui; Bai, Yanqiang

Objective: Many important metabolic and signaling pathways have been identified as being affected by microgravity, thereby altering cellular functions such as proliferation, differentiation, maturation and cell survival. It has been demonstrated that microgravity could induce all kinds of stress response such as endoplasmic reticulum stress and oxidative stress et al. ATF4 belongs to the ATF/CREB family of basic region leucine zipper transcription factors. ATF4 is induced by stress signals including anoxia/hypoxia, ER stress, amino acid deprivation and oxidative stress. ATF4 regulates the expression of genes involved in oxidative stress, amino acid synthesis, differentiation, metastasis and angiogenesis. The aim of this study was to examine the changes of ATF4 under microgravity, and to investigate the role of ATF4 in microgravity induced stress. MethodsMEF cells were cultured in clinostat to simulate microgravity. Reverse transcription polymerase chain reaction (RT-PCR) and western blotting were used to examine mRNA and protein levels of ATF4 expression under simulated microgravity in MEF cells. ROS levels were measured with the use of the fluorescent signal H2DCF-DA. GFP-XBP1 stably transfected cell lines was used to detect the extent of ER stress under microgravity by the intensity of GFP. Dual luciferase reporter assay was used to detect the activity of ATF4. Co-immunoprecipitation was performed to analyze protein interaction. Results: ATF4 protein levels in MEF cells increased under simulated microgravity. However, ATF4 mRNA levels were consistent. XBP1 splicing can be induced due to ER stress caused by simulated microgravity. At the same time, ROS levels were also increased. Increased ATF4 could promote the expression of CHOP, which is responsible for cell apoptosis. ATF4 also play an important role in cellular anti-oxidant stress. In ATF4 -/-MEF cells, the ROS levels after H2O2 treatment were obviously higher than that of wild type cells. HDAC4 was

Trauma- and Stress-Induced Response in Veterans with Alcohol Dependence and Comorbid Post-Traumatic Stress Disorder.

Science.gov (United States)

Ralevski, Elizabeth; Southwick, Steven; Jackson, Eric; Jane, Jane Serrita; Russo, Melanie; Petrakis, Ismene

2016-08-01

Alcohol dependence (AD) and post-traumatic stress disorder (PTSD) commonly co-occur, and the co-occurrence is associated with worse prognosis than either disorder absent the other. Craving is an important construct related to relapse, but the relationship between PTSD symptoms, craving, and relapse is not well understood. Several studies have documented the relationship between stress and craving in individuals without comorbid PTSD, but the effect on those with comorbid PTSD is not well known. A small literature suggests that trauma imagery affects craving. This is the first study to explore the effects of trauma-induced and stress-induced scripts on alcohol craving, affect, cardiovascular, and cortisol responses in the laboratory. Veterans (n = 25) diagnosed with AD and PTSD who were participating in a randomized clinical treatment trial took part in this laboratory study. Baseline assessment included PTSD symptoms and drinking quantity and frequency over 3 months before study initiation. In the laboratory, participants were exposed to neutral, stressful, and trauma scripts randomly assigned. Main outcomes included craving, anxiety, mood states, salivary cortisol, and cardiovascular responses. Both stress and trauma scripts produced greater increases in craving, negative affect, and cardiovascular reactivity, compared to neutral scripts. Trauma scripts produced significantly stronger craving for alcohol and greater cardiovascular reactivity than stress scripts. Also, trauma-induced but not stress-induced craving was positively correlated with baseline levels of drinking. There were no changes in cortisol levels from pre- to postexposure of any scripts. The results highlight that trauma cues are more salient in inducing alcohol craving than stress cues and higher reactivity is related to more baseline drinking. This finding is consistent with clinical observations that show an association between PTSD symptoms and alcohol relapse. It also underscores the

Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells

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Wang, Xin; Xu, Mei; Frank, Jacqueline A. [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Ke, Zun-ji [Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai, China 201203 (China); Luo, Jia, E-mail: jialuo888@uky.edu [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai, China 201203 (China)

2017-04-01

Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. - Highlights: • Thiamine deficiency (TD) causes death of human neurons in culture. • TD induces both endoplasmic reticulum (ER) stress and oxidative stress. • Alleviating ER stress and oxidative stress reduces TD-induced

Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells

International Nuclear Information System (INIS)

Wang, Xin; Xu, Mei; Frank, Jacqueline A.; Ke, Zun-ji; Luo, Jia

2017-01-01

Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. - Highlights: • Thiamine deficiency (TD) causes death of human neurons in culture. • TD induces both endoplasmic reticulum (ER) stress and oxidative stress. • Alleviating ER stress and oxidative stress reduces TD-induced

Stress induced reorientation of vanadium hydride

International Nuclear Information System (INIS)

Beardsley, M.B.

1977-10-01

The critical stress for the reorientation of vanadium hydride was determined for the temperature range 180 0 to 280 0 K using flat tensile samples containing 50 to 500 ppM hydrogen by weight. The critical stress was observed to vary from a half to a third of the macroscopic yield stress of pure vanadium over the temperature range. The vanadium hydride could not be stress induced to precipitate above its stress-free precipitation temperature by uniaxial tensile stresses or triaxial tensile stresses induced by a notch

Petroselinum Crispum is Effective in Reducing Stress-Induced Gastric Oxidative Damage

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Ayşin Akıncı

2017-02-01

Full Text Available Background: Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. Aims: In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. Study Design: Animal experimentation. Methods: Forty male Wistar albino rats were divided into five groups: control, stress, stress + standard diet, stress + parsley-added diet and stress + lansoprazole (LPZ groups. Subjects were exposed to 72 hours of fasting and later immobilized and exposed to the cold at +4 degrees for 8 hours to create a severe stress condition. Samples from the animals’ stomachs were arranged for microscopic and biochemical examinations. Results: Gastric mucosal injury was obvious in rats exposed to stress. The histopathologic damage score of the stress group (7.00±0.57 was higher than that of the control group (1.50±0.22 (p<0.05. Significant differences in histopathologic damage score were found between the stress and stress + parsley-added diet groups (p<0.05, the stress and stress + standard diet groups (p<0.05, and the stress and stress + LPZ groups (p<0.05. The mean tissue malondialdehyde levels of the stress + parsley-added group and the stress + LPZ group were lower than that of the stress group (p<0.05. Parsley supported the cellular antioxidant system by increasing the mean tissue glutathione level (53.31±9.50 and superoxide dismutase (15.18±1.05 and catalase (16.68±2.29 activities. Conclusion: Oral administration of parsley is effective in reducing stress-induced gastric injury by supporting the cellular antioxidant defence system

Role of serotonin in the intestinal mucosal epithelium barrier in weaning mice undergoing stress-induced diarrhea.

Science.gov (United States)

Dong, Yulan; Wang, Zixu; Qin, Zhuoming; Cao, Jing; Chen, Yaoxing

2018-02-01

Stress-induced diarrhea is a frequent and challenging threat to humans and domestic animals. Serotonin (5-HT) has been shown to be involved in the pathological process of stress-induced diarrhea. However, the role of 5-HT in stress-induced diarrhea remains unclear. A stress-induced diarrhea model was established in 21-day-old ICR weaning mice through an intragastric administration of 0.25 mL of 0.4 g/mL folium sennae and restraint of the hind legs with adhesive tape for 4 h to determine whether 5-HT regulates the mucosal barrier to cause diarrhea. Mice with decreased levels of 5-HT were pretreated with an intraperitoneal injection of 300 mg/kg p-chlorophenylalanine (PCPA), a 5-HT synthesis inhibitor. After 5 days of treatment, the stress level, body weight and intestinal mucosal morphology indexes were measured. Compared to the controls, the mice with stress-induced diarrhea displayed a stress reaction, with increased corticosterone levels, as well as increased 5-HT-positive cells. However, the mice with stress-induced diarrhea exhibited decreased body weights, villus height to crypt depth ratios (V/C), and Occludin and Claudin1 expression. The PCPA injection reversed these effects in mice with different degrees of stress-induced diarrhea. Based on these findings, inhibition of 5-HT synthesis relieved the stress response and improved the health of the intestinal tract, including both the intestinal absorption capacity, as determined by the villus height and crypt depth, and the mucosal barrier function, as determined by the tight junction proteins of epithelial cell.

Does student debt affect dental students' and dentists' stress levels?

Science.gov (United States)

Boyles, J D; Ahmed, B

2017-10-27

Introduction Many studies have shown financial worries and debt to induce stress in individuals, this combined with the existing stress of being a dentist raises the question of how student debt affects students' and dentists' stress levels.Objectives Determine whether student debt has had any noticeable effect on student stress levels; investigate whether student debt has any effect on dentists' career choice; investigate whether the increase in tuition fees has influenced the number of applicants to study dentistry at the University of Birmingham.Method Anonymous questionnaires were completed by 70 4th year and 38 5th year BDS and 22 Dental Core Trainees (DCTs). Participants circled the response which best fitted their situation regarding statements on their level of stress and future career path. Ethical approval granted. Application figures to study dentistry obtained from head of admissions.Results Forty-two percent of males and 63% of females strongly agreed with the statement that having no debt would reduce their stress levels. Of those with debt >£40,000, 11% strongly agreed and 42% agreed that their total amount of student debt causes them stress. Whereas, those whose debt is stress. Seventy-seven percent of participants who had parental or family financial support reported this reduced their stress levels. Student debt was found to deter females from undertaking further study more than it deters males (P stressed about their total student loan(s) (P stress (P stress; students reporting a higher level of debt also report more stress and concern about paying off their student debt. Having no student debt would reduce stress levels, although to what extent is undetermined. Applications to study dentistry have fallen since the increase in tuition fees.

Induction of the Wnt antagonist Dickkopf-1 is involved in stress-induced hippocampal damage.

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Francesco Matrisciano

Full Text Available The identification of mechanisms that mediate stress-induced hippocampal damage may shed new light into the pathophysiology of depressive disorders and provide new targets for therapeutic intervention. We focused on the secreted glycoprotein Dickkopf-1 (Dkk-1, an inhibitor of the canonical Wnt pathway, involved in neurodegeneration. Mice exposed to mild restraint stress showed increased hippocampal levels of Dkk-1 and reduced expression of β-catenin, an intracellular protein positively regulated by the canonical Wnt signalling pathway. In adrenalectomized mice, Dkk-1 was induced by corticosterone injection, but not by exposure to stress. Corticosterone also induced Dkk-1 in mouse organotypic hippocampal cultures and primary cultures of hippocampal neurons and, at least in the latter model, the action of corticosterone was reversed by the type-2 glucocorticoid receptor antagonist mifepristone. To examine whether induction of Dkk-1 was causally related to stress-induced hippocampal damage, we used doubleridge mice, which are characterized by a defective induction of Dkk-1. As compared to control mice, doubleridge mice showed a paradoxical increase in basal hippocampal Dkk-1 levels, but no Dkk-1 induction in response to stress. In contrast, stress reduced Dkk-1 levels in doubleridge mice. In control mice, chronic stress induced a reduction in hippocampal volume associated with neuronal loss and dendritic atrophy in the CA1 region, and a reduced neurogenesis in the dentate gyrus. Doubleridge mice were resistant to the detrimental effect of chronic stress and, instead, responded to stress with increases in dendritic arborisation and neurogenesis. Thus, the outcome of chronic stress was tightly related to changes in Dkk-1 expression in the hippocampus. These data indicate that induction of Dkk-1 is causally related to stress-induced hippocampal damage and provide the first evidence that Dkk-1 expression is regulated by corticosteroids in the central

Restoration of hippocampal growth hormone reverses stress-induced hippocampal impairment

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Caitlin M. Vander Weele

2013-06-01

Full Text Available Though growth hormone (GH is synthesized by hippocampal neurons, where its expression is influenced by stress exposure, its function is poorly characterized. Here, we show that a regimen of chronic stress that impairs hippocampal function in rats also leads to a profound decrease in hippocampal GH levels. Restoration of hippocampal GH in the dorsal hippocampus via viral-mediated gene transfer completely reversed stress-related impairment of two hippocampus-dependent behavioral tasks, auditory trace fear conditioning and contextual fear conditioning, without affecting hippocampal function in unstressed control rats. GH overexpression reversed stress-induced decrements in both fear acquisition and long-term fear memory. These results suggest that loss of hippocampal GH contributes to hippocampal dysfunction following prolonged stress and demonstrate that restoring hippocampal GH levels following stress can promote stress resilience.

Transcription regulator TRIP-Br2 mediates ER stress-induced brown adipocytes dysfunction.

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Qiang, Guifen; Whang Kong, Hyerim; Gil, Victoria; Liew, Chong Wee

2017-01-09

In contrast to white adipose tissue, brown adipose tissue (BAT) is known to play critical roles for both basal and inducible energy expenditure. Obesity is associated with reduction of BAT function; however, it is not well understood how obesity promotes BAT dysfunction, especially at the molecular level. Here we show that the transcription regulator TRIP-Br2 mediates ER stress-induced inhibition of lipolysis and thermogenesis in BAT. Using in vitro, ex vivo, and in vivo approaches, we demonstrate that obesity-induced inflammation upregulates brown adipocytes TRIP-Br2 expression via the ER stress pathway and amelioration of ER stress in mice completely abolishes high fat diet-induced upregulation of TRIP-Br2 in BAT. We find that increased TRIP-Br2 significantly inhibits brown adipocytes thermogenesis. Finally, we show that ablation of TRIP-Br2 ameliorates ER stress-induced inhibition on lipolysis, fatty acid oxidation, oxidative metabolism, and thermogenesis in brown adipocytes. Taken together, our current study demonstrates a role for TRIP-Br2 in ER stress-induced BAT dysfunction, and inhibiting TRIP-Br2 could be a potential approach for counteracting obesity-induced BAT dysfunction.

Protective effects of gallic acid against spinal cord injury-induced oxidative stress.

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Yang, Yong Hong; Wang, Zao; Zheng, Jie; Wang, Ran

2015-08-01

The present study aimed to investigate the role of gallic acid in oxidative stress induced during spinal cord injury (SCI). In order to measure oxidative stress, the levels of lipid peroxide, protein carbonyl, reactive oxygen species and nitrates/nitrites were determined. In addition, the antioxidant status during SCI injury and the protective role of gallic acid were investigated by determining glutathione levels as well as the activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase. Adenosine triphophatase (ATPase) enzyme activities were determined to evaluate the role of gallic acid in SCI-induced deregulation of the activity of enzymes involved in ion homeostasis. The levels of inflammatory markers such as nuclear factor (NF)-κB and cycloxygenase (COX)-2 were determined by western blot analysis. Treatment with gallic acid was observed to significantly mitigate SCI-induced oxidative stress and the inflammatory response by reducing the oxidative stress, decreasing the expression of NF-κB and COX-2 as well as increasing the antioxidant status of cells. In addition, gallic acid modulated the activity of ATPase enzymes. Thus the present study indicated that gallic acid may have a role as a potent antioxidant and anti-inflammatory agent against SCI.

Heat-stress and light-stress induce different cellular pathologies in the symbiotic dinoflagellate during coral bleaching.

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Downs, C A; McDougall, Kathleen E; Woodley, Cheryl M; Fauth, John E; Richmond, Robert H; Kushmaro, Ariel; Gibb, Stuart W; Loya, Yossi; Ostrander, Gary K; Kramarsky-Winter, Esti

2013-01-01

Coral bleaching is a significant contributor to the worldwide degradation of coral reefs and is indicative of the termination of symbiosis between the coral host and its symbiotic algae (dinoflagellate; Symbiodinium sp. complex), usually by expulsion or xenophagy (symbiophagy) of its dinoflagellates. Herein, we provide evidence that during the earliest stages of environmentally induced bleaching, heat stress and light stress generate distinctly different pathomorphological changes in the chloroplasts, while a combined heat- and light-stress exposure induces both pathomorphologies; suggesting that these stressors act on the dinoflagellate by different mechanisms. Within the first 48 hours of a heat stress (32°C) under low-light conditions, heat stress induced decomposition of thylakoid structures before observation of extensive oxidative damage; thus it is the disorganization of the thylakoids that creates the conditions allowing photo-oxidative-stress. Conversely, during the first 48 hours of a light stress (2007 µmoles m(-2) s(-1) PAR) at 25°C, condensation or fusion of multiple thylakoid lamellae occurred coincidently with levels of oxidative damage products, implying that photo-oxidative stress causes the structural membrane damage within the chloroplasts. Exposure to combined heat- and light-stresses induced both pathomorphologies, confirming that these stressors acted on the dinoflagellate via different mechanisms. Within 72 hours of exposure to heat and/or light stresses, homeostatic processes (e.g., heat-shock protein and anti-oxidant enzyme response) were evident in the remaining intact dinoflagellates, regardless of the initiating stressor. Understanding the sequence of events during bleaching when triggered by different environmental stressors is important for predicting both severity and consequences of coral bleaching.

Heat-stress and light-stress induce different cellular pathologies in the symbiotic dinoflagellate during coral bleaching.

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C A Downs

Full Text Available Coral bleaching is a significant contributor to the worldwide degradation of coral reefs and is indicative of the termination of symbiosis between the coral host and its symbiotic algae (dinoflagellate; Symbiodinium sp. complex, usually by expulsion or xenophagy (symbiophagy of its dinoflagellates. Herein, we provide evidence that during the earliest stages of environmentally induced bleaching, heat stress and light stress generate distinctly different pathomorphological changes in the chloroplasts, while a combined heat- and light-stress exposure induces both pathomorphologies; suggesting that these stressors act on the dinoflagellate by different mechanisms. Within the first 48 hours of a heat stress (32°C under low-light conditions, heat stress induced decomposition of thylakoid structures before observation of extensive oxidative damage; thus it is the disorganization of the thylakoids that creates the conditions allowing photo-oxidative-stress. Conversely, during the first 48 hours of a light stress (2007 µmoles m(-2 s(-1 PAR at 25°C, condensation or fusion of multiple thylakoid lamellae occurred coincidently with levels of oxidative damage products, implying that photo-oxidative stress causes the structural membrane damage within the chloroplasts. Exposure to combined heat- and light-stresses induced both pathomorphologies, confirming that these stressors acted on the dinoflagellate via different mechanisms. Within 72 hours of exposure to heat and/or light stresses, homeostatic processes (e.g., heat-shock protein and anti-oxidant enzyme response were evident in the remaining intact dinoflagellates, regardless of the initiating stressor. Understanding the sequence of events during bleaching when triggered by different environmental stressors is important for predicting both severity and consequences of coral bleaching.

Pre-cold stress increases acid stress resistance and induces amino ...

African Journals Online (AJOL)

Pre-cold stress increases acid stress resistance and induces amino acid homeostasis in Lactococcus lactis NZ9000. ... Purpose: To investigate the effects of pre-cold stress treatments on subsequent acid stress resistance ... from 32 Countries:.

Molecular Adaptations to Social Defeat Stress and Induced Depression in Mice.

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Bondar, Natalya; Bryzgalov, Leonid; Ershov, Nikita; Gusev, Fedor; Reshetnikov, Vasiliy; Avgustinovich, Damira; Tenditnik, Mikhail; Rogaev, Evgeny; Merkulova, Tatiana

2018-04-01

Chronic stress is a risk factor for major depression. Social defeat stress is a well-validated murine model of depression. However, little is known about the gene activity dynamics during the development of a depression-like state. We analyzed the effects of social defeat stress of varying duration (10 and 30 days) on the behavioral patterns and prefrontal-cortex transcriptome of C57BL/6 mice. The 10-day exposure to social defeat stress resulted in a high level of social avoidance with no signs of depression-associated behavior. Most animals exposed to 30 days of social defeat stress demonstrated clear hallmarks of depression, including a higher level of social avoidance, increased immobility in the forced swimming test, and anhedonic behavior. The monitoring of transcriptome changes revealed widespread alterations in gene expression on the 10th day. Surprisingly, the expression of only a few genes were affected by the 30th day of stress, apparently due to a reversal of the majority of the early stress-induced changes to the original basal state. Moreover, we have found that glucocorticoid-sensitive genes are clearly stimulated targets on the 10th day of stress, but these genes stop responding to the elevated corticosterone level by the 30th day of stress. The majority of genes altered by the 30-day stress were downregulated, with the most relevant ones participating in chromatin modifications and neuroplasticity (e.g., guanine nucleotide exchange factors of the Rho-family of GTPases). Very different molecular responses occur during short-term and long-term social stress in mice. The early-stress response is associated with social avoidance and with upregulation and downregulation of many genes, including those related to signal transduction and cell adhesion pathways. Downregulation of a few genes, in particular, genes for histone-modifying methyltransferases, is a signature response to prolonged stress that induces symptoms of depression. Altogether, our data

Stress-induced rise in serum anti-brain autoantibody levels in the rat.

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Andrejević, S; Bukilica, M; Dimitrijević, M; Laban, O; Radulovic, J; Kovacevic-Jovanovic, V; Stanojevic, S; Vasiljevic, T; Marković, B M

1997-02-01

Sera from Wistar rats subjected to different stress procedures were tested by ELISA for the presence of autoantibodies with specificity for neuron-specific enolase (NSE) and S100 protein that are preferentially localized in neurons and glia, respectively. Autoantibodies were present in sera of animals before exposure to stress, and raised with age. Anti-NSE and anti-S100 autoantibody levels were increased one day after termination of restraint (2 hours daily, 10 days) and electric tail shock (80 shocks daily, 19 days), and in fifth and tenth week of overcrowding stress. Differences between stressed and control animals were not present one month following restraint and electric tail shock and in twentieth week of overcrowding.

MicroRNA-122 is involved in oxidative stress in isoniazid-induced liver injury in mice.

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Song, L; Zhang, Z R; Zhang, J L; Zhu, X B; He, L; Shi, Z; Gao, L; Li, Y; Hu, B; Feng, F M

2015-10-27

Many studies have shown that the pathogenesis of liver injury includes oxidative stress. MicroRNA-122 may be a marker for the early diagnosis of drug-induced liver injury. However, the relationship between microRNA-122 and oxidative stress in anti-tuberculosis drug-induced liver injury remains unknown. We measured changes in tissue microRNA-122 levels and indices of oxidative stress during liver injury in mice after administration of isoniazid, a first-line anti-tuberculosis drug. We quantified microRNA-122 expression and indices of oxidative stress at 7 time points, including 1, 3, and 5 days and 1, 2, 3, and 4 weeks. The tissue microRNA-122 levels and oxidative stress significantly changed at 3 and 5 days, suggesting that isoniazid-induced liver injury reduces oxidative stress and microRNA-122 expression compared to in the control group (P microRNA-122, began to change at 5 days (P microRNA-122 profile may affect oxidative stress by regulating mitochondrial ribosome protein S11 gene during isoniazid-induced liver injury, which may contribute to the response mechanisms of microRNA-122 and oxidative stress.

Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells.

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Wang, Xin; Xu, Mei; Frank, Jacqueline A; Ke, Zun-Ji; Luo, Jia

2017-04-01

Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Blockade of Drp1 rescues oxidative stress-induced osteoblast dysfunction

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Gan, Xueqi; Huang, Shengbin; Yu, Qing [Department of Pharmacology and Toxicology and Higuchi Bioscience Center, University of Kansas, Lawrence, KS, 66047 (United States); State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 (China); Yu, Haiyang [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 (China); Yan, Shirley ShiDu, E-mail: shidu@ku.edu [Department of Pharmacology and Toxicology and Higuchi Bioscience Center, University of Kansas, Lawrence, KS, 66047 (United States)

2015-12-25

Osteoblast dysfunction, induced by oxidative stress, plays a critical role in the pathophysiology of osteoporosis. However, the underlying mechanisms remain unclarified. Imbalance of mitochondrial dynamics has been closely linked to oxidative stress. Here, we reveal an unexplored role of dynamic related protein 1(Drp1), the major regulator in mitochondrial fission, in the oxidative stress-induced osteoblast injury model. We demonstrate that levels of phosphorylation and expression of Drp1 significantly increased under oxidative stress. Blockade of Drp1, through pharmaceutical inhibitor or gene knockdown, significantly protected against H{sub 2}O{sub 2}-induced osteoblast dysfunction, as shown by increased cell viability, improved cellular alkaline phosphatase (ALP) activity and mineralization and restored mitochondrial function. The protective effects of blocking Drp1 in H{sub 2}O{sub 2}-induced osteoblast dysfunction were evidenced by increased mitochondrial function and suppressed production of reactive oxygen species (ROS). These findings provide new insights into the role of the Drp1-dependent mitochondrial pathway in the pathology of osteoporosis, indicating that the Drp1 pathway may be targetable for the development of new therapeutic approaches in the prevention and the treatment of osteoporosis. - Highlights: • Oxidative stress is an early pathological event in osteoporosis. • Imbalance of mitochondrial dynamics are linked to oxidative stress in osteoporosis. • The role of the Drp1-dependent mitochondrial pathway in osteoporosis.

Hypoxic-induced stress protein expression in rat cardiac myocytes

International Nuclear Information System (INIS)

Howard, G.; Geoghegan, T.E.

1986-01-01

Mammalian stress proteins can be induced in cells and tissues exposed to a variety of conditions including hyperthermia and diminished O 2 supply. The authors have previously shown that the expression of three stress proteins (71, 85, and 95 kDa) was induced in cardiac tissue from mice exposed to hypoxic conditions. The expression of mRNAs coding for the 85 and 95 kDa proteins increase with time of exposure to hypoxia, while the mRNA coding for the 71 kDa protein is transiently induced. The authors extended these studies to investigate the expression of stress proteins in isolated rat cardiac myocytes. Freshly prepared myocytes were exposed to control, hypoxic, anoxic, or heat-shock environments for up to 16 h. The proteins were then labeled for 6 hours with [ 35 S]methionine. Analysis of the solubilized proteins by SDS-PAGE and autoradiography showed that there was a 6-fold increase in synthesis of the 85 kDa protein upon exposure to hypoxia but not heat-shock conditions. The 71 kDa protein was present at high levels in both control and treated myocyte protein preparations, and presumably had been induced during the isolation procedure. Total RNA isolated from intact rat heart and isolated myocytes was compared by cell-free translation analysis and showed induction of RNAs coding for several stress proteins in the myocyte preparation. The induced proteins at 85 and 95 kDa have molecular weights similar to reported cell stress and/or glucose-regulated proteins

Chronic lead exposure induces cochlear oxidative stress and potentiates noise-induced hearing loss.

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Jamesdaniel, Samson; Rosati, Rita; Westrick, Judy; Ruden, Douglas M

2018-08-01

Acquired hearing loss is caused by complex interactions of multiple environmental risk factors, such as elevated levels of lead and noise, which are prevalent in urban communities. This study delineates the mechanism underlying lead-induced auditory dysfunction and its potential interaction with noise exposure. Young-adult C57BL/6 mice were exposed to: 1) control conditions; 2) 2 mM lead acetate in drinking water for 28 days; 3) 90 dB broadband noise 2 h/day for two weeks; and 4) both lead and noise. Blood lead levels were measured by inductively coupled plasma mass spectrometry analysis (ICP-MS) lead-induced cochlear oxidative stress signaling was assessed using targeted gene arrays, and the hearing thresholds were assessed by recording auditory brainstem responses. Chronic lead exposure downregulated cochlear Sod1, Gpx1, and Gstk1, which encode critical antioxidant enzymes, and upregulated ApoE, Hspa1a, Ercc2, Prnp, Ccl5, and Sqstm1, which are indicative of cellular apoptosis. Isolated exposure to lead or noise induced 8-12 dB and 11-25 dB shifts in hearing thresholds, respectively. Combined exposure induced 18-30 dB shifts, which was significantly higher than that observed with isolated exposures. This study suggests that chronic exposure to lead induces cochlear oxidative stress and potentiates noise-induced hearing impairment, possibly through parallel pathways. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Endoplasmic reticulum stress as a novel mechanism in amiodarone-induced destructive thyroiditis.

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Lombardi, Angela; Inabnet, William Barlow; Owen, Randall; Farenholtz, Kaitlyn Ellen; Tomer, Yaron

2015-01-01

Amiodarone (AMIO) is one of the most effective antiarrhythmic drugs available; however, its use is limited by a serious side effect profile, including thyroiditis. The mechanisms underlying AMIO thyroid toxicity have been elusive; thus, identification of novel approaches in order to prevent thyroiditis is essential in patients treated with AMIO. Our aim was to evaluate whether AMIO treatment could induce endoplasmic reticulum (ER) stress in human thyroid cells and the possible implications of this effect in AMIO-induced destructive thyroiditis. Here we report that AMIO, but not iodine, significantly induced the expression of ER stress markers including Ig heavy chain-binding protein (BiP), phosphoeukaryotic translation initiation factor 2α (eIF2α), CCAAT/enhancer-binding protein homologous protein (CHOP) and spliced X-box binding protein-1 (XBP-1) in human thyroid ML-1 cells and human primary thyrocytes. In both experimental systems AMIO down-regulated thyroglobulin (Tg) protein but had little effect on Tg mRNA levels, suggesting a mechanism involving Tg protein degradation. Indeed, pretreatment with the specific proteasome inhibitor MG132 reversed AMIO-induced down-regulation of Tg protein levels, confirming a proteasome-dependent degradation of Tg protein. Corroborating our findings, pretreatment of ML-1 cells and human primary thyrocytes with the chemical chaperone 4-phenylbutyric acid completely prevented the effect of AMIO on both ER stress induction and Tg down-regulation. We identified ER stress as a novel mechanism contributing to AMIO-induced destructive thyroiditis. Our data establish that AMIO-induced ER stress impairs Tg expression via proteasome activation, providing a valuable therapeutic avenue for the treatment of AMIO-induced destructive thyroiditis.

Local and systemic oxidative stress and glucocorticoid receptor levels in chronic obstructive pulmonary disease patients

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Zeng, Mian; Li, Yue; Jiang, Yujie; Lu, Guifang; Huang, Xiaomei; Guan, Kaipan

2013-01-01

BACKGROUND: Previous studies have indicated that oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). OBJECTIVES: To study local and systemic oxidative stress status in COPD patients, and to clarify the relationship between local and systemic oxidative stress. METHODS: Lipid peroxide malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and GSH peroxidase (GSH-PX) levels in induced sputum and plasma, as well as glucocorticoid receptor (GR) levels in peripheral blood leukocytes were examined in 43 acute exacerbation of COPD patients (group A), 35 patients with stable COPD (group B) and 28 healthy controls (14 smokers [group C]; 14 nonsmokers [group D]). RESULTS: MDA levels in induced sputum and plasma decreased progressively in groups A to D, with significant differences between any two groups (P<0.001). GSH, SOD and GSH-PX levels in both induced sputum and plasma increased progressively in groups A to D, with significant differences between any two groups (P<0.001). GR levels in peripheral blood leukocytes decreased progressively in groups D to A (all comparisons P<0.001). Pearson analysis revealed strong correlations between MDA, GSH, SOD and GSH-PX levels in plasma and induced sputum. The activity of SOD in plasma and sputum were both positively correlated with GR levels (partial correlation coefficients 0.522 and 0.574, respectively [P<0.001]). CONCLUSIONS: Oxidative stress levels were elevated in COPD patients. There was a correlation between local and systemic oxidative status in COPD, and between decreased SOD activity and decreased GR levels in COPD patients. PMID:23457673

Melatonin mediated antidepressant-like effect in the hippocampus of chronic stress-induced depression rats: Regulating vesicular monoamine transporter 2 and monoamine oxidase A levels.

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Stefanovic, Bojana; Spasojevic, Natasa; Jovanovic, Predrag; Jasnic, Nebojsa; Djordjevic, Jelena; Dronjak, Sladjana

2016-10-01

The hippocampus is sensitive to stress which activates norepinephrine terminals deriving from the locus coeruleus. Melatonin exerts positive effects on the hippocampal neurogenic process and on depressive-like behaviour. Thus, in the present study, an examination was made of the effect of chronic melatonin treatment on norepinephrine content, synthesis, uptake, vesicular transport and degradation in the hippocampus of rats exposed to CUMS. This entailed quantifying the norephinephrine, mRNA and protein levels of DBH, NET, VMAT 2, MAO-A and COMT. The results show that CUMS evoked prolonged immobility. Melatonin treatment decreased immobility in comparison with the placebo group, reflecting an antidepressant-like effect. Compared with the placebo group, a dramatic decrease in norepinephrine content, decreased VMAT2 mRNA and protein and increased MAO-A protein levels in the hippocampus of the CUMS rats were observed. However, no significant differences in the levels of DBH, NET, COMT mRNA and protein and MAO-A mRNA levels between the placebo and the stressed groups were found. The results showed the restorative effects of melatonin on the stress-induced decline in the norepinephrine content of the hippocampus. It was observed that melatonin treatment in the CUMS rats prevented the stress-induced decrease in VMAT2 mRNA and protein levels, whereas it reduced the increase of the mRNA of COMT and protein levels of MAO-A. Chronic treatment with melatonin failed to alter the gene expression of DBH or NET in the hippocampus of the CUMS rats. Additionally, the results show that melatonin enhances VMAT2 expression and norepinephrine storage, whilst it reduces norepinephrine degrading enzymes. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Imagery Scripts and a Computerized Subtraction Stress Task Both Induce Stress in Methamphetamine Users: A Controlled Laboratory Study

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Kathleen J. Garrison

2010-01-01

Full Text Available Patients treated for methamphetamine (MA dependence have a high rate of relapse, and stress is thought to play a key role. We sought to develop a computerized procedure for experimentally inducing stress in MA users. In a within-subjects design, we compared a computerized subtraction stress task (SST to personalized stress-imagery scripts and a control condition (neutral imagery in 9 former MA users, recruited in San Francisco in 2006–2007. We assessed blood hormone levels, anxiety and craving for MA on visual analog scales, and the Positive and Negative Affect Schedule and made linear mixed-effects models to analyze the results. Both the SST and stress scripts were effective in inducing self-report markers of stress in MA users. Because the SST is easily reproducible and requires less time of staff and participants, it may be a useful alternative for measuring stress reactivity in drug users.

DinB Upregulation Is the Sole Role of the SOS Response in Stress-Induced Mutagenesis in Escherichia coli

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Galhardo, Rodrigo S.; Do, Robert; Yamada, Masami; Friedberg, Errol C.; Hastings, P. J.; Nohmi, Takehiko; Rosenberg, Susan M.

2009-01-01

Stress-induced mutagenesis is a collection of mechanisms observed in bacterial, yeast, and human cells in which adverse conditions provoke mutagenesis, often under the control of stress responses. Control of mutagenesis by stress responses may accelerate evolution specifically when cells are maladapted to their environments, i.e., are stressed. It is therefore important to understand how stress responses increase mutagenesis. In the Escherichia coli Lac assay, stress-induced point mutagenesis requires induction of at least two stress responses: the RpoS-controlled general/starvation stress response and the SOS DNA-damage response, both of which upregulate DinB error-prone DNA polymerase, among other genes required for Lac mutagenesis. We show that upregulation of DinB is the only aspect of the SOS response needed for stress-induced mutagenesis. We constructed two dinB(oc) (operator-constitutive) mutants. Both produce SOS-induced levels of DinB constitutively. We find that both dinB(oc) alleles fully suppress the phenotype of constitutively SOS-“off” lexA(Ind−) mutant cells, restoring normal levels of stress-induced mutagenesis. Thus, dinB is the only SOS gene required at induced levels for stress-induced point mutagenesis. Furthermore, although spontaneous SOS induction has been observed to occur in only a small fraction of cells, upregulation of dinB by the dinB(oc) alleles in all cells does not promote a further increase in mutagenesis, implying that SOS induction of DinB, although necessary, is insufficient to differentiate cells into a hypermutable condition. PMID:19270270

Hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation in rat mesenteric arteries is mediated by intracellular methylglyoxal levels in a pathway dependent on oxidative stress

DEFF Research Database (Denmark)

Brouwers, O; Niessen, P M; Haenen, G

2010-01-01

-hydro-5-methylimidazolone (MG-H1) was detected with an antibody against MG-H1 and quantified with ultra-performance liquid chromatography (tandem) mass spectrometry. Reactive oxygen species formation was measured with a 5-(and-6)-chloromethyl-2'7'-dichlorodihydrofluorescein diacetate acetyl ester probe...... for AGE ligand S100b did (p cells and adventitia by fivefold accompanied by an eightfold increase in the oxidative stress marker nitrotyrosine. Antioxidant pre-incubation prevented methylglyoxal......-induced impairment of vasoreactivity. CONCLUSIONS/INTERPRETATION: These data show that hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation is mediated by increased intracellular methylglyoxal levels in a pathway dependent on oxidative stress....

[Stress-induced cellular adaptive mutagenesis].

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Zhu, Linjiang; Li, Qi

2014-04-01

The adaptive mutations exist widely in the evolution of cells, such as antibiotic resistance mutations of pathogenic bacteria, adaptive evolution of industrial strains, and cancerization of human somatic cells. However, how these adaptive mutations are generated is still controversial. Based on the mutational analysis models under the nonlethal selection conditions, stress-induced cellular adaptive mutagenesis is proposed as a new evolutionary viewpoint. The hypothetic pathway of stress-induced mutagenesis involves several intracellular physiological responses, including DNA damages caused by accumulation of intracellular toxic chemicals, limitation of DNA MMR (mismatch repair) activity, upregulation of general stress response and activation of SOS response. These responses directly affect the accuracy of DNA replication from a high-fidelity manner to an error-prone one. The state changes of cell physiology significantly increase intracellular mutation rate and recombination activity. In addition, gene transcription under stress condition increases the instability of genome in response to DNA damage, resulting in transcription-associated DNA mutagenesis. In this review, we summarize these two molecular mechanisms of stress-induced mutagenesis and transcription-associated DNA mutagenesis to help better understand the mechanisms of adaptive mutagenesis.

Severe, multimodal stress exposure induces PTSD-like characteristics in a mouse model of single prolonged stress.

Science.gov (United States)

Perrine, Shane A; Eagle, Andrew L; George, Sophie A; Mulo, Kostika; Kohler, Robert J; Gerard, Justin; Harutyunyan, Arman; Hool, Steven M; Susick, Laura L; Schneider, Brandy L; Ghoddoussi, Farhad; Galloway, Matthew P; Liberzon, Israel; Conti, Alana C

2016-04-15

Appropriate animal models of posttraumatic stress disorder (PTSD) are needed because human studies remain limited in their ability to probe the underlying neurobiology of PTSD. Although the single prolonged stress (SPS) model is an established rat model of PTSD, the development of a similarly-validated mouse model emphasizes the benefits and cross-species utility of rodent PTSD models and offers unique methodological advantages to that of the rat. Therefore, the aims of this study were to develop and describe a SPS model for mice and to provide data that support current mechanisms relevant to PTSD. The mouse single prolonged stress (mSPS) paradigm, involves exposing C57Bl/6 mice to a series of severe, multimodal stressors, including 2h restraint, 10 min group forced swim, exposure to soiled rat bedding scent, and exposure to ether until unconsciousness. Following a 7-day undisturbed period, mice were tested for cue-induced fear behavior, effects of paroxetine on cue-induced fear behavior, extinction retention of a previously extinguished fear memory, dexamethasone suppression of corticosterone (CORT) response, dorsal hippocampal glucocorticoid receptor protein and mRNA expression, and prefrontal cortex glutamate levels. Exposure to mSPS enhanced cue-induced fear, which was attenuated by oral paroxetine treatment. mSPS also disrupted extinction retention, enhanced suppression of stress-induced CORT response, increased mRNA expression of dorsal hippocampal glucocorticoid receptors and decreased prefrontal cortex glutamate levels. These data suggest that the mSPS model is a translationally-relevant model for future PTSD research with strong face, construct, and predictive validity. In summary, mSPS models characteristics relevant to PTSD and this severe, multimodal stress modifies fear learning in mice that coincides with changes in the hypothalamo-pituitary-adrenal (HPA) axis, brain glucocorticoid systems, and glutamatergic signaling in the prefrontal cortex

Relationship between general intelligence, emotional intelligence, stress levels and stress reactivity.

Science.gov (United States)

Singh, Yogesh; Sharma, Ratna

2012-07-01

Stressful life events and daily life stresses have both deleterious and cumulative effects on human body. In several studies, stress has been shown to affect various parameter of higher mental function like attention, concentration, learning and memory. Present study was designed to explore the relationship among GI level, EI level, psychological stress levels and acute stress reactivity in young normal healthy subjects. The study was conducted on thirty four healthy male student volunteers to study a) acute stress reactivity in subjects with varying levels of General Intelligence (GI) and Emotional Intelligence (EI) and b) correlation between GI, EI, acute stress and perceived stress. Baseline GI and EI and acute stress and perceived stress scores were measured by standard assessment scales. Using median value of GI and EI scores as cutoff values, subjects were categorized into four groups. Among different GI-EI groups, acute stress reactivity was similar but salivary Cortisol (especially post stressor level) and perceived stress level was a differentiating factor. High level of EI was associated inversely with acute and chronic perceived stress level. Significant correlation was found between acute and chronic perceived stress levels. Level of general intelligence showed no relation to acute or chronic stress levels as well as acute stress reactivity. The differences in various groups of GI and EI had no effect on the baseline and post stress performance on Sternberg memory test and all the three conditions of Stroop test. In conclusion emotional intelligence as an attribute is better suited to handle day to day acute stress and chronic perceived stress.

Exercise training attenuates sympathetic activation and oxidative stress in diet-induced obesity.

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Li, G; Liu, J-Y; Zhang, H-X; Li, Q; Zhang, S-W

2015-01-01

It is known that excessive sympathetic activity and oxidative stress are enhanced in obesity. This study aimed to clarify whether exercise training (ET) attenuates sympathetic activation and oxidative stress in obesity. The obesity was induced by high-fat diet (HFD) for 12 weeks. Male Sprague-Dawley rats were assigned to four groups: regular diet (RD) plus sedentary (RD-S), RD plus ET (RD-ET), HFD plus sedentary (HFD-S), and HFD plus ET (HFD-ET). The rats in RD-ET and HFD-ET groups were trained on a motorized treadmill for 60 min/day, five days/week for 8 weeks. The sympathetic activity was evaluated by the plasma norepinephrine (NE) level. The superoxide anion, malondialdehyde and F2-isoprostanes levels in serum and muscles were measured to evaluate oxidative stress. The ET prevented the increases in the body weight, arterial pressure and white adipose tissue mass in HFD rats. The NE level in plasma and oxidative stress related parameters got lower in HFD-ET group compared with HFD-S group. We have found decreased mRNA and protein levels of toll-like receptor (TLR)-2 and TLR-4 by ET in HFD rats. These findings suggest that ET may be effective for attenuating sympathetic activation and oxidative stress in diet-induced obesity.

TRH and TRH receptor system in the basolateral amygdala mediate stress-induced depression-like behaviors.

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Choi, Juli; Kim, Ji-eun; Kim, Tae-Kyung; Park, Jin-Young; Lee, Jung-Eun; Kim, Hannah; Lee, Eun-Hwa; Han, Pyung-Lim

2015-10-01

Chronic stress is a potent risk factor for depression, but the mechanism by which stress causes depression is not fully understood. To investigate the molecular mechanism underlying stress-induced depression, C57BL/6 inbred mice were treated with repeated restraint to induce lasting depressive behavioral changes. Behavioral states of individual animals were evaluated using the forced swim test, which measures psychomotor withdrawals, and the U-field test, which measures sociability. From these behavioral analyses, individual mice that showed depression-like behaviors in both psychomotor withdrawal and sociability tests, and individuals that showed a resiliency to stress-induced depression in both tests were selected. Among the neuropeptides expressed in the amygdala, thyrotropin-releasing hormone (TRH) was identified as being persistently up-regulated in the basolateral amygdala (BLA) in individuals exhibiting severe depressive behaviors in the two behavior tests, but not in individuals displaying a stress resiliency. Activation of TRH receptors by local injection of TRH in the BLA in normal mice produced depressive behaviors, mimicking chronic stress effects, whereas siRNA-mediated suppression of either TRH or TRHR1 in the BLA completely blocked stress-induced depressive symptoms. The TRHR1 agonist, taltirelin, injection in the BLA increased the level of p-ERK, which mimicked the increased p-ERK level in the BLA that was induced by treatment with repeated stress. Stereotaxic injection of U0126, a potent inhibitor of the ERK pathway, within the BLA blocked stress-induced behavioral depression. These results suggest that repeated stress produces lasting depression-like behaviors via the up-regulation of TRH and TRH receptors in the BLA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Changing stress levels through gaining information on stress

Directory of Open Access Journals (Sweden)

S.N. Madu

2002-09-01

Full Text Available Objective: The aim of this research was to find out the effect of the Information Phase of a Stress Management Program (SMP on the perceptions of participants about their stress levels. Method: A total sample of 100 workers (nursing staff, private business men and women, laboratory assistants, the protective services [foreman and security staff], as well as people in human resources departments took part in this study. All the participants were from the Northern and Gauteng Provinces in South Africa. The Combined Hassles and Uplifts Scale (Folkman & Lazarus, 1989 was used as an instrument to measure the perceived stress level of participants in a SMP. Result: A significant reduction in stress levels was achieved among those who received the Information Phase of the SMP only, as well as those who received the whole stress management techniques. There was no significant difference between the amount of reduction in perceived stress-levels achieved among those that received the Information Phase of the SMP only, compared to that of those who received the whole techniques. Conclusion: The authors conclude that where the resources are limited, only the information phase of a SMP may be given to desiring clients. That should help to save time and money spent on participating in SMPs. This should however not discourage the use of the whole SPM, where affordable. Keywords: Stress Management Programs, Information Phase, Perception, Stress Level.

Ocimum basilicum improve chronic stress-induced neurodegenerative changes in mice hippocampus.

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Ayuob, Nasra Naeim; El Wahab, Manal Galal Abd; Ali, Soad Shaker; Abdel-Tawab, Hanem Saad

2018-01-22

Alzheimer's disease (AD), one of the progressive neurodegenerative diseases might be associated with exposure to stress and altered living conditions. This study aimed to evaluate the effectiveness of Ocimum basilicum (OB) essential oils in improving the neurodegenerative-like changes induced in mice after exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice divided into four groups (n = 10); the control, CUMS, CUMS + Fluoxetine, CUMS + OB were used. Behavioral tests, serum corticosterone level, hippocampus protein level of the glucocorticoid receptors (GRs) and brain-dreived neurotropic factor (BDNF) were determined after exposure to CUMS. Hippocampus was histopathologically examined. Data were analyzed using statistical package for the social sciences (SPSS) and P value of less than 0.05 was considered significant. OB diminished the depression manifestation as well as impaired short term memory observed in the mice after exposure to the CUMS as evidenced by the forced swimming and elevated plus maze test. OB also up-regulated the serum corticosterone level, hippocampal protein level of the glucocorticoid receptor and the brain-derived neurotropic factor and reduced the neurodegenerative and atrophic changes induced in the hippocampus after exposure to CUMS. Essential oils of OB alleviated the memory impairment and hippocampal neurodegenerative changes induced by exposure to the chronic unpredictable stress indicating that it is the time to test its effectiveness on patients suffering from Alzheimer disease.

Sirt3 confers protection against acrolein-induced oxidative stress in cochlear nucleus neurons.

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Qu, Juan; Wu, Yong-Xiang; Zhang, Ting; Qiu, Yang; Ding, Zhong-Jia; Zha, Ding-Jun

2018-03-01

Acrolein is a ubiquitous dietary and environmental pollutant, which can also be generated endogenously during cellular stress. However, the molecular mechanisms underlying acrolein-induced neurotoxicity, especially in ototoxicity conditions, have not been fully determined. In this study, we investigated the mechanisms on acrolein-induced toxicity in primary cultured cochlear nucleus neurons with focus on Sirt3, a mitochondrial deacetylase. We found that acrolein treatment induced neuronal injury and programmed cell death (PCD) in a dose dependent manner in cochlear nucleus neurons, which was accompanied by increased intracellular reactive oxygen species (ROS) generation and lipid peroxidation. Acrolein exposure also significantly reduced the mitochondrial membrane potential (MMP) levels, promoted cytochrome c release and decreased mitochondrial ATP production. In addition, increased ER tracker fluorescence and activation of ER stress factors were observed after acrolein treatment, and the ER stress inhibitors were shown to attenuate acrolein-induced toxicity in cochlear nucleus neurons. The results of western blot and RT-PCR showed that acrolein markedly decreased the expression of Sirt3 at both mRNA and protein levels, and reduced the activity of downstream mitochondrial enzymes. Furthermore, overexpression of Sirt3 by lentivirus transfection partially prevented acrolein-induced neuronal injury in cochlear nucleus neurons. These results demonstrated that acrolein induces mitochondrial dysfunction and ER stress in cochlear nucleus neurons, and Sirt3 acts as an endogenous protective factor in acrolein-induced ototoxicity. Copyright © 2017. Published by Elsevier Ltd.

Sirtuin1 and autophagy protect cells from fluoride-induced cell stress

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Suzuki, Maiko; Bartlett, John D.

2014-01-01

Sirtuin1 (SIRT1) is an (NAD+)-dependent deacetylase functioning in the regulation of metabolism, cell survival and organismal lifespan. Active SIRT1 regulates autophagy during cell stress, including calorie restriction, endoplasmic reticulum stress and oxidative stress. Previously, we reported that fluoride induces endoplasmic reticulum (ER) stress in ameloblasts responsible for enamel formation, suggesting that ER-stress plays a role in dental fluorosis. However, the molecular mechanism of how cells respond to fluoride-induced cell stress is unclear. Here, we demonstrate that fluoride activates SIRT1 and initiates autophagy to protect cells from fluoride exposure. Fluoride treatment of ameloblast-derived cells (LS8) significantly increased Sirt1 expression and induced SIRT1 phosphorylation resulting in the augmentation of SIRT1 deacetylase activity. To demonstrate that fluoride exposure initiates autophagy, we characterized the expression of autophagy related genes (Atg); Atg5, Atg7 and Atg8/LC3 and showed that both their transcript and protein levels were significantly increased following fluoride treatment. To confirm that SIRT1 plays a protective role in fluoride toxicity, we used resveratrol (RES) to augmented SIRT1 activity in fluoride treated LS8 cells. RES increased autophagy, inhibited apoptosis, and decreased fluoride cytotoxicity. Rats treated with fluoride (0, 50 and 100 ppm) in drinking water for 6 weeks had significantly elevated expression levels of Sirt1, Atg5, Atg7 and Atg8/LC3 in their maturation stage enamel organs. Increased protein levels of p-SIRT1, ATG5 and ATG8/LC3 were present in fluoride-treated rat maturation stage ameloblasts. Therefore, the SIRT1/autophagy pathway may play a critical role as a protective response to help prevent dental fluorosis. PMID:24296261

Sirtuin1 and autophagy protect cells from fluoride-induced cell stress.

Science.gov (United States)

Suzuki, Maiko; Bartlett, John D

2014-02-01

Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase functioning in the regulation of metabolism, cell survival and organismal lifespan. Active SIRT1 regulates autophagy during cell stress, including calorie restriction, endoplasmic reticulum (ER) stress and oxidative stress. Previously, we reported that fluoride induces ER-stress in ameloblasts responsible for enamel formation, suggesting that ER-stress plays a role in dental fluorosis. However, the molecular mechanism of how cells respond to fluoride-induced cell stress is unclear. Here, we demonstrate that fluoride activates SIRT1 and initiates autophagy to protect cells from fluoride exposure. Fluoride treatment of ameloblast-derived cells (LS8) significantly increased Sirt1 expression and induced SIRT1 phosphorylation resulting in the augmentation of SIRT1 deacetylase activity. To demonstrate that fluoride exposure initiates autophagy, we characterized the expression of autophagy related genes (Atg); Atg5, Atg7 and Atg8/LC3 and showed that both their transcript and protein levels were significantly increased following fluoride treatment. To confirm that SIRT1 plays a protective role in fluoride toxicity, we used resveratrol (RES) to augment SIRT1 activity in fluoride treated LS8 cells. RES increased autophagy, inhibited apoptosis, and decreased fluoride cytotoxicity. Rats treated with fluoride (0, 50, 100 and 125ppm) in drinking water for 6weeks had significantly elevated expression levels of Sirt1, Atg5, Atg7 and Atg8/LC3 in their maturation stage enamel organs. Increased protein levels of p-SIRT1, ATG5 and ATG8/LC3 were present in fluoride-treated rat maturation stage ameloblasts. Therefore, the SIRT1/autophagy pathway may play a critical role as a protective response to help prevent dental fluorosis. Copyright © 2013 Elsevier B.V. All rights reserved.

Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress.

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Mehta, Vineet; Parashar, Arun; Udayabanu, Malairaman

2017-03-15

It is now evident that chronic stress is associated with anxiety, depression and cognitive dysfunction and very few studies have focused on identifying possible methods to prevent these stress-induced disorders. Previously, we identified abundance of quercetin in Urtica dioica extract, which efficiently attenuated stress related complications. Therefore, current study was designed to investigate the effect of quercetin on chronic unpredicted stress (CUS) induced behavioral dysfunction, oxidative stress and neuroinflammation in the mouse hippocampus. Animals were subjected to unpredicted stress for 21days, during which 30mg/kg quercetin was orally administered to them. Effect of CUS and quercetin treatment on animal behavior was assessed between day 22-26. Afterward, the hippocampus was processed to evaluate neuronal damage, oxidative and inflammatory stress. Results revealed that stressed animals were highly anxious (Elevated Plus Maze and Open Field), showed depressive-like behavior (sucrose preference task), performed poorly in short-term and long-term associative memory task (passive avoidance step-through task) and displayed reduced locomotion (open field). Quercetin alleviated behavioral dysfunction in chronically stressed animals. Compared to CUS, quercetin treatment significantly reduced anxiety, attenuated depression, improved cognitive dysfunction and normalized locomotor activity. Further, CUS elevated the levels of oxidative stress markers (TBARS, nitric oxide), lowered antioxidants (total thiol, catalase), enhanced expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2) in the hippocampus and damaged hippocampal neurons. Quercetin treatment significantly lowered oxidative and inflammatory stress and prevented neural damage. In conclusion, quercetin can efficiently prevent stress induced neurological complications by rescuing brain from oxidative and inflammatory stress. Copyright © 2017 Elsevier Inc. All rights reserved.

Individual variation in baseline and stress-induced corticosterone and prolactin levels predicts parental effort by nesting mourning doves

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Miller, David A.; Vleck, Carol M.; Otis, David L.

2009-01-01

Endocrine systems have an important mechanistic role in structuring life-history trade-offs. During breeding, individual variation in prolactin (PRL) and corticosterone (CORT) levels affects behavioral and physiological processes that drive trade-offs between reproduction and self-maintenance. We examined patterns in baseline (BL) and stress induced (SI; level following a standard capture-restraint protocol) levels of PRL and CORT for breeding mourning doves (Zenaida macroura). We determined whether the relationship of adult condition and parental effort to hormone levels in wild birds was consistent with life-history predictions. Both BL PRL and BL CORT level in adults were positively related to nestling weight at early nestling ages, consistent with the prediction of a positive relationship of hormone levels to current parental effort of adults and associated increased energy demand. Results are consistent with the two hormones acting together at baseline levels to limit negative effects of CORT on reproduction while maintaining beneficial effects such as increased foraging for nestling feeding. Our data did not support predictions that SI responses would vary in response to nestling or adult condition. The magnitude of CORT response in the parents to our capture-restraint protocol was negatively correlated with subsequent parental effort. Average nestling weights for adults with the highest SI CORT response were on average 10–15% lighter than expected for their age in follow-up visits after the stress event. Our results demonstrated a relationship between individual hormone levels and within population variation in parental effort and suggested that hormonal control plays an important role in structuring reproductive decisions for mourning doves.

Effects of PEG-induced osmotic stress on growth and dhurrin levels of forage sorghum

DEFF Research Database (Denmark)

O'Donnell, Natalie H.; Møller, Birger Lindberg; Neale, Alan D.

2013-01-01

Sorghum (Sorghum bicolor L. Moench) is a valuable forage crop in regions with low soil moisture. Sorghum may accumulate high concentrations of the cyanogenic glucoside dhurrin when drought stressed resulting in possible cyanide (HCN) intoxication of grazing animals. In addition, high concentratio...... of plant growth and root activity, increasing the rate of nitrate uptake. Data presented in this article support a role for cyanogenic glucosides in mitigating oxidative stress....... of nitrate, also potentially toxic to ruminants, may accumulate during or shortly after periods of drought. Little is known about the degree and duration of drought-stress required to induce dhurrin accumulation, or how changes in dhurrin concentration are influenced by plant size or nitrate metabolism....... Given that finely regulating soil moisture under controlled conditions is notoriously difficult, we exposed sorghum plants to varying degrees of osmotic stress by growing them for different lengths of time in hydroponic solutions containing polyethylene glycol (PEG). Plants grown in medium containing 20...

Acute restraint stress induces endothelial dysfunction: role of vasoconstrictor prostanoids and oxidative stress.

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Carda, Ana P P; Marchi, Katia C; Rizzi, Elen; Mecawi, André S; Antunes-Rodrigues, José; Padovan, Claudia M; Tirapelli, Carlos R

2015-01-01

We hypothesized that acute stress would induce endothelial dysfunction. Male Wistar rats were restrained for 2 h within wire mesh. Functional and biochemical analyses were conducted 24 h after the 2-h period of restraint. Stressed rats showed decreased exploration on the open arms of an elevated-plus maze (EPM) and increased plasma corticosterone concentration. Acute restraint stress did not alter systolic blood pressure, whereas it increased the in vitro contractile response to phenylephrine and serotonin in endothelium-intact rat aortas. NG-nitro-l-arginine methyl ester (l-NAME; nitric oxide synthase, NOS, inhibitor) did not alter the contraction induced by phenylephrine in aortic rings from stressed rats. Tiron, indomethacin and SQ29548 reversed the increase in the contractile response to phenylephrine induced by restraint stress. Increased systemic and vascular oxidative stress was evident in stressed rats. Restraint stress decreased plasma and vascular nitrate/nitrite (NOx) concentration and increased aortic expression of inducible (i) NOS, but not endothelial (e) NOS. Reduced expression of cyclooxygenase (COX)-1, but not COX-2, was observed in aortas from stressed rats. Restraint stress increased thromboxane (TX)B(2) (stable TXA(2) metabolite) concentration but did not affect prostaglandin (PG)F2α concentration in the aorta. Restraint reduced superoxide dismutase (SOD) activity, whereas concentrations of hydrogen peroxide (H(2)O(2)) and reduced glutathione (GSH) were not affected. The major new finding of our study is that restraint stress increases vascular contraction by an endothelium-dependent mechanism that involves increased oxidative stress and the generation of COX-derived vasoconstrictor prostanoids. Such stress-induced endothelial dysfunction could predispose to the development of cardiovascular diseases.

Abiotic stressors and stress responses: What commonalities appear between species across biological organization levels?

International Nuclear Information System (INIS)

Sulmon, Cécile; Baaren, Joan van; Cabello-Hurtado, Francisco; Gouesbet, Gwenola; Hennion, Françoise; Mony, Cendrine; Renault, David; Bormans, Myriam; El Amrani, Abdelhak; Wiegand, Claudia; Gérard, Claudia

2015-01-01

Organisms are regularly subjected to abiotic stressors related to increasing anthropogenic activities, including chemicals and climatic changes that induce major stresses. Based on various key taxa involved in ecosystem functioning (photosynthetic microorganisms, plants, invertebrates), we review how organisms respond and adapt to chemical- and temperature-induced stresses from molecular to population level. Using field-realistic studies, our integrative analysis aims to compare i) how molecular and physiological mechanisms related to protection, repair and energy allocation can impact life history traits of stressed organisms, and ii) to what extent trait responses influence individual and population responses. Common response mechanisms are evident at molecular and cellular scales but become rather difficult to define at higher levels due to evolutionary distance and environmental complexity. We provide new insights into the understanding of the impact of molecular and cellular responses on individual and population dynamics and assess the potential related effects on communities and ecosystem functioning. - Highlights: • Responses to chemical and thermal stressors are reviewed across organization levels. • Common responses between taxa are evident at the molecular and cellular scales. • At individual level, energy allocation connects species-specific stress responses. • Commonality decreases at higher levels due to increasing environmental complexity. - The commonality of stress responses to chemical and thermal stressors among taxa is evident at the molecular and cellular scales but remains unclear at higher levels of organization

Effects of Kombucha on oxidative stress induced nephrotoxicity in rats.

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Gharib, Ola Ali

2009-11-27

Trichloroethylene (TCE) may induce oxidative stress which generates free radicals and alters antioxidants or oxygen-free radical scavenging enzymes. Twenty male albino rats were divided into four groups: (1) the control group treated with vehicle, (2) Kombucha (KT)-treated group, (3) TCE-treated group and (4) KT/TCE-treated group. Kidney lipid peroxidation, glutathione content, nitric oxide (NO) and total blood free radical concentrations were evaluated. Serum urea, creatinine level, gamma-glutamyl transferase (GGT) and lactate dehydrogenase (LDH) activities were also measured. TCE administration increased the malondiahyde (MDA) and NO contents in kidney, urea and creatinine concentrations in serum, total free radical level in blood and GGT and LDH activities in serum, whereas it decreased the glutathione (GSH) level in kidney homogenate. KT administration significantly improved lipid peroxidation and oxidative stress induced by TCE. The present study indicates that Kombucha may repair damage caused by environmental pollutants such as TCE and may be beneficial to patient suffering from renal impairment.

Agmatine attenuates stress- and lipopolysaccharide-induced fever in rats

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Aricioglu, Feyza; Regunathan, Soundar

2010-01-01

Physiological stress evokes a number of responses, including a rise in body temperature, which has been suggested to be the result of an elevation in the thermoregulatory set point. This response seems to share similar mechanisms with infectious fever. The aim of the present study was to investigate the effect of agmatine on different models of stressors [(restraint and lipopolysaccaride (LPS)] on body temperature. Rats were either restrained for 4 h or injected with LPS, both of these stressors caused an increase in body temperature. While agmatine itself had no effect on body temperature, treatment with agmatine (20, 40, 80 mg/kg intraperitoneally) dose dependently inhibited stress- and LPS-induced hyperthermia. When agmatine (80 mg/kg) was administered 30 min later than LPS (500 μg/kg) it also inhibited LPS-induced hyperthermia although the effect became significant only at later time points and lower maximal response compared to simultaneous administration. To determine if the decrease in body temperature is associated with an anti-inflammatory effect of agmatine, the nitrite/nitrate levels in plasma was measured. Agmatine treatment inhibited LPS-induced production of nitrates dose dependently. As an endogenous molecule, agmatine has the capacity to inhibit stress- and LPS-induced increases in body temperature. PMID:15936786

Serotonergic involvement in stress-induced vasopressin and oxytocin secretion

DEFF Research Database (Denmark)

Jørgensen, Henrik; Knigge, Ulrich; Kjaer, Andreas

2002-01-01

OBJECTIVE: To investigate the involvement of serotonin (5-hydroxytryptamine - 5-HT) receptors in mediation of stress-induced arginine vasopressin (AVP) and oxytocin (OT) secretion in male rats. DESIGN: Experiments on laboratory rats with control groups. METHODS: Different stress paradigms were...... the swim stress-induced OT response. CONCLUSION: 5-HT(2A), 5-HT(2C) and possibly 5-HT(3) and 5-HT(4) receptors, but not 5-HT(1A) receptors, are involved in the restraint stress-induced AVP secretion. 5-HT does not seem to be involved in the dehydration- or hemorrhage-induced AVP response. The restraint...... stress-induced OT response seems to be mediated via 5-HT(1A), 5-HT(2A) and 5-HT(2C) receptors. The dehydration and hemorrhage-induced OT responses are at least mediated by the 5-HT(2A) and 5-HT(2C) receptors. The 5-HT(3) and 5-HT(4) receptors are not involved in stress-induced OT secretion....

Increased reactive oxygen species levels cause ER stress and cytotoxicity in andrographolide treated colon cancer cells.

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Banerjee, Aditi; Banerjee, Vivekjyoti; Czinn, Steven; Blanchard, Thomas

2017-04-18

Chemotherapy continues to play an essential role in the management of many cancers including colon cancer, the third leading cause of death due to cancer in the United States. Many naturally occurring plant compounds have been demonstrated to possess anti-cancer cell activity and have the potential to supplement existing chemotherapy strategies. The plant metabolite andrographolide induces cell death in cancer cells and apoptosis is dependent upon the induction of endoplasmic reticulum stress (ER stress) leading to the unfolded protein response (UPR). The goal of the present study was to determine the mechanism by which andrographolide induces ER stress and to further evaluate its role in promoting cell death pathways. The T84 and COLO 205 cancer cell lines were used to demonstrate that andrographolide induces increased ROS levels, corresponding anti-oxidant response molecules, and reduced mitochondrial membrane potential. No increases in ROS levels were detected in control colon fibroblast cells. Andrographolide-induced cell death, UPR signaling, and CHOP, Bax, and caspase 3 apoptosis elements were all inhibited in the presence of the ROS scavenger NAC. Additionally, andrographolide-induced suppression of cyclins B1 and D1 were also reversed in the presence of NAC. Finally, Akt phosphorylation and phospho-mTOR levels that are normally suppressed by andrographolide were also expressed at normal levels in the absence of ROS. These data demonstrate that andrographolide induces ER stress leading to apoptosis through the induction of ROS and that elevated ROS also play an important role in down-regulating cell cycle progression and cell survival pathways as well.

Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat Diet.

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Ma, Xiaoqing; Du, Wenhua; Shao, Shanshan; Yu, Chunxiao; Zhou, Lingyan; Jing, Fei

2018-01-01

Purpose. We investigated whether a DDP-4 inhibitor, vildagliptin, alleviated ER stress induced by a high fat diet and improved hepatic lipid deposition. Methods. C57BL/6 mice received standard chow diet (CD), high fat diet (HFD), and HFD administered with vildagliptin (50 mg/Kg) (V-HFD). After administration for 12 weeks, serum alanine aminotransferase, glucose, cholesterol, triglyceride, and insulin levels were analyzed. Samples of liver underwent histological examination and transmission electron microscopy, real-time PCR for gene expression levels, and western blots for protein expression levels. ER stress was induced in HepG2 cells with palmitic acid and the effects of vildagliptin were investigated. Results. HFD mice showed increased liver weight/body weight (20.27%) and liver triglycerides (314.75%) compared to CD mice, but these decreased by 9.27% and 21.83%, respectively, in V-HFD mice. In the liver, HFD induced the expression of ER stress indicators significantly, which were obviously decreased by vildagliptin. In vitro, the expressions of molecular indicators of ER stress were reduced in HepG2 when vildagliptin was administered. Conclusions. Vildagliptin alleviates hepatic ER stress in a mouse high fat diet model. In HepG2 cells, vildagliptin directly reduced ER stress. Therefore, vildagliptin may be a potential agent for nonalcoholic fatty liver disease.

Oxidative stress inhibits adhesion and transendothelial migration, and induces apoptosis and senescence of induced pluripotent stem cells.

Science.gov (United States)

Wu, Yi; Zhang, Xueqing; Kang, Xueling; Li, Ning; Wang, Rong; Hu, Tiantian; Xiang, Meng; Wang, Xinhong; Yuan, Wenjun; Chen, Alex; Meng, Dan; Chen, Sifeng

2013-09-01

Oxidative stress caused by cellular accumulation of reactive oxygen species (ROS) is a major contributor to disease and cell death. However, how induced pluripotent stem cells (iPSC) respond to different levels of oxidative stress is largely unknown. Here, we investigated the effect of H2 O2 -induced oxidative stress on iPSC function in vitro. Mouse iPSC were treated with H2 O2 (25-100 μmol/L). IPSC adhesion, migration, viability, apoptosis and senescence were analysed. Expression of adhesion-related genes, stress defence genes, and osteoblast- and adipocyte-associated genes were determined by reverse transcription polymerase chain reaction. The present study found that H2 O2 (25-100 μmol/L) decreased iPSC adhesion to matrix proteins and endothelial cells, and downregulated gene expression levels of adhesion-related molecules, such as integrin alpha 7, cadherin 1 and 5, melanoma cell adhesion molecule, vascular cell adhesion molecule 1, and monocyte chemoattractant protein-1. H2 O2 (100 μmol/L) decreased iPSC viability and inhibited the capacity of iPSC migration and transendothelial migration. iPSC were sensitive to H2 O2 -induced G2/M arrest, senescence and apoptosis when exposed to H2 O2 at concentrations above 25 μmol/L. H2 O2 increased the expression of stress defence genes, including catalase, cytochrome B alpha, lactoperoxidase and thioredoxin domain containing 2. H2 O2 upregulated the expression of osteoblast- and adipocyte-associated genes in iPSC during their differentiation; however, short-term H2 O2 -induced oxidative stress did not affect the protein expression of the pluripotency markers, octamer-binding transcription factor 4 and sex-determining region Y-box 2. The present results suggest that iPSC are sensitive to H2 O2 toxicity, and inhibition of oxidative stress might be a strategy for improving their functions. © 2013 Wiley Publishing Asia Pty Ltd.

The exponential rise of induced seismicity with increasing stress levels in the Groningen gas field and its implications for controlling seismic risk

Science.gov (United States)

Bourne, S. J.; Oates, S. J.; van Elk, J.

2018-06-01

Induced seismicity typically arises from the progressive activation of recently inactive geological faults by anthropogenic activity. Faults are mechanically and geometrically heterogeneous, so their extremes of stress and strength govern the initial evolution of induced seismicity. We derive a statistical model of Coulomb stress failures and associated aftershocks within the tail of the distribution of fault stress and strength variations to show initial induced seismicity rates will increase as an exponential function of induced stress. Our model provides operational forecasts consistent with the observed space-time-magnitude distribution of earthquakes induced by gas production from the Groningen field in the Netherlands. These probabilistic forecasts also match the observed changes in seismicity following a significant and sustained decrease in gas production rates designed to reduce seismic hazard and risk. This forecast capability allows reliable assessment of alternative control options to better inform future induced seismic risk management decisions.

Stress-induced magnetic anisotropy in nanocrystalline alloys

International Nuclear Information System (INIS)

Varga, L.K.; Gercsi, Zs.; Kovacs, Gy.; Kakay, A.; Mazaleyrat, F.

2003-01-01

Stress-annealing experiments were extended to both nanocrystalline alloy families, Finemet and Nanoperm (Hitperm), and, for comparison, to amorphous Fe 62 Nb 8 B 30 alloy. For both Finemet and bulk amorphous, stress-annealing results in a strong induced transversal anisotropy (flattening of hysteresis loop) but yields longitudinal induced anisotropy (square hysteresis loop) in Nanoperm and Hitperm. These results are interpreted in terms of back-stress theory

Age-related effects of chronic restraint stress on ethanol drinking, ethanol-induced sedation, and on basal and stress-induced anxiety response.

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Fernández, Macarena Soledad; Fabio, María Carolina; Miranda-Morales, Roberto Sebastián; Virgolini, Miriam B; De Giovanni, Laura N; Hansen, Cristian; Wille-Bille, Aranza; Nizhnikov, Michael E; Spear, Linda P; Pautassi, Ricardo Marcos

2016-03-01

Adolescents are sensitive to the anxiolytic effect of ethanol, and evidence suggests that they may be more sensitive to stress than adults. Relatively little is known, however, about age-related differences in stress modulation of ethanol drinking or stress modulation of ethanol-induced sedation and hypnosis. We observed that chronic restraint stress transiently exacerbated free-choice ethanol drinking in adolescent, but not in adult, rats. Restraint stress altered exploration patterns of a light-dark box apparatus in adolescents and adults. Stressed animals spent significantly more time in the white area of the maze and made significantly more transfers between compartments than their non-stressed peers. Behavioral response to acute stress, on the other hand, was modulated by prior restraint stress only in adults. Adolescents, unlike adults, exhibited ethanol-induced motor stimulation in an open field. Stress increased the duration of loss of the righting reflex after a high ethanol dose, yet this effect was similar at both ages. Ethanol-induced sleep time was much higher in adult than in adolescent rats, yet stress diminished ethanol-induced sleep time only in adults. The study indicates age-related differences that may increase the risk for initiation and escalation in alcohol drinking. Copyright © 2016 Elsevier Inc. All rights reserved.

Stress-induced accumulation of wheat germ agglutinin and abscisic acid in roots of wheat seedlings

International Nuclear Information System (INIS)

Cammue, B.P.A.; Broekaert, W.F.; Kellens, J.T.C.; Peumans, W.J.; Raikhel, N.V.

1989-01-01

Wheat germ agglutinin (WGA) levels in roots of 2-day-old wheat seedlings increased up to three-fold when stressed by air-drying. Similar results were obtained when seedling roots were incubated either in 0.5 molar mannitol or 180 grams per liter polyethylene glycol 6,000, with a peak level of WGA after 5 hours of stress. Longer periods of osmotic treatment resulted in a gradual decline of WGA in the roots. Since excised wheat roots incorporate more [ 35 S]cysteine into WGA under stress conditions, the observed increase of lectin levels is due to de novo synthesis. Measurement of abscisic acid (ABA) levels in roots of control and stressed seedlings indicated a 10-fold increase upon air-drying. Similarly, a five- and seven-fold increase of ABA content of seedling roots was found after 2 hours of osmotic stress by polyethylene glycol 6,000 and mannitol, respectively. Finally, the stress-induced increase of WGA in wheat roots could be inhibited by growing seedlings in the presence of fluridone, an inhibitor of ABA synthesis. These results indicate that roots of water-stressed wheat seedlings (a) contain more WGA as a result of an increased de novo synthesis of this lectin, and (b) exhibit higher ABA levels. The stress-induced increase of lectin accumulation seems to be under control of ABA

Positive associations between upregulated levels of stress-induced phosphoprotein 1 and matrix metalloproteinase-9 in endometriosis/adenomyosis.

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Wang, Hsin-Shih; Tsai, Chia-Lung; Chang, Pi-Yueh; Chao, Angel; Wu, Ren-Chin; Chen, Shun-Hua; Wang, Chin-Jung; Yen, Chih-Feng; Lee, Yun-Shien; Wang, Tzu-Hao

2018-01-01

Stress-induced phosphoprotein-1 (STIP1), an adaptor protein that coordinates the functions of HSP70 and HSP90 in protein folding, has been implicated in the development of human gynecologic malignancies. This case-control study investigates STIP1 serum levels and tissue expression in relation to endometriosis/adenomyosis in Taiwanese population. Female patients with surgically confirmed endometriosis/adenomyosis were compared with women free of endometriosis/adenomyosis. Serum STIP1 levels were measured using an enzyme-linked immunosorbent assay and surgical tissues were analyzed by immunohistochemistry. Both epithelial and stromal cells in surgical tissues of endometriosis and adenomyosis expressed STIP1 and MMP-9. Notably, MMP-9 expression was significantly decreased when STIP1 expression was knocked-down. In vitro experiments revealed that STIP1 was capable of binding to the MMP-9 promoter and enhanced its transcriptional expression. The preoperative serum STIP1 levels of patients with endometriosis/adenomyosis were significantly higher than those of the controls. In brief, our data suggest an association between STIP1 levels and endometriosis/adenomyosis.

Stress-induced neuroinflammation is mediated by GSK3-dependent TLR4 signaling that promotes susceptibility to depression-like behavior.

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Cheng, Yuyan; Pardo, Marta; Armini, Rubia de Souza; Martinez, Ana; Mouhsine, Hadley; Zagury, Jean-Francois; Jope, Richard S; Beurel, Eleonore

2016-03-01

Most psychiatric and neurological diseases are exacerbated by stress. Because this may partially result from stress-induced inflammation, we examined factors involved in this stress response. After a paradigm of inescapable foot shock stress that causes learned helplessness depression-like behavior, eighteen cytokines and chemokines increased in mouse hippocampus, peaking 6-12h after stress. A 24h prior pre-conditioning stress accelerated the rate of stress-induced hippocampal cytokine and chemokine increases, with most reaching peak levels after 1-3h, often without altering the maximal levels. Toll-like receptor 4 (TLR4) was involved in this response because most stress-induced hippocampal cytokines and chemokines were attenuated in TLR4 knockout mice. Stress activated glycogen synthase kinase-3 (GSK3) in wild-type mouse hippocampus, but not in TLR4 knockout mice. Administration of the antidepressant fluoxetine or the GSK3 inhibitor TDZD-8 reduced the stress-induced increases of most hippocampal cytokines and chemokines. Stress increased hippocampal levels of the danger-associated molecular pattern (DAMP) protein high mobility group box 1 (HMGB1), activated the inflammatory transcription factor NF-κB, and the NLRP3 inflammasome. Knockdown of HMGB1 blocked the acceleration of cytokine and chemokine increases in the hippocampus caused by two successive stresses. Fluoxetine treatment blocked stress-induced up-regulation of HMGB1 and subsequent NF-κB activation, whereas TDZD-8 administration attenuated NF-κB activation downstream of HMGB1. To test if stress-induced cytokines and chemokines contribute to depression-like behavior, the learned helplessness model was assessed. Antagonism of TNFα modestly reduced susceptibility to learned helplessness induction, whereas TLR4 knockout mice were resistant to learned helplessness. Thus, stress-induces a broad inflammatory response in mouse hippocampus that involves TLR4, GSK3, and downstream inflammatory signaling, and

Stress-induced neuroinflammation is mediated by GSK3-dependent TLR4 signaling that promotes susceptibility to depression-like behavior

Science.gov (United States)

Cheng, Yuyan; Pardo, Marta; de Souza Armini, Rubia; Martinez, Ana; Mouhsine, Hadley; Zagury, Jean-Francois; Jope, Richard S.; Beurel, Eleonore

2016-01-01

Most psychiatric and neurological diseases are exacerbated by stress. Because this may partially result from stress-induced inflammation, we examined factors involved in this stress response. After a paradigm of inescapable foot shock stress that causes learned helplessness depression-like behavior, eighteen cytokines and chemokines increased in mouse hippocampus, peaking 6 to 12 hr after stress. A 24 hr prior pre-conditioning stress accelerated the rate of stress-induced hippocampal cytokine and chemokine increases, with most reaching peak levels after 1 to 3 hr, often without altering the maximal levels. Toll-like receptor 4 (TLR4) was involved in this response because most stress-induced hippocampal cytokines and chemokines were attenuated in TLR4 knockout mice. Stress activated glycogen synthase kinase-3 (GSK3) in wild-type mouse hippocampus, but not in TLR4 knockout mice. Administration of the antidepressant fluoxetine or the GSK3 inhibitor TDZD-8 reduced the stress-induced increases of most hippocampal cytokines and chemokines. Stress increased hippocampal levels of the danger-associated molecular pattern (DAMP) protein high mobility group box 1 (HMGB1), activated the inflammatory transcription factor NF-κB, and the NLRP3 inflammasome. Knockdown of HMGB1 blocked the acceleration of cytokine and chemokine increases in the hippocampus caused by two successive stresses. Fluoxetine treatment blocked stress-induced up-regulation of HMGB1 and subsequent NF-κB activation, whereas TDZD-8 administration attenuated NF-κB activation downstream of HMGB1. To test if stress-induced cytokines and chemokines contribute to depression-like behavior, the learned helplessness model was assessed. Antagonism of TNFα modestly reduced susceptibility to learned helplessness induction, whereas TLR4 knockout mice were resistant to learned helplessness. Thus, stress-induces a broad inflammatory response in mouse hippocampus that involves TLR4, GSK3, and downstream inflammatory

Neuromodulatory Effects of Hesperidin in Mitigating Oxidative Stress in Streptozotocin Induced Diabetes

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Mohammad Ashafaq

2014-01-01

Full Text Available Oxidative stress has been implicated in pathogenesis of streptozotocin- (STZ- induced diabetes mellitus and its complication in central nervous system (CNS. Recent studies have provided insights on antioxidants and their emergence as potential therapeutic and nutraceutical. The present study examined the hypothesis that hesperidin (HP ameliorates oxidative stress and may be a limiting factor in the extent of CNS complication following diabetes. To test this hypothesis rats were divided into four groups: control, diabetic, diabetic-HP treated, and vehicle for HP treatment group. Diabetes mellitus was induced by a single injection of STZ (65 mg/kg body weight. Three days after STZ injection, HP was given (50 mg/kg b.wt. orally once daily for four weeks. The results of the present investigation suggest that the significant elevated levels of oxidative stress markers were observed in STZ-treated animals, whereas significant depletion in the activity of nonenzymatic antioxidants and enzymatic antioxidants was witnessed in diabetic rat brain. Neurotoxicity biomarker activity was also altered significantly. HP treatment significantly attenuated the altered levels of oxidative stress and neurotoxicity biomarkers. Our results demonstrate that HP exhibits potent antioxidant and neuroprotective effects on the brain tissue against the diabetic oxidative damage in STZ-induced rodent model.

Agmatine attenuates chronic unpredictable mild stress induced behavioral alteration in mice.

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Taksande, Brijesh G; Faldu, Dharmesh S; Dixit, Madhura P; Sakaria, Jay N; Aglawe, Manish M; Umekar, Milind J; Kotagale, Nandkishor R

2013-11-15

Chronic stress exposure and resulting dysregulation of the hypothalamic pituitary adrenal axis develops susceptibility to variety of neurological and psychiatric disorders. Agmatine, a putative neurotransmitter has been reported to be released in response to various stressful stimuli to maintain the homeostasis. Present study investigated the role of agmatine on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alteration in mice. Exposure of mice to CUMS protocol for 28 days resulted in diminished performance in sucrose preference test, splash test, forced swim test and marked elevation in plasma corticosterone levels. Chronic agmatine (5 and 10 mg/kg, ip, once daily) treatment started on day-15 and continued till the end of the CUMS protocol significantly increased sucrose preference, improved self-care and motivational behavior in the splash test and decreased duration of immobility in the forced swim test. Agmatine treatment also normalized the elevated corticosterone levels and prevented the body weight changes in chronically stressed animals. The pharmacological effect of agmatine was comparable to selective serotonin reuptake inhibitor, fluoxetine (10mg/kg, ip). Results of present study clearly demonstrated the anti-depressant like effect of agmatine in chronic unpredictable mild stress induced depression in mice. Thus the development of drugs based on brain agmatinergic modulation may represent a new potential approach for the treatment of stress related mood disorders like depression. © 2013 Published by Elsevier B.V.

The effect of diffusion induced lattice stress on the open-circuit voltage in silicon solar cells

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Weizer, V. G.; Godlewski, M. P.

1984-01-01

It is demonstrated that diffusion induced stresses in low resistivity silicon solar cells can significantly reduce both the open-circuit voltage and collection efficiency. The degradation mechanism involves stress induced changes in both the minority carrier mobility and the diffusion length. Thermal recovery characteristics indicate that the stresses are relieved at higher temperatures by divacancy flow (silicon self diffusion). The level of residual stress in as-fabricated cells was found to be negligible in the cells tested.

Cadmium-induced teratogenicity: Association with ROS-mediated endoplasmic reticulum stress in placenta

International Nuclear Information System (INIS)

Wang, Zhen; Wang, Hua; Xu, Zhong Mei; Ji, Yan-Li; Chen, Yuan-Hua; Zhang, Zhi-Hui; Zhang, Cheng; Meng, Xiu-Hong; Zhao, Mei; Xu, De-Xiang

2012-01-01

The placenta is essential for sustaining the growth of the fetus. An increased endoplasmic reticulum (ER) stress has been associated with the impaired placental and fetal development. Cadmium (Cd) is a potent teratogen that caused fetal malformation and growth restriction. The present study investigated the effects of maternal Cd exposure on placental and fetal development. The pregnant mice were intraperitoneally injected with CdCl 2 (4.5 mg/kg) on gestational day 9. As expected, maternal Cd exposure during early limb development significantly increased the incidences of forelimb ectrodactyly in fetuses. An obvious impairment in the labyrinth, a highly developed tissue of blood vessels, was observed in placenta of mice treated with CdCl 2 . In addition, maternal Cd exposure markedly repressed cell proliferation and increased apoptosis in placenta. An additional experiment showed that maternal Cd exposure significantly upregulated the expression of GRP78, an ER chaperone. Moreover, maternal Cd exposure induced the phosphorylation of placental eIF2α, a downstream molecule of PERK signaling. In addition, maternal Cd exposure significantly increased the level of placental CHOP, another target of PERK signaling, indicating that the unfolded protein response (UPR) signaling was activated in placenta of mice treated with CdCl 2 . Interestingly, alpha-phenyl-N-t-butylnitrone, a free radical spin-trapping agent, significantly alleviated Cd-induced placental ER stress and UPR. Taken together, these results suggest that reactive oxygen species (ROS)-mediated ER stress might be involved in Cd-induced impairment on placental and fetal development. Antioxidants may be used as pharmacological agents to protect against Cd-induced fetal malformation and growth restriction. -- Highlights: ► Cd induces fetal malformation and growth restriction. ► Cd induced placental ER stress and UPR. ► PBN alleviates Cd-induced ER stress and UPR in placenta. ► ROS-mediated ER stress might

Protective effects of red grape (Vitis vinifera) juice through restoration of antioxidant defense, endocrine swing and Hsf1, Hsp72 levels in heat stress induced testicular dysregulation of Wister rat.

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Halder, Soma; Sarkar, Mrinmoy; Dey, Sananda; Kumar Bhunia, Sujay; Ranjan Koley, Alok; Giri, Biplab

2018-01-01

Ability of red grape juice (RGJ), a known antioxidant, on testis of adult Wister rat to protect from oxidative stress induced damages by heat stress has been investigated in this study. Heat stress was induced maintaining body and testicular temperature at 43°C for 30min/day for 15 days using a hyperthermia induction chamber. Four groups of rats (n=6 per group) comprising of Group-I (control) -kept at 32°C, Group-II -exposed to heat stress alone, Group-III received RGJ (0.8ml/rat/day) alone and Group-IV -exposed to heat stress and received RGJ at same dose. Analysis of blood and testicular tissue exhibited significant reduction in serum testosterone, testicular superoxide dismutase, testicular catalase and testicular glutathione (all p rise in the level of serum corticosteroid, testicular lipid peroxidase and the apoptotic enzyme caspase-3 of testis (all p < 0.001) were observed along with substantial increase in testicular Hsp72 and Hsf-1, and decrease in 17β-HSD3 were noted in heat stressed rats compared to controls. In Group-IV rats, RGJ administration could restore these parameters to normal levels. The signs of retention were clear in Group-IV rats and found to be significantly different as compared to that of the Group-II rats. In testicular histology of rats exposed to heat stress alone revealed remarkable germ cell degeneration and tubular deformations which were prevented by RGJ treatment (Group-IV). The reduced number of sperm level in Group-II also restored in RGJ treatment (Group-IV). The above results indicate that consumption of RGJ may substantially protect testis from heat stress induce dysfunctions. Copyright © 2017 Elsevier Ltd. All rights reserved.

A study on anti-stress property of Nardostachys jatamamsi on stress induced Drosophila melanogaster

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Shilpashree R.

2011-09-01

Full Text Available Stress is a feeling that’s created when we react to particular events. It s the body’s way of rising to a challenge and preparing to meet a tough situation with focus, strength, stamina, and heightened alertness. As a result of the stress immune system can be suppressed by chronic stress opening to increased infections and increasing the risk of autoimmune diseases. So one has to learn away to overcome stress. Here is an attempt made to overcome the stress induced in Drosophila melanogaster a model organism, in this study. Methotrexate is used to induce the stress at different concentration taking different group of flies and a Nardostachys jatamamsi plant extract having antistress property is used to relieve the stress induced. This stress relieve measured by the various stress related enzymes like catalase and Superoxide dismutase by this antistress property of the plant Nardostachys jatamamsi was shown.

Taurine ameliorated homocysteine-induced H9C2 cardiomyocyte apoptosis by modulating endoplasmic reticulum stress.

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Zhang, Zhimin; Zhao, Lianyou; Zhou, Yanfen; Lu, Xuanhao; Wang, Zhengqiang; Wang, Jipeng; Li, Wei

2017-05-01

Homocysteine (Hcy)-triggered endoplasmic reticulum (ER) stress-mediated endothelial cell apoptosis has been suggested as a cause of Hcy-dependent vascular injury. However, whether ER stress is the molecular mechanism linking Hcy and cardiomyocytes death is unclear. Taurine has been reported to exert cardioprotective effects via various mechanisms. However, whether taurine protects against Hcy-induced cardiomyocyte death by attenuating ER stress is unknown. This study aimed to evaluate the opposite effects of taurine on Hcy-induced cardiomyocyte apoptosis and their underlying mechanisms. Our results demonstrated that low-dose or short-term Hcy treatment increased the expression of glucose-regulated protein 78 (GRP78) and activated protein kinase RNA-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6), which in turn prevented apoptotic cell death. High-dose Hcy or prolonged Hcy treatment duration significantly up-regulated levels of C/EBP homologous protein (CHOP), cleaved caspase-12, p-c-Jun N-terminal kinase (JNK), and then triggered apoptotic events. High-dose Hcy also resulted in a decrease in mitochondrial membrane potential (Δψm) and an increase in cytoplasmic cytochrome C and the expression of cleaved caspase-9. Pretreatment of cardiomyocytes with sodium 4-phenylbutyric acid (an ER stress inhibitor) significantly inhibited Hcy-induced apoptosis. Furthermore, blocking the PERK pathway partly alleviated Hcy-induced ER stress-modulated cardiomyocyte apoptosis, and down-regulated the levels of Bax and cleaved caspase-3. Experimental taurine pretreatment inhibited the expression of ER stress-related proteins, and protected against apoptotic events triggered by Hcy-induced ER stress. Taken together, our results suggest that Hcy triggered ER stress in cardiomyocytes, which was the crucial molecular mechanism mediating Hcy-induced cardiomyocyte apoptosis, and the adverse effect of Hcy could be prevented by taurine.

Xanthine Oxidase Inhibitor, Allopurinol, Prevented Oxidative Stress, Fibrosis, and Myocardial Damage in Isoproterenol Induced Aged Rats.

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Sagor, Md Abu Taher; Tabassum, Nabila; Potol, Md Abdullah; Alam, Md Ashraful

2015-01-01

We evaluated the preventive effect of allopurinol on isoproterenol (ISO) induced myocardial infarction in aged rats. Twelve- to fourteen-month-old male Long Evans rats were divided into three groups: control, ISO, and ISO + allopurinol. At the end of the study, all rats were sacrificed for blood and organ sample collection to evaluate biochemical parameters and oxidative stress markers analyses. Histopathological examinations were also conducted to assess inflammatory cell infiltration and fibrosis in heart and kidneys. Our investigation revealed that the levels of oxidative stress markers were significantly increased while the level of cellular antioxidants, catalase activity, and glutathione concentration in ISO induced rats decreased. Treatment with allopurinol to ISO induced rats prevented the elevated activities of AST, ALT, and ALP enzymes, and the levels of lipid peroxidation products and increased reduced glutathione concentration. ISO induced rats also showed massive inflammatory cells infiltration and fibrosis in heart and kidneys. Furthermore, allopurinol treatment prevented the inflammatory cells infiltration and fibrosis in ISO induced rats. In conclusion, the results of our study suggest that allopurinol treatment is capable of protecting heart of ISO induced myocardial infarction in rats probably by preventing oxidative stress, inflammation, and fibrosis.

Emodin opposes chronic unpredictable mild stress induced depressive-like behavior in mice by upregulating the levels of hippocampal glucocorticoid receptor and brain-derived neurotrophic factor.

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Li, Meng; Fu, Qiang; Li, Ying; Li, Shanshan; Xue, Jinsong; Ma, Shiping

2014-10-01

Emodin, the major active component of Rhubarb, has shown neuroprotective activity. This study is attempted to investigate whether emodin possesses beneficial effects on chronic unpredictable mild stress (CUMS)-induced behavioral deficits (depression-like behaviors) and explore the possible mechanisms. ICR mice were subjected to chronic unpredictable mild stress for 42 consecutive days. Then, emodin and fluoxetine (positive control drug) were administered for 21 consecutive days at the last three weeks of CUMS procedure. The classical behavioral tests: open field test (OFT), sucrose preference test (SPT), tail suspension test (TST) and forced swimming test (FST) were applied to evaluate the antidepressant effects of emodin. Then plasma corticosterone concentration, hippocampal glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF) levels were tested to probe the mechanisms. Our results indicated that 6 weeks of CUMS exposure induced significant depression-like behavior, with high, plasma corticosterone concentration and low hippocampal GR and BDNF expression levels. Whereas, chronic emodin (20, 40 and 80 mg/kg) treatments reversed the behavioral deficiency induced by CUMS exposure. Treatment with emodin normalized the change of plasma corticosterone level, which demonstrated that emodin could partially restore CUMS-induced HPA axis impairments. Besides, hippocampal GR (mRNA and protein) and BDNF (mRNA) expressions were also up-regulated after emodin treatments. In conclusion, emodin remarkably improved depression-like behavior in CUMS mice and its antidepressant activity is mediated, at least in part, by the up-regulating GR and BDNF levels in hippocampus. Copyright © 2014 Elsevier B.V. All rights reserved.

Ion beam induced stress formation and relaxation in germanium

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Steinbach, T., E-mail: Tobias.Steinbach@uni-jena.de [Institut für Festkörperphysik, Friedrich-Schiller-Universität Jena, Max-Wien-Platz 1, D-07743 Jena (Germany); Reupert, A.; Schmidt, E.; Wesch, W. [Institut für Festkörperphysik, Friedrich-Schiller-Universität Jena, Max-Wien-Platz 1, D-07743 Jena (Germany)

2013-07-15

Ion irradiation of crystalline solids leads not only to defect formation and amorphization but also to mechanical stress. In the past, many investigations in various materials were performed focusing on the ion beam induced damage formation but only several experiments were done to investigate the ion beam induced stress evolution. Especially in microelectronic devices, mechanical stress leads to several unwanted effects like cracking and peeling of surface layers as well as changing physical properties and anomalous diffusion of dopants. To study the stress formation and relaxation process in semiconductors, crystalline and amorphous germanium samples were irradiated with 3 MeV iodine ions at different ion fluence rates. The irradiation induced stress evolution was measured in situ with a laser reflection technique as a function of ion fluence, whereas the damage formation was investigated by means of Rutherford backscattering spectrometry. The investigations show that mechanical stress builds up at low ion fluences as a direct consequence of ion beam induced point defect formation. However, further ion irradiation causes a stress relaxation which is attributed to the accumulation of point defects and therefore the creation of amorphous regions. A constant stress state is reached at high ion fluences if a homogeneous amorphous surface layer was formed and no further ion beam induced phase transition took place. Based on the results, we can conclude that the ion beam induced stress evolution seems to be mainly dominated by the creation and accumulation of irradiation induced structural modification.

Laser-induced stresses versus mechanical stress power measurements during laser ablation of solids

International Nuclear Information System (INIS)

Shannon, M.A.; Russo, R.E.

1995-01-01

Laser-induced stresses resulting from high-power laser-material interactions have been studied extensively. However, the rate of change in mechanical energy, or stress power, due to laser-induced stresses has only recently been investigated. An unanswered question for monitoring laser-material interactions in the far-field is whether stress power differs from stresses measured, particularly with respect to laser-energy coupling to a solid target. This letter shows experimental acoustic data which demonstrate that stress power measured in the far field of the target shows changes in laser-energy coupling, whereas the stresses measured do not. For the ambient medium above the target, stress power and stress together reflect changes in laser-energy coupling. copyright 1995 American Institute of Physics

Prolactin prevents acute stress-induced hypocalcemia and ulcerogenesis by acting in the brain of rat.

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Fujikawa, Takahiko; Soya, Hideaki; Tamashiro, Kellie L K; Sakai, Randall R; McEwen, Bruce S; Nakai, Naoya; Ogata, Masato; Suzuki, Ikukatsu; Nakashima, Kunio

2004-04-01

Stress causes hypocalcemia and ulcerogenesis in rats. In rats under stressful conditions, a rapid and transient increase in circulating prolactin (PRL) is observed, and this enhanced PRL induces PRL receptors (PRLR) in the choroid plexus of rat brain. In this study we used restraint stress in water to elucidate the mechanism by which PRLR in the rat brain mediate the protective effect of PRL against stress-induced hypocalcemia and ulcerogenesis. We show that rat PRL acts through the long form of PRLR in the hypothalamus. This is followed by an increase in the long form of PRLR mRNA expression in the choroid plexus of the brain, which provides protection against restraint stress in water-induced hypocalcemia and gastric erosions. We also show that PRL induces the expression of PRLR protein and corticotropin-releasing factor mRNA in the paraventricular nucleus. These results suggest that the PRL levels increase in response to stress, and it moves from the circulation to the cerebrospinal fluid to act on the central nervous system and thereby plays an important role in helping to protect against acute stress-induced hypocalcemia and gastric erosions.

Exercise-Induced Oxidative Stress Responses in the Pediatric Population

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Alexandra Avloniti

2017-01-01

Full Text Available Adults demonstrate an upregulation of their pro- and anti-oxidant mechanisms in response to acute exercise while systematic exercise training enhances their antioxidant capacity, thereby leading to a reduced generation of free radicals both at rest and in response to exercise stress. However, less information exists regarding oxidative stress responses and the underlying mechanisms in the pediatric population. Evidence suggests that exercise-induced redox perturbations may be valuable in order to monitor exercise-induced inflammatory responses and as such training overload in children and adolescents as well as monitor optimal growth and development. The purpose of this review was to provide an update on oxidative stress responses to acute and chronic exercise in youth. It has been documented that acute exercise induces age-specific transient alterations in both oxidant and antioxidant markers in children and adolescents. However, these responses seem to be affected by factors such as training phase, training load, fitness level, mode of exercise etc. In relation to chronic adaptation, the role of training on oxidative stress adaptation has not been adequately investigated. The two studies performed so far indicate that children and adolescents exhibit positive adaptations of their antioxidant system, as adults do. More studies are needed in order to shed light on oxidative stress and antioxidant responses, following acute exercise and training adaptations in youth. Available evidence suggests that small amounts of oxidative stress may be necessary for growth whereas the transition to adolescence from childhood may promote maturation of pro- and anti-oxidant mechanisms. Available evidence also suggests that obesity may negatively affect basal and exercise-related antioxidant responses in the peripubertal period during pre- and early-puberty.

Finite element calculation of stress induced heating of superconductors

International Nuclear Information System (INIS)

Akin, J.E.; Moazed, A.

1976-01-01

This research is concerned with the calculation of the amount of heat generated due to the development of mechanical stresses in superconducting composites. An emperical equation is used to define the amount of stress-induced heat generation per unit volume. The equation relates the maximum applied stress and the experimental measured hysteresis loop of the composite stress-strain diagram. It is utilized in a finite element program to calculate the total stress-induced heat generation for the superconductor. An example analysis of a solenoid indicates that the stress-induced heating can be of the same order of magnitude as eddy current effects

Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat Diet

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Xiaoqing Ma

2018-01-01

Full Text Available Purpose. We investigated whether a DDP-4 inhibitor, vildagliptin, alleviated ER stress induced by a high fat diet and improved hepatic lipid deposition. Methods. C57BL/6 mice received standard chow diet (CD, high fat diet (HFD, and HFD administered with vildagliptin (50 mg/Kg (V-HFD. After administration for 12 weeks, serum alanine aminotransferase, glucose, cholesterol, triglyceride, and insulin levels were analyzed. Samples of liver underwent histological examination and transmission electron microscopy, real-time PCR for gene expression levels, and western blots for protein expression levels. ER stress was induced in HepG2 cells with palmitic acid and the effects of vildagliptin were investigated. Results. HFD mice showed increased liver weight/body weight (20.27% and liver triglycerides (314.75% compared to CD mice, but these decreased by 9.27% and 21.83%, respectively, in V-HFD mice. In the liver, HFD induced the expression of ER stress indicators significantly, which were obviously decreased by vildagliptin. In vitro, the expressions of molecular indicators of ER stress were reduced in HepG2 when vildagliptin was administered. Conclusions. Vildagliptin alleviates hepatic ER stress in a mouse high fat diet model. In HepG2 cells, vildagliptin directly reduced ER stress. Therefore, vildagliptin may be a potential agent for nonalcoholic fatty liver disease.

Effects of Kombucha on oxidative stress induced nephrotoxicity in rats

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Gharib Ola

2009-11-01

Full Text Available Abstract Background Trichloroethylene (TCE may induce oxidative stress which generates free radicals and alters antioxidants or oxygen-free radical scavenging enzymes. Methods Twenty male albino rats were divided into four groups: (1 the control group treated with vehicle, (2 Kombucha (KT-treated group, (3 TCE-treated group and (4 KT/TCE-treated group. Kidney lipid peroxidation, glutathione content, nitric oxide (NO and total blood free radical concentrations were evaluated. Serum urea, creatinine level, gamma-glutamyl transferase (GGT and lactate dehydrogenase (LDH activities were also measured. Results TCE administration increased the malondiahyde (MDA and NO contents in kidney, urea and creatinine concentrations in serum, total free radical level in blood and GGT and LDH activities in serum, whereas it decreased the glutathione (GSH level in kidney homogenate. KT administration significantly improved lipid peroxidation and oxidative stress induced by TCE. Conclusion The present study indicates that Kombucha may repair damage caused by environmental pollutants such as TCE and may be beneficial to patient suffering from renal impairment.

Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

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Magdalena Cristóbal-García

2015-01-01

Full Text Available We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks and short-term (3 weeks effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW, OA+Allopurinol (AP, 150 mg/L drinking water, OA+Tempol (T, 15 mg/kg BW, or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase and oxidative stress markers (lipid and protein oxidation along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.

Stress leads to contrasting effects on the levels of brain derived neurotrophic factor in the hippocampus and amygdala.

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Harini Lakshminarasimhan

Full Text Available Recent findings on stress induced structural plasticity in rodents have identified important differences between the hippocampus and amygdala. The same chronic immobilization stress (CIS, 2 h/day causes growth of dendrites and spines in the basolateral amygdala (BLA, but dendritic atrophy in hippocampal area CA3. CIS induced morphological changes also differ in their temporal longevity--BLA hypertrophy, unlike CA3 atrophy, persists even after 21 days of stress-free recovery. Furthermore, a single session of acute immobilization stress (AIS, 2 h leads to a significant increase in spine density 10 days, but not 1 day, later in the BLA. However, little is known about the molecular correlates of the differential effects of chronic and acute stress. Because BDNF is known to be a key regulator of dendritic architecture and spines, we investigated if the levels of BDNF expression reflect the divergent effects of stress on the hippocampus and amygdala. CIS reduces BDNF in area CA3, while it increases it in the BLA of male Wistar rats. CIS-induced increase in BDNF expression lasts for at least 21 days after the end of CIS in the BLA. But CIS-induced decrease in area CA3 BDNF levels, reverses to normal levels within the same period. Finally, BDNF is up regulated in the BLA 1 day after AIS and this increase persists even 10 days later. In contrast, AIS fails to elicit any significant change in area CA3 at either time points. Together, these findings demonstrate that both acute and chronic stress trigger opposite effects on BDNF levels in the BLA versus area CA3, and these divergent changes also follow distinct temporal profiles. These results point to a role for BDNF in stress-induced structural plasticity across both hippocampus and amygdala, two brain areas that have also been implicated in the cognitive and affective symptoms of stress-related psychiatric disorders.

Hepcidin is an antibacterial, stress-inducible peptide of the biliary system.

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Pavel Strnad

Full Text Available BACKGROUND/AIMS: Hepcidin (gene name HAMP, an IL-6-inducible acute phase peptide with antimicrobial properties, is the key negative regulator of iron metabolism. Liver is the primary source of HAMP synthesis, but it is also produced by other tissues such as kidney or heart and is found in body fluids such as urine or cerebrospinal fluid. While the role of hepcidin in biliary system is unknown, a recent study demonstrated that conditional gp130-knockout mice display diminished hepcidin levels and increased rate of biliary infections. METHODS: Expression and localization of HAMP in biliary system was analyzed by real time RT-PCR, in-situ hybridization, immunostaining and -blotting, while prohepcidin levels in human bile were determined by ELISA. RESULTS: Hepcidin was detected in mouse/human gallbladder and bile duct epithelia. Biliary HAMP is stress-inducible, in that it is increased in biliary cell lines upon IL-6 stimulation and in gallbladder mucosa of patients with acute cholecystitis. Hepcidin is also present in the bile and elevated prohepcidin levels were observed in bile of primary sclerosing cholangitis (PSC patients with concurrent bacterial cholangitis compared to PSC subjects without bacterial infection (median values 22.3 vs. 8.9; p = 0.03. In PSC-cholangitis subjects, bile prohepcidin levels positively correlated with C-reactive protein and bilirubin levels (r = 0.48 and r = 0.71, respectively. In vitro, hepcidin enhanced the antimicrobial capacity of human bile (p<0.05. CONCLUSION: Hepcidin is a stress-inducible peptide of the biliary epithelia and a potential marker of biliary stress. In the bile, hepcidin may serve local functions such as protection from bacterial infections.

Stress- and glucocorticoid-induced priming of neuroinflammatory responses: potential mechanisms of stress-induced vulnerability to drugs of abuse.

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Frank, Matthew G; Watkins, Linda R; Maier, Steven F

2011-06-01

Stress and stress-induced glucocorticoids (GCs) sensitize drug abuse behavior as well as the neuroinflammatory response to a subsequent pro-inflammatory challenge. Stress also predisposes or sensitizes individuals to develop substance abuse. There is an emerging evidence that glia and glia-derived neuroinflammatory mediators play key roles in the development of drug abuse. Drugs of abuse such as opioids, psychostimulants, and alcohol induce neuroinflammatory mediators such as pro-inflammatory cytokines (e.g. interleukin (IL)-1β), which modulate drug reward, dependence, and tolerance as well as analgesic properties. Drugs of abuse may directly activate microglial and astroglial cells via ligation of Toll-like receptors (TLRs), which mediate the innate immune response to pathogens as well as xenobiotic agents (e.g. drugs of abuse). The present review focuses on understanding the immunologic mechanism(s) whereby stress primes or sensitizes the neuroinflammatory response to drugs of abuse and explores whether stress- and GC-induced sensitization of neuroimmune processes predisposes individuals to drug abuse liability and the role of neuroinflammatory mediators in the development of drug addiction. Copyright © 2011 Elsevier Inc. All rights reserved.

Melamine Induces Oxidative Stress in Mouse Ovary.

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Xiao-Xin Dai

Full Text Available Melamine is a nitrogen heterocyclic triazine compound which is widely used as an industrial chemical. Although melamine is not considered to be acutely toxic with a high LD50 in animals, food contaminated with melamine expose risks to the human health. Melamine has been reported to be responsible for the renal impairment in mammals, its toxicity on the reproductive system, however, has not been adequately assessed. In the present study, we examined the effect of melamine on the follicle development and ovary formation. The data showed that melamine increased reactive oxygen species (ROS levels, and induced granulosa cell apoptosis as well as follicle atresia. To further analyze the mechanism by which melamine induces oxidative stress, the expression and activities of two key antioxidant enzymes superoxide dismutase (SOD and glutathione peroxidase (GPX were analyzed, and the concentration of malondialdehyde (MDA were compared between control and melamine-treated ovaries. The result revealed that melamine changed the expression and activities of SOD and GPX in the melamine-treated mice. Therefore, we demonstrate that melamine causes damage to the ovaries via oxidative stress pathway.

Buffer modulation of menadione-induced oxidative stress in Saccharomyces cerevisiae.

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Lushchak, Oleh V; Bayliak, Maria M; Korobova, Olha V; Levine, Rodney L; Lushchak, Volodymyr I

2009-01-01

The objective of this study was to compare, in vivo, the effects of bicarbonate and phosphate buffers on survival and menadione-induced oxidative stress in yeast cells. The latter were treated with different concentrations of menadione in the presence of these two buffers. At 25 mM concentration of buffers, menadione only slightly reduced yeast surviving; at 50 mM concentration, cell killing by menadione was much more pronounced in bicarbonate than in phosphate buffer. Although the content of protein carbonyl groups did not show development of oxidative stress under menadione-induced stress, inactivation of aconitase and decrease in glutathione level mirrored its induction. However, cellular glutathione and aconitase activity decrease did not correlate with yeast survival. In vitro, aconitase was more quickly inactivated in 50 mM carbonate, than in 50 mM phosphate buffer. The possible involvement of the carbonate radical in these processes is discussed.

STRESS INDUCED OBESITY: LESSONS FROM RODENT MODELS OF STRESS

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Zachary Robert Patterson

2013-07-01

Full Text Available Stress is defined as the behavioral and physiological responses generated in the face of, or in anticipation of, a perceived threat. The stress response involves activation of the sympathetic nervous system and recruitment of the hypothalamic-pituitary-adrenal (HPA axis. When an organism encounters a stressor (social, physical, etc., these endogenous stress systems are stimulated in order to generate a fight-or-flight response, and manage the stressful situation. As such, an organism is forced to liberate energy resources in attempt to meet the energetic demands posed by the stressor. A change in the energy homeostatic balance is thus required to exploit an appropriate resource and deliver useable energy to the target muscles and tissues involved in the stress response. Acutely, this change in energy homeostasis and the liberation of energy is considered advantageous, as it is required for the survival of the organism. However, when an organism is subjected to a prolonged stressor, as is the case during chronic stress, a continuous irregularity in energy homeostasis is considered detrimental and may lead to the development of metabolic disturbances such as cardiovascular disease, type II diabetes mellitus and obesity. This concept has been studied extensively using animal models, and the neurobiological underpinnings of stress induced metabolic disorders are beginning to surface. However, different animal models of stress continue to produce divergent metabolic phenotypes wherein some animals become anorexic and loose body mass while others increase food intake and body mass and become vulnerable to the development of metabolic disturbances. It remains unclear exactly what factors associated with stress models can be used to predict the metabolic outcome of the organism. This review will explore a variety of rodent stress models and discuss the elements that influence the metabolic outcome in order to further our understanding of stress-induced

Biological effects of laser-induced stress waves

International Nuclear Information System (INIS)

Doukas, A.; Lee, S.; McAuliffe, D.

1995-01-01

Laser-induced stress waves can be generated by one of the following mechanisms: Optical breakdown, ablation or rapid heating of an absorbing medium. These three modes of laser interaction with matter allow the investigation of cellular and tissue responses to stress waves with different characteristics and under different conditions. The most widely studied phenomena are those of the collateral damage seen in photodisruption in the eye and in 193 run ablation of cornea and skin. On the other hand, the therapeutic application of laser-induced stress waves has been limited to the disruption of noncellular material such as renal stones, atheromatous plaque and vitreous strands. The effects of stress waves to cells and tissues can be quite disparate. Stress waves can fracture tissue, damage cells, and increase the permeability of the plasma membrane. The viability of cell cultures exposed to stress waves increases with the peak stress and the number of pulses applied. The rise time of the stress wave also influences the degree of cell injury. In fact, cell viability, as measured by thymidine incorporation, correlates better with the stress gradient than peak stress. Recent studies have also established that stress waves induce a transient increase of the permeability of the plasma membrane in vitro. In addition, if the stress gradient is below the damage threshhold, the cells remain viable. Thus, stress waves can be useful as a means of drug delivery, increasing the intracellular drug concentration and allowing the use of drugs which are impermeable to the cell membrane. The present studies show that it is important to create controllable stress waves. The wavelength tunability and the micropulse structure of the free electron laser is ideal for generating stress waves with independently adjustable parameters, such as rise time, duration and peak stress

Hesperidin, a citrus bioflavonoid, alleviates trichloroethylene-induced oxidative stress in Drosophila melanogaster.

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Abolaji, Amos Olalekan; Babalola, Oluwatoyin Victoria; Adegoke, Abimbola Kehinde; Farombi, Ebenezer Olatunde

2017-10-01

Trichloroethylene (TCE) is a chlorinated organic pollutant of groundwater with diverse toxic effects in animals and humans. Here, we investigated the ameliorative role of hesperidin, a citrus bioflavonoid on TCE-induced toxicity in Drosophila melanogaster. Four groups of D. melanogaster (50 flies/vial, with 5 vials/group) were exposed to ethanol (2.5%, control), HSP (400mg/10g diet), TCE (10μM/10g diet) and TCE (10μM/10g diet)+HSP (400mg/10g diet) respectively in the diet for 5days. Then, selected oxidative stress and antioxidant markers were evaluated. The results showed that TCE significantly increased the level of reactive oxygen species (ROS) and inhibited catalase, glutathione S-transferase and acetylcholinesterase (AChE) activities with concurrent depletion of total thiol level. However, co-administration of TCE and hesperidin mitigated TCE-induced depletion of antioxidants, and restored ROS level and AChE activity in the flies (p<0.05). Overall, hesperidin offered protective potency on TCE-induced oxidative stress in the flies via anti-oxidative mechanism. Copyright © 2017 Elsevier B.V. All rights reserved.

HCV-Induced Oxidative Stress: Battlefield-Winning Strategy

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Khadija Rebbani

2016-01-01

Full Text Available About 150 million people worldwide are chronically infected with hepatitis C virus (HCV. The persistence of the infection is controlled by several mechanisms including the induction of oxidative stress. HCV relies on this strategy to redirect lipid metabolism machinery and escape immune response. The 3β-hydroxysterol Δ24-reductase (DHCR24 is one of the newly discovered host markers of oxidative stress. This protein, as HCV-induced oxidative stress responsive protein, may play a critical role in the pathogenesis of HCV chronic infection and associated liver diseases, when aberrantly expressed. The sustained expression of DHCR24 in response to HCV-induced oxidative stress results in suppression of nuclear p53 activity by blocking its acetylation and increasing its interaction with MDM2 in the cytoplasm leading to its degradation, which may induce hepatocarcinogenesis.

Effects of induced stress on seismic forward modelling and inversion

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Tromp, Jeroen; Trampert, Jeannot

2018-05-01

We demonstrate how effects of induced stress may be incorporated in seismic modelling and inversion. Our approach is motivated by the accommodation of pre-stress in global seismology. Induced stress modifies both the equation of motion and the constitutive relationship. The theory predicts that induced pressure linearly affects the unstressed isotropic moduli with a slope determined by their adiabatic pressure derivatives. The induced deviatoric stress produces anisotropic compressional and shear wave speeds; the latter result in shear wave splitting. For forward modelling purposes, we determine the weak form of the equation of motion under induced stress. In the context of the inverse problem, we determine induced stress sensitivity kernels, which may be used for adjoint tomography. The theory is illustrated by considering 2-D propagation of SH waves and related Fréchet derivatives based on a spectral-element method.

Pre-cold stress increases acid stress resistance and induces amino ...

African Journals Online (AJOL)

pre-adapted to cold stress revealed induction of amino acid homeostasis and energy ... substrate, thereby reducing yeast and mould ..... spontaneous mutation of llmg_1816 (gdpp) induced by .... species to UV-B-induced damage in bacteria. J.

An efficient chronic unpredictable stress protocol to induce stress-related responses in C57BL/6 mice.

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Monteiro, Susana; Roque, Susana; de Sá-Calçada, Daniela; Sousa, Nuno; Correia-Neves, Margarida; Cerqueira, João José

2015-01-01

Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS) protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent, and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alterations typical of the chronic stress-response. Unfortunately C57BL/6 mice, one of the most widely used mouse strains, due to the great variety of genetically modified lines, seem to be resistant to the commonly used 4-week-long CUS protocol. The definition of an alternative CUS protocol allowing the use of C57BL/6 mice in chronic stress experiments is a need. Here, we show that by extending the CUS protocol to 8 weeks is possible to induce a chronic stress-response in C57BL/6 mice, as revealed by abrogated body weight gain, increased adrenals weight, and an overactive hypothalamic-pituitary-adrenal axis with increased levels of serum corticosterone. Moreover, we also observed stress-associated behavioral alterations, including the potentiation of anxious-like and depressive-like behaviors and a reduction of exploratory behavior, as well as subtle stress-related changes in the cell population of the thymus and of the spleen. The present protocol for C57BL/6 mice consistently triggers the spectrum of CUS-induced changes observed in rats and, thus, will be highly useful to researchers that need to use this particular mouse strain as an animal model of neuropsychiatric disorders and/or immune deregulation related to CUS.

Oxidative stress induces senescence in human mesenchymal stem cells

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Brandl, Anita [Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Meyer, Matthias; Bechmann, Volker [Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Nerlich, Michael [Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Angele, Peter, E-mail: Peter.Angele@klinik.uni-regensburg.de [Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany)

2011-07-01

Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of MSCs, subject to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by rtPCR. Sub-lethal doses of oxidative stress reduced proliferation rates and induced senescent-morphological features and senescence-associated {beta}-galactosidase positivity. Prolonged low dose treatment with hydrogen peroxide had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. Following acute oxidant insult p21 was up-regulated prior to returning to initial levels. TRF1 was significantly reduced, TRF2 showed a slight up-regulation. SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells. Compared to fibroblasts and chondrocytes, MSCs showed an increased tolerance to oxidative stress regarding proliferation, telomere biology and gene expression with an impaired stress tolerance in aged cells.

Mycobacterium tuberculosis has diminished capacity to counteract redox stress induced by elevated levels of endogenous superoxide.

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Tyagi, Priyanka; Dharmaraja, Allimuthu T; Bhaskar, Ashima; Chakrapani, Harinath; Singh, Amit

2015-07-01

Mycobacterium tuberculosis (Mtb) has evolved protective and detoxification mechanisms to maintain cytoplasmic redox balance in response to exogenous oxidative stress encountered inside host phagocytes. In contrast, little is known about the dynamic response of this pathogen to endogenous oxidative stress generated within Mtb. Using a noninvasive and specific biosensor of cytoplasmic redox state of Mtb, we for first time discovered a surprisingly high sensitivity of this pathogen to perturbation in redox homeostasis induced by elevated endogenous reactive oxygen species (ROS). We synthesized a series of hydroquinone-based small molecule ROS generators and found that ATD-3169 permeated mycobacteria to reliably enhance endogenous ROS including superoxide radicals. When Mtb strains including multidrug-resistant (MDR) and extensively drug-resistant (XDR) patient isolates were exposed to this compound, a dose-dependent, long-lasting, and irreversible oxidative shift in intramycobacterial redox potential was detected. Dynamic redox potential measurements revealed that Mtb had diminished capacity to restore cytoplasmic redox balance in comparison with Mycobacterium smegmatis (Msm), a fast growing nonpathogenic mycobacterial species. Accordingly, Mtb strains were extremely susceptible to inhibition by ATD-3169 but not Msm, suggesting a functional linkage between dynamic redox changes and survival. Microarray analysis showed major realignment of pathways involved in redox homeostasis, central metabolism, DNA repair, and cell wall lipid biosynthesis in response to ATD-3169, all consistent with enhanced endogenous ROS contributing to lethality induced by this compound. This work provides empirical evidence that the cytoplasmic redox poise of Mtb is uniquely sensitive to manipulation in steady-state endogenous ROS levels, thus revealing the importance of targeting intramycobacterial redox metabolism for controlling TB infection. Copyright © 2015 The Authors. Published by

Neural correlates of stress- and food cue-induced food craving in obesity: association with insulin levels.

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Jastreboff, Ania M; Sinha, Rajita; Lacadie, Cheryl; Small, Dana M; Sherwin, Robert S; Potenza, Marc N

2013-02-01

Obesity is associated with alterations in corticolimbic-striatal brain regions involved in food motivation and reward. Stress and the presence of food cues may each motivate eating and engage corticolimibic-striatal neurocircuitry. It is unknown how these factors interact to influence brain responses and whether these interactions are influenced by obesity, insulin levels, and insulin sensitivity. We hypothesized that obese individuals would show greater responses in corticolimbic-striatal neurocircuitry after exposure to stress and food cues and that brain activations would correlate with subjective food craving, insulin levels, and HOMA-IR. Fasting insulin levels were assessed in obese and lean subjects who were exposed to individualized stress and favorite-food cues during functional MRI. Obese, but not lean, individuals exhibited increased activation in striatal, insular, and hypothalamic regions during exposure to favorite-food and stress cues. In obese but not lean individuals, food craving, insulin, and HOMA-IR levels correlated positively with neural activity in corticolimbic-striatal brain regions during favorite-food and stress cues. The relationship between insulin resistance and food craving in obese individuals was mediated by activity in motivation-reward regions including the striatum, insula, and thalamus. These findings demonstrate that obese, but not lean, individuals exhibit increased corticolimbic-striatal activation in response to favorite-food and stress cues and that these brain responses mediate the relationship between HOMA-IR and food craving. Improving insulin sensitivity and in turn reducing corticolimbic-striatal reactivity to food cues and stress may diminish food craving and affect eating behavior in obesity.

Encapsulation-Induced Stress Helps Saccharomyces cerevisiae Resist Convertible Lignocellulose Derived Inhibitors

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Johan O. Westman

2012-09-01

Full Text Available The ability of macroencapsulated Saccharomyces cerevisiae CBS8066 to withstand readily and not readily in situ convertible lignocellulose-derived inhibitors was investigated in anaerobic batch cultivations. It was shown that encapsulation increased the tolerance against readily convertible furan aldehyde inhibitors and to dilute acid spruce hydrolysate, but not to organic acid inhibitors that cannot be metabolized anaerobically. Gene expression analysis showed that the protective effect arising from the encapsulation is evident also on the transcriptome level, as the expression of the stress-related genes YAP1, ATR1 and FLR1 was induced upon encapsulation. The transcript levels were increased due to encapsulation already in the medium without added inhibitors, indicating that the cells sensed low stress level arising from the encapsulation itself. We present a model, where the stress response is induced by nutrient limitation, that this helps the cells to cope with the increased stress added by a toxic medium, and that superficial cells in the capsules degrade convertible inhibitors, alleviating the inhibition for the cells deeper in the capsule.

Sodium Phenylbutyrate and Edaravone Abrogate Chronic Restraint Stress-Induced Behavioral Deficits: Implication of Oxido-Nitrosative, Endoplasmic Reticulum Stress Cascade, and Neuroinflammation.

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Jangra, Ashok; Sriram, Chandra Shaker; Dwivedi, Shubham; Gurjar, Satendra Singh; Hussain, Md Iftikar; Borah, Probodh; Lahkar, Mangala

2017-01-01

Chronic stress exposure can produce deleterious effects on the hippocampus (HC) which eventually leads to cognitive impairment and depression. Endoplasmic reticulum (ER) stress has been reported as one of the major culprits in the development of stress-induced cognitive impairment and depression. We investigated the neuroprotective efficacy of sodium phenylbutyrate (SPB), an ER stress inhibitor, and edaravone, a free radical scavenger, against chronic restraint stress (CRS)-induced cognitive deficits and anxiety- and depressive-like behavior in mice. Adult male Swiss albino mice were restrained for 6 h/day for 28 days and injected (i.p.) with SPB (40 and 120 mg/kg) or edaravone (3 and 10 mg/kg) for the last seven days. After stress cessation, the anxiety- and depressive-like behavior along with spatial learning and memory were examined. Furthermore, oxido-nitrosative stress, proinflammatory cytokines, and gene expression level of ER stress-related genes were assessed in HC and prefrontal cortex (PFC). CRS-exposed mice showed anxiety- and depressive-like behavior, which was significantly improved by SPB and edaravone treatment. In addition, SPB and edaravone treatment significantly alleviated CRS-induced spatial learning and memory impairment. Furthermore, CRS-evoked oxido-nitrosative stress, neuroinflammation, and depletion of Brain-derived neurotrophic factor were significantly ameliorated by SPB and edaravone treatment. We found significant up-regulation of ER stress-related genes in both HC and PFC regions, which were suppressed by SPB and edaravone treatment in CRS mice. Our study provides evidence that SPB and edaravone exerted neuroprotective effects on CRS-induced cognitive deficits and anxiety- and depressive-like behavior, which is possibly coupled with inhibition of oxido-nitrosative stress, neuroinflammation, and ER stress cascade.

The Role of Musk in Relieving the Neurodegenerative Changes Induced After Exposure to Chronic Stress.

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Abd El Wahab, Manal Galal; Ali, Soad Shaker; Ayuob, Nasra Naeim

2018-06-01

This study aimed to evaluate the effect induced by musk on Alzheimer's disease-such as neurodegenerative changes in mice exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice were divided into 4 groups (n = 10); control, CUMS, CUMS + fluoxetine, CUMS + musk. At the end of the experiment, behavior of the mice was assessed. Serum corticosterone level, hippocampal protein level of the glucocorticoid receptors, and brain-derived neurotropic factor were also assessed. Hippocampus was histopathologically examined. Musk improved depressive status induced after exposure to CUMS as evidenced by the forced swimming and open field tests and improved the short-term memory as evidenced by the elevated plus maze test. Musk reduced both corticosterone levels and the hippocampal neurodegenerative changes observed after exposure to CUMS. These improvements were comparable to those induced by fluoxetine. Musk alleviated the memory impairment and neurodegenerative changes induced after exposure to the chronic stress.

A large-scale perspective on stress-induced alterations in resting-state networks

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Maron-Katz, Adi; Vaisvaser, Sharon; Lin, Tamar; Hendler, Talma; Shamir, Ron

2016-02-01

Stress is known to induce large-scale neural modulations. However, its neural effect once the stressor is removed and how it relates to subjective experience are not fully understood. Here we used a statistically sound data-driven approach to investigate alterations in large-scale resting-state functional connectivity (rsFC) induced by acute social stress. We compared rsfMRI profiles of 57 healthy male subjects before and after stress induction. Using a parcellation-based univariate statistical analysis, we identified a large-scale rsFC change, involving 490 parcel-pairs. Aiming to characterize this change, we employed statistical enrichment analysis, identifying anatomic structures that were significantly interconnected by these pairs. This analysis revealed strengthening of thalamo-cortical connectivity and weakening of cross-hemispheral parieto-temporal connectivity. These alterations were further found to be associated with change in subjective stress reports. Integrating report-based information on stress sustainment 20 minutes post induction, revealed a single significant rsFC change between the right amygdala and the precuneus, which inversely correlated with the level of subjective recovery. Our study demonstrates the value of enrichment analysis for exploring large-scale network reorganization patterns, and provides new insight on stress-induced neural modulations and their relation to subjective experience.

Light and abiotic stresses regulate the expression of GDP-L-galactose phosphorylase and levels of ascorbic acid in two kiwifruit genotypes via light-responsive and stress-inducible cis-elements in their promoters.

Science.gov (United States)

Li, Juan; Liang, Dong; Li, Mingjun; Ma, Fengwang

2013-09-01

Ascorbic acid (AsA) plays an essential role in plants by protecting cells against oxidative damage. GDP-L-galactose phosphorylase (GGP) is the first committed gene for AsA synthesis. Our research examined AsA levels, regulation of GGP gene expression, and how these are related to abiotic stresses in two species of Actinidia (kiwifruit). When leaves were subjected to continuous darkness or light, ABA or MeJA, heat, or a hypoxic environment, we found some correlation between the relative levels of GGP mRNA and AsA concentrations. In transformed tobacco plants, activity of the GGP promoter was induced by all of these treatments. However, the degree of inducibility in the two kiwifruit species differed among the GGP promoter deletions. We deduced that the G-box motif, a light-responsive element, may have an important function in regulating GGP transcripts under various light conditions in both A. deliciosa and A. eriantha. Other elements such as ABRE, the CGTCA motif, and HSE might also control the promoter activities of GGP in kiwifruit. Altogether, these data suggest that GGP expression in the two kiwifruit species is regulated by light or abiotic stress via the relative cis-elements in their promoters. Furthermore, GGP has a critical role in modulating AsA concentrations in kiwifruit species under abiotic stresses.

Indagation of serum and salivary reactive oxygen metabolite and cortisol levels in chronic periodontitis and stress-induced chronic periodontitis patients.

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Sudhakar, Uma; Thyagarajan, Ramakrishnan; Jeyapal, Bhagyameena; Jagadeesh, Sushuruthi; Jayakumar, Parvathee

2017-01-01

Periodontal disease is not a conventional bacterial infection but is an inflammatory disease initiated by immune response against a group of microorganisms in susceptible hosts. There are many intriguing researches that unfold the secrets of chronic periodontitis. The current researches in chronic periodontitis are directed toward an approach that respects the scientific relationship between the various risk factors, the genetic factors, and the progression of the disease. This study aims to evaluate the cortisol and reactive oxygen metabolites (ROM) concentration in serum and to find out their association in periodontal health and disease. In this study, totally thirty patients have been taken and divided into two groups of chronic periodontitis (Group I) and stress-induced chronic periodontitis (Group II) and evaluated the correlation between the ROM and cortisol levels in them. This is the first study, where both the levels of ROM and cortisol are checked in the serum and saliva. The analysis is done to check the association between them. The data were statistically analyzed using software program (SPSSV 16), Pearson correlation, and paired t -test. Comparison of the mean ROM levels in Group I and Group II showed that mean ROM level in Group II is highly significant than Group I. Our study suggests that stress can have a role in the progression of periodontal disease by increasing the cortisol and ROM levels.

Central mechanisms of stress-induced headache.

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Cathcart, S; Petkov, J; Winefield, A H; Lushington, K; Rolan, P

2010-03-01

Stress is the most commonly reported trigger of an episode of chronic tension-type headache (CTTH); however, the causal significance has not been experimentally demonstrated to date. Stress may trigger CTTH through hyperalgesic effects on already sensitized pain pathways in CTTH sufferers. This hypothesis could be partially tested by examining pain sensitivity in an experimental model of stress-induced headache in CTTH sufferers. Such examinations have not been reported to date. We measured pericranial muscle tenderness and pain thresholds at the finger, head and shoulder in 23 CTTH sufferers (CTH-S) and 25 healthy control subjects (CNT) exposed to an hour-long stressful mental task, and in 23 CTTH sufferers exposed to an hour-long neutral condition (CTH-N). Headache developed in 91% of CTH-S, 4% of CNT, and 17% of CTH-N subjects. Headache sufferers had increased muscle tenderness and reduced pain thresholds compared with healthy controls. During the task, muscle tenderness increased and pain thresholds decreased in the CTH-S group compared with CTH-N and CNT groups. Pre-task muscle tenderness and reduction in pain threshold during task were predictive of the development and intensity of headache following task. The main findings are that stress induced a headache in CTTH sufferers, and this was associated with pre-task muscle tenderness and stress-induced reduction in pain thresholds. The results support the hypothesis that stress triggers CTTH through hyperalgesic effects on already increased pain sensitivity in CTTH sufferers, reducing the threshold to noxious input from pericranial structures.

An efficient chronic unpredictable stress protocol to induce stress-related responses in C57BL/6 mice

Directory of Open Access Journals (Sweden)

Susana eMonteiro

2015-02-01

Full Text Available Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alterations typical of the chronic stress response. Unfortunately C57BL/6 mice, one of the most widely used mouse strains, due to the great variety of genetically modified lines, seem to be resistant to the commonly used 4-week-long CUS protocol. The definition of an alternative CUS protocol allowing the use of C57BL/6 mice in chronic stress experiments is a need. Here we show that by extending the CUS protocol to 8 weeks is possible to induce a chronic stress response in C57BL/6 mice, as revealed by abrogated body weight gain, increased adrenals weight and an overactive hypothalamic-pituitary-adrenal (HPA axis with increased levels of serum corticosterone. Moreover, we also observed stress-associated behavioral alterations, including the potentiation of anxious-like and depressive-like behaviors and a reduction of exploratory behavior, as well as subtle stress-related changes in the cell population of the thymus and of the spleen.The present protocol for C57BL/6 mice consistently triggers the spectrum of CUS-induced changes observed in rats and, thus, will be highly useful to researchers that need to use this particular mouse strain as an animal model of neuropsychiatric disorders and/or immune deregulation related to chronic unpredictable stress.

Does stress induce (para)sex? Implications for Candida albicans evolution.

Science.gov (United States)

Berman, Judith; Hadany, Lilach

2012-05-01

Theory predicts that stress is a key factor in explaining the evolutionary role of sex in facultatively sexual organisms, including microorganisms. Organisms capable of reproducing both sexually and asexually are expected to mate more frequently when stressed, and such stress-induced mating is predicted to facilitate adaptation. Here, we propose that stress has an analogous effect on the parasexual cycle in Candida albicans, which involves alternation of generations between diploid and tetraploid cells. The parasexual cycle can generate high levels of diversity, including aneuploidy, yet it apparently occurs only rarely in nature. We review the evidence that stress facilitates four major steps in the parasexual cycle and suggest that parasex occurs much more frequently under stress conditions. This may explain both the evolutionary significance of parasex and its apparent rarity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Diabetic Cardiovascular Disease Induced by Oxidative Stress

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Yosuke Kayama

2015-10-01

Full Text Available Cardiovascular disease (CVD is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM. DM can lead to multiple cardiovascular complications, including coronary artery disease (CAD, cardiac hypertrophy, and heart failure (HF. HF represents one of the most common causes of death in patients with DM and results from DM-induced CAD and diabetic cardiomyopathy. Oxidative stress is closely associated with the pathogenesis of DM and results from overproduction of reactive oxygen species (ROS. ROS overproduction is associated with hyperglycemia and metabolic disorders, such as impaired antioxidant function in conjunction with impaired antioxidant activity. Long-term exposure to oxidative stress in DM induces chronic inflammation and fibrosis in a range of tissues, leading to formation and progression of disease states in these tissues. Indeed, markers for oxidative stress are overexpressed in patients with DM, suggesting that increased ROS may be primarily responsible for the development of diabetic complications. Therefore, an understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of diabetes-induced CVD. The current review focuses on the relationship between diabetes-induced CVD and oxidative stress, while highlighting the latest insights into this relationship from findings on diabetic heart and vascular disease.

Metformin induces oxidative stress in white adipocytes and raises uncoupling protein 2 levels.

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Anedda, Andrea; Rial, Eduardo; González-Barroso, M Mar

2008-10-01

Metformin is a drug widely used to treat type 2 diabetes. It enhances insulin sensitivity by improving glucose utilization in tissues like liver or muscle. Metformin inhibits respiration, and the decrease in cellular energy activates the AMP-activated protein kinase that in turn switches on catabolic pathways. Moreover, metformin increases lipolysis and beta-oxidation in white adipose tissue, thereby reducing the triglyceride stores. The uncoupling proteins (UCPs) are transporters that lower the efficiency of mitochondrial oxidative phosphorylation. UCP2 is thought to protect against oxidative stress although, alternatively, it could play an energy dissipation role. The aim of this work was to analyse the involvement of UCP2 on the effects of metformin in white adipocytes. We studied the effect of this drug in differentiating 3T3-L1 adipocytes and found that metformin causes oxidative stress since it increases the levels of reactive oxygen species (ROS) and lowers the aconitase activity. Variations in UCP2 protein levels parallel those of ROS. Metformin also increases lipolysis in these cells although only when the levels of ROS and UCP2 have decreased. Hence, UCP2 does not appear to be needed to facilitate fatty acid oxidation. Furthermore, treatment of C57BL/6 mice with metformin also augmented the levels of UCP2 in epididymal white adipose tissue. We conclude that metformin treatment leads to the overexpression of UCP2 in adipocytes to minimize the oxidative stress that is probably due to the inhibition of respiration caused by the drug.

Evaluation of mechano-chemical degradation induced stresses of polyolefin pipes

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Choi, Byoung Ho [Korea Univ., Seoul (Korea, Republic of); Chudnovsky, Alexander [The University of Illinois, Chicago (United States)

2008-07-01

The fracture phenomena in engineering thermoplastics resulting from chemical degradation is usually observed in the form of a microcrack network within a surface layer of degraded polymer exposed to a combined action of mechanical stresses and chemically aggressive environment. Degradation of polymers is usually manifested in a reduction of molecular weight, increase of crystallinity in semi crystalline polymers, increase of material density, a subtle increase in yield strength, and a dramatic reduction in toughness. The critical level of degradation for fracture initiation depends on the rates of toughness deterioration and build-up of the degradation related stresses as well as on the manufacturing and service stresses. In this paper, the evaluation of mechano-chemical degradation induced stress is attempted, and the application of the evaluated stress to the fracture initiation of polymer pipes is presented.

Evaluation of mechano-chemical degradation induced stresses of polyolefin pipes

International Nuclear Information System (INIS)

Choi, Byoung Ho; Chudnovsky, Alexander

2008-01-01

The fracture phenomena in engineering thermoplastics resulting from chemical degradation is usually observed in the form of a microcrack network within a surface layer of degraded polymer exposed to a combined action of mechanical stresses and chemically aggressive environment. Degradation of polymers is usually manifested in a reduction of molecular weight, increase of crystallinity in semi crystalline polymers, increase of material density, a subtle increase in yield strength, and a dramatic reduction in toughness. The critical level of degradation for fracture initiation depends on the rates of toughness deterioration and build-up of the degradation related stresses as well as on the manufacturing and service stresses. In this paper, the evaluation of mechano-chemical degradation induced stress is attempted, and the application of the evaluated stress to the fracture initiation of polymer pipes is presented

The role of heat shock protein 70 in oxidant stress and inflammatory injury in quail spleen induced by cold stress.

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Ren, Jiayi; Liu, Chunpeng; Zhao, Dan; Fu, Jing

2018-05-15

The aim of this study was to investigate the role of heat shock protein 70 (Hsp70) in oxidative stress and inflammatory damage in the spleen of quails which were induced by cold stress. One hundred ninety-two 15-day-old male quails were randomly divided into 12 groups and kept at 12 ± 1 °C to examine acute and chronic cold stress. We first detected the changes in activities of antioxidant enzymes in the spleen tissue under acute and chronic cold stress. The activities of glutathione peroxidase (GSH-Px) fluctuated in acute cold stress groups, while they were significantly decreased (p stress. The activities of superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS), and nitric oxide (NO) content were decreased significantly (p stress groups. Malondialdehyde (MDA) content was significantly increased (p stress except the 0.5 h group of acute cold stress. Besides, histopathological analysis showed that quail's spleen tissue was inflammatory injured seriously in both the acute and chronic cold stress groups. Additionally, the inflammatory factors (cyclooxygenase-2 (COX-2), prostaglandin E synthase (PTGES), iNOS, nuclear factor-kappa B (NF-κB), and tumor necrosis factor-a (TNF-α)) and Hsp70 mRNA levels were increased in both of the acute and chronic cold stress groups compared with the control groups. These results suggest that oxidative stress and inflammatory injury could be induced by cold stress in spleen tissues of quails. Furthermore, the increased expression of Hsp70 may play a role in protecting the spleen against oxidative stress and inflammatory damage caused by cold stress.

Gemfibrozil pretreatment proved protection against acute restraint stress-induced changes in the male rats' hippocampus.

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Khalaj, Leila; Nejad, Sara Chavoshi; Mohammadi, Marzieh; Zadeh, Sadaf Sarraf; Pour, Marieh Hossein; Ahmadiani, Abolhassan; Khodagholi, Fariba; Ashabi, Ghorbangol; Alamdary, Shabnam Zeighamy; Samami, Elham

2013-08-21

Stress predisposes the brain to various neuropathological disorders. Fibrates like gemfibrozil, commonly used for hyperlipidemia, have not yet been examined for their protective/deteriorative potential against restraint stress-induced disturbances. Pretreatment of rats with a range of gemfibrozil concentrations showed significant protection against stress consequences at 90 mg/kg of gemfibrozil, as it resulted in the highest level of antioxidant defense system potentiation among other doses. It also reduced plasma corticosterone compared with the stressed animals. Administration of gemfibrozil (90 mg/kg) before stress induction was able to significantly induce the protein levels of some protective factors including hemeoxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone-1 (NQO-1) in the antioxidant nuclear factor erythroid-derived 2-like 2 (Nrf-2) pathway, as well as mitochondrial pro-survival proteins, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and nuclear respiratory factor 1 (NRF-1). In parallel, the level of cleaved caspase-3 and apoptosis-inducing factor (AIF), two proteins involved in apoptotic cell death, and the number of damaged neurons detected in hematoxylin-eosin (H&E) stained hippocampus sections were suppressed in the presence of gemfibrozil. Herein, although gemfibrozil demonstrated protection against the restraint stress, considering its dose and context-dependent effects reported in the previous studies, as well as its common application in clinic, further investigations are essential to unravel its exact beneficial/deleterious effects in various neuronal contexts. Copyright © 2013 Elsevier B.V. All rights reserved.

Ghrelin mediates stress-induced food-reward behavior in mice.

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Chuang, Jen-Chieh; Perello, Mario; Sakata, Ichiro; Osborne-Lawrence, Sherri; Savitt, Joseph M; Lutter, Michael; Zigman, Jeffrey M

2011-07-01

The popular media and personal anecdotes are rich with examples of stress-induced eating of calorically dense "comfort foods." Such behavioral reactions likely contribute to the increased prevalence of obesity in humans experiencing chronic stress or atypical depression. However, the molecular substrates and neurocircuits controlling the complex behaviors responsible for stress-based eating remain mostly unknown, and few animal models have been described for probing the mechanisms orchestrating this response. Here, we describe a system in which food-reward behavior, assessed using a conditioned place preference (CPP) task, is monitored in mice after exposure to chronic social defeat stress (CSDS), a model of prolonged psychosocial stress, featuring aspects of major depression and posttraumatic stress disorder. Under this regime, CSDS increased both CPP for and intake of high-fat diet, and stress-induced food-reward behavior was dependent on signaling by the peptide hormone ghrelin. Also, signaling specifically in catecholaminergic neurons mediated not only ghrelin's orexigenic, antidepressant-like, and food-reward behavioral effects, but also was sufficient to mediate stress-induced food-reward behavior. Thus, this mouse model has allowed us to ascribe a role for ghrelin-engaged catecholaminergic neurons in stress-induced eating.

Secondhand smoke exposure induces acutely airway acidification and oxidative stress.

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Kostikas, Konstantinos; Minas, Markos; Nikolaou, Eftychia; Papaioannou, Andriana I; Liakos, Panagiotis; Gougoura, Sofia; Gourgoulianis, Konstantinos I; Dinas, Petros C; Metsios, Giorgos S; Jamurtas, Athanasios Z; Flouris, Andreas D; Koutedakis, Yiannis

2013-02-01

Previous studies have shown that secondhand smoke induces lung function impairment and increases proinflammatory cytokines. The aim of the present study was to evaluate the acute effects of secondhand smoke on airway acidification and airway oxidative stress in never-smokers. In a randomized controlled cross-over trial, 18 young healthy never-smokers were assessed at baseline and 0, 30, 60, 120, 180 and 240 min after one-hour secondhand smoke exposure at bar/restaurant levels. Exhaled NO and CO measurements, exhaled breath condensate collection (for pH, H(2)O(2) and NO(2)(-)/NO(3)(-) measurements) and spirometry were performed at all time-points. Secondhand smoke exposure induced increases in serum cotinine and exhaled CO that persisted until 240 min. Exhaled breath condensate pH decreased immediately after exposure (p secondhand smoke induced airway acidification and increased airway oxidative stress, accompanied by significant impairment of lung function. Despite the reversal in EBC pH and lung function, airway oxidative stress remained increased 4 h after the exposure. Clinical trial registration number (EudraCT): 2009-013545-28. Copyright © 2012 Elsevier Ltd. All rights reserved.

Impact of mechanical stress induced in silica vacuum windows on laser-induced damage.

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Gingreau, Clémence; Lanternier, Thomas; Lamaignère, Laurent; Donval, Thierry; Courchinoux, Roger; Leymarie, Christophe; Néauport, Jérôme

2018-04-15

At the interface between vacuum and air, optical windows must keep their optical properties, despite being subjected to mechanical stress. In this Letter, we investigate the impact of such stress on the laser-induced damage of fused silica windows at the wavelength of 351 nm in the nanosecond regime. Different stress values, from 1 to 30 MPa, both tensile and compressive, were applied. No effect of the stress on the laser-induced damage was evidenced.

Prioritized expression of BTN2 of Saccharomyces cerevisiae under pronounced translation repression induced by severe ethanol stress

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Yukina Yamauchi

2016-08-01

Full Text Available Severe ethanol stress (>9% ethanol, v/v as well as glucose deprivation rapidly induces a pronounced repression of overall protein synthesis in budding yeast Saccharomyces cerevisiae. Therefore, transcriptional activation in yeast cells under severe ethanol stress does not always indicate the production of expected protein levels. Messenger RNAs of genes containing heat shock elements can be intensively translated under glucose deprivation, suggesting that some mRNAs are preferentially translated even under severe ethanol stress. In the present study, we tried to identify the mRNA that can be preferentially translated under severe ethanol stress. BTN2 encodes a v-SNARE binding protein, and its null mutant shows hypersensitivity to ethanol. We found that BTN2 mRNA was efficiently translated under severe ethanol stress but not under mild ethanol stress. Moreover, the increased Btn2 protein levels caused by severe ethanol stress were smoothly decreased with the elimination of ethanol stress. These findings suggested that severe ethanol stress extensively induced BTN2 expression. Further, the BTN2 promoter induced protein synthesis of non-native genes such as CUR1, GIC2, and YUR1 in the presence of high ethanol concentrations, indicating that this promoter overcame severe ethanol stress-induced translation repression. Thus, our findings provide an important clue about yeast response to severe ethanol stress and suggest that the BTN2 promoter can be used to improve the efficiency of ethanol production and stress tolerance of yeast cells by modifying gene expression in the presence of high ethanol concentration.

Repeated restraint stress exposure during early withdrawal accelerates incubation of cue-induced cocaine craving.

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Glynn, Ryan M; Rosenkranz, J Amiel; Wolf, Marina E; Caccamise, Aaron; Shroff, Freya; Smith, Alyssa B; Loweth, Jessica A

2018-01-01

A major challenge for treating cocaine addiction is the propensity for abstinent users to relapse. Two important triggers for relapse are cues associated with prior drug use and stressful life events. To study their interaction in promoting relapse during abstinence, we used the incubation model of craving and relapse in which cue-induced drug seeking progressively intensifies ('incubates') during withdrawal from extended-access cocaine self-administration. We tested rats for cue-induced cocaine seeking on withdrawal day (WD) 1. Rats were then subjected to repeated restraint stress or control conditions (seven sessions held between WD6 and WD14). All rats were tested again for cue-induced cocaine seeking on WD15, 1 day after the last stress or control session. Although controls showed a time-dependent increase in cue-induced cocaine seeking (incubation), rats exposed to repeated stress in early withdrawal exhibited a more robust increase in seeking behavior between WD1 and WD15. In separate stressed and control rats, equivalent cocaine seeking was observed on WD48. These results indicate that repeated stress in early withdrawal accelerates incubation of cocaine craving, although craving plateaus at the same level were observed in controls. However, 1 month after the WD48 test, rats subjected to repeated stress in early withdrawal showed enhanced cue-induced cocaine seeking following acute (24 hours) food deprivation stress. Together, these data indicate that chronic stress exposure enhances the initial rate of incubation of craving during early withdrawal, resulting in increased vulnerability to cue-induced relapse during this period, and may lead to a persistent increase in vulnerability to the relapse-promoting effects of stress. © 2016 Society for the Study of Addiction.

Shear Stress Induces Phenotypic Modulation of Vascular Smooth Muscle Cells via AMPK/mTOR/ULK1-Mediated Autophagy.

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Sun, Liqian; Zhao, Manman; Liu, Aihua; Lv, Ming; Zhang, Jingbo; Li, Youxiang; Yang, Xinjian; Wu, Zhongxue

2018-03-01

Phenotypic modulation of vascular smooth muscle cells (VSMCs) is involved in the pathophysiological processes of the intracranial aneurysms (IAs). Although shear stress has been implicated in the proliferation, migration, and phenotypic conversion of VSMCs, the molecular mechanisms underlying these events are currently unknown. In this study, we investigated whether shear stress(SS)-induced VSMC phenotypic modulation was mediated by autophagy involved in adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/Unc-51-like kinase 1 (ULK1) pathway. The results show that shear stress could inhibit the expression of key VSMC contractile genes and induce pro-inflammatory/matrix-remodeling genes levels, contributing to VSMCs phenotypic switching from a contractile to a synthetic phenotype. More importantly, Shear stress also markedly increased the levels of the autophagy marker microtubule-associated protein light chain 3-II (LC3II), Beclin-1, and p62 degradation. The autophagy inhibitor 3-methyladenine (3-MA) significantly blocked shear-induced phenotypic modulation of VSMCs. To further explore the molecular mechanism involved in shear-induced autophagy, we found that shear stress could activate AMPK/mTOR/ULK1 signaling pathway in VSMCs. Compound C, a pharmacological inhibitor of AMPK, significantly reduced the levels of p-AMPK and p-ULK, enhanced p-mTOR level, and finally decreased LC3II and Beclin-1 level, which suggested that activated AMPK/mTOR/ULK1 signaling was related to shear-mediated autophagy. These results indicate that shear stress promotes VSMC phenotypic modulation through the induction of autophagy involved in activating the AMPK/mTOR/ULK1 pathway.

Romo1 expression contributes to oxidative stress-induced death of lung epithelial cells

International Nuclear Information System (INIS)

Shin, Jung Ar; Chung, Jin Sil; Cho, Sang-Ho; Kim, Hyung Jung; Yoo, Young Do

2013-01-01

Highlights: •Romo1 mediates oxidative stress-induced mitochondrial ROS production. •Romo1 induction by oxidative stress plays an important role in oxidative stress-induced apoptosis. •Romo1 overexpression correlates with epithelial cell death in patients with IPF. -- Abstract: Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an important role in pathogenesis in lung diseases such as idiopathic pulmonary fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial cell death is not fully understood. Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the mitochondria and mediates mitochondrial ROS production through complex III of the mitochondrial electron transport chain. Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H 2 O 2 ) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H 2 O 2 treatment. In immunohistochemical staining of lung tissues from patients with IPF, Romo1 was mainly localized in hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells were also detected in most patients with IPF but not in normal controls. These findings suggest that Romo1 mediates apoptosis induced by oxidative stress in lung epithelial cells

Romo1 expression contributes to oxidative stress-induced death of lung epithelial cells

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Shin, Jung Ar [Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul 135-270 (Korea, Republic of); Chung, Jin Sil [Laboratory of Molecular Cell Biology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Cho, Sang-Ho [Department of Pathology, Pochon CHA University, College of Medicine, Gyeonggi-do (Korea, Republic of); Kim, Hyung Jung, E-mail: khj57@yuhs.ac.kr [Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul 135-270 (Korea, Republic of); Yoo, Young Do, E-mail: ydy1130@korea.ac.kr [Laboratory of Molecular Cell Biology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of)

2013-09-20

Highlights: •Romo1 mediates oxidative stress-induced mitochondrial ROS production. •Romo1 induction by oxidative stress plays an important role in oxidative stress-induced apoptosis. •Romo1 overexpression correlates with epithelial cell death in patients with IPF. -- Abstract: Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an important role in pathogenesis in lung diseases such as idiopathic pulmonary fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial cell death is not fully understood. Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the mitochondria and mediates mitochondrial ROS production through complex III of the mitochondrial electron transport chain. Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H{sub 2}O{sub 2}) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H{sub 2}O{sub 2} treatment. In immunohistochemical staining of lung tissues from patients with IPF, Romo1 was mainly localized in hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells were also detected in most patients with IPF but not in normal controls. These findings suggest that Romo1 mediates apoptosis induced by oxidative stress in lung epithelial cells.

Isolation stress and chronic mild stress induced immobility in the defensive burying behavior and a transient increased ethanol intake in Wistar rats.

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Vázquez-León, Priscila; Martínez-Mota, Lucía; Quevedo-Corona, Lucía; Miranda-Páez, Abraham

2017-09-01

Stress can be experienced with or without adverse effects, of which anxiety and depression are two of the most important due to the frequent comorbidity with alcohol abuse in humans. Historically, stress has been considered a cause of drug use, particularly alcohol abuse due to its anxiolytic effects. In the present work we exposed male Wistar rats to two different stress conditions: single housing (social isolation, SI), and chronic mild stress (CMS). We compared both stressed groups to group-housed rats and rats without CMS (GH) to allow the determination of a clear behavioral response profile related to their respective endocrine stress response and alcohol intake pattern. We found that SI and CMS, to a greater extent, induced short-lasting increased sucrose consumption, a transient increase in serum corticosterone level, high latency/immobility, and low burying behavior in the defensive burying behavior (DBB) test, and a transient increase in alcohol intake. Thus, the main conclusion was that stress caused by both SI and CMS induced immobility in the DBB test and, subsequently, induced a transient increased voluntary ethanol intake in Wistar rats with a free-choice home-cage drinking paradigm. Copyright © 2017 Elsevier Inc. All rights reserved.

Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

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Beverley Greenwood-Van Meerveld

2017-11-01

Full Text Available Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS. Early life stress (ELS is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for

Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

Science.gov (United States)

Greenwood-Van Meerveld, Beverley; Johnson, Anthony C.

2017-01-01

Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS). Early life stress (ELS) is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for stress-induced

Reward dependence moderates smoking-cue- and stress-induced cigarette cravings.

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Michalowski, Alexandra; Erblich, Joel

2014-12-01

Cigarette cravings following exposure to smoking cues in a smoker's environment are thought to play an important role in cessation failure. The possibility that dispositional factors may impact cue-induced cravings, though intriguing, has received little attention. According to Cloninger's Tridimensional Personality Theory, factors such as reward dependence (RD), harm avoidance (HA), and novelty seeking (NS) may figure prominently in risk for addiction, as well as relapse, in individuals attempting to abstain from drug and alcohol use. Particularly interesting in this regard is the possibility that smokers with higher levels of RD, who are especially sensitive to reward signals, will have heightened craving reactions to smoking cues. To that end, non-treatment-seeking nicotine dependent smokers (n=96, mean age=41.1, 47% African American, 17% Caucasian, 22% Hispanic, 19.3cigs/day, FTND=7.5) underwent a classic experimental cue-induction, during which they were exposed to imagery of: (1) smoking, (2) neutral, and (3) stress cues, and reported their cigarette cravings (0-100) before and after each exposure. Participants also completed the Tridimensional Personality Questionnaire. Not surprisingly, smoking and stress cues (but not neutral cues) elicited significant elevations in craving (p'scues (pcues (pcues. Furthermore, the similar effects of RD on stress-induced craving suggest that both cue-and stress-induced cravings may be influenced by a common underlying disposition. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structure-dependent behavior of stress-induced voiding in Cu interconnects

International Nuclear Information System (INIS)

Wu Zhenyu; Yang Yintang; Chai Changchun; Li Yuejin; Wang Jiayou; Li Bin; Liu Jing

2010-01-01

Stress modeling and cross-section failure analysis by focused-ion-beam have been used to investigate stress-induced voiding phenomena in Cu interconnects. The voiding mechanism and the effect of the interconnect structure on the stress migration have been studied. The results show that the most concentrated tensile stress appears and voids form at corners of vias on top surfaces of Cu M1 lines. A simple model of stress induced voiding in which vacancies arise due to the increase of the chemical potential under tensile stress and diffuse under the force of stress gradient along the main diffusing path indicates that stress gradient rather than stress itself determines the voiding rate. Cu interconnects with larger vias show less resistance to stress-induced voiding due to larger stress gradient at corners of vias.

Endoplasmic reticulum (ER) stress and cAMP/PKA pathway mediated Zn-induced hepatic lipolysis.

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Song, Yu-Feng; Hogstrand, Christer; Wei, Chuan-Chuan; Wu, Kun; Pan, Ya-Xiong; Luo, Zhi

2017-09-01

The present study was performed to determine the effect of Zn exposure influencing endoplasmic reticulum (ER) stress, explore the underlying molecular mechanism of Zn-induced hepatic lipolysis in a fish species of significance for aquaculture, yellow catfish Pelteobagrus fulvidraco. We found that waterborne Zn exposure evoked ER stress and unfolded protein response (UPR), and activated cAMP/PKA pathway, and up-regulated hepatic lipolysis. The increase in ER stress and lipolysis were associated with activation of cAMP/PKA signaling pathway. Zn also induced an increase in intracellular Ca 2+ level, which could be partially prevented by dantrolene (RyR receptor inhibitor) and 2-APB (IP3 receptor inhibitor), demonstrating that the disturbed Ca 2+ homeostasis in ER contributed to ER stress and dysregulation of lipolysis. Inhibition of ER stress by PBA attenuated UPR, inhibited the activation of cAMP/PKA pathway and resulted in down-regulation of lipolysis. Inhibition of protein kinase RNA-activated-like ER kinase (PERK) by GSK2656157 and inositol-requiring enzyme (IRE) by STF-083010 differentially influenced Zn-induced changes of lipid metabolism, indicating that PERK and IRE pathways played different regulatory roles in Zn-induced lipolysis. Inhibition of PKA by H89 blocked the Zn-induced activation of cAMP/PKA pathway with a concomitant inhibition of ER stress-mediated lipolysis. Taken together, our findings highlight the importance of the ER stress-cAMP/PKA axis in Zn-induced lipolysis, which provides new insights into Zn toxicology in fish and probably in other vertebrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oxidative stress induced by zearalenone in porcine granulosa cells and its rescue by curcumin in vitro.

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Xunsi Qin

Full Text Available Oxidative stress (OS, as a signal of aberrant intracellular mechanisms, plays key roles in maintaining homeostasis for organisms. The occurrence of OS due to the disorder of normal cellular redox balance indicates the overproduction of reactive oxygen species (ROS and/or deficiency of antioxidants. Once the balance is broken down, repression of oxidative stress is one of the most effective ways to alleviate it. Ongoing studies provide remarkable evidence that oxidative stress is involved in reproductive toxicity induced by various stimuli, such as environmental toxicants and food toxicity. Zearalenone (ZEA, as a toxic compound existing in contaminated food products, is found to induce mycotoxicosis that has a significant impact on the reproduction of domestic animals, especially pigs. However, there is no information about how ROS and oxidative stress is involved in the influence of ZEA on porcine granulosa cells, or whether the stress can be rescued by curcumin. In this study, ZEA-induced effect on porcine granulosa cells was investigated at low concentrations (15 μM, 30 μM and 60 μM. In vitro ROS levels, the mRNA level and activity of superoxide dismutase, glutathione peroxidase and catalase were obtained. The results showed that in comparison with negative control, ZEA increased oxidative stress with higher ROS levels, reduced the expression and activity of antioxidative enzymes, increased the intensity of fluorogenic probes 2', 7'-Dichlorodihydrofluorescin diacetate and dihydroethidium in flow cytometry assay and fluorescence microscopy. Meanwhile, the activity of glutathione (GSH did not change obviously following 60 μM ZEA treatment. Furthermore, the underlying protective mechanisms of curcumin on the ZEA-treated porcine granulosa cells were investigated. The data revealed that curcumin pre-treatment significantly suppressed ZEA-induced oxidative stress. Collectively, porcine granulosa cells were sensitive to ZEA, which may induce

Stress-induced variation in evolution: from behavioural plasticity to genetic assimilation.

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Badyaev, Alexander V

2005-05-07

Extreme environments are closely associated with phenotypic evolution, yet the mechanisms behind this relationship are poorly understood. Several themes and approaches in recent studies significantly further our understanding of the importance that stress-induced variation plays in evolution. First, stressful environments modify (and often reduce) the integration of neuroendocrinological, morphological and behavioural regulatory systems. Second, such reduced integration and subsequent accommodation of stress-induced variation by developmental systems enables organismal 'memory' of a stressful event as well as phenotypic and genetic assimilation of the response to a stressor. Third, in complex functional systems, a stress-induced increase in phenotypic and genetic variance is often directional, channelled by existing ontogenetic pathways. This accounts for similarity among individuals in stress-induced changes and thus significantly facilitates the rate of adaptive evolution. Fourth, accumulation of phenotypically neutral genetic variation might be a common property of locally adapted and complex organismal systems, and extreme environments facilitate the phenotypic expression of this variance. Finally, stress-induced effects and stress-resistance strategies often persist for several generations through maternal, ecological and cultural inheritance. These transgenerational effects, along with both the complexity of developmental systems and stressor recurrence, might facilitate genetic assimilation of stress-induced effects. Accumulation of phenotypically neutral genetic variance by developmental systems and phenotypic accommodation of stress-induced effects, together with the inheritance of stress-induced modifications, ensure the evolutionary persistence of stress-response strategies and provide a link between individual adaptability and evolutionary adaptation.

Enhanced 15-HPETE production during oxidant stress induces apoptosis of endothelial cells.

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Sordillo, Lorraine M; Weaver, James A; Cao, Yu-Zhang; Corl, Chris; Sylte, Matt J; Mullarky, Isis K

2005-05-01

Oxidant stress plays an important role in the etiology of vascular diseases by increasing rates of endothelial cell apoptosis, but few data exist on the mechanisms involved. Using a unique model of oxidative stress based on selenium deficiency (-Se), the effects of altered eicosanoid production on bovine aortic endothelial cells (BAEC) apoptosis was evaluated. Oxidant stress significantly increased the immediate oxygenation product of arachidonic acid metabolized by the 15-lipoxygenase pathway, 15-hydroxyperoxyeicosatetraenoic acid (15-HPETE). Treatment of -Se BAEC with TNFalpha/cyclohexamide (CHX) exhibited elevated levels of apoptosis, which was significantly reduced by the addition of a specific 15-lipoxygenase inhibitor PD146176. Furthermore, the addition of 15-HPETE to PD146176-treated BAEC, partially restored TNF/CHX-induced apoptosis. Increased exposure to 15-HPETE induced apoptosis, as determined by internucleosomal DNA fragmentation, chromatin condensation, caspase-3 activation, and caspase-9 activation, which suggests mitochondrial dysfunction. The expression of Bcl-2 protein also was decreased in -Se BAEC. Addition of a caspase-9 inhibitor (LEHD-fmk) completely blocked 15-HPETE-induced chromatin condensation in -Se BAEC, suggesting that 15-HPETE-induced apoptosis is caspase-9 dependent. Increased apoptosis of BAEC as a result of oxidant stress and subsequent production of 15-HPETE may play a critical role in a variety of inflammatory based diseases.

FMRFamide signaling promotes stress-induced sleep in Drosophila.

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Lenz, Olivia; Xiong, Jianmei; Nelson, Matthew D; Raizen, David M; Williams, Julie A

2015-07-01

Enhanced sleep in response to cellular stress is a conserved adaptive behavior across multiple species, but the mechanism of this process is poorly understood. Drosophila melanogaster increases sleep following exposure to septic or aseptic injury, and Caenorhabditis elegans displays sleep-like quiescence following exposure to high temperatures that stress cells. We show here that, similar to C. elegans, Drosophila responds to heat stress with an increase in sleep. In contrast to Drosophila infection-induced sleep, heat-induced sleep is not sensitive to the time-of-day of the heat pulse. Moreover, the sleep response to heat stress does not require Relish, the NFκB transcription factor that is necessary for infection-induced sleep, indicating that sleep is induced by multiple mechanisms from different stress modalities. We identify a sleep-regulating role for a signaling pathway involving FMRFamide neuropeptides and their receptor FR. Animals mutant for either FMRFamide or for the FMRFamide receptor (FR) have a reduced recovery sleep in response to heat stress. FR mutants, in addition, show reduced sleep responses following infection with Serratia marcescens, and succumb to infection at a faster rate than wild-type controls. Together, these findings support the hypothesis that FMRFamide and its receptor promote an adaptive increase in sleep following stress. Because an FMRFamide-like neuropeptide plays a similar role in C. elegans, we propose that FRMFamide neuropeptide signaling is an ancient regulator of recovery sleep which occurs in response to cellular stress. Copyright © 2015 Elsevier Inc. All rights reserved.

Cannabinoids ameliorate impairments induced by chronic stress to synaptic plasticity and short-term memory.

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Abush, Hila; Akirav, Irit

2013-07-01

Repeated stress is one of the environmental factors that precipitates and exacerbates mental illnesses like depression and anxiety as well as cognitive impairments. We have previously shown that cannabinoids can prevent the effects of acute stress on learning and memory. Here we aimed to find whether chronic cannabinoid treatment would alleviate the long-term effects of exposure to chronic restraint stress on memory and plasticity as well as on behavioral and neuroendocrine measures of anxiety and depression. Late adolescent rats were exposed to chronic restraint stress for 2 weeks followed each day by systemic treatment with vehicle or with the CB1/2 receptor agonist WIN55,212-2 (1.2 mg/kg). Thirty days after the last exposure to stress, rats demonstrated impaired long-term potentiation (LTP) in the ventral subiculum-nucleus accumbens (NAc) pathway, impaired performance in the prefrontal cortex (PFC)-dependent object-recognition task and the hippocampal-dependent spatial version of this task, increased anxiety levels, and significantly reduced expression of glucocorticoid receptors (GRs) in the amygdala, hippocampus, PFC, and NAc. Chronic WIN55,212-2 administration prevented the stress-induced impairment in LTP levels and in the spatial task, with no effect on stress-induced alterations in unconditioned anxiety levels or GR levels. The CB1 antagonist AM251 (0.3 mg/kg) prevented the ameliorating effects of WIN55,212-2 on LTP and short-term memory. Hence, the beneficial effects of WIN55,212-2 on memory and plasticity are mediated by CB1 receptors and are not mediated by alterations in GR levels in the brain areas tested. Our findings suggest that cannabinoid receptor activation could represent a novel approach to the treatment of cognitive deficits that accompany a variety of stress-related neuropsychiatric disorders.

Obesity-induced endoplasmic reticulum stress suppresses nuclear factor-Y expression.

Science.gov (United States)

Liu, Yulan; Zhang, Yuwei; Zhang, Yanjie; Zhang, Jinlong; Liu, Yin; Feng, Peiqun; Su, Zhiguang

2017-02-01

Nuclear transcription factor Y (NF-Y) is an evolutionarily conserved transcription factor composed of three subunits, NF-YA, NF-YB, and NF-YC. NF-Y plays crucial roles in pre-adipocyte maintenance and/or commitment to adipogenesis. NF-YA dysfunction in adipocyte resulted in an age-dependent progressive loss of adipose tissue associated with metabolic complications. Endoplasmic reticulum (ER) stress has emerged as an important mediator in the pathogenesis of obesity. However, it is not known if NF-YA is involved in the ER stress-mediated pathogenesis of obesity. We first examined the effects of ER stress on the NF-YA expression in cultured 3T3-L1 adipocytes; then in ob/ob genetic obesity mice, we tested the effect of chemical chaperones alleviating ER stress on the expression levels of NF-YA. Subsequently, we inhibited the new mRNA synthesis using actinomycin D in 3T3-L1 cells to explore the mechanism modulating NF-YA expression. Finally, we evaluated the involvement of PPARg in the regulation of NF-YA expression by ER stress. We demonstrated that both obesity- and chemical chaperone -induced ER stress suppressed NF-YA expression and alleviation of ER stress by chemical chaperone could recover NF-YA expression in ob/ob mice. Moreover, we showed that ER stress suppressed NF-YA mRNA transcription through the involvement of peroxisome proliferator-activated receptor gamma (PPARg). Activation of PPARg ameliorates the ER stress-induced NF-YA suppression. Our findings may point to a possible role of NF-YA in stress conditions that occur in chronic obesity, ER stress might be involved in the pathogenesis of obesity through NF-YA depletion.

Oxidative stress is involved in Dasatinib-induced apoptosis in rat primary hepatocytes

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Xue, Tao; Luo, Peihua; Zhu, Hong; Zhao, Yuqin [Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Wu, Honghai; Gai, Renhua; Wu, Youping [Center for Drug Safety Evaluation and Research of Zhejiang University, Hangzhou 310058 (China); Yang, Bo [Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Yang, Xiaochun, E-mail: yangxiaochun@zju.edu.cn [Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Center for Drug Safety Evaluation and Research of Zhejiang University, Hangzhou 310058 (China); He, Qiaojun, E-mail: qiaojunhe@zju.edu.cn [Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Center for Drug Safety Evaluation and Research of Zhejiang University, Hangzhou 310058 (China)

2012-06-15

Dasatinib, a multitargeted inhibitor of BCR–ABL and SRC kinases, exhibits antitumor activity and extends the survival of patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). However, some patients suffer from hepatotoxicity, which occurs through an unknown mechanism. In the present study, we found that Dasatinib could induce hepatotoxicity both in vitro and in vivo. Dasatinib reduced the cell viability of rat primary hepatocytes, induced the release of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) in vitro, and triggered the ballooning degeneration of hepatocytes in Sprague–Dawley rats in vivo. Apoptotic markers (chromatin condensation, cleaved caspase-3 and cleaved PARP) were detected to indicate that the injury induced by Dasatinib in hepatocytes in vitro was mediated by apoptosis. This result was further validated in vivo using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays. Here we found that Dasatinib dramatically increased the level of reactive oxygen species (ROS) in hepatocytes, reduced the intracellular glutathione (GSH) content, attenuated the activity of superoxide dismutase (SOD), generated malondialdehyde (MDA), a product of lipid peroxidation, decreased the mitochondrial membrane potential, and activated nuclear factor erythroid 2-related factor 2 (Nrf2) and mitogen-activated protein kinases (MAPK) related to oxidative stress and survival. These results confirm that oxidative stress plays a pivotal role in Dasatinib-mediated hepatotoxicity. N-acetylcysteine (NAC), a typical antioxidant, can scavenge free radicals, attenuate oxidative stress, and protect hepatocytes against Dasatinib-induced injury. Thus, relieving oxidative stress is a viable strategy for reducing Dasatinib-induced hepatotoxicity. -- Highlights: ►Dasatinib shows potential hepatotoxicity both in vitro and in vivo. ►Apoptosis plays a vital role in Dasatinib-induced

Oxidative stress reduces levels of dysbindin-1A via its PEST domain.

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Yap, Mei-Yi Alicia; Lo, Yew-Long; Talbot, Konrad; Ong, Wei-Yi

2014-12-01

Oxidative stress resulting from the generation of reactive oxygen species has been proposed as an etiological factor in schizophrenia. The present study tests the hypothesis that oxidative stress can affect levels of dysbindin-1A, encoded by Dtnbp1, a genetic risk factor for schizophrenia, via its PEST domain. In vitro studies on SH-SY5Y cells indicate that oxidative stress triggers proteasomal degradation of dysbindin-1A, and that this requires interactions with its PEST domain, which may be a TRIM32 target. We specifically found (a) that oxidative stress induced in SH-SY5Y cells by 500 µM hydrogen peroxide reduced levels of full-length dysbindin-1, but did not reduce levels of that protein lacking its PEST domain and (b) that levels of full-length dysbindin-1, but not dysbindin-1 lacking its PEST domain, were higher in cells treated with the proteasome inhibitor MG132. Oxidative stress thus emerges as the first known cellular factor regulating dysbindin-1 isoforms with PEST domains. These findings are consistent with the previously noted fact that phosphorylation of PEST domains often marks proteins for proteasomal degradation, and raises the possibility that treatments reducing oxidative stress in the brain, especially during development, may lower schizophrenia risk. Copyright © 2014 Elsevier Ltd. All rights reserved.

Trichodermin induces cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress in human chondrosarcoma cells

International Nuclear Information System (INIS)

Su, Chen-Ming; Wang, Shih-Wei; Lee, Tzong-Huei; Tzeng, Wen-Pei; Hsiao, Che-Jen; Liu, Shih-Chia; Tang, Chih-Hsin

2013-01-01

Chondrosarcoma is the second most common primary bone tumor, and it responds poorly to both chemotherapy and radiation treatment. Nalanthamala psidii was described originally as Myxosporium in 1926. This is the first study to investigate the anti-tumor activity of trichodermin (trichothec-9-en-4-ol, 12,13-epoxy-, acetate), an endophytic fungal metabolite from N. psidii against human chondrosarcoma cells. We demonstrated that trichodermin induced cell apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 cells) instead of primary chondrocytes. In addition, trichodermin triggered endoplasmic reticulum (ER) stress protein levels of IRE1, p-PERK, GRP78, and GRP94, which were characterized by changes in cytosolic calcium levels. Furthermore, trichodermin induced the upregulation of Bax and Bid, the downregulation of Bcl-2, and the dysfunction of mitochondria, which released cytochrome c and activated caspase-3 in human chondrosarcoma. In addition, animal experiments illustrated reduced tumor volume, which led to an increased number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells and an increased level of cleaved PARP protein following trichodermin treatment. Together, this study demonstrates that trichodermin is a novel anti-tumor agent against human chondrosarcoma cells both in vitro and in vivo via mitochondrial dysfunction and ER stress. - Highlights: • Trichodermin induces chondrosarcoma apoptosis. • ER stress is involved in trichodermin-induced cell death. • Trichodermin induces chondrosarcoma death in vivo.

Trichodermin induces cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress in human chondrosarcoma cells

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Su, Chen-Ming [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Wang, Shih-Wei [Department of Medicine, Mackay Medical College, New Taipei City, Taiwan (China); Lee, Tzong-Huei [Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan (China); Tzeng, Wen-Pei [Graduate Institute of Sports and Health, National Changhua University of Education, Changhua, Taiwan (China); Hsiao, Che-Jen [School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Liu, Shih-Chia [Department of Orthopaedics, Mackay Memorial Hospital, Taipei, Taiwan (China); Tang, Chih-Hsin, E-mail: chtang@mail.cmu.edu.tw [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan (China); Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan (China)

2013-10-15

Chondrosarcoma is the second most common primary bone tumor, and it responds poorly to both chemotherapy and radiation treatment. Nalanthamala psidii was described originally as Myxosporium in 1926. This is the first study to investigate the anti-tumor activity of trichodermin (trichothec-9-en-4-ol, 12,13-epoxy-, acetate), an endophytic fungal metabolite from N. psidii against human chondrosarcoma cells. We demonstrated that trichodermin induced cell apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 cells) instead of primary chondrocytes. In addition, trichodermin triggered endoplasmic reticulum (ER) stress protein levels of IRE1, p-PERK, GRP78, and GRP94, which were characterized by changes in cytosolic calcium levels. Furthermore, trichodermin induced the upregulation of Bax and Bid, the downregulation of Bcl-2, and the dysfunction of mitochondria, which released cytochrome c and activated caspase-3 in human chondrosarcoma. In addition, animal experiments illustrated reduced tumor volume, which led to an increased number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells and an increased level of cleaved PARP protein following trichodermin treatment. Together, this study demonstrates that trichodermin is a novel anti-tumor agent against human chondrosarcoma cells both in vitro and in vivo via mitochondrial dysfunction and ER stress. - Highlights: • Trichodermin induces chondrosarcoma apoptosis. • ER stress is involved in trichodermin-induced cell death. • Trichodermin induces chondrosarcoma death in vivo.

Salubrious effects of oxytocin on social stress-induced deficits

Science.gov (United States)

Smith, Adam S.; Wang, Zuoxin

2012-01-01

Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While social interactions can attenuate stress and promote health, disruption, confrontations, isolation, or neglect in the social environment can each be major stressors. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to mental and physical health. In contrast, social support can ameliorate stress-induced physiological and immunological deficits, reducing the risk of subsequent psychological distress and improving an individual's overall well-being. For better clinical treatment of these physiological and mental pathologies, it is necessary to understand the regulatory mechanisms of stress-induced pathologies as well as determine the underlying biological mechanisms that regulate social buffering of the stress system. A number of ethologically relevant animal models of social stress and species that form strong adult social bonds have been utilized to study the etiology, treatment, and prevention of stress-related disorders. While undoubtedly a number of biological pathways contribute to the social buffering of the stress response, the convergence of evidence denotes the regulatory effects of oxytocin in facilitating social bond-promoting behaviors and their effect on the stress response. Thus, oxytocin may be perceived as a common regulatory element of the social environment, stress response, and stress-induced risks on mental and physical health. PMID:22178036

Stress-induced eating in women with binge-eating disorder and obesity.

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Klatzkin, Rebecca R; Gaffney, Sierra; Cyrus, Kathryn; Bigus, Elizabeth; Brownley, Kimberly A

2018-01-01

The purpose of the current study was to investigate stress-induced eating in women with binge-eating disorder (BED) and obesity. Three groups of women [obese with BED (n=9); obese non-BED (n=11); and normal weight (NW) non-BED (n=12)], rated their levels of hunger and psychological distress before and after completing the Trier Social Stress Test, followed by food anticipation and then consumption of their preferred snack food. We differentiated between the motivational and hedonic components of eating by measuring the amount of food participants poured into a serving bowl compared to the amount consumed. Stress did not affect poured and consumed calories differently between groups. Across all subjects, calories poured and consumed were positively correlated with post-stress hunger, but calories poured was positively correlated with post-stress anxiety and negative affect. These results indicate that stress-related psychological factors may be more strongly associated with the motivational drive to eat (i.e. amount poured) rather than the hedonic aspects of eating (i.e. amount consumed) for women in general. Exploratory correlation analyses per subgroup suggest that post-stress hunger was positively associated with calories poured and consumed in both non-BED groups. In the obese BED group, calories consumed was negatively associated with dietary restraint and, although not significantly, positively associated with stress-induced changes in anxiety.These findings suggest that stress-induced snacking in obese BED women may be influenced by psychological factors more so than homeostatic hunger mechanisms. After controlling for dietary restraint and negative affect, the NW non-BED women ate a greater percentage of the food they poured than both obese groups, suggesting that obesity may be associated with a heightened motivational drive to eat coupled with a reduction in hedonic pleasure from eating post-stress. Further studies that incorporate novel approaches to

Depletion of norepinephrine of the central nervous system Down-regulates the blood glucose level in d-glucose-fed and restraint stress models.

Science.gov (United States)

Park, Soo-Hyun; Kim, Sung-Su; Lee, Jae-Ryeong; Sharma, Naveen; Suh, Hong-Won

2016-05-04

DSP-4[N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride] is a neurotoxin that depletes norepinephrine. The catecholaminergic system has been implicated in the regulation of blood glucose level. In the present study, the effect of DSP-4 administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) on blood glucose level was examined in d-glucose-fed and restraint stress mice models. Mice were pretreated once i.c.v. or i.t. with DSP-4 (10-40μg) for 3days, and d-glucose (2g/kg) was fed orally. Blood glucose level was measured 0 (prior to glucose feeding or restraint stress), 30, 60, and 120min after d-glucose feeding or restraint stress. The i.c.v. or i.t. pretreatment with DSP-4 attenuated blood glucose level in the d-glucose-fed model. Plasma corticosterone level was downregulated in the d-glucose-fed model, whereas plasma insulin level increased in the d-glucose-fed group. The i.c.v. or i.t. pretreatment with DSP-4 reversed the downregulation of plasma corticosterone induced by feeding d-glucose. In addition, the d-glucose-induced increase in plasma insulin was attenuated by the DSP-4 pretreatment. Furthermore, i.c.v. or i.t. pretreatment with DSP-4 reduced restraint stress-induced increases in blood glucose levels. Restraint stress increased plasma corticosterone and insulin levels. The i.c.v. pretreatment with DSP-4 attenuated restraint stress-induced plasma corticosterone and insulin levels. Our results suggest that depleting norepinephrine at the supraspinal and spinal levels appears to be responsible for downregulating blood glucose levels in both d-glucose-fed and restraint stress models. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Type 2 diabetes mellitus induces congenital heart defects in murine embryos by increasing oxidative stress, endoplasmic reticulum stress, and apoptosis.

Science.gov (United States)

Wu, Yanqing; Reece, E Albert; Zhong, Jianxiang; Dong, Daoyin; Shen, Wei-Bin; Harman, Christopher R; Yang, Peixin

2016-09-01

Maternal type 1 and 2 diabetes mellitus are strongly associated with high rates of severe structural birth defects, including congenital heart defects. Studies in type 1 diabetic embryopathy animal models have demonstrated that cellular stress-induced apoptosis mediates the teratogenicity of maternal diabetes leading to congenital heart defect formation. However, the mechanisms underlying maternal type 2 diabetes mellitus-induced congenital heart defects remain largely unknown. We aim to determine whether oxidative stress, endoplasmic reticulum stress, and excessive apoptosis are the intracellular molecular mechanisms underlying maternal type 2 diabetes mellitus-induced congenital heart defects. A mouse model of maternal type 2 diabetes mellitus was established by feeding female mice a high-fat diet (60% fat). After 15 weeks on the high-fat diet, the mice showed characteristics of maternal type 2 diabetes mellitus. Control dams were either fed a normal diet (10% fat) or the high-fat diet during pregnancy only. Female mice from the high-fat diet group and the 2 control groups were mated with male mice that were fed a normal diet. At E12.5, embryonic hearts were harvested to determine the levels of lipid peroxides and superoxide, endoplasmic reticulum stress markers, cleaved caspase 3 and 8, and apoptosis. E17.5 embryonic hearts were harvested for the detection of congenital heart defect formation using India ink vessel patterning and histological examination. Maternal type 2 diabetes mellitus significantly induced ventricular septal defects and persistent truncus arteriosus in the developing heart, along with increasing oxidative stress markers, including superoxide and lipid peroxidation; endoplasmic reticulum stress markers, including protein levels of phosphorylated-protein kinase RNA-like endoplasmic reticulum kinase, phosphorylated-IRE1α, phosphorylated-eIF2α, C/EBP homologous protein, and binding immunoglobulin protein; endoplasmic reticulum chaperone gene

Indagation of serum and salivary reactive oxygen metabolite and cortisol levels in chronic periodontitis and stress-induced chronic periodontitis patients

Directory of Open Access Journals (Sweden)

Uma Sudhakar

2017-01-01

Full Text Available Background: Periodontal disease is not a conventional bacterial infection but is an inflammatory disease initiated by immune response against a group of microorganisms in susceptible hosts. There are many intriguing researches that unfold the secrets of chronic periodontitis. The current researches in chronic periodontitis are directed toward an approach that respects the scientific relationship between the various risk factors, the genetic factors, and the progression of the disease. Aim: This study aims to evaluate the cortisol and reactive oxygen metabolites (ROM concentration in serum and to find out their association in periodontal health and disease. Materials and Methods: In this study, totally thirty patients have been taken and divided into two groups of chronic periodontitis (Group I and stress-induced chronic periodontitis (Group II and evaluated the correlation between the ROM and cortisol levels in them. This is the first study, where both the levels of ROM and cortisol are checked in the serum and saliva. The analysis is done to check the association between them. Statistical Analysis: The data were statistically analyzed using software program (SPSSV 16, Pearson correlation, and paired t-test. Results: Comparison of the mean ROM levels in Group I and Group II showed that mean ROM level in Group II is highly significant than Group I. Conclusion: Our study suggests that stress can have a role in the progression of periodontal disease by increasing the cortisol and ROM levels.

Cardiovascular Reactivity in Patients With Major Depressive Disorder With High- or Low-Level Depressive Symptoms: A Cross-Sectional Comparison of Cardiovascular Reactivity to Laboratory-Induced Mental Stress.

Science.gov (United States)

Wang, Mei-Yeh; Chiu, Chen-Huan; Lee, Hsin-Chien; Su, Chien-Tien; Tsai, Pei-Shan

2016-03-01

Depression increases the risk of adverse cardiac events. Cardiovascular reactivity is defined as the pattern of cardiovascular responses to mental stress. An altered pattern of cardiovascular reactivity is an indicator of subsequent cardiovascular disease. Because depression and adverse cardiac events may have a dose-dependent association, this study examined the differences in cardiovascular reactivity to mental stress between patients with major depressive disorder (MDD) with high depression levels and those with low depression levels. Moreover, autonomic nervous system regulation is a highly plausible biological mechanism for the pattern of cardiovascular reactivity to mental stress. The association between cardiovascular reactivity and parameters of heart rate variability (HRV), an index for quantifying autonomic nervous system activity modulation, was thus examined. This study included 88 patients with MDD. HRV was measured before stress induction. The Stroop Color and Word Test and mirror star-tracing task were used to induce mental stress. We observed no significant association between depressive symptom level and any of the cardiovascular reactivity parameters. Cardiovascular reactivity to mental stress was comparable between patients with MDD with high-level depressive symptoms and those with low-level depressive symptoms. After adjusting for confounding variables, the high-frequency domain of HRV was found to be an independent predictor of the magnitude of heart rate reactivity (β = -.33, p = .002). In conclusion, the magnitude of cardiovascular reactivity may be independent of depression severity in patients with MDD. The autonomic regulation of cardiovascular responses to mental stress primarily influences heart rate reactivity in patients with MDD. © The Author(s) 2015.

Cocaine induces astrocytosis through ER stress-mediated activation of autophagy

Science.gov (United States)

Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

2016-01-01

ABSTRACT Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation. PMID:27337297

REPEATED ACUTE STRESS INDUCED ALTERATIONS IN CARBOHYDRATE METABOLISM IN RAT

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Nirupama R.

2010-09-01

Full Text Available Acute stress induced alterations in the activity levels of rate limiting enzymes and concentration of intermediates of different pathways of carbohydrate metabolism have been studied. Adult male Wistar rats were restrained (RS for 1 h and after an interval of 4 h they were subjected to forced swimming (FS exercise and appropriate controls were maintained. Five rats were killed before the commencement of the experiment (initial controls, 5 control and equal number of stressed rats were killed 2 h after RS and remaining 5 rats in each group were killed 4 h after FS. There was a significant increase in the adrenal 3β- hydroxy steroid dehydrogenase activity following RS, which showed further increase after FS compared to controls and thereby indicated stress response of rats. There was a significant increase in the blood glucose levels following RS which showed further increase and reached hyperglycemic condition after FS. The hyperglycemic condition due to stress was accompanied by significant increases in the activities of glutamate- pyruvate transaminase, glutamate- oxaloacetate transaminase, glucose -6- phosphatase and lactate dehydrogenase and significant decrease in the glucose -6- phosphate dehydrogenase and pyruvate dehydrogenase activities, whereas pyruvate kinase activity did not show any alteration compared to controls. Further, the glycogen and total protein contents of the liver were decreased whereas those of pyruvate and lactate showed significant increase compared to controls after RS as well as FS.The results put together indicate that acute stress induced hyperglycemia results due to increased gluconeogenesis and glycogenolysis without alteration in glycolysis. The study first time reveals that after first acute stress exposure, the subsequent stressful experience augments metabolic stress response leading to hyperglycemia. The results have relevance to human health as human beings are exposed to several stressors in a day and

Impact of work-induced stress on perceived workers' productivity in ...

African Journals Online (AJOL)

Impact of work-induced stress on perceived workers' productivity in banking ... The study investigated the relationship among work-induced stress, job performance, ... tend to reduce effects of work-related stress on workers' health and welfare.

Effect of Applied Stress and Temperature on Residual Stresses Induced by Peening Surface Treatments in Alloy 600

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Telang, A.; Gnäupel-Herold, T.; Gill, A.; Vasudevan, V. K.

2018-04-01

In this study, the effects of applied tensile stress and temperature on laser shock peening (LSP) and cavitation shotless peening (CSP)-induced compressive residual stresses were investigated using neutron and x-ray diffraction. Residual stresses on the surface, measured in situ, were lower than the applied stress in LSP- and CSP-treated Alloy 600 samples (2 mm thick). The residual stress averaged over the volume was similar to the applied stress. Compressive residual stresses on the surface and balancing tensile stresses in the interior relax differently due to hardening induced by LSP. Ex situ residual stress measurements, using XRD, show that residual stresses relaxed as the applied stress exceeded the yield strength of the LSP- and CSP-treated Alloy 600. Compressive residual stresses induced by CSP and LSP decreased by 15-25% in magnitude, respectively, on exposure to 250-450 °C for more than 500 h with 10-11% of relaxation occurring in the first few hours. Further, 80% of the compressive residual stresses induced by LSP and CSP treatments in Alloy 600 were retained even after long-term aging at 350 °C for 2400 h.

The role of substance P in the maintenance of colonic hypermotility induced by repeated stress in rats.

Science.gov (United States)

Lu, Ping; Luo, Hesheng; Quan, Xiaojing; Fan, Han; Tang, Qincai; Yu, Guang; Chen, Wei; Xia, Hong

2016-04-01

The mechanism underlying chronic stress-induced gastrointestinal (GI) dysmotility has not been fully elucidated and GI hormones have been indicated playing a role in mediating stress-induced changes in GI motor function. Our objective was to study the possible role of substance P (SP) in the colonic hypermotility induced by repeated water avoidance stress (WAS) which mimics irritable bowel syndrome. Male Wistar rats were submitted to WAS or sham WAS (SWAS) (1h/day) for up to 10 consecutive days. Enzyme Immunoassay Kit was used to detect the serum level of SP. The expression of neurokinin-1 receptor (NK1R) was investigated by Immunohistochemistry and Western blotting. The spontaneous contraction of muscle strip was studied in an organ bath system. L-type calcium channel currents (ICa,L) of smooth muscle cells (SMCs) were recorded by whole-cell patch-clamp technique. Fecal pellet expulsion and spontaneous contraction of proximal colon in rats were increased after repeated WAS. The serum level of SP was elevated following WAS. Immunohistochemistry proved the expression of NK1R in mucosa, muscularis and myenteric plexus. Western blotting demonstrated stress-induced up-regulation of NK1R in colon devoid of mucosa and submucosa. Repeated WAS increased the contractile activities of longitudinal muscle and circular muscle strips induced by SP and this effect was reversed by a selective NK1R antagonist. The ICa,L of SMCs in the WAS rats were drastically increased compared to controls after addition of SP. Increased serum SP level and up-regulated NK1R in colon may contribute to stress-induced colonic hypermotility. And L-type calcium channels play a potentially important role in the process of WAS-induced dysmotility. Copyright © 2016 Elsevier Ltd. All rights reserved.

Resveratrol alleviates diabetes-induced testicular dysfunction by inhibiting oxidative stress and c-Jun N-terminal kinase signaling in rats

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Faid, Iman; Al-Hussaini, Heba; Kilarkaje, Narayana, E-mail: knarayana@hsc.edu.kw

2015-12-15

Diabetes adversely affects reproductive functions in humans and animals. The present study investigated the effects of Resveratrol on diabetes-induced alterations in oxidative stress, c-Jun N-terminal kinase (JNK) signaling and apoptosis in the testis. Adult male Wistar rats (13–15 weeks; n = 6/group) were segregated into 1) normal control, 2) Resveratrol-treated (5 mg/kg; ip; given during last 3 weeks), 3) Streptozotocin-induced diabetic and, 4) Resveratrol-treated diabetic groups, and euthanized on day 42 after the confirmation of diabetes. Resveratrol did not normalize blood glucose levels in diabetic rats. Resveratrol supplementation recovered diabetes-induced decreases in reproductive organ weights, sperm count and motility, intra-testicular levels of superoxide dismutase, catalase, and glutathione peroxidase and an increase in 4-hydroxynonenal activities (P < 0.05). Resveratrol also recovered diabetes-induced increases in JNK signaling pathway proteins, namely, ASK1 (apoptosis signal-regulating kinase 1), JNKs (46 and 54 kDa isoforms) and p-JNK to normal control levels (P < 0.05). Interestingly, the expression of a down-stream target of ASK1, MKK4 (mitogen-activated protein kinase kinase 4) and its phosphorylated form (p-MKK4) did not change in experimental groups. Resveratrol inhibited diabetes-induced increases in AP-1 (activator protein-1) components, c-Jun and ATF2 (activating transcription factor 2), but not their phosphorylated forms, to normal control levels (P < 0.05). Further, Resveratrol inhibited diabetes-induced increase in cleaved-caspase-3 to normal control levels. In conclusion, Resveratrol alleviates diabetes-induced apoptosis in testis by modulating oxidative stress, JNK signaling pathway and caspase-3 activities, but not by inhibiting hyperglycemia, in rats. These results suggest that Resveratrol supplementation may be a useful strategy to treat diabetes-induced testicular dysfunction. - Highlights: • Resveratrol up-regulates glutathione

Resveratrol alleviates diabetes-induced testicular dysfunction by inhibiting oxidative stress and c-Jun N-terminal kinase signaling in rats

International Nuclear Information System (INIS)

Faid, Iman; Al-Hussaini, Heba; Kilarkaje, Narayana

2015-01-01

Diabetes adversely affects reproductive functions in humans and animals. The present study investigated the effects of Resveratrol on diabetes-induced alterations in oxidative stress, c-Jun N-terminal kinase (JNK) signaling and apoptosis in the testis. Adult male Wistar rats (13–15 weeks; n = 6/group) were segregated into 1) normal control, 2) Resveratrol-treated (5 mg/kg; ip; given during last 3 weeks), 3) Streptozotocin-induced diabetic and, 4) Resveratrol-treated diabetic groups, and euthanized on day 42 after the confirmation of diabetes. Resveratrol did not normalize blood glucose levels in diabetic rats. Resveratrol supplementation recovered diabetes-induced decreases in reproductive organ weights, sperm count and motility, intra-testicular levels of superoxide dismutase, catalase, and glutathione peroxidase and an increase in 4-hydroxynonenal activities (P < 0.05). Resveratrol also recovered diabetes-induced increases in JNK signaling pathway proteins, namely, ASK1 (apoptosis signal-regulating kinase 1), JNKs (46 and 54 kDa isoforms) and p-JNK to normal control levels (P < 0.05). Interestingly, the expression of a down-stream target of ASK1, MKK4 (mitogen-activated protein kinase kinase 4) and its phosphorylated form (p-MKK4) did not change in experimental groups. Resveratrol inhibited diabetes-induced increases in AP-1 (activator protein-1) components, c-Jun and ATF2 (activating transcription factor 2), but not their phosphorylated forms, to normal control levels (P < 0.05). Further, Resveratrol inhibited diabetes-induced increase in cleaved-caspase-3 to normal control levels. In conclusion, Resveratrol alleviates diabetes-induced apoptosis in testis by modulating oxidative stress, JNK signaling pathway and caspase-3 activities, but not by inhibiting hyperglycemia, in rats. These results suggest that Resveratrol supplementation may be a useful strategy to treat diabetes-induced testicular dysfunction. - Highlights: • Resveratrol up-regulates glutathione

Social factors modulate restraint stress induced hyperthermia in mice.

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Watanabe, Shigeru

2015-10-22

Stress-induced hyperthermia (SIH) was examined in three different social conditions in mice by thermographic measurement of the body surface temperature. Placing animals in cylindrical holders induced restraint stress. I examined the effect of the social factors in SIH using the thermograph (body surface temperature). Mice restrained in the holders alone showed SIH. Mice restrained in the holders at the same time as other similarly restrained cage mates (social equality condition) showed less hyperthermia. Interestingly, restrained mice with free moving cage mates (social inequality condition) showed the highest hyperthermia. These results are consistent with a previous experiment measuring the memory-enhancing effects of stress and the stress-induced elevation of corticosterone, and suggest that social inequality enhances stress. Copyright © 2015 Elsevier B.V. All rights reserved.

Apelin-APJ system is responsible for stress-induced increase in atrial natriuretic peptide expression in rat heart.

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Izgut-Uysal, Vecihe Nimet; Acar, Nuray; Birsen, Ilknur; Ozcan, Filiz; Ozbey, Ozlem; Soylu, Hakan; Avci, Sema; Tepekoy, Filiz; Akkoyunlu, Gokhan; Yucel, Gultekin; Ustunel, Ismail

2018-04-01

The cardiovascular system is a primary target of stress and stress is the most important etiologic factor in cardiovascular diseases. Stressors increase expressions of atrial natriuretic peptide (ANP) and apelin in cardiac tissue. The aim of the present study was to investigate whether stress-induced apelin has an effect on the expression of ANP in the right atrium of rat heart. The rats were divided into the control, stress and F13A+stress groups. In the stress and F13A+stress groups, the rats were subjected to water immersion and restraint stress (WIRS) for 6h. In the F13A+stress group, apelin receptor antagonist F13A, was injected intravenously immediately before application of WIRS. The plasma samples were obtained for the measurement of corticosterone and atrial natriuretic peptide. The atrial samples were used for immunohistochemistry and western blot analysis. F13A administration prevented the rise of plasma corticosterone and ANP levels induced by WIRS. While WIRS application increased the expressions of apelin, HIF-1α and ANP in atrial tissue, while F13A prevented the stress-induced increase in the expression of HIF-1α and ANP. Stress-induced apelin induces ANP expression in atrial tissue and may play a role in cardiovascular homeostasis by increasing ANP expression under WIRS conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lipopolysaccharide-Induced Behavioral Alterations Are Alleviated by Sodium Phenylbutyrate via Attenuation of Oxidative Stress and Neuroinflammatory Cascade.

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Jangra, Ashok; Sriram, Chandra Shaker; Lahkar, Mangala

2016-08-01

Oxido-nitrosative stress, neuroinflammation, and reduced level of neurotrophins are implicated in the pathophysiology of anxiety and depressive illness. A few recent studies have revealed the role of endoplasmic reticulum (ER) stress in the pathophysiology of stress and depression. The aim of the present study is to investigate the neuroprotective potential of sodium phenylbutyrate (SPB), an ER stress inhibitor against lipopolysaccharide (LPS)-induced anxiety and depressive-like behavior in Swiss albino mice. Anxiety and depressive-like behavior was induced by LPS (0.83 mg/kg; i.p.) administration. Various behavioral tests were conducted to evaluate the anxiety and depressive-like behavior in mice. Real-time PCR was employed for the detection and expression of ER stress markers (78-kDa glucose-regulated protein (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)). Pretreatment with SPB significantly ameliorated the LPS-induced anxiety and depressive-like behavior as revealed by behavioral paradigm results. LPS-induced oxidative stress was ameliorated by SPB pretreatment in hippocampus (HC) and prefrontal cortex (PFC) region. Neuroinflammation was significantly reduced by SPB pretreatment in LPS-treated mice as evident from reduction in proinflammatory cytokines (IL-1β and TNF-α). Importantly, LPS administration significantly up-regulated the GRP78 mRNA expression level in the HC which suggests the involvement of unfolded protein response (UPR) in LPS-evoked behavioral anomalies. These results highlight the neuroprotective potential of SPB in LPS-induced anxiety and depressive illness model which may be partially due to inhibition of oxidative stress-neuroinflammatory cascade.

Chronic variable stress improves glucose tolerance in rats with sucrose-induced prediabetes

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Packard, Amy E. B.; Ghosal, Sriparna; Herman, James P.; Woods, Stephen C.; Ulrich-Lai, Yvonne M.

2014-01-01

The incidence of type-2 diabetes (T2D) and the burden it places on individuals, as well as society as a whole, compels research into the causes, factors and progression of this disease. Epidemiological studies suggest that chronic stress exposure may contribute to the development and progression of T2D in human patients. To address the interaction between chronic stress and the progression of T2D, we developed a dietary model of the prediabetic state in rats utilizing unlimited access to 30% sucrose solution (in addition to unlimited access to normal chow and water), which led to impaired glucose tolerance despite elevated insulin levels. We then investigated the effects of a chronic variable stress paradigm (CVS; twice daily exposure to an unpredictable stressor for 2 weeks) on metabolic outcomes in this prediabetic model. Chronic stress improved glucose tolerance in prediabetic rats following a glucose challenge. Importantly, pair-fed control groups revealed that the beneficial effect of chronic stress did not result from the decreased food intake or body weight gain that occurred during chronic stress. The present work suggests that chronic stress in rodents can ameliorate the progression of diet-induced prediabetic disease independent of chronic stress-induced decreases in food intake and body weight. PMID:25001967

Salidroside Suppresses HUVECs Cell Injury Induced by Oxidative Stress through Activating the Nrf2 Signaling Pathway

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Yao Zhu

2016-08-01

Full Text Available Oxidative stress plays an important role in the pathogenesis of cardiovascular diseases. Salidroside (SAL, one of the main effective constituents of Rhodiola rosea, has been reported to suppress oxidative stress-induced cardiomyocyte injury and necrosis by promoting transcription of nuclear factor E2-related factor 2 (Nrf2-regulated genes such as heme oxygenase-1 (HO-1 and NAD(PH dehydrogenase (quinone1 (NQO1. However, it has not been indicated whether SAL might ameliorate endothelial injury induced by oxidative stress. Here, our study demonstrated that SAL might suppress HUVEC cell injury induced by oxidative stress through activating the Nrf2 signaling pathway. The results of our study indicated that SAL decreased the levels of intercellular reactive oxygen species (ROS and malondialdehyde (MDA, and improved the activities of superoxide dismutase (SOD and catalase (CAT, resulting in protective effects against oxidative stress-induced cell damage in HUVECs. It suppressed oxidative stress damage by inducing Nrf2 nuclear translocation and activating the expression of Nrf2-regulated antioxidant enzyme genes such as HO-1 and NQO1 in HUVECs. Knockdown of Nrf2 with siRNA abolished the cytoprotective effects against oxidative stress, decreased the expression of Nrf2, HO-1, and NQO1, and inhibited the nucleus translocation of Nrf2 in HUVECs. This study is the first to demonstrate that SAL suppresses HUVECs cell injury induced by oxidative stress through activating the Nrf2 signaling pathway.

Salidroside Improves Homocysteine-Induced Endothelial Dysfunction by Reducing Oxidative Stress

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Sin Bond Leung

2013-01-01

Full Text Available Hyperhomocysteinemia is associated with an increased risk for cardiovascular diseases through increased oxidative stress. Salidroside is an active ingredient of the root of Rhodiola rosea with documented antioxidative, antihypoxia and neuroprotective properties. However, the vascular benefits of salidroside against endothelial dysfunction have yet to be explored. The present study, therefore, aimed to investigate the protective effect of salidroside on homocysteine-induced endothelial dysfunction. Functional studies on the rat aortas were performed to delineate the vascular effect of salidroside. DHE imaging was used to evaluate the reactive oxygen species (ROS level in aortic wall and endothelial cells. Western blotting was performed to assess the protein expression associated with oxidative stress and nitric oxide (NO bioavailability. Exposure to homocysteine attenuated endothelium-dependent relaxations in rat aortas while salidroside pretreatment rescued it. Salidroside inhibited homocystein-induced elevation in the NOX2 expression and ROS overproduction in both aortas and cultured endothelial cells and increased phosphorylation of eNOS which was diminished by homocysteine. The present study shows that salidroside is effective in preserving the NO bioavailability and thus protects against homocysteine-induced impairment of endothelium-dependent relaxations, largely through inhibiting the NOX2 expression and ROS production. Our results indicate a therapeutic potential of salidroside in the management of oxidative-stress-associated cardiovascular dysfunction.

Salidroside Improves Homocysteine-Induced Endothelial Dysfunction by Reducing Oxidative Stress

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Leung, Sin Bond; Zhang, Huina; Lau, Chi Wai; Huang, Yu; Lin, Zhixiu

2013-01-01

Hyperhomocysteinemia is associated with an increased risk for cardiovascular diseases through increased oxidative stress. Salidroside is an active ingredient of the root of Rhodiola rosea with documented antioxidative, antihypoxia and neuroprotective properties. However, the vascular benefits of salidroside against endothelial dysfunction have yet to be explored. The present study, therefore, aimed to investigate the protective effect of salidroside on homocysteine-induced endothelial dysfunction. Functional studies on the rat aortas were performed to delineate the vascular effect of salidroside. DHE imaging was used to evaluate the reactive oxygen species (ROS) level in aortic wall and endothelial cells. Western blotting was performed to assess the protein expression associated with oxidative stress and nitric oxide (NO) bioavailability. Exposure to homocysteine attenuated endothelium-dependent relaxations in rat aortas while salidroside pretreatment rescued it. Salidroside inhibited homocystein-induced elevation in the NOX2 expression and ROS overproduction in both aortas and cultured endothelial cells and increased phosphorylation of eNOS which was diminished by homocysteine. The present study shows that salidroside is effective in preserving the NO bioavailability and thus protects against homocysteine-induced impairment of endothelium-dependent relaxations, largely through inhibiting the NOX2 expression and ROS production. Our results indicate a therapeutic potential of salidroside in the management of oxidative-stress-associated cardiovascular dysfunction. PMID:23589720

Endoplasmic reticulum stress-induced resistance to doxorubicin is reversed by paeonol treatment in human hepatocellular carcinoma cells.

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Lulu Fan

Full Text Available BACKGROUND: Endoplasmic reticulum stress (ER stress is generally activated in solid tumors and results in tumor cell anti-apoptosis and drug resistance. Paeonol (Pae, 2-hydroxy-4-methoxyacetophenone, is a natural product extracted from the root of Paeonia Suffruticosa Andrew. Although Pae displays anti-neoplastic activity and increases the efficacy of chemotherapeutic drugs in various cell lines and in animal models, studies related to the effect of Pae on ER stress-induced resistance to chemotherapeutic agents in hepatocellular carcinoma (HCC are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the effect of the endoplasmic reticulum (ER stress response during resistance of human hepatocellular carcinoma cells to doxorubicin. Treatment with the ER stress-inducer tunicamycin (TM before the addition of doxorubicin reduced the rate of apoptosis induced by doxorubicin. Interestingly, co-pretreatment with tunicamycin and Pae significantly increased apoptosis induced by doxorubicin. Furthermore, induction of ER stress resulted in increasing expression of COX-2 concomitant with inactivation of Akt and up-regulation of the pro-apoptotic transcription factor CHOP (GADD153 in HepG2 cells. These cellular changes in gene expression and Akt activation may be an important resistance mechanism against doxorubicin in hepatocellular carcinoma cells undergoing ER stress. However, co-pretreatment with tunicamycin and Pae decreased the expression of COX-2 and levels of activation of Akt as well as increasing the levels of CHOP in HCC cells. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that Pae reverses ER stress-induced resistance to doxorubicin in human hepatocellular carcinoma cells by targeting COX-2 mediated inactivation of PI3K/AKT/CHOP.

Effect of stress during handling, seawater acclimation, confinement, and induced spawning on plasma ion levels and somatolactin-expressing cells in mature female Liza ramada.

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Khalil, Noha A; Hashem, Amal M; Ibrahim, Amal A E; Mousa, Mostafa A

2012-08-01

The present experiments were designed to determine the effect of different stress factors; handling, seawater acclimation, confinement, and induced spawning on plasma cortisol, hydro mineral balance as well as changes in size, number and integrated intensity of somatolactin (SL)-expressing cells in Liza ramada mature females confined to fresh water ponds. The plasma levels of cortisol, PO(4)(3-), Na(+), and K(+) were higher, while Ca(2+) and Mg(2+) were lower than controls during transportation without anesthesia. By using clove oil (5 mg L(-1)) as an anesthetic during transportation, the plasma cortisol, PO(4) (3-), Na(+), and K(+) were similar to controls, while Ca(2+) and Mg(2+) were higher. During seawater acclimation, the plasma cortisol and minerals were significantly higher except Na(+) which was lower than controls. In addition, during induction of spawning, the plasma levels of cortisol, PO(4)(3-), Na(+), K(+), and Mg(2+) were significantly higher than controls. The SL-producing cells are located in the pars intermedia (PI) bordering the neurohypophysis. The stress affected the number, size, and immunostaining of SL-expressing cells. During seawater acclimation, the size and the integrated intensity of SL immunoreactivity were lower, but the number of these cells was higher than controls. Furthermore, the number, size, and the integrated intensity of SL immunoreactivity were significantly lower than controls during handling and after spawning, which was opposite to confinement. The response of SL-expressing cells in PI in parallel with changes in cortisol and hydro mineral balance induced by stress support the possible role of SL in the adaptive response of fish to stress. © 2012 WILEY PERIODICALS, INC.

Role of Growth Arrest and DNA Damage–inducible α in Akt Phosphorylation and Ubiquitination after Mechanical Stress-induced Vascular Injury

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Mitra, Sumegha; Sammani, Saad; Wang, Ting; Boone, David L.; Meyer, Nuala J.; Dudek, Steven M.; Moreno-Vinasco, Liliana; Garcia, Joe G. N.

2011-01-01

Rationale: The stress-induced growth arrest and DNA damage–inducible α (GADD45a) gene is up-regulated by mechanical stress with GADD45a knockout (GADD45a−/−) mice demonstrating both increased susceptibility to ventilator-induced lung injury (VILI) and reduced levels of the cell survival and vascular permeability signaling effector (Akt). However, the functional role of GADD45a in the pathogenesis of VILI is unknown. Objectives: We sought to define the role of GADD45a in the regulation of Akt activation induced by mechanical stress. Methods: VILI-challenged GADD45a−/− mice were administered a constitutively active Akt1 vector and injury was assessed by bronchoalveolar lavage cell counts and protein levels. Human pulmonary artery endothelial cells (EC) were exposed to 18% cyclic stretch (CS) under conditions of GADD45a silencing and used for immunoprecipitation, Western blotting or immunofluoresence. EC were also transfected with mutant ubiquitin vectors to characterize site-specific Akt ubiquitination. DNA methylation was measured using methyl-specific polymerase chain reaction assay. Measurements and Main Results: Studies exploring the linkage of GADD45a with mechanical stress and Akt regulation revealed VILI-challenged GADD45a−/− mice to have significantly reduced lung injury on overexpression of Akt1 transgene. Increased mechanical stress with 18% CS in EC induced Akt phosphorylation via E3 ligase tumor necrosis factor receptor–associated factor 6 (TRAF6)–mediated Akt K63 ubiquitination resulting in Akt trafficking and activation at the membrane. GADD45a is essential to this process because GADD45a-silenced endothelial cells and GADD45a−/− mice exhibited increased Akt K48 ubiquitination leading to proteasomal degradation. These events involve loss of ubiquitin carboxyl terminal hydrolase 1 (UCHL1), a deubiquitinating enzyme that normally removes K48 polyubiquitin chains bound to Akt thus promoting Akt K63 ubiquitination. Loss of GADD45a

Correlation between passive film-induced stress and stress corrosion cracking of α-Ti in a methanol solution at various potentials

International Nuclear Information System (INIS)

Guo, X.Z.; Gao, K.W.; Chu, W.Y.; Qiao, L.J.

2003-01-01

The flow stress of a specimen of α-Ti before unloading is different with the yield stress of the same specimen after unloading and forming a passive film through immersing in a methanol solution at various constant potentials. The difference is the passive film-induced stress. The film-induced stress and susceptibility to stress corrosion cracking (SCC) in the methanol solution at various potentials were measured. At the stable open-circuit potential and under anodic polarization, both film-induced tensile stress σ p and susceptibility to SCC had a maximum value. The film-induced stress and SCC susceptibility, however, decreased steeply with a decrease in potential under cathodic polarization. When the potential V≤-280 mV SCE , the film-induced stress became compressive; correspondingly, susceptibility to SCC was zero. Therefore, the variation of film-induced stress with potential was consistent with that of susceptibility to SCC. A large film-induced tensile stress is the necessary condition for SCC of α-Ti in the methanol solution. The symbol and amount of the film-induced stress were related to the compositions of the passive film, which have been analyzed using the X-ray photoelectron spectrum (XPS)

Clonidine blocks stress-induced craving in cocaine users.

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Jobes, Michelle L; Ghitza, Udi E; Epstein, David H; Phillips, Karran A; Heishman, Stephen J; Preston, Kenzie L

2011-11-01

Reactivity to stressors and environmental cues, a putative cause of relapse in addiction, may be a useful target for relapse-prevention medication. In rodents, alpha-2 adrenergic agonists such as clonidine block stress-induced reinstatement of drug seeking, but not drug cue-induced reinstatement. The objective of this study is to test the effect of clonidine on stress- and cue-induced craving in human cocaine users. Healthy, non-treatment-seeking cocaine users (n = 59) were randomly assigned to three groups receiving clonidine 0, 0.1, or 0.2 mg orally under double-blind conditions. In a single test session, each participant received clonidine or placebo followed 3 h later by exposure to two pairs of standardized auditory-imagery scripts (neutral/stress and neutral/drug). Subjective measures of craving were collected. Subjective responsivity ("crave cocaine" Visual Analog Scale) to stress scripts was significantly attenuated in the 0.1- and 0.2-mg clonidine groups; for drug-cue scripts, this attenuation occurred only in the 0.2-mg group. Other subjective measures of craving showed similar patterns of effects but Dose × Script interactions were not significant. Clonidine was effective in reducing stress-induced (and, at a higher dose, cue-induced) craving in a pattern consistent with preclinical findings, although this was significant on only one of several measures. Our results, though modest and preliminary, converge with other evidence to suggest that alpha-2 adrenergic agonists may help prevent relapse in drug abusers experiencing stress or situations that remind them of drug use.

Corticosterone mediates some but not other behavioural changes induced by prenatal stress in rats.

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Salomon, S; Bejar, C; Schorer-Apelbaum, D; Weinstock, M

2011-02-01

The effect of daily varied stress from days 13-21 of gestation in Wistar rats was investigated by tests of learning and memory and anxiogenic behaviour in the 60-day-old offspring of both sexes. Prenatal stress decreased the anogenital distance in males at 1 day of age. Anxiogenic behaviour in the elevated plus maze was seen in prenatally-stressed rats of both genders. There was no significant gender difference in the rate of spatial learning in the Morris water maze but prenatal stress only slowed that of males. In the object recognition test with an inter-trial interval of 40 min, females but not males, discriminated between a familiar and novel object. Prenatal stress did not affect object discrimination in females but feminised that in males. Maternal adrenalectomy with replacement of basal corticosterone levels in the drinking fluid prevented all of the above effects of prenatal stress in the offspring. To mimic the peak corticosterone levels and time course of elevation in response to stress, corticosterone (3 mg/kg) was injected twice (0 and 30 min) on days 13-16 and once on days 17-20 of gestation to adrenalectomised mothers. This treatment re-instated anxiogenic behaviour similar to that induced by prenatal stress, indicating that it is mediated by exposure of the foetal brain to raised levels of corticosterone. However, steroid administration to adrenalectomised dams did not decrease anogenital distance, feminise object recognition memory or slow spatial learning in their male offspring. The findings indicate that other adrenal hormones are necessary to induce these effects of prenatal stress. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

A Standardized Chinese Herbal Decoction, Kai-Xin-San, Restores Decreased Levels of Neurotransmitters and Neurotrophic Factors in the Brain of Chronic Stress-Induced Depressive Rats

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Zhu, Kevin Yue; Mao, Qing-Qiu; Ip, Siu-Po; Choi, Roy Chi-Yan; Dong, Tina Ting-Xia; Lau, David Tai-Wai; Tsim, Karl Wah-Keung

2012-01-01

Kai-xin-san (KXS), a Chinese herbal decoction being prescribed by Sun Simiao in Beiji Qianjin Yaofang about 1400 years ago, contains Ginseng Radix et Rhizoma, Polygalae Radix, Acori tatarinowii Rhizoma, and Poria. KXS has been used to treat stress-related psychiatric disease with the symptoms of depression and forgetfulness in ancient China until today. However, the mechanism of its antidepression action is still unknown. Here, the chronic mild-stress-(CMS-) induced depressive rats were applied in exploring the action mechanisms of KXS treatment. Daily intragastric administration of KXS for four weeks significantly alleviated the CMS-induced depressive symptoms displayed by enhanced sucrose consumption. In addition, the expressions of those molecular bio-markers relating to depression in rat brains were altered by the treatment of KXS. These KXS-regulated brain biomarkers included: (i) the levels of dopamine, norepinephrine, and serotonin (ii) the transcript levels of proteins relating to neurotransmitter metabolism; (iii) the transcript levels of neurotrophic factors and their receptors. The results suggested that the anti-depressant-like action of KXS might be mediated by an increase of neurotransmitters and expression of neurotrophic factors and its corresponding receptors in the brain. Thus, KXS could serve as alternative medicine, or health food supplement, for patients suffering from depression. PMID:22973399

A Standardized Chinese Herbal Decoction, Kai-Xin-San, Restores Decreased Levels of Neurotransmitters and Neurotrophic Factors in the Brain of Chronic Stress-Induced Depressive Rats

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Kevin Yue Zhu

2012-01-01

Full Text Available Kai-xin-san (KXS, a Chinese herbal decoction being prescribed by Sun Simiao in Beiji Qianjin Yaofang about 1400 years ago, contains Ginseng Radix et Rhizoma, Polygalae Radix, Acori tatarinowii Rhizoma, and Poria. KXS has been used to treat stress-related psychiatric disease with the symptoms of depression and forgetfulness in ancient China until today. However, the mechanism of its antidepression action is still unknown. Here, the chronic mild-stress-(CMS- induced depressive rats were applied in exploring the action mechanisms of KXS treatment. Daily intragastric administration of KXS for four weeks significantly alleviated the CMS-induced depressive symptoms displayed by enhanced sucrose consumption. In addition, the expressions of those molecular bio-markers relating to depression in rat brains were altered by the treatment of KXS. These KXS-regulated brain biomarkers included: (i the levels of dopamine, norepinephrine, and serotonin (ii the transcript levels of proteins relating to neurotransmitter metabolism; (iii the transcript levels of neurotrophic factors and their receptors. The results suggested that the anti-depressant-like action of KXS might be mediated by an increase of neurotransmitters and expression of neurotrophic factors and its corresponding receptors in the brain. Thus, KXS could serve as alternative medicine, or health food supplement, for patients suffering from depression.

Stress-induced and cue-induced craving for alcohol in heavy drinkers: Preliminary evidence of genetic moderation by the OPRM1 and CRH-BP genes.

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Ray, Lara A

2011-01-01

Neurobiological theories of addiction have highlighted disruption in stress pathways as a central feature of addictive disorders, and pharmacological treatments targeting stress mechanisms hold great promise. This study examines genetic determinants of stress-induced and cue-induced craving in heavy drinkers by testing single-nucleotide polymorphisms (SNPs) of the corticotrophin-releasing hormone binding protein (CRH-BP) gene and the mu-opioid receptor (OPRM1) gene. This study combines guided imagery stress exposure and in vivo alcohol cue exposure in a sample of 64 (23 women) non-treatment-seeking heavy drinkers. Analyses, uncorrected for multiple comparisons, revealed that a tag SNP of the CRH-BP gene (rs10055255) moderated stress-induced craving in this sample. The same SNP predicted greater affective responses to the stress manipulation, including greater levels of subjective tension and negative mood. The Asp40 allele of the OPRM1 was associated with greater cue-induced alcohol craving following the neutral imagery condition. These initial results extend recent preclinical and clinical findings implicating the CRH-BP in stress-related alcoholism and confirm the role of the Asp40 allele of the OPRM1 gene in reward-driven alcohol phenotypes. Human laboratory models of stress and cue-induced craving may be useful in pharmacotherapy development targeting dysregulation of stress systems. Larger studies are needed to validate these preliminary findings, which should also be extended to clinical samples. Copyright © 2010 by the Research Society on Alcoholism.

Characterization of stress-induced suppression of long-term potentiation in the hippocampal CA1 field of freely moving rats.

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Hirata, Riki; Togashi, Hiroko; Matsumoto, Machiko; Yamaguchi, Taku; Izumi, Takeshi; Yoshioka, Mitsuhiro

2008-08-21

Several lines of evidence have shown that exposure to stress impairs long-term potentiation (LTP) in the CA1 field of the hippocampus, but the detailed mechanisms for this effect remain to be clarified. The present study elucidated the synaptic mechanism of stress-induced LTP suppression in conscious, freely moving rats using electrophysiological approaches. Open field stress (i.e., novel environment stress) and elevated platform stress (i.e., uncontrollable stress) were employed. Basal synaptic transmission was significantly reduced during exposure to elevated platform stress but not during exposure to open field stress. LTP induction was blocked by elevated platform stress but not influenced by open field stress. Significant increases in serum corticosterone levels were observed in the elevated platform stress group compared with the open field stress group. Furthermore, LTP suppression induced by elevated platform stress was prevented by pretreatment with an anxiolytic drug diazepam (1 mg/kg, i.p.). These results suggest that stress-induced LTP suppression depends on the relative intensity of the stressor. The inhibitory synaptic response induced by an intense psychological stress, such as elevated platform stress, may be attributable to LTP impairment in the CA1 field of the hippocampus.

Short-term pre- and post-operative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception.

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Cao, Jing; Wang, Po-Kai; Tiwari, Vinod; Liang, Lingli; Lutz, Brianna Marie; Shieh, Kun-Ruey; Zang, Wei-Dong; Kaufman, Andrew G; Bekker, Alex; Gao, Xiao-Qun; Tao, Yuan-Xiang

2015-12-02

Chronic stress has been reported to increase basal pain sensitivity and/or exacerbate existing persistent pain. However, most surgical patients have normal physiological and psychological health status such as normal pain perception before surgery although they do experience short-term stress during pre- and post-operative periods. Whether or not this short-term stress affects persistent postsurgical pain is unclear. In this study, we showed that pre- or post-surgical exposure to immobilization 6 h daily for three consecutive days did not change basal responses to mechanical, thermal, or cold stimuli or peak levels of incision-induced hypersensitivity to these stimuli; however, immobilization did prolong the duration of incision-induced hypersensitivity in both male and female rats. These phenomena were also observed in post-surgical exposure to forced swimming 25 min daily for 3 consecutive days. Short-term stress induced by immobilization was demonstrated by an elevation in the level of serum corticosterone, an increase in swim immobility, and a decrease in sucrose consumption. Blocking this short-term stress via intrathecal administration of a selective glucocorticoid receptor antagonist, RU38486, or bilateral adrenalectomy significantly attenuated the prolongation of incision-induced hypersensitivity to mechanical, thermal, and cold stimuli. Our results indicate that short-term stress during the pre- or post-operative period delays postoperative pain recovery although it does not affect basal pain perception. Prevention of short-term stress may facilitate patients' recovery from postoperative pain.

Possible antidepressant effects of vanillin against experimentally induced chronic mild stress in rats

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Amira M. Abo-youssef

2016-06-01

Full Text Available Vanillin is a flavoring agent widely used in food and beverages such as chocolates and dairy products and it is also used to mask unpleasant tastes in medicine. It has been reported to have antioxidant, anti-inflammatory and antiapoptotic properties. The current study was designed to investigate the protective effects of vanillin against experimentally induced stress in rats. Briefly rats were subdivided into four groups. Three groups were subjected to chronic mild stress and the fourth group served as normal control group. One week before induction of stress drugs or saline was administered daily and continued for another nine weeks. At the end of the experimental period behavioral tests including sucrose preference test, forced swim test and elevated plus maze test were assessed. In addition, brain biochemical parameters including MDA, GSH, NO and serotonin were determined. Vanillin succeeded to restore the behavioral and biochemical changes associated with stress. It significantly increased sucrose consumption in sucrose preference test and time spent in open arm in elevated plus maze test as compared to stress control group. It also reduced immobility time in forced swim test and time spent in closed arm in elevated plus maze test. Additionally, it significantly decreased brain MDA and NO levels and significantly increased brain GSH and Serotonin levels compared to stress control group. It could be concluded that vanillin showed beneficial protective effects against experimentally induced stress in rats.

Protective effect of nicotinamide adenine dinucleotide (NAD+) against spinal cord ischemia-reperfusion injury via reducing oxidative stress-induced neuronal apoptosis.

Science.gov (United States)

Xie, Lei; Wang, Zhenfei; Li, Changwei; Yang, Kai; Liang, Yu

2017-02-01

As previous studies demonstrate that oxidative stress and apoptosis play crucial roles in ischemic pathogenesis and nicotinamide adenine dinucleotide (NAD + ) treatment attenuates oxidative stress-induced cell death among primary neurons and astrocytes as well as significantly reduce cerebral ischemic injury in rats. We used a spinal cord ischemia injury (SCII) model in rats to verify our hypothesis that NAD + could ameliorate oxidative stress-induced neuronal apoptosis. Adult male rats were subjected to transient spinal cord ischemia for 60min, and different doses of NAD + were administered intraperitoneally immediately after the start of reperfusion. Neurological function was determined by Basso, Beattie, Bresnahan (BBB) scores. The oxidative stress level was assessed by superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. The degree of apoptosis was analyzed by deoxyuridinetriphosphate nick-end labeling (TUNEL) staining and protein levels of cleaved caspase-3 and AIF (apoptosis inducing factor). The results showed that NAD + at 50 or 100mg/kg significantly decreased the oxidative stress level and neuronal apoptosis in the spinal cord of ischemia-reperfusion rats compared with saline, as accompanied with the decreased oxidative stress, NAD + administration significantly restrained the neuronal apoptosis after ischemia injury while improved the neurological and motor function. These findings suggested that NAD + might protect against spinal cord ischemia-reperfusion via reducing oxidative stress-induced neuronal apoptosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aging induced ER stress alters sleep and sleep homeostasis

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Brown, Marishka K.; Chan, May T.; Zimmerman, John E.; Pack, Allan I.; Jackson, Nicholas E.; Naidoo, Nirinjini

2013-01-01

Alterations in the quality, quantity and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response (UPR). The effectiveness of the adaptive UPR is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical ...

Hydrogen-peroxide-induced oxidative stress responses in Desulfovibrio vulgaris Hildenborough

Energy Technology Data Exchange (ETDEWEB)

Zhou, A.; He, Z.; Redding-Johanson, A.M.; Mukhopadhyay, A.; Hemme, C.L.; Joachimiak, M.P.; Bender, K.S.; Keasling, J.D.; Stahl, D.A.; Fields, M.W.; Hazen, T.C.; Arkin, A.P.; Wall, J.D.; Zhou, J.; Luo, F.; Deng, Y.; He, Q.

2010-07-01

To understand how sulphate-reducing bacteria respond to oxidative stresses, the responses of Desulfovibrio vulgaris Hildenborough to H{sub 2}O{sub 2}-induced stresses were investigated with transcriptomic, proteomic and genetic approaches. H{sub 2}O{sub 2} and induced chemical species (e.g. polysulfide, ROS) and redox potential shift increased the expressions of the genes involved in detoxification, thioredoxin-dependent reduction system, protein and DNA repair, and decreased those involved in sulfate reduction, lactate oxidation and protein synthesis. A gene coexpression network analysis revealed complicated network interactions among differentially expressed genes, and suggested possible importance of several hypothetical genes in H{sub 2}O{sub 2} stress. Also, most of the genes in PerR and Fur regulons were highly induced, and the abundance of a Fur regulon protein increased. Mutant analysis suggested that PerR and Fur are functionally overlapped in response to stresses induced by H{sub 2}O{sub 2} and reaction products, and the upregulation of thioredoxin-dependent reduction genes was independent of PerR or Fur. It appears that induction of those stress response genes could contribute to the increased resistance of deletion mutants to H{sub 2}O{sub 2}-induced stresses. In addition, a conceptual cellular model of D. vulgaris responses to H{sub 2}O{sub 2} stress was constructed to illustrate that this bacterium may employ a complicated molecular mechanism to defend against the H{sub 2}O{sub 2}-induced stresses.

Aging induced ER stress alters sleep and sleep homeostasis

Science.gov (United States)

Brown, Marishka K.; Chan, May T.; Zimmerman, John E.; Pack, Allan I.; Jackson, Nicholas E.; Naidoo, Nirinjini

2014-01-01

Alterations in the quality, quantity and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response (UPR). The effectiveness of the adaptive UPR is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of x-box binding protein 1 (XBP1) and upregulation of phosphorylated elongation initiation factor 2 α (p-eIF2α), in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged/sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep/ sleep debt discharge. PMID:24444805

Effect of Mucuna pruriens (Linn.) on oxidative stress-induced structural alteration of corpus cavernosum in streptozotocin-induced diabetic rat.

Science.gov (United States)

Suresh, Sekar; Prakash, Seppan

2011-07-01

Erectile dysfunction is one of the major secondary complications of diabetes. Mucuna pruriens (M. pruriens), a leguminous plant identified for its antidiabetic, aphrodisiac, and fertility enhancing properties, has been the choice of Indian traditional medicine. The objective of the present study was to analyze the efficacy of M. pruriens on free radicals-mediated penile tissue alterations in hyperglycemic male rats. Methods.  Male albino rats were divided as group I (sham) control, group II (STZ) diabetes-induced (streptozotocin 60 mg/kg of body weight [bw] in 0.1 M citrate buffer), group III (STZ + MP) diabetic rats administered with 200 mg/kg bw of ethanolic extract of M. pruriens seed, group IV (STZ + SIL) diabetic rats administered with 5 mg/kg bw of sildenafil citrate, group V (sham + MP) administered with 200 mg/kg bw of extract alone, and group VI (sham + SIL) administered with 5 mg/kg bw of sildenafil citrate. The M. pruriens and sildenafil citrate were given (gavage) once daily for a period of 60 days. At the end of 60 days, the animals were sacrificed and subjected to analysis of reactive oxygen species levels, enzymic and nonenzymic antioxidant levels, levels of NOx, histological, and histomorphometrical study of penile tissue. Remedial use of M. pruriens seed extract on diabetes-induced erectile tissue damage. Significantly high levels of oxidative stress and low levels of antioxidants in the penile tissue seem to contribute to the increased collagen deposition and fibrosis of erectile tissue in STZ rats. Relatively, there was increased damage in STZ + SIL group. Supplementation of M. pruriens in STZ + MP group has revealed the potency to overcome oxidative stress, and good preservation of penile histoarchitecture.  The ethanolic extract of M. pruriens seed significantly recovered or protected erectile tissue from the oxidative stress-induced degeneration by its antioxidant potentials. These findings propound to serve mankind by the treatment of

Escitalopram and NHT normalized stress-induced anhedonia and molecular neuroadaptations in a mouse model of depression.

Directory of Open Access Journals (Sweden)

Or Burstein

Full Text Available Anhedonia is defined as a diminished ability to obtain pleasure from otherwise positive stimuli. Anxiety and mood disorders have been previously associated with dysregulation of the reward system, with anhedonia as a core element of major depressive disorder (MDD. The aim of the present study was to investigate whether stress-induced anhedonia could be prevented by treatments with escitalopram or novel herbal treatment (NHT in an animal model of depression. Unpredictable chronic mild stress (UCMS was administered for 4 weeks on ICR outbred mice. Following stress exposure, animals were randomly assigned to pharmacological treatment groups (i.e., saline, escitalopram or NHT. Treatments were delivered for 3 weeks. Hedonic tone was examined via ethanol and sucrose preferences. Biological indices pertinent to MDD and anhedonia were assessed: namely, hippocampal brain-derived neurotrophic factor (BDNF and striatal dopamine receptor D2 (Drd2 mRNA expression levels. The results indicate that the UCMS-induced reductions in ethanol or sucrose preferences were normalized by escitalopram or NHT. This implies a resemblance between sucrose and ethanol in their hedonic-eliciting property. On a neurobiological aspect, UCMS-induced reduction in hippocampal BDNF levels was normalized by escitalopram or NHT, while UCMS-induced reduction in striatal Drd2 mRNA levels was normalized solely by NHT. The results accentuate the association of stress and anhedonia, and pinpoint a distinct effect for NHT on striatal Drd2 expression.

Activation of ATP-sensitive potassium channel by iptakalim normalizes stress-induced HPA axis disorder and depressive behaviour by alleviating inflammation and oxidative stress in mouse hypothalamus.

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Zhao, Xiao-Jie; Zhao, Zhan; Yang, Dan-Dan; Cao, Lu-Lu; Zhang, Ling; Ji, Juan; Gu, Jun; Huang, Ji-Ye; Sun, Xiu-Lan

2017-04-01

Stress-induced disturbance of the hypothalamic-pituitary-adrenal (HPA) axis is strongly implicated in incidence of mood disorders. A heightened neuroinflammatory response and oxidative stress play a fundamental role in the dysfunction of the HPA axis. We have previously demonstrated that iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could prevent oxidative injury and neuroinflammation against multiple stimuli-induced brain injury. The present study was to demonstrate the impacts of Ipt in stress-induced HPA axis disorder and depressive behavior. We employed 2 stress paradigms: 8 weeks of continuous restraint stress (chronic restraint stress, CRS) and 2h of restraint stress (acute restraint stress, ARS), to mimic both chronic stress and severe acute stress. Prolonged (4 weeks) and short-term (a single injection) Ipt treatment was administered 30min before each stress paradigm. We found that HPA axis was altered after stress, with different responses to CRS (lower ACTH and CORT, higher AVP, but normal CRH) and ARS (higher CRH, ACTH and CORT, but normal AVP). Both prolonged and short-term Ipt treatment normalized stress-induced HPA axis disorders and abnormal behaviors in mice. CRS and ARS up-regulated mRNA levels of inflammation-related molecules (TNFα, IL-1β, IL-6 and TLR4) and oxidative stress molecules (gp91phox, iNOS and Nrf2) in the mouse hypothalamus. Double immunofluorescence showed CRS and ARS increased microglia activation (CD11b and TNFα) and oxidative stress in neurons (NeuN and gp91phox), which were alleviated by Ipt. Therefore, the present study reveals that Ipt could prevent against stress-induced HPA axis disorders and depressive behavior by alleviating inflammation and oxidative stress in the hypothalamus. Copyright © 2017 Elsevier Inc. All rights reserved.

Ghrelin-reactive immunoglobulins and anxiety, depression and stress-induced cortisol response in adolescents. The TRAILS study.

Science.gov (United States)

François, Marie; Schaefer, Johanna M; Bole-Feysot, Christine; Déchelotte, Pierre; Verhulst, Frank C; Fetissov, Sergueï O

2015-06-03

Ghrelin, a hunger hormone, has been implicated in the regulation of stress-response, anxiety and depression. Ghrelin-reactive immunoglobulins (Ig) were recently identified in healthy and obese humans showing abilities to increase ghrelin's stability and orexigenic effects. Here we studied if ghrelin-reactive Ig are associated with anxiety and depression and with the stress-induced cortisol response in a general population of adolescents. Furthermore, to test the possible infectious origin of ghrelin-reactive Ig, their levels were compared with serum IgG against common viruses. We measured ghrelin-reactive IgM, IgG and IgA in serum samples of 1199 adolescents from the Dutch TRAILS study and tested their associations with 1) anxiety and depression symptoms assessed with the Youth Self-Report, 2) stress-induced salivary cortisol levels and 3) IgG against human herpesvirus 1, 2, 4 and 6 and Influenza A and B viruses. Ghrelin-reactive IgM and IgG correlated positively with levels of antibodies against Influenza A virus. Ghrelin-reactive IgM correlated negatively with antibodies against Influenza B virus. Ghrelin-reactive IgM correlated positively with anxiety scores in girls and ghrelin-reactive IgG correlated with stress-induced cortisol secretion, but these associations were weak and not significant after correction for multiple testing. These data indicate that production of ghrelin-reactive autoantibodies could be influenced by viral infections. Serum levels of ghrelin-reactive autoantibodies probably do not play a role in regulating anxiety, depression and the stress-response in adolescents from the general population. Copyright © 2015 Elsevier Inc. All rights reserved.

Stress-induced core temperature changes in pigeons (Columba livia).

Science.gov (United States)

Bittencourt, Myla de Aguiar; Melleu, Fernando Falkenburger; Marino-Neto, José

2015-02-01

Changes in body temperature are significant physiological consequences of stressful stimuli in mammals and birds. Pigeons (Columba livia) prosper in (potentially) stressful urban environments and are common subjects in neurobehavioral studies; however, the thermal responses to stress stimuli by pigeons are poorly known. Here, we describe acute changes in the telemetrically recorded celomatic (core) temperature (Tc) in pigeons given a variety of potentially stressful stimuli, including transfer to a novel cage (ExC) leading to visual isolation from conspecifics, the presence of the experimenter (ExpR), gentle handling (H), sham intracelomatic injections (SI), and the induction of the tonic immobility (TI) response. Transfer to the ExC cage provoked short-lived hyperthermia (10-20 min) followed by a long-lasting and substantial decrease in Tc, which returned to baseline levels 2 h after the start of the test. After a 2-hour stay in the ExC, the other potentially stressful stimuli evoked only weak, marginally significant hyperthermic (ExpR, IT) or hypothermic (SI) responses. Stimuli delivered 26 h after transfer to the ExC induced definite and intense increases in Tc (ExpR, H) or hypothermic responses (SI). These Tc changes appear to be unrelated to modifications in general activity (as measured via telemetrically recorded actimetric data). Repeated testing failed to affect the hypothermic responses to the transference to the ExC, even after nine trials and at 1- or 8-day intervals, suggesting that the social (visual) isolation from conspecifics may be a strong and poorly controllable stimulus in this species. The present data indicated that stress-induced changes in Tc may be a consistent and reliable physiological parameter of stress but that they may also show stressor type-, direction- and species-specific attributes. Copyright © 2014 Elsevier Inc. All rights reserved.

A combination of high stress-induced tense and energetic arousal compensates for impairing effects of stress on memory retrieval in men.

Science.gov (United States)

Boehringer, Andreas; Schwabe, Lars; Schachinger, Hartmut

2010-09-01

Stress can both impair and enhance memory retrieval. Glucocorticoids mediate impairing effects of stress on memory retrieval. Little is known, however, about factors that facilitate post-stress memory performance. Here, we asked whether stress-induced arousal mediates facilitative stress effects on memory retrieval. Two arousal dimensions were separated: tense arousal, which is characterized by feelings ranging from tension and anxiety to calmness and quietness, and energetic arousal, which is associated with feelings ranging from energy and vigor to states of fatigue and tiredness. Fifty-one men (mean age +/- SEM: 24.57 +/- 0.61 years) learned emotional and neutral words. Memory for these words was tested 165 min later, after participants were exposed to a psychosocial stress or a non-arousing control condition. Changes in heart rate, self-reported (energetic and tense) arousal, and saliva cortisol in response to the stress/control condition were measured. Overall, stress impaired memory retrieval. However, stressed participants with large increases in both tense and energetic arousal performed comparably to controls. Neither salivary cortisol level nor autonomic arousal predicted memory performance after controlling for changes in energetic and tense arousal. The present data indicate that stress-induced concurrent changes in tense and energetic arousal can compensate for impairing effects of stress on memory retrieval. This finding could help to explain some of the discrepancies in the literature on stress and memory.

Heavy metals induce oxidative stress and trigger oxidative stress-mediated heat shock protein (hsp) modulation in the intertidal copepod Tigriopus japonicus.

Science.gov (United States)

Kim, Bo-Mi; Rhee, Jae-Sung; Jeong, Chang-Bum; Seo, Jung Soo; Park, Gyung Soo; Lee, Young-Mi; Lee, Jae-Seong

2014-11-01

Heat shock proteins (hsps) are induced by a wide range of environmental stressors including heavy metals in aquatic organisms. However, the effect of heavy metals on zooplankton at the molecular level remains still unclear. In this study, we measured the intracellular reactive oxygen species (ROS) level and the antioxidant enzyme activities for 96 h after exposure to five heavy metals: arsenic (As), cadmium (Cd), copper (Cu), silver (Ag), and zinc (Zn) in the intertidal copepod Tigriopus japonicus. Activities of the antioxidant enzymes were highly elevated in metal-exposed copepods, indicating that heavy metals can induce oxidative stress by generating ROS, and stimulate the involvement of antioxidant enzymes as cellular defense mechanisms. Subsequently, transcriptional changes in hsp gene families were further investigated in the metal-exposed groups for 96 h. The ROS level and glutathione (GSH) content were significantly increased in Ag-, As-, and Cu-exposed copepods, while they were only slightly elevated in Cd- and Zn-exposed groups. Based on the numbers of significantly modulated hsp genes and their expression levels for 96 h, we measured the effect of heavy metals to stress genes of T. japonicus in the following order: Cu > Zn > Ag > As > Cd, implying that Cu acts as a stronger oxidative stress inducer than other heavy metals. Of them, the expression of hsp20 and hsp70 genes was substantially modulated by exposure to heavy metals, indicating that these genes would provide a sensitive molecular biomarker for aquatic monitoring of heavy metal pollution. Copyright © 2014 Elsevier Inc. All rights reserved.

Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish

Energy Technology Data Exchange (ETDEWEB)

Christen, Verena [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Capelle, Martinus [Crucell, P.O. Box 2048, NL-2301 Leiden (Netherlands); Fent, Karl, E-mail: karl.fent@fhnw.ch [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Swiss Federal Institute of Technology Zürich, Department of Environmental Systems Science, CH-8092 Zürich (Switzerland)

2013-10-15

Silver nanoparticles (AgNPs) find increasing applications, and therefore humans and the environment are increasingly exposed to them. However, potential toxicological implications are not sufficiently known. Here we investigate effects of AgNPs (average size 120 nm) on zebrafish in vitro and in vivo, and compare them to human hepatoma cells (Huh7). AgNPs are incorporated in zebrafish liver cells (ZFL) and Huh7, and in zebrafish embryos. In ZFL cells AgNPs lead to induction of reactive oxygen species (ROS), endoplasmatic reticulum (ER) stress response, and TNF-α. Transcriptional alterations also occur in pro-apoptotic genes p53 and Bax. The transcriptional profile differed in ZFL and Huh7 cells. In ZFL cells, the ER stress marker BiP is induced, concomitant with the ER stress marker ATF-6 and spliced XBP-1 after 6 h and 24 h exposure to 0.5 g/L and 0.05 g/L AgNPs, respectively. This indicates the induction of different pathways of the ER stress response. Moreover, AgNPs induce TNF-α. In zebrafish embryos exposed to 0.01, 0.1, 1 and 5 mg/L AgNPs hatching was affected and morphological defects occurred at high concentrations. ER stress related gene transcripts BiP and Synv are significantly up-regulated after 24 h at 0.1 and 5 mg/L AgNPs. Furthermore, transcriptional alterations occurred in the pro-apoptotic genes Noxa and p21. The ER stress response was strong in ZFL cells and occurred in zebrafish embryos as well. Our data demonstrate for the first time that AgNPs lead to induction of ER stress in zebrafish. The induction of ER stress can have several consequences including the activation of apoptotic and inflammatory pathways. - Highlights: • Effects of silver nanoparticles (120 nm AgNPs) are investigated in zebrafish. • AgNPs induce all ER stress reponses in vitro in zebrafish liver cells. • AgNPs induce weak ER stress in zebrafish embryos. • AgNPs induce oxidative stress and transcripts of pro-apoptosis genes.

Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish

International Nuclear Information System (INIS)

Christen, Verena; Capelle, Martinus; Fent, Karl

2013-01-01

Silver nanoparticles (AgNPs) find increasing applications, and therefore humans and the environment are increasingly exposed to them. However, potential toxicological implications are not sufficiently known. Here we investigate effects of AgNPs (average size 120 nm) on zebrafish in vitro and in vivo, and compare them to human hepatoma cells (Huh7). AgNPs are incorporated in zebrafish liver cells (ZFL) and Huh7, and in zebrafish embryos. In ZFL cells AgNPs lead to induction of reactive oxygen species (ROS), endoplasmatic reticulum (ER) stress response, and TNF-α. Transcriptional alterations also occur in pro-apoptotic genes p53 and Bax. The transcriptional profile differed in ZFL and Huh7 cells. In ZFL cells, the ER stress marker BiP is induced, concomitant with the ER stress marker ATF-6 and spliced XBP-1 after 6 h and 24 h exposure to 0.5 g/L and 0.05 g/L AgNPs, respectively. This indicates the induction of different pathways of the ER stress response. Moreover, AgNPs induce TNF-α. In zebrafish embryos exposed to 0.01, 0.1, 1 and 5 mg/L AgNPs hatching was affected and morphological defects occurred at high concentrations. ER stress related gene transcripts BiP and Synv are significantly up-regulated after 24 h at 0.1 and 5 mg/L AgNPs. Furthermore, transcriptional alterations occurred in the pro-apoptotic genes Noxa and p21. The ER stress response was strong in ZFL cells and occurred in zebrafish embryos as well. Our data demonstrate for the first time that AgNPs lead to induction of ER stress in zebrafish. The induction of ER stress can have several consequences including the activation of apoptotic and inflammatory pathways. - Highlights: • Effects of silver nanoparticles (120 nm AgNPs) are investigated in zebrafish. • AgNPs induce all ER stress reponses in vitro in zebrafish liver cells. • AgNPs induce weak ER stress in zebrafish embryos. • AgNPs induce oxidative stress and transcripts of pro-apoptosis genes

Inhibition of a Descending Prefrontal Circuit Prevents Ketamine-Induced Stress Resilience in Females

DEFF Research Database (Denmark)

Dolzani, S. D.; Baratta, M. V.; Moss, J. M.

2018-01-01

. The NMDA receptor antagonist ketamine has recently emerged as a prophylactic capable of preventing neurochemical and behavioral outcomes of a future stressor. Despite promising results of preclinical studies performed in male rats, the effects of proactive ketamine in female rats remains unknown....... This is alarming given that stress-related disorders affect females at nearly twice the rate of males. Here we explore the prophylactic effects of ketamine on stress-induced anxiety-like behavior and the neural circuit-level processes that mediate these effects in female rats. Ketamine given one week prior...... to an uncontrollable stressor (inescapable tailshock; IS) reduced typical stress-induced activation of the serotonergic (5-HT) dorsal raphe nucleus (DRN) and eliminated DRN-dependent juvenile social exploration (JSE) deficits 24 h after the stressor. Proactive ketamine altered prelimbic cortex (PL) neural ensembles so...

Lead induced oxidative stress: beneficial effects of Kombucha tea.

Science.gov (United States)

Dipti, P; Yogesh, B; Kain, A K; Pauline, T; Anju, B; Sairam, M; Singh, B; Mongia, S S; Kumar, G Ilavazhagan Devendra; Selvamurthy, W

2003-09-01

To evaluate the effect of oral administration of Kombucha tea (K-tea) on lead induced oxidative stress. Sprague Dawley rats were administered 1 mL of 3.8% lead acetate solution daily alone or in combination with K-tea orally for 45 d, and the antioxidant status and lipid peroxidation were evaluated. Oral administration of lead acetate to rats enhanced lipid peroxidation and release of creatine phosphokinase and decreased levels of reduced glutathione (GSH) and antioxidant enzymes (superoxide dismutase, SOD and glutathione peroxidase, GPx). Lead treatment did not alter humoral immunity, but inhibited DTH response when compared to the control. Lead administration also increased DNA fragmentation in liver. Oral administration of Kombucha tea to rats exposed to lead decreased lipid peroxidation and DNA damage with a concomitant increase in the reduced glutathione level and GPx activity. Kombucha tea supplementation relieved the lead induced immunosuppression to appreciable levels. The results suggest that K-tea has potent antioxidant and immunomodulating properties.

Uncovering a Dual Regulatory Role for Caspases During Endoplasmic Reticulum Stress-induced Cell Death.

Science.gov (United States)

Anania, Veronica G; Yu, Kebing; Gnad, Florian; Pferdehirt, Rebecca R; Li, Han; Ma, Taylur P; Jeon, Diana; Fortelny, Nikolaus; Forrest, William; Ashkenazi, Avi; Overall, Christopher M; Lill, Jennie R

2016-07-01

Many diseases are associated with endoplasmic reticulum (ER) stress, which results from an accumulation of misfolded proteins. This triggers an adaptive response called the "unfolded protein response" (UPR), and prolonged exposure to ER stress leads to cell death. Caspases are reported to play a critical role in ER stress-induced cell death but the underlying mechanisms by which they exert their effect continue to remain elusive. To understand the role caspases play during ER stress, a systems level approach integrating analysis of the transcriptome, proteome, and proteolytic substrate profile was employed. This quantitative analysis revealed transcriptional profiles for most human genes, provided information on protein abundance for 4476 proteins, and identified 445 caspase substrates. Based on these data sets many caspase substrates were shown to be downregulated at the protein level during ER stress suggesting caspase activity inhibits their cellular function. Additionally, RNA sequencing revealed a role for caspases in regulation of ER stress-induced transcriptional pathways and gene set enrichment analysis showed expression of multiple gene targets of essential transcription factors to be upregulated during ER stress upon inhibition of caspases. Furthermore, these transcription factors were degraded in a caspase-dependent manner during ER stress. These results indicate that caspases play a dual role in regulating the cellular response to ER stress through both post-translational and transcriptional regulatory mechanisms. Moreover, this study provides unique insight into progression of the unfolded protein response into cell death, which may help identify therapeutic strategies to treat ER stress-related diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Halobenzoquinone-Induced Alteration of Gene Expression Associated with Oxidative Stress Signaling Pathways.

Science.gov (United States)

Li, Jinhua; Moe, Birget; Liu, Yanming; Li, Xing-Fang

2018-06-05

Halobenzoquinones (HBQs) are emerging disinfection byproducts (DBPs) that effectively induce reactive oxygen species and oxidative damage in vitro. However, the impacts of HBQs on oxidative-stress-related gene expression have not been investigated. In this study, we examined alterations in the expression of 44 genes related to oxidative-stress-induced signaling pathways in human uroepithelial cells (SV-HUC-1) upon exposure to six HBQs. The results show the structure-dependent effects of HBQs on the studied gene expression. After 2 h of exposure, the expression levels of 9 to 28 genes were altered, while after 8 h of exposure, the expression levels of 29 to 31 genes were altered. Four genes ( HMOX1, NQO1, PTGS2, and TXNRD1) were significantly upregulated by all six HBQs at both exposure time points. Ingenuity pathway analysis revealed that the Nrf2 pathway was significantly responsive to HBQ exposure. Other canonical pathways responsive to HBQ exposure included GSH redox reductions, superoxide radical degradation, and xenobiotic metabolism signaling. This study has demonstrated that HBQs significantly alter the gene expression of oxidative-stress-related signaling pathways and contributes to the understanding of HBQ-DBP-associated toxicity.

Sex and stress: Men and women show different cortisol responses to psychological stress induced by the Trier social stress test and the Iowa singing social stress test.

Science.gov (United States)

Reschke-Hernández, Alaine E; Okerstrom, Katrina L; Bowles Edwards, Angela; Tranel, Daniel

2017-01-02

Acute psychological stress affects each of us in our daily lives and is increasingly a topic of discussion for its role in mental illness, aging, cognition, and overall health. A better understanding of how such stress affects the body and mind could contribute to the development of more effective clinical interventions and prevention practices. Over the past 3 decades, the Trier Social Stress Test (TSST) has been widely used to induce acute stress in a laboratory setting based on the principles of social evaluative threat, namely, a judged speech-making task. A comparable alternative task may expand options for examining acute stress in a controlled laboratory setting. This study uses a within-subjects design to examine healthy adult participants' (n = 20 men, n = 20 women) subjective stress and salivary cortisol responses to the standard TSST (involving public speaking and math) and the newly created Iowa Singing Social Stress Test (I-SSST). The I-SSST is similar to the TSST but with a new twist: public singing. Results indicated that men and women reported similarly high levels of subjective stress in response to both tasks. However, men and women demonstrated different cortisol responses; men showed a robust response to both tasks, and women displayed a lesser response. These findings are in line with previous literature and further underscore the importance of examining possible sex differences throughout various phases of research, including design, analysis, and interpretation of results. Furthermore, this nascent examination of the I-SSST suggests a possible alternative for inducing stress in the laboratory. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Exogenous FABP4 induces endoplasmic reticulum stress in HepG2 liver cells.

Science.gov (United States)

Bosquet, Alba; Guaita-Esteruelas, Sandra; Saavedra, Paula; Rodríguez-Calvo, Ricardo; Heras, Mercedes; Girona, Josefa; Masana, Lluís

2016-06-01

Fatty acid binding protein 4 (FABP4) is an intracellular fatty acid (FA) carrier protein that is, in part, secreted into circulation. Circulating FABP4 levels are increased in obesity, diabetes and other insulin resistance (IR) diseases. FAs contribute to IR by promoting endoplasmic reticulum stress (ER stress) and altering the insulin signaling pathway. The effect of FABP4 on ER stress in the liver is not known. The aim of this study was to investigate whether exogenous FABP4 (eFABP4) is involved in the lipid-induced ER stress in the liver. HepG2 cells were cultured with eFABP4 (40 ng/ml) with or without linoleic acid (LA, 200 μM) for 18 h. The expression of ER stress-related markers was determined by Western blotting (ATF6, EIF2α, IRE1 and ubiquitin) and real-time PCR (ATF6, CHOP, EIF2α and IRE1). Apoptosis was studied by flow cytometry using Annexin V-FITC and propidium iodide staining. eFABP4 increased the ER stress markers ATF6 and IRE1 in HepG2 cells. This effect led to insulin resistance mediated by changes in AKT and JNK phosphorylation. Furthermore, eFABP4 significantly induced both apoptosis, as assessed by flow cytometry, and CHOP expression, without affecting necrosis and ubiquitination. The presence of LA increased the ER stress response induced by eFABP4. eFABP4, per se, induces ER stress and potentiates the effect of LA in HepG2 cells, suggesting that FABP4 could be a link between obesity-associated metabolic abnormalities and hepatic IR mechanisms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Levels of occupational stress and stressful activities for nurses working in emergency

Directory of Open Access Journals (Sweden)

José Ricardo Ferreira da Fonseca

2014-12-01

Full Text Available The study aimed to identify stress levels, areas and their activities identified as stressful by nurses working in the emergence in Manaus, AM, Brazil. It is an epidemiological, cross-sectional design, with 36 emergency nurses from December 2010 to January 2011. The Bianchi Stress Scale with 57 questions was used. The nurses were at risk for high levels of stress. The most stressful areas were the operation of the unit, conditions of work and personnel administration, and the most stressful activity was the request for equipment review and repair. The difference by Friedman test between the areas was significant (p <0.05, Dunn post-test significant (p <0.05 when compared by peers. The accumulation of management activities with the assistance activities can generate higher levels of stress, it is necessary to invest in improving the work environment and management support to minimize the stress experienced at work.

p,p'-DDT induces testicular oxidative stress-induced apoptosis in adult rats.

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Marouani, Neila; Hallegue, Dorsaf; Sakly, Mohsen; Benkhalifa, Moncef; Ben Rhouma, Khémais; Tebourbi, Olfa

2017-05-26

The 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT) is a known persistent organic pollutant and male reproductive toxicant. The present study is designed to test the hypothesis that oxidative stress mediates p,p'-DDT-induced apoptosis in testis. Male Wistar rats received an intraperitoneal (ip) injection of the pesticide at doses of 50 and 100mg/kg for 10 consecutive days. The oxidative stress was evaluated by biomarkers such lipid peroxidation (LPO) and metallothioneins (MTs) levels. Antioxidant enzymes activities was assessed by determination of superoxide dismutase (SOD), catalase (CAT) and hydrogen peroxide (H 2 O 2 ) production. In addition, glutathione-dependent enzymes and reducing power in testis was evaluated by glutathione peroxidase (Gpx), glutathione reductase (GR), glutathione S-transferase (GST) activities and reduced and oxidized glutathione (GSH - GSSG) levels. Apoptosis was evaluated by DNA fragmentation detected by agarose gel electrophoresis. Germinal cells apoptosis and the apoptotic index was assessed through the TUNEL assay. After 10 days of treatment, an increase in LPO level and H 2 O 2 production occurred, while MTs level, SOD and CAT activities were decreased. Also, the Gpx, GR, GST, and GSH activities were decreased, whereas GSSG activity was increased. Testicular tissues of treated rats showed pronounced degradation of the DNA into oligonucleotides as seen in the typical electrophoretic DNA ladder pattern. Intense apoptosis was observed in germinal cells of DDT-exposed rats. In addition, the apoptotic index was significantly increased in testis of DDT-treated rats. These results clearly suggest that DDT sub-acute treatment causes oxidative stress in rat testis leading to apoptosis.

Protective Effects of Alkaloid Compounds from Nelumbinis Plumula on tert-Butyl Hydroperoxide-Induced Oxidative Stress

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Ze-Bin Guo

2013-08-01

Full Text Available This study was conducted to investigate the effect of Nelumbinis Plumula total alkaloid (NPA and its main alkaloid components on oxidative stress induced by tert-butyl hydroperoxide (t-BHP in the human hepatocellular HepG2 cell line. According to HPLC analysis, several major alkaloid compounds such as liensinine, isoliensinine and neferine were present in NPA. The cytotoxic effects in 0.55 mM t-BHP-induced HepG2 cells were significantly inhibited by NPA and the major compound in NPA, neferine, showed the strongest activities. The protective effect of neferine against oxidative stress induced by t-BHP may be associated with decreased ROS formation, TBARS generation, LDH release and increased GSH levels, suggesting their involvement of the cytoprotective on oxidative stress. The effects were comparable with quercetin, which was used as positive control. Overall, total alkaloid and alkaloid compounds from Nelumbinis Plumula displayed a significant cytoprotective effect against oxidative stress. Further study is needed to elucidate the relationship between the chemical structures of the components in NPA and their protective effect on oxidative stress.

Brain prolactin is involved in stress-induced REM sleep rebound.

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Machado, Ricardo Borges; Rocha, Murilo Ramos; Suchecki, Deborah

2017-03-01

REM sleep rebound is a common behavioural response to some stressors and represents an adaptive coping strategy. Animals submitted to multiple, intermittent, footshock stress (FS) sessions during 96h of REM sleep deprivation (REMSD) display increased REM sleep rebound (when compared to the only REMSD ones, without FS), which is correlated to high plasma prolactin levels. To investigate whether brain prolactin plays a role in stress-induced REM sleep rebound two experiments were carried out. In experiment 1, rats were either not sleep-deprived (NSD) or submitted to 96h of REMSD associated or not to FS and brains were evaluated for PRL immunoreactivity (PRL-ir) and determination of PRL concentrations in the lateral hypothalamus and dorsal raphe nucleus. In experiment 2, rats were implanted with cannulas in the dorsal raphe nucleus for prolactin infusion and were sleep-recorded. REMSD associated with FS increased PRL-ir and content in the lateral hypothalamus and all manipulations increased prolactin content in the dorsal raphe nucleus compared to the NSD group. Prolactin infusion in the dorsal raphe nucleus increased the time and length of REM sleep episodes 3h after the infusion until the end of the light phase of the day cycle. Based on these results we concluded that brain prolactin is a major mediator of stress-induced REMS. The effect of PRL infusion in the dorsal raphe nucleus is discussed in light of the existence of a bidirectional relationship between this hormone and serotonin as regulators of stress-induced REM sleep rebound. Copyright © 2016 Elsevier Inc. All rights reserved.

Zinc prevents sickness behavior induced by lipopolysaccharides after a stress challenge in rats.

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Thiago B Kirsten

Full Text Available Sickness behavior is considered part of the specific beneficial adaptive behavioral and neuroimmune changes that occur in individuals in response to infectious/inflammatory processes. However, in dangerous and stressful situations, sickness behavior should be momentarily abrogated to prioritize survival behaviors, such as fight or flight. Taking this assumption into account, we experimentally induced sickness behavior in rats using lipopolysaccharides (LPS, an endotoxin that mimics infection by gram-negative bacteria, and then exposed these rats to a restraint stress challenge. Zinc has been shown to play a regulatory role in the immune and nervous systems. Therefore, the objective of this study was to examine the effects of zinc treatment on the sickness response of stress-challenged rats. We evaluated 22-kHz ultrasonic vocalizations, open-field behavior, tumor necrosis factor α (TNF-α, corticosterone, and brain-derived neurotrophic factor (BDNF plasma levels. LPS administration induced sickness behavior in rats compared to controls, i.e., decreases in the distance traveled, average velocity, rearing frequency, self-grooming, and number of vocalizations, as well as an increase in the plasma levels of TNF-α, compared with controls after a stressor challenge. LPS also decreased BDNF expression but did not influence anxiety parameters. Zinc treatment was able to prevent sickness behavior in LPS-exposed rats after the stress challenge, restoring exploratory/motor behaviors, communication, and TNF-α levels similar to those of the control group. Thus, zinc treatment appears to be beneficial for sick animals when they are facing risky/stressful situations.

Mineralocorticoid receptor blockade prevents stress-induced modulation of multiple memory systems in the human brain.

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Schwabe, Lars; Tegenthoff, Martin; Höffken, Oliver; Wolf, Oliver T

2013-12-01

Accumulating evidence suggests that stress may orchestrate the engagement of multiple memory systems in the brain. In particular, stress is thought to favor dorsal striatum-dependent procedural over hippocampus-dependent declarative memory. However, the neuroendocrine mechanisms underlying these modulatory effects of stress remain elusive, especially in humans. Here, we targeted the role of the mineralocorticoid receptor (MR) in the stress-induced modulation of dorsal striatal and hippocampal memory systems in the human brain using a combination of event-related functional magnetic resonance imaging and pharmacologic blockade of the MR. Eighty healthy participants received the MR antagonist spironolactone (300 mg) or a placebo and underwent a stressor or control manipulation before they performed, in the scanner, a classification task that can be supported by the hippocampus and the dorsal striatum. Stress after placebo did not affect learning performance but reduced explicit task knowledge and led to a relative increase in the use of more procedural learning strategies. At the neural level, stress promoted striatum-based learning at the expense of hippocampus-based learning. Functional connectivity analyses showed that this shift was associated with altered coupling of the amygdala with the hippocampus and dorsal striatum. Mineralocorticoid receptor blockade before stress prevented the stress-induced shift toward dorsal striatal procedural learning, same as the stress-induced alterations of amygdala connectivity with hippocampus and dorsal striatum, but resulted in significantly impaired performance. Our findings indicate that the stress-induced shift from hippocampal to dorsal striatal memory systems is mediated by the amygdala, required to preserve performance after stress, and dependent on the MR. © 2013 Society of Biological Psychiatry.

Taurine protects cisplatin induced cardiotoxicity by modulating inflammatory and endoplasmic reticulum stress responses.

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Chowdhury, Sayantani; Sinha, Krishnendu; Banerjee, Sharmistha; Sil, Parames C

2016-11-12

Oxidative stress, ER stress, inflammation, and apoptosis results in the pathogenesis of cisplatin-induced cardiotoxicity. The present study was designed to investigate the signaling mechanisms involved in the ameliorating effect of taurine, a conditionally essential amino acid, against cisplatin-mediated cardiac ER stress dependent apoptotic death and inflammation. Mice were simultaneously treated with taurine (150 mg kg -1 body wt, i.p.) and cisplatin (10 mg kg -1 body wt, i.p.) for a week. Cisplatin exposure significantly altered serum creatine kinase and troponin T levels. In addition, histological studies revealed disintegration in the normal radiation pattern of cardiac muscle fibers. However, taurine administration could abate such adverse effects of cisplatin. Taurine administration significantly mitigated the reactive oxygen species production, alleviated the overexpression of nuclear factor-κB (NF-κB), and inhibited the elevation of proinflammatoy cytokines, adhesion molecules, and chemokines. Cisplatin exposure resulted in the unfolded protein response (UPR)-regulated CCAAT/enhancer binding protein (CHOP) up-regulation, induction of GRP78: a marker of ER stress and eIF2α signaling. Increase in calpain-1 expression level, activation of caspase-12 and caspase-3, cleavage of the PARP protein as well as the inhibition of antiapoptotic protein Bcl-2 were reflected on cisplatin-triggered apoptosis. Taurine could, however, combat against such cisplatin induced cardiac-abnormalities. The above mentioned findings suggest that taurine plays a beneficial role in providing protection against cisplatin-induced cardiac damage by modulating inflammatory responses and ER stress. © 2016 BioFactors, 42(6):647-664, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

Boosting recovery rather than buffering reactivity: Higher stress-induced oxytocin secretion is associated with increased cortisol reactivity and faster vagal recovery after acute psychosocial stress.

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Engert, Veronika; Koester, Anna M; Riepenhausen, Antje; Singer, Tania

2016-12-01

Animal models and human studies using paradigms designed to stimulate endogenous oxytocin release suggest a stress-buffering role of oxytocin. We here examined the involvement of stress-induced peripheral oxytocin secretion in reactivity and recovery phases of the human psychosocial stress response. Healthy male and female participants (N=114) were subjected to a standardized laboratory stressor, the Trier Social Stress Test. In addition to plasma oxytocin, cortisol was assessed as a marker of hypothalamic-pituitary-adrenal (HPA-) axis activity, alpha-amylase and heart rate as markers of sympathetic activity, high frequency heart rate variability as a marker of vagal tone and self-rated anxiety as an indicator of subjective stress experience. On average, oxytocin levels increased by 51% following psychosocial stress. The stress-induced oxytocin secretion, however, did not reduce stress reactivity. To the contrary, higher oxytocin secretion was associated with greater cortisol reactivity and peak cortisol levels in both sexes. In the second phase of the stress response the opposite pattern was observed, with higher oxytocin secretion associated with faster vagal recovery. We suggest that after an early stage of oxytocin and HPA-axis co-activation, the stress-reducing action of oxytocin unfolds. Due to the time lag it manifests as a recovery-boosting rather than a reactivity-buffering effect. By reinforcing parasympathetic autonomic activity, specifically during stress recovery, oxytocin may provide an important protective function against the health-compromising effects of sustained stress. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical Detection Based on Adsorption-Induced and Photo-Induced Stresses in MEMS Devices

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Datskos, P.G.

1999-04-05

Recently there has been an increasing demand to perform real-time in-situ chemical detection of hazardous materials, contraband chemicals, and explosive chemicals. Currently, real-time chemical detection requires rather large analytical instrumentation that are expensive and complicated to use. The advent of inexpensive mass produced MEMS (micro-electromechanical systems) devices opened-up new possibilities for chemical detection. For example, microcantilevers were found to respond to chemical stimuli by undergoing changes in their bending and resonance frequency even when a small number of molecules adsorb on their surface. In our present studies, we extended this concept by studying changes in both the adsorption-induced stress and photo-induced stress as target chemicals adsorb on the surface of microcantilevers. For example, microcantilevers that have adsorbed molecules will undergo photo-induced bending that depends on the number of absorbed molecules on the surface. However, microcantilevers that have undergone photo-induced bending will adsorb molecules on their surfaces in a distinctly different way. Depending on the photon wavelength and microcantilever material, the microcantilever can be made to bend by expanding or contracting the irradiated surface. This is important in cases where the photo-induced stresses can be used to counter any adsorption-induced stresses and increase the dynamic range. Coating the surface of the microstructure with a different material can provide chemical specificity for the target chemicals. However, by selecting appropriate photon wavelengths we can change the chemical selectivity due to the introduction of new surface states in the MEMS device. We will present and discuss our results on the use of adsorption-induced and photo-induced bending of microcantilevers for chemical detection.

High salt intake enhances swim stress-induced PVN vasopressin cell activation and active stress coping.

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Mitchell, N C; Gilman, T L; Daws, L C; Toney, G M

2018-07-01

Stress contributes to many psychiatric disorders; however, responsivity to stressors can vary depending on previous or current stress exposure. Relatively innocuous heterotypic (differing in type) stressors can summate to result in exaggerated neuronal and behavioral responses. Here we investigated the ability of prior high dietary sodium chloride (salt) intake, a dehydrating osmotic stressor, to enhance neuronal and behavioral responses of mice to an acute psychogenic swim stress (SS). Further, we evaluated the contribution of the osmo-regulatory stress-related neuropeptide arginine vasopressin (VP) in the hypothalamic paraventricular nucleus (PVN), one of only a few brain regions that synthesize VP. The purpose of this study was to determine the impact of high dietary salt intake on responsivity to heterotypic stress and the potential contribution of VPergic-mediated neuronal activity on high salt-induced stress modulation, thereby providing insight into how dietary (homeostatic) and environmental (psychogenic) stressors might interact to facilitate psychiatric disorder vulnerability. Salt loading (SL) with 4% saline for 7 days was used to dehydrate and osmotically stress mice prior to exposure to an acute SS. Fluid intake and hematological measurements were taken to quantify osmotic dehydration, and serum corticosterone levels were measured to index stress axis activation. Immunohistochemistry (IHC) was used to stain for the immediate early gene product c-Fos to quantify effects of SL on SS-induced activation of neurons in the PVN and extended amygdala - brain regions that are synaptically connected and implicated in responding to osmotic stress and in modulation of SS behavior, respectively. Lastly, the role of VPergic PVN neurons and VP type 1 receptor (V1R) activity in the amygdala in mediating effects of SL on SS behavior was evaluated by quantifying c-Fos activation of VPergic PVN neurons and, in functional experiments, by nano-injecting the V1R selective

Genome wide transcriptional response of Saccharomyces cerevisiae to stress-induced perturbations

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Hilal eTaymaz-Nikerel

2016-02-01

Full Text Available Cells respond to environmental and/or genetic perturbations in order to survive and proliferate. Characterization of the changes after various stimuli at different -omics levels is crucial to comprehend the adaptation of cells to changing conditions. Genome wide quantification and analysis of transcript levels, the genes affected by perturbations, extends our understanding of cellular metabolism by pointing out the mechanisms that play role in sensing the stress caused by those perturbations and related signaling pathways, and in this way guides us to achieve endeavors such as rational engineering of cells or interpretation of disease mechanisms. Saccharomyces cerevisiae as a model system has been studied in response to different perturbations and corresponding transcriptional profiles were followed either statically or/and dynamically, short- and long- term. This review focuses on response of yeast cells to diverse stress inducing perturbations including nutritional changes, ionic stress, salt stress, oxidative stress, osmotic shock, as well as to genetic interventions such as deletion and over-expression of genes. It is aimed to conclude on common regulatory phenomena that allow yeast to organize its transcriptomic response after any perturbation under different external conditions.

Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling

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Lovelace, Erica S.; Wagoner, Jessica; MacDonald, James; Bammler, Theo; Bruckner, Jacob; Brownell, Jessica; Beyer, Richard; Zink, Erika M.; Kim, Young-Mo; Kyle, Jennifer E.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Metz, Thomas O.; Farin, Federico; Oberlies, Nicholas H.; Polyak, Steve

2015-08-28

Silymarin (SM), a natural product, is touted as a liver protectant and preventer of both chronic inflammation and diseases. To define how SM elicits these effects at a systems level, we performed transcriptional profiling, metabolomics, and signaling studies in human liver and T cell lines. Multiple pathways associated with cellular stress and metabolism were modulated by SM treatment within 0.5 to four hours: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed suppression of glycolytic, TCA cycle, and amino acid metabolism by SM treatment. Antiinflammatory effects arose with prolonged (i.e. 24 hours) SM exposure, with suppression of multiple proinflammatory mRNAs and nuclear factor kappa B (NF-κB) and forkhead box O (FOXO) signaling. Studies with murine knock out cells revealed that SM inhibition of both mTOR and NF-κB was partially AMPK dependent, while SM inhibition of the mTOR pathway in part required DDIT4. Thus, SM activates stress and repair responses that culminate in an anti-inflammatory phenotype. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Therefore, natural products like SM may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation.

Acute stress-induced cortisol elevations mediate reward system activity during subconscious processing of sexual stimuli.

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Oei, Nicole Y L; Both, Stephanie; van Heemst, Diana; van der Grond, Jeroen

2014-01-01

Stress is thought to alter motivational processes by increasing dopamine (DA) secretion in the brain's "reward system", and its key region, the nucleus accumbens (NAcc). However, stress studies using functional magnetic resonance imaging (fMRI), mainly found evidence for stress-induced decreases in NAcc responsiveness toward reward cues. Results from both animal and human PET studies indicate that the stress hormone cortisol may be crucial in the interaction between stress and dopaminergic actions. In the present study we therefore investigated whether cortisol mediated the effect of stress on DA-related responses to -subliminal-presentation of reward cues using the Trier Social Stress Test (TSST), which is known to reliably enhance cortisol levels. Young healthy males (n = 37) were randomly assigned to the TSST or control condition. After stress induction, brain activation was assessed using fMRI during a backward-masking paradigm in which potentially rewarding (sexual), emotionally negative and neutral stimuli were presented subliminally, masked by pictures of inanimate objects. A region of interest analysis showed that stress decreased activation in the NAcc in response to masked sexual cues (voxel-corrected, pcortisol levels were related to stronger NAcc activation, showing that cortisol acted as a suppressor variable in the negative relation between stress and NAcc activation. The present findings indicate that cortisol is crucially involved in the relation between stress and the responsiveness of the reward system. Although generally stress decreases activation in the NAcc in response to rewarding stimuli, high stress-induced cortisol levels suppress this relation, and are associated with stronger NAcc activation. Individuals with a high cortisol response to stress might on one hand be protected against reductions in reward sensitivity, which has been linked to anhedonia and depression, but they may ultimately be more vulnerable to increased reward

Olive leaf down-regulates the oxidative stress and immune dysregulation in streptozotocin-induced diabetic mice.

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Park, Jung-Hyun; Jung, Ji-Hye; Yang, Jin-Young; Kim, Hyun-Sook

2013-11-01

Type 1 diabetes is an endocrinologic disorder characterized by uncontrolled glucose regulation and oxidative stress. Olive leaves have been studied extensively for their antioxidant activity and capacity to improve immune function. We hypothesized that olive leaf powder supplementation will be effective in inhibiting the oxidative stress and immune dysregulation in streptozotocin (STZ)-induced diabetic mice. Mice were assigned to 1 of 5 groups: control (C), STZ-induced diabetes (D), and STZ-induced diabetes supplemented with very low dose (VLOL), low dose (LOL), or high dose of olive leaf powder (HOL). Blood glucose in the VLOL and LOL groups was lower than that in the D group (P LOL groups. Nitric oxide levels decreased in the VLOL and LOL groups, as compared with the D group. The messenger RNA expression levels of inducible nitric oxide synthase were significantly decreased in the VLOL and HOL groups, and interferon-γ levels were significantly decreased in the liver of the VLOL, LOL, and HOL groups compared with the levels in the D group. Interleukin-17 levels were significantly decreased in the VLOL and HOL groups. Th1 and Th17 cytokine levels were increased in the D group but decreased in all the experimental groups. Th2 cytokine levels were increased in all olive leaf-supplemented groups compared with those in the D group. These results indicate a reduction in the levels of proinflammatory cytokines, suggesting that olive leaves have the potential to provide therapeutic inhibition of diabetic complications. © 2013.

Implication of snail in metabolic stress-induced necrosis.

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Cho Hee Kim

2011-03-01

Full Text Available Necrosis, a type of cell death accompanied by the rupture of the plasma membrane, promotes tumor progression and aggressiveness by releasing the pro-inflammatory and angiogenic cytokine high mobility group box 1. It is commonly found in the core region of solid tumors due to hypoxia and glucose depletion (GD resulting from insufficient vascularization. Thus, metabolic stress-induced necrosis has important clinical implications for tumor development; however, its regulatory mechanisms have been poorly investigated.Here, we show that the transcription factor Snail, a key regulator of epithelial-mesenchymal transition, is induced in a reactive oxygen species (ROS-dependent manner in both two-dimensional culture of cancer cells, including A549, HepG2, and MDA-MB-231, in response to GD and the inner regions of a multicellular tumor spheroid system, an in vitro model of solid tumors and of human tumors. Snail short hairpin (sh RNA inhibited metabolic stress-induced necrosis in two-dimensional cell culture and in multicellular tumor spheroid system. Snail shRNA-mediated necrosis inhibition appeared to be linked to its ability to suppress metabolic stress-induced mitochondrial ROS production, loss of mitochondrial membrane potential, and mitochondrial permeability transition, which are the primary events that trigger necrosis.Taken together, our findings demonstrate that Snail is implicated in metabolic stress-induced necrosis, providing a new function for Snail in tumor progression.

Chronic Restraint Stress Induces an Isoform-Specific Regulation on the Neural Cell Adhesion Molecule in the Hippocampus

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Touyarot, K.; Sandi, C.

2002-01-01

Existing evidence indicates that 21-days exposure of rats to restraint stress induces dendritic atrophy in pyramidal cells of the hippocampus. This phenomenon has been related to altered performance in hippocampal-dependent learning tasks. Prior studies have shown that hippocampal expression of cell adhesion molecules is modified by such stress treatment, with the neural cell adhesion molecule (NCAM) decreasing and L1 increasing, their expression, at both the mRNA and protein levels. Given that NCAM comprises several isoforms, we investigated here whether chronic stress might differentially affect the expression of the three major isoforms (NCAM-120, NCAM-140, NCAM-180) in the hippocampus. In addition, as glucocorticoids have been implicated in the deleterious effects induced by chronic stress, we also evaluated plasma corticosterone levels and the hippocampal expression of the corticosteroid mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). The results showed that the protein concentration of the NCAM-140 isoform decreased in the hippoampus of stressed rats. This effect was isoform-specific, because NCAM-120 and NCAM-180 levels were not significantly modified. In addition, whereas basal levels of plasma corticosterone tended to be increased, MR and GR concentrations were not significantly altered. Although possible changes in NCAM-120, NCAM-180 and corticosteroid receptors at earlier time points of the stress period cannot be ignored; this study suggests that a down-regulation of NCAM-140 might be implicated in the structural alterations consistently shown to be induced in the hippocampus by chronic stress exposure. As NCAM-140 is involved in cell-cell adhesion and neurite outgrowth, these findings suggest that this molecule might be one of the molecular mechanisms involved in the complex interactions among neurodegeneration-related events. PMID:12757368

Cardioprotective effect of amlodipine in oxidative stress induced by experimental myocardial infarction in rats

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Sudhira Begum

2007-12-01

Full Text Available The present study investigated whether the administration of amlodipine ameliorates oxidative stress induced by experimental myocardial infarction in rats. Adrenaline was administered and myocardial damage was evaluated biochemically [significantly increased serum aspertate aminotransferase (AST, lactate dehydrogenase (LDH and malondialdehyde (MDA levels of myocardial tissue] and histologically (morphological changes of myocardium. Amlodipine was administered as pretreatment for 14 days in adrenaline treated rats. Statistically significant amelioration in all the biochemical parameters supported by significantly improved myocardial morphology was observed in amlodipine pretreatment. It was concluded that amlodipine afforded cardioprotection by reducing oxidative stress induced in experimental myocardial infarction of catecholamine assault.

Increased response to oxidative stress challenge of nano-copper-induced apoptosis in mesangial cells

International Nuclear Information System (INIS)

Xu, Pengjuan; Li, Zhigui; Zhang, Xiaochen; Yang, Zhuo

2014-01-01

Recently, many studies reported that nanosized copper particles (nano-Cu, the particle size was around 15–30 nm), one of the nanometer materials, could induce nephrotoxicity. To detect the effect of nano-Cu on mesangial cells (MCs), and investigate the underlying mechanism, MCs were treated with different concentrations of nano-Cu (1, 10, and 30 μg/mL) to determine the oxidative stress and apoptotic changes. It was revealed that nano-Cu could induce a decreased viability in MCs together with a significant increase in the number of apoptotic cells by using cell counting kit-8 assay and flow cytometry. The apoptotic morphological changes induced by nano-Cu in MCs were demonstrated by Hochest33342 staining. Results showed that nano-Cu induced the nuclear fragmentation in MCs. Meanwhile, nano-Cu significantly increased the levels of reactive oxygen species, especially increased the levels of H 2 O 2 . It also decreased the activity of total SOD enzyme. In addition, when pre-treated with N-(2-mercaptopropionyl)-glycine, the cell apoptosis induced by nano-Cu was significantly decreased. These results suggest that oxidative stress plays an important role in the nano-Cu toxicity in MCs, which may be the main mechanism of nano-Cu-induced nephrotoxicity

Iron-induced neuronal damage in a rat model of post-traumatic stress disorder.

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Zhao, Ming; Yu, Zhibo; Zhang, Yang; Huang, Xueling; Hou, Jingming; Zhao, YanGang; Luo, Wei; Chen, Lin; Ou, Lan; Li, Haitao; Zhang, Jiqiang

2016-08-25

Previous studies have shown that iron redistribution and deposition in the brain occurs in some neurodegenerative diseases, and oxidative damage due to abnormal iron level is a primary cause of neuronal death. In the present study, we used the single prolonged stress (SPS) model to mimic post-traumatic stress disorder (PTSD), and examined whether iron was involved in the progression of PTSD. The anxiety-like behaviors of the SPS group were assessed by the elevated plus maze (EPM) and open field tests, and iron levels were measured by inductively coupled plasma optical emission spectrometer (ICP-OES). Expression of glucocorticoid receptors and transferrin receptor 1 (TfR1) and ferritin (Fn) was detected by Western blot and immunohistochemistry in selected brain areas; TfR1 and Fn mRNA expression were detected by quantitative-polymerase chain reaction (Q-PCR). Ultrastructures of the hippocampus were observed under a transmission electron microscope. Our results showed that SPS exposure induced anxiety-like symptoms and increased the level of serum cortisol and the concentration of iron in key brain areas such as the hippocampus, prefrontal cortex, and striatum. The stress induced region-specific changes in both protein and mRNA levels of TfR1 and Fn. Moreover, swelling mitochondria and cell apoptosis were observed in neurons in brain regions with iron accumulation. We concluded that SPS stress increased iron in some cognition-related brain regions and subsequently cause neuronal injury, indicating that the iron may function in the pathology of PTSD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Oxidative stress-induced autophagy: Role in pulmonary toxicity

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Malaviya, Rama; Laskin, Jeffrey D.; Laskin, Debra L.

2014-01-01

Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress. - Highlights: • Exposure to pulmonary toxicants is associated with oxidative stress. • Oxidative stress is known to induce autophagy. • Autophagy is upregulated in the lung following exposure to pulmonary toxicants. • Autophagy may be protective or pathogenic

Oxidative stress-induced autophagy: Role in pulmonary toxicity

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Malaviya, Rama [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States)

2014-03-01

Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress. - Highlights: • Exposure to pulmonary toxicants is associated with oxidative stress. • Oxidative stress is known to induce autophagy. • Autophagy is upregulated in the lung following exposure to pulmonary toxicants. • Autophagy may be protective or pathogenic.

Oxidative stress and neurological disorders in relation to blood lead levels in children.

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Ahamed, M; Fareed, Mohd; Kumar, A; Siddiqui, W A; Siddiqui, M K J

2008-01-01

Oxidative stress plays a pivotal role in the pathogenesis of neurological disorders. Free radical generation appears to be the mode of lead toxicity. We evaluated the effects of blood lead levels on oxidative stress parameters in children suffering from neurological disorders. Thirty children (aged 3-12 years) with neurological disorders (cerebral palsy [n = 12], seizures [n = 11], and encephalopathy [n = 7]) were recruited in the study group. Sixty healthy children (aged 3-12 years) from similar socio-economic environments and not suffering from any chronic disease were taken as the controls. Blood lead levels and oxidant/antioxidant status were determined. Mean blood lead level was significantly higher while delta-aminolevulinic acid dehydratase (delta-ALAD) activity, a biomarker for lead exposure, was significantly lower in the study group as compared to the control group (P children with neurological disorders. Lead-induced oxidative stress as an underlying mechanism for neurological diseases in children warranted further investigation.

Acid-induced autophagy protects human lung cancer cells from apoptosis by activating ER stress.

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Xie, Wen-Yue; Zhou, Xiang-Dong; Li, Qi; Chen, Ling-Xiu; Ran, Dan-Hua

2015-12-10

An acidic tumor microenvironment exists widely in solid tumors. However, the detailed mechanism of cell survival under acidic stress remains unclear. The aim of this study is to clarify whether acid-induced autophagy exists and to determine the function and mechanism of autophagy in lung cancer cells. We have found that acute low pH stimulated autophagy by increasing LC3-positive punctate vesicles, increasing LC3 II expression levels and reducing p62 protein levels. Additionally, autophagy was inhibited by the addition of Baf or knockdown of Beclin 1, and cell apoptosis was increased markedly. In mouse tumors, the expression of cleaved caspase3 and p62 was enhanced by oral treatment with sodium bicarbonate, which can raise the intratumoral pH. Furthermore, the protein levels of ER stress markers, including p-PERK, p-eIF2α, CHOP, XBP-1s and GRP78, were also increased in response to acidic pH. The antioxidant NAC, which reduces ROS accumulation, alleviated acid-mediated ER stress and autophagy, and knocking down GRP78 reduced autophagy activation under acidic conditions, which suggests that autophagy was induced by acidic pH through ER stress. Taken together, these results indicate that the acidic microenvironment in non-small cell lung cancer cells promotes autophagy by increasing ROS-ER stress, which serves as a survival adaption in this setting. Copyright © 2015 Elsevier Inc. All rights reserved.

Single-prolonged stress induces endoplasmic reticulum-dependent apoptosis in the hippocampus in a rat model of post-traumatic stress disorder.

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Fang Han

Full Text Available BACKGROUND: Our previous research indicated that apoptosis induced atrophy in the hippocampus of post-traumatic stress disorder (PTSD rats. Endoplasmic reticulum (ER stress-induced apoptosis has been implicated in the development of several disorder diseases. The aim of this study was to investigate whether endoplasmic reticulum-related pathway is involved in single-prolonged stress (SPS induces apoptosis in the hippocampus of PTSD rats by examining the expression levels of three important indicators in the ER-related apoptotic pathway: Glucose-regulated protein (GRP 78, caspase-12 and Ca(2+/CaM/CaMkinaseIIα (CaMkIIα. METHODS: Wistar rats were sacrificed at 1, 4 and 7 days after SPS. SPS is a reliable animal model of PTSD. The apoptotic cells in the hippocampus were assessed by TUNEL method and transmission electron microscopy (TEM. Free intracellular Ca(2+ concentration was measured. GRP78 expression was examined by immunohistochemistry, western blotting and RT-PCR. mRNA of caspase-12 and CaM/CaMkIIα were determined by RT-PCR. RESULTS: Our results showed that apoptotic cells were increased in the SPS rats. TEM analysis revealed characteristic morphological changes of apoptosis in these cells. We observed that GRP78 was significantly up-regulated during early PTSD, and then recovered at 7 days after SPS. By RT-PCR, we observed that the change in caspase-12 expression level was similar to that in GRP78. Moreover, the free intracellular Ca(2+ concentration was significantly higher at 1 day after SPS and decreased in 7 days. CaM expression increased significantly, while CaMKIIα expression decreased significantly in the hippocampus at 1 day after SPS. CONCLUSION: SPS induced change in the expression levels of GRP78, caspase-12 and Ca(2+/CaM/CaMkIIα in the hippocampus of PTSD rats indicated that the endoplasmic reticulum pathway may be involved in PTSD-induced apoptosis.

Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells

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Lefevre, Sophie [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); ED515 UPMC, 4 place Jussieu 75005 Paris (France); Sliwa, Dominika [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Rustin, Pierre [Inserm, U676, Physiopathology and Therapy of Mitochondrial Disease Laboratory, 75019 Paris (France); Universite Paris-Diderot, Faculte de Medecine Denis Diderot, IFR02 Paris (France); Camadro, Jean-Michel [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Santos, Renata, E-mail: santos.renata@ijm.univ-paris-diderot.fr [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France)

2012-02-10

Highlights: Black-Right-Pointing-Pointer Yeast frataxin-deficiency leads to increased proportion of fragmented mitochondria. Black-Right-Pointing-Pointer Oxidative stress induces complete mitochondrial fragmentation in {Delta}yfh1 cells. Black-Right-Pointing-Pointer Oxidative stress increases mitochondrial fragmentation in patient fibroblasts. Black-Right-Pointing-Pointer Inhibition of mitochondrial fission in {Delta}yfh1 induces oxidative stress resistance. -- Abstract: Friedreich ataxia (FA) is the most common recessive neurodegenerative disease. It is caused by deficiency in mitochondrial frataxin, which participates in iron-sulfur cluster assembly. Yeast cells lacking frataxin ({Delta}yfh1 mutant) showed an increased proportion of fragmented mitochondria compared to wild-type. In addition, oxidative stress induced complete fragmentation of mitochondria in {Delta}yfh1 cells. Genetically controlled inhibition of mitochondrial fission in these cells led to increased resistance to oxidative stress. Here we present evidence that in yeast frataxin-deficiency interferes with mitochondrial dynamics, which might therefore be relevant for the pathophysiology of FA.

Environmental stress induces trinucleotide repeat mutagenesis in human cells.

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Chatterjee, Nimrat; Lin, Yunfu; Santillan, Beatriz A; Yotnda, Patricia; Wilson, John H

2015-03-24

The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)-the cause of multiple human diseases-have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential.

Lycopene Prevents Amyloid [Beta]-Induced Mitochondrial Oxidative Stress and Dysfunctions in Cultured Rat Cortical Neurons.

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Qu, Mingyue; Jiang, Zheng; Liao, Yuanxiang; Song, Zhenyao; Nan, Xinzhong

2016-06-01

Brains affected by Alzheimer's disease (AD) show a large spectrum of mitochondrial alterations at both morphological and genetic level. The causal link between β-amyloid (Aβ) and mitochondrial dysfunction has been established in cellular models of AD. We observed previously that lycopene, a member of the carotenoid family of phytochemicals, could counteract neuronal apoptosis and cell damage induced by Aβ and other neurotoxic substances, and that this neuroprotective action somehow involved the mitochondria. The present study aims to investigate the effects of lycopene on mitochondria in cultured rat cortical neurons exposed to Aβ. It was found that lycopene attenuated Aβ-induced oxidative stress, as evidenced by the decreased intracellular reactive oxygen species generation and mitochondria-derived superoxide production. Additionally, lycopene ameliorated Aβ-induced mitochondrial morphological alteration, opening of the mitochondrial permeability transition pores and the consequent cytochrome c release. Lycopene also improved mitochondrial complex activities and restored ATP levels in Aβ-treated neuron. Furthermore, lycopene prevented mitochondrial DNA damages and improved the protein level of mitochondrial transcription factor A in mitochondria. Those results indicate that lycopene protects mitochondria against Aβ-induced damages, at least in part by inhibiting mitochondrial oxidative stress and improving mitochondrial function. These beneficial effects of lycopene may account for its protection against Aβ-induced neurotoxicity.

Mangifera indica L. leaf extract alleviates doxorubicin induced cardiac stress

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Bhatt, Laxit; Joshi, Viraj

2017-01-01

Aim: The study was undertaken to evaluate the cardioprotective effect of the alcoholic leaf extract of Mangifera indica L. against cardiac stress caused by doxorubicin (DOX). Materials and Methods: Rats were treated with 100 mg/kg of M. indica leaf extract (MILE) in alone and interactive groups for 21 days. Apart from the normal and MILE control groups, all the groups were subjected to DOX (15 mg/kg, i.p.) toxicity for 21 days and effects of different treatments were analyzed by changes in serum biomarkers, tissue antioxidant levels, electrocardiographic parameters, lipid profile, and histopathological evaluation. Results: The MILE treated group showed decrease in serum biomarker enzyme levels and increase in tissue antioxidants levels. Compared to DOX control group, MILE treated animals showed improvement in lipid profile, electrocardiographic parameters, histological score, and mortality. Conclusion: These findings clearly suggest the protective role of alcoholic leaf extract of M. indica against oxidative stress induced by DOX. PMID:28894627

Prickly pear cactus (Opuntia ficus indica var. saboten) protects against stress-induced acute gastric lesions in rats.

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Kim, Seung Hyun; Jeon, Byung Ju; Kim, Dae Hyun; Kim, Tae Il; Lee, Hee Kyoung; Han, Dae Seob; Lee, Jong-Hwan; Kim, Tae Bum; Kim, Jung Wha; Sung, Sang Hyun

2012-11-01

The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6 h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague-Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800-1600 mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-α and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSM's gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production.

Psychological stress, cocaine and natural reward each induce endoplasmic reticulum stress genes in rat brain.

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Pavlovsky, A A; Boehning, D; Li, D; Zhang, Y; Fan, X; Green, T A

2013-08-29

Our prior research has shown that the transcription of endoplasmic reticulum (ER) stress transcription factors activating transcription factor 3 (ATF3) and ATF4 are induced by amphetamine and restraint stress in rat striatum. However, presently the full extent of ER stress responses to psychological stress or cocaine, and which of the three ER stress pathways is activated is unknown. The current study examines transcriptional responses of key ER stress target genes subsequent to psychological stress or cocaine. Rats were subjected to acute or repeated restraint stress or cocaine treatment and mRNA was isolated from dorsal striatum, medial prefrontal cortex and nucleus accumbens brain tissue. ER stress gene mRNA expression was measured using quantitative polymerase chain reaction (PCR) and RNA sequencing. Restraint stress and cocaine-induced transcription of the classic ER stress-induced genes (BIP, CHOP, ATF3 and GADD34) and of two other ER stress components x-box binding protein 1 (XBP1) and ATF6. In addition, rats living in an enriched environment (large group cage with novel toys changed daily) exhibited rapid induction of GADD34 and ATF3 after 30 min of exploring novel toys, suggesting these genes are also involved in normal non-pathological signaling. However, environmental enrichment, a paradigm that produces protective addiction and depression phenotypes in rats, attenuated the rapid induction of ATF3 and GADD34 after restraint stress. These experiments provide a sensitive measure of ER stress and, more importantly, these results offer good evidence of the activation of ER stress mechanisms from psychological stress, cocaine and natural reward. Thus, ER stress genes may be targets for novel therapeutic targets for depression and addiction. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Stress-induced enhancement of mouse amygdalar synaptic plasticity depends on glucocorticoid and ß-adrenergic activity.

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Ratna Angela Sarabdjitsingh

Full Text Available BACKGROUND: Glucocorticoid hormones, in interaction with noradrenaline, enable the consolidation of emotionally arousing and stressful experiences in rodents and humans. Such interaction is thought to occur at least partly in the basolateral nucleus of the amygdala (BLA which is crucially involved in emotional memory formation. Extensive evidence points to long-term synaptic potentiation (LTP as a mechanism contributing to memory formation. Here we determined in adolescent C57/Bl6 mice the effects of stress on LTP in the LA-BLA pathway and the specific roles of corticosteroid and β-adrenergic receptor activation in this process. PRINCIPAL FINDINGS: Exposure to 20 min of restraint stress (compared to control treatment prior to slice preparation enhanced subsequent LTP induction in vitro, without affecting baseline fEPSP responses. The role of glucocorticoid receptors, mineralocorticoid receptors and β2-adrenoceptors in the effects of stress was studied by treating mice with the antagonists mifepristone, spironolactone or propranolol respectively (or the corresponding vehicles prior to stress or control treatment. In undisturbed controls, mifepristone and propranolol administration in vivo did not influence LTP induced in vitro. By contrast, spironolactone caused a gradually attenuating form of LTP, both in unstressed and stressed mice. Mifepristone treatment prior to stress strongly reduced the ability to induce LTP in vitro. Propranolol normalized the stress-induced enhancement of LTP to control levels during the first 10 min after high frequency stimulation, after which synaptic responses further declined. CONCLUSIONS: Acute stress changes BLA electrical properties such that subsequent LTP induction is facilitated. Both β-adrenergic and glucocorticoid receptors are involved in the development of these changes. Mineralocorticoid receptors are important for the maintenance of LTP in the BLA, irrespective of stress-induced changes in the

Temporal pore pressure induced stress changes during injection and depletion

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Müller, Birgit; Heidbach, Oliver; Schilling, Frank; Fuchs, Karl; Röckel, Thomas

2016-04-01

Induced seismicity is observed during injection of fluids in oil, gas or geothermal wells as a rather immediate response close to the injection wells due to the often high-rate pressurization. It was recognized even earlier in connection with more moderate rate injection of fluid waste on a longer time frame but higher induced event magnitudes. Today, injection-related induced seismicity significantly increased the number of events with M>3 in the Mid U.S. However, induced seismicity is also observed during production of fluids and gas, even years after the onset of production. E.g. in the Groningen gas field production was required to be reduced due to the increase in felt and damaging seismicity after more than 50 years of exploitation of that field. Thus, injection and production induced seismicity can cause severe impact in terms of hazard but also on economic measures. In order to understand the different onset times of induced seismicity we built a generic model to quantify the role of poro-elasticity processes with special emphasis on the factors time, regional crustal stress conditions and fault parameters for three case studies (injection into a low permeable crystalline rock, hydrothermal circulation and production of fluids). With this approach we consider the spatial and temporal variation of reservoir stress paths, the "early" injection-related induced events during stimulation and the "late" production induced ones. Furthermore, in dependence of the undisturbed in situ stress field conditions the stress tensor can change significantly due to injection and long-term production with changes of the tectonic stress regime in which previously not critically stressed faults could turn to be optimally oriented for fault reactivation.

Ursodeoxycholic Acid (UDCA) Exerts Anti-Atherogenic Effects by Inhibiting Endoplasmic Reticulum (ER) Stress Induced by Disturbed Flow.

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Chung, Jihwa; Kim, Kyoung Hwa; Lee, Seok Cheol; An, Shung Hyun; Kwon, Kihwan

2015-10-01

Disturbed blood flow with low-oscillatory shear stress (OSS) is a predominant atherogenic factor leading to dysfunctional endothelial cells (ECs). Recently, it was found that disturbed flow can directly induce endoplasmic reticulum (ER) stress in ECs, thereby playing a critical role in the development and progression of atherosclerosis. Ursodeoxycholic acid (UDCA), a naturally occurring bile acid, has long been used to treat chronic cholestatic liver disease and is known to alleviate endoplasmic reticulum (ER) stress at the cellular level. However, its role in atherosclerosis remains unexplored. In this study, we demonstrated the anti-atherogenic activity of UDCA via inhibition of disturbed flow-induced ER stress in atherosclerosis. UDCA effectively reduced ER stress, resulting in a reduction in expression of X-box binding protein-1 (XBP-1) and CEBP-homologous protein (CHOP) in ECs. UDCA also inhibits the disturbed flow-induced inflammatory responses such as increases in adhesion molecules, monocyte adhesion to ECs, and apoptosis of ECs. In a mouse model of disturbed flow-induced atherosclerosis, UDCA inhibits atheromatous plaque formation through the alleviation of ER stress and a decrease in adhesion molecules. Taken together, our results revealed that UDCA exerts anti-atherogenic activity in disturbed flow-induced atherosclerosis by inhibiting ER stress and the inflammatory response. This study suggests that UDCA may be a therapeutic agent for prevention or treatment of atherosclerosis.

Influence of music training on academic examination-induced stress in Thai adolescents.

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Laohawattanakun, Janejira; Chearskul, Supornpim; Dumrongphol, Hattaya; Jutapakdeegul, Nuanchan; Yensukjai, Juntima; Khumphan, Nipaporn; Niltiean, Songwit; Thangnipon, Wipawan

2011-01-10

Several pieces of evidence suggest that academic examinations fulfill the classical requirement of a psychological stressor. Academic examinations represent a stressful challenge to many students, but studies on examination-dependent corticosteroid response, a sensitive physiological indicator of a stress response, are inconsistent. In addition, several studies showed that music can decrease cortisol and adrenocorticotropic hormone (ACTH) levels, and other studies have found that music also may enhance a variety of cognitive functions, such as attention, learning, communication and memory. The present study investigated cortisol response in saliva of Thai adolescents taking academic examinations and analyzed the differences of the stress response between musician and control subjects. Also, we observed whether the academic examination-dependent corticosteroid response affected learning and memory in the test subjects, which comprised 30 musician and 30 control students, age ranging from 15 to 17 years. Mathematical examinations were used as the stressor. Pre- and post-academic examination saliva cortisol levels were measured including self-estimated stress levels. Results showed that the pre-academic examination saliva cortisol concentrations of the musician group are significantly lower than those of the control group, whereas there is no difference in the stress inventory scores. Interestingly, among students with grade point average (GPA) of >3.50, pre-academic examination cortisol levels are significantly lower in the musician compared with control group. This study suggests that under academic examination-induced stress condition, music training can reduce saliva cortisol level in Thai adolescents. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Acute stress blocks the caffeine-induced enhancement of contextual memory retrieval in mice.

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Pierard, Chistophe; Krazem, Ali; Henkous, Nadia; Decorte, Laurence; Béracochéa, Daniel

2015-08-15

This study investigated in mice the dose-effect of caffeine on memory retrieval in non-stress and stress conditions. C57 Bl/6 Jico mice learned two consecutive discriminations (D1 and D2) in a four-hole board which involved either distinct contextual (CSD) or similar contextual (SSD) cues. All mice received an i.p. injection of vehicle or caffeine (8, 16 or 32mg/kg) 30min before the test session. Results showed that in non-stress conditions, the 16mg/kg caffeine dose induced a significant enhancement of D1 performance in CSD but not in SSD. Hence, we studied the effect of an acute stress (electric footshocks) administered 15min before the test session on D1 performance in caffeine-treated mice. Results showed that stress significantly decreased D1 performance in vehicle-treated controls and the memory-enhancing effect induced by the 16mg/kg caffeine dose in non-stress condition is no longer observed. Interestingly, whereas caffeine-treated mice exhibited weaker concentrations of plasma corticosterone as compared to vehicles in non-stress condition, stress significantly increased plasma corticosterone concentrations in caffeine-treated mice which reached similar level to that of controls. Overall, the acute stress blocked both the endocrinological and memory retrieval enhancing effects of caffeine. Copyright © 2015 Elsevier B.V. All rights reserved.

Stress induces pain transition by potentiation of AMPA receptor phosphorylation.

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Li, Changsheng; Yang, Ya; Liu, Sufang; Fang, Huaqiang; Zhang, Yong; Furmanski, Orion; Skinner, John; Xing, Ying; Johns, Roger A; Huganir, Richard L; Tao, Feng

2014-10-08

Chronic postsurgical pain is a serious issue in clinical practice. After surgery, patients experience ongoing pain or become sensitive to incident, normally nonpainful stimulation. The intensity and duration of postsurgical pain vary. However, it is unclear how the transition from acute to chronic pain occurs. Here we showed that social defeat stress enhanced plantar incision-induced AMPA receptor GluA1 phosphorylation at the Ser831 site in the spinal cord and greatly prolonged plantar incision-induced pain. Interestingly, targeted mutation of the GluA1 phosphorylation site Ser831 significantly inhibited stress-induced prolongation of incisional pain. In addition, stress hormones enhanced GluA1 phosphorylation and AMPA receptor-mediated electrical activity in the spinal cord. Subthreshold stimulation induced spinal long-term potentiation in GluA1 phosphomimetic mutant mice, but not in wild-type mice. Therefore, spinal AMPA receptor phosphorylation contributes to the mechanisms underlying stress-induced pain transition. Copyright © 2014 the authors 0270-6474/14/3413737-10$15.00/0.

Axin1 up-regulated 1 accelerates stress-induced cardiomyocytes apoptosis through activating Wnt/β-catenin signaling.

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Ye, Xing; Lin, Junyi; Lin, Zebin; Xue, Aimin; Li, Liliang; Zhao, Ziqin; Liu, Li; Shen, Yiwen; Cong, Bin

2017-10-15

Stress-induced cardiomyocyte apoptosis contributes to the pathogenesis of a variety of cardiovascular diseases, but how stress induces cardiomyocyte apoptosis remains largely unclear. The present study aims to investigate the effects of Axin1 up-regulated 1 (Axud1), a novel pro-apoptotic protein, on the cardiomyocyte survival and the underlying mechanisms. To this end, a rat model under restraint stress (RS) was established and in vitro stress-induced cardiomyocytes culture was achieved. Our data showed that Axud1 was upregulated in the rat myocardia after exposure to RS. Anti-apoptotic Bcl-2 was decreased, whereas pro-apoptotic Bax and Cleaved caspase-3 (Cc3) were increased in a time-dependent manner. The Wnt/β-catenin signaling was observed to be interestingly activated in heart undergoing RS. In addition, the treatment of norepinephrine (NE) to in vitro cardiomyocytes increased Axud1 level and induced cell apoptosis. Wnt/β-catenin signaling was consistently activated. Knockdown of Axud1 using specific siRNA blunted NE-induced cardiomyocytes apoptosis and also inactivated the Wnt/β-catenin signaling. XAV-939, an inhibitor of Wnt/β-catenin signaling, partially reversed the pro-apoptotic effect of NE. In conclusion, Axud1 accelerated stress-induced cardiomyocytes apoptosis through activation of Wnt/β-catenin signaling pathway. Our data provided novel evidence that therapeutic strategies against Axud1 or Wnt/β-catenin signaling might be promising in relation to RS-induced myocardial injury. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Study of the effect induced by heating and irradiation stress on Salmonella

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Ghazouani, Sarra

2013-01-01

In this study, we evaluated the effect of exposure to a temperature of 55 degree for 30 min and to 2 kGy gamma irradiation dose (100 Gy/min) on the viability and gene expression of Salmonella. Our results indicate that the exposure to heat and irradiation showed levels of stress vary from one type of stress to another, a different serovars and even there is variability within the same serovars of different origins and isolation. They were able to induce a decrease in viability. The analysis of the differential expression of 16S rRNA genes by RT-PCR after exposure to stress showed that the level of mRNA expression of 16S rRNA is unstable during the exhibition, and may not be used as reference gene for the analysis of differential expression of genes of Salmonella.

Acute stress reduces wound-induced activation of microbicidal potential of ex vivo isolated human monocyte-derived macrophages.

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Ulrike Kuebler

Full Text Available BACKGROUND: Psychological stress delays wound healing but the precise underlying mechanisms are unclear. Macrophages play an important role in wound healing, in particular by killing microbes. We hypothesized that (a acute psychological stress reduces wound-induced activation of microbicidal potential of human monocyte-derived macrophages (HMDM, and (b that these reductions are modulated by stress hormone release. METHODS: Fourty-one healthy men (mean age 35 ± 13 years were randomly assigned to either a stress or stress-control group. While the stress group underwent a standardized short-term psychological stress task after catheter-induced wound infliction, stress-controls did not. Catheter insertion was controlled. Assessing the microbicidal potential, we investigated PMA-activated superoxide anion production by HMDM immediately before and 1, 10 and 60 min after stress/rest. Moreover, plasma norepinephrine and epinephrine and salivary cortisol were repeatedly measured. In subsequent in vitro studies, whole blood was incubated with norepinephrine in the presence or absence of phentolamine (norepinephrine blocker before assessing HMDM microbicidal potential. RESULTS: Compared with stress-controls, HMDM of the stressed subjects displayed decreased superoxide anion-responses after stress (p's <.05. Higher plasma norepinephrine levels statistically mediated lower amounts of superoxide anion-responses (indirect effect 95% CI: 4.14-44.72. Norepinephrine-treated HMDM showed reduced superoxide anion-production (p<.001. This effect was blocked by prior incubation with phentolamine. CONCLUSIONS: Our results suggest that acute psychological stress reduces wound-induced activation of microbicidal potential of HMDM and that this reduction is mediated by norepinephrine. This might have implications for stress-induced impairment in wound healing.

PEG-induced osmotic stress in Mentha x piperita L.: Structural features and metabolic responses.

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Búfalo, Jennifer; Rodrigues, Tatiane Maria; de Almeida, Luiz Fernando Rolim; Tozin, Luiz Ricardo Dos Santos; Marques, Marcia Ortiz Mayo; Boaro, Carmen Silvia Fernandes

2016-08-01

The present study investigated whether osmotic stress induced by the exposure of peppermint (Mentha x piperita L.) to moderate and severe stress for short periods of time changes the plant's physiological parameters, leaf anatomy and ultrastructure and essential oil. Plants were exposed to two levels of polyethyleneglycol (50 g L(-1) and 100 g L(-1) of PEG) in a hydroponic experiment. The plants exposed to 50 g L(-1) maintained metabolic functions similar to those of the control group (0 g L(-1)) without changes in gas exchange or structural characteristics. The increase in antioxidant enzyme activity reduced the presence of free radicals and protected membranes, including chloroplasts and mitochondria. In contrast, the osmotic stress caused by 100 g L(-1) of PEG inhibited leaf gas exchange, reduced the essential oil content and changed the oil composition, including a decrease in menthone and an increase in menthofuran. These plants also showed an increase in peroxidase activity, but this increase was not sufficient to decrease the lipid peroxidation level responsible for damaging the membranes of organelles. Morphological changes were correlated with the evaluated physiological features: plants exposed to 100 g L(-1) of PEG showed areas with collapsed cells, increases in mesophyll thickness and the area of the intercellular space, cuticle shrinkage, morphological changes in plastids, and lysis of mitochondria. In summary, our results revealed that PEG-induced osmotic stress in M. x piperita depends on the intensity level of the osmotic stress applied; severe osmotic stress changed the structural characteristics, caused damage at the cellular level, and reduced the essential oil content and quality. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Angiotensin II receptor blocker ameliorates stress-induced adipose tissue inflammation and insulin resistance.

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Motoharu Hayashi

Full Text Available A strong causal link exists between psychological stress and insulin resistance as well with hypertension. Meanwhile, stress-related responses play critical roles in glucose metabolism in hypertensive patients. As clinical trials suggest that angiotensin-receptor blocker delays the onset of diabetes in hypertensive patients, we investigated the effects of irbesartan on stress-induced adipose tissue inflammation and insulin resistance. C57BL/6J mice were subjected to 2-week intermittent restraint stress and orally treated with vehicle, 3 and 10 mg/kg/day irbesartan. The plasma concentrations of lipid and proinflammatory cytokines [Monocyte Chemoattractant Protein-1 (MCP-1, tumor necrosis factor-α, and interleukin-6] were assessed with enzyme-linked immunosorbent assay. Monocyte/macrophage accumulation in inguinal white adipose tissue (WAT was observed with CD11b-positive cell counts and mRNA expressions of CD68 and F4/80 using immunohistochemistry and RT-PCR methods respectively. The mRNA levels of angiotensinogen, proinflammatory cytokines shown above, and adiponectin in WAT were also assessed with RT-PCR method. Glucose metabolism was assessed by glucose tolerance tests (GTTs and insulin tolerance tests, and mRNA expression of insulin receptor substrate-1 (IRS-1 and glucose transporter 4 (GLUT4 in WAT. Restraint stress increased monocyte accumulation, plasma free fatty acids, expression of angiotensinogen and proinflammatory cytokines including MCP-1, and reduced adiponectin. Irbesartan reduced stress-induced monocyte accumulation in WAT in a dose dependent manner. Irbesartan treatment also suppressed induction of adipose angiotensinogen and proinflammatory cytokines in WAT and blood, and reversed changes in adiponectin expression. Notably, irbesartan suppressed stress-induced reduction in adipose tissue weight and free fatty acid release, and improved insulin tolerance with restoration of IRS-1 and GLUT4 mRNA expressions in WAT. The results

Stress-induced antinociception in fish reversed by naloxone.

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Carla Patrícia Bejo Wolkers

Full Text Available Pain perception in non-mammalian vertebrates such as fish is a controversial issue. We demonstrate that, in the fish Leporinus macrocephalus, an imposed restraint can modulate the behavioral response to a noxious stimulus, specifically the subcutaneous injection of 3% formaldehyde. In the first experiment, formaldehyde was applied immediately after 3 or 5 min of the restraint. Inhibition of the increase in locomotor activity in response to formaldehyde was observed, which suggests a possible restraint-induced antinociception. In the second experiment, the noxious stimulus was applied 0, 5, 10 and 15 min after the restraint, and both 3 and 5 min of restraint promoted short-term antinociception of approximately 5 min. In experiments 3 and 4, an intraperitoneal injection of naloxone (30 mg.kg(-1 was administered 30 min prior to the restraint. The 3- minute restraint-induced antinociception was blocked by pretreatment with naloxone, but the corresponding 5-minute response was not. One possible explanation for this result is that an opioid and a non-preferential μ-opioid and/or non-opioid mechanism participate in this response modulation. Furthermore, we observed that both the 3- and 5- minutes restraint were severely stressful events for the organism, promoting marked increases in serum cortisol levels. These data indicate that the response to a noxious stimulus can be modulated by an environmental stressor in fish, as is the case in mammals. To our knowledge, this study is the first evidence for the existence of an endogenous antinociceptive system that is activated by an acute standardized stress in fish. Additionally, it characterizes the antinociceptive response induced by stress in terms of its time course and the opioid mediation, providing information for understanding the evolution of nociception modulation.

Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats

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Rashid, Kahkashan; Sil, Parames C.

2015-01-01

The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. - Highlights: • STZ induced cellular stress plays a vital role in pancreatic dysfunction. • Cellular stress causes inflammation, pancreatic islet cell death and diabetes. • Deregulation of Nrf-2

Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats

Energy Technology Data Exchange (ETDEWEB)

Rashid, Kahkashan; Sil, Parames C., E-mail: parames@jcbose.ac.in

2015-02-01

The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. - Highlights: • STZ induced cellular stress plays a vital role in pancreatic dysfunction. • Cellular stress causes inflammation, pancreatic islet cell death and diabetes. • Deregulation of Nrf-2

Modulation of Hypercholesterolemia-Induced Oxidative/Nitrative Stress in the Heart

Science.gov (United States)

Sárközy, Márta; Pipicz, Márton; Dux, László; Csont, Tamás

2016-01-01

Hypercholesterolemia is a frequent metabolic disorder associated with increased risk for cardiovascular morbidity and mortality. In addition to its well-known proatherogenic effect, hypercholesterolemia may exert direct effects on the myocardium resulting in contractile dysfunction, aggravated ischemia/reperfusion injury, and diminished stress adaptation. Both preclinical and clinical studies suggested that elevated oxidative and/or nitrative stress plays a key role in cardiac complications induced by hypercholesterolemia. Therefore, modulation of hypercholesterolemia-induced myocardial oxidative/nitrative stress is a feasible approach to prevent or treat deleterious cardiac consequences. In this review, we discuss the effects of various pharmaceuticals, nutraceuticals, some novel potential pharmacological approaches, and physical exercise on hypercholesterolemia-induced oxidative/nitrative stress and subsequent cardiac dysfunction as well as impaired ischemic stress adaptation of the heart in hypercholesterolemia. PMID:26788247

Periodontal disease level-butyric acid amounts locally administered in the rat gingival mucosa induce ER stress in the systemic blood.

Science.gov (United States)

Cueno, Marni E; Saito, Yuko; Ochiai, Kuniyasu

2016-05-01

Periodontal diseases have long been postulated to contribute to systemic diseases and, likewise, it has been proposed that periodontal disease treatment may ameliorate certain systemic diseases. Short-chain fatty acids (SCFA) are major secondary metabolites produced by oral anaerobic bacteria and, among the SCFAs, butyric acid (BA) in high amounts contribute to periodontal disease development. Periodontal disease level-butyric acid (PDL-BA) is found among patients suffering from periodontal disease and has previously shown to induce oxidative stress, whereas, oxidative stress is correlated to endoplasmic reticulum (ER) stress. This would imply that PDL-BA may likewise stimulate ER stress, however, this was never elucidated. A better understanding of the correlation between PDL-BA and systemic ER stress stimulation could shed light on the possible systemic effects of PDL-BA-related periodontal diseases. Here, PDL-BA was injected into the gingival mucosa and the systemic blood obtained from the rat jugular was collected at 0, 15, 60, and 180 min post-injection. Collected blood samples were purified and only the blood cytosol was used throughout this study. Subsequently, we measured blood cytosolic GADD153, Ca(2+), representative apoptotic and inflammatory caspases, and NF-κB amounts. We found that PDL-BA presence increased blood cytosolic GADD153 and Ca(2+) amounts. Moreover, we observed that blood cytosolic caspases and NF-κB were activated only at 60 and 180 min post-injection in the rat gingival mucosa. This suggests that PDL-BA administered through the gingival mucosa may influence the systemic blood via ER stress stimulation and, moreover, prolonged PDL-BA retention in the gingival mucosa may play a significant role in ER stress-related caspase and NF-κB activation. In a periodontal disease scenario, we propose that PDL-BA-related ER stress stimulation leading to the simultaneous activation of apoptosis and inflammation may contribute to periodontal disease

Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.

Science.gov (United States)

Verma, Dinesh Kumar; Joshi, Neeraj; Raju, Kunumuri Sivarama; Wahajuddin, Muhammad; Singh, Rama Kant; Singh, Sarika

2015-01-01

Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells

Anomalous Transport in Natural Fracture Networks Induced by Tectonic Stress

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Kang, P. K.; Lei, Q.; Lee, S.; Dentz, M.; Juanes, R.

2017-12-01

Fluid flow and transport in fractured rock controls many natural and engineered processes in the subsurface. However, characterizing flow and transport through fractured media is challenging due to the high uncertainty and large heterogeneity associated with fractured rock properties. In addition to these "static" challenges, geologic fractures are always under significant overburden stress, and changes in the stress state can lead to changes in the fracture's ability to conduct fluids. While confining stress has been shown to impact fluid flow through fractures in a fundamental way, the impact of confining stress on transportthrough fractured rock remains poorly understood. The link between anomalous (non-Fickian) transport and confining stress has been shown, only recently, at the level of a single rough fracture [1]. Here, we investigate the impact of geologic (tectonic) stress on flow and tracer transport through natural fracture networks. We model geomechanical effects in 2D fractured rock by means of a finite-discrete element method (FEMDEM) [2], which can capture the deformation of matrix blocks, reactivation of pre-existing fractures, and propagation of new cracks, upon changes in the stress field. We apply the model to a fracture network extracted from the geological map of an actual rock outcrop to obtain the aperture field at different stress conditions. We then simulate fluid flow and particle transport through the stressed fracture networks. We observe that anomalous transport emerges in response to confining stress on the fracture network, and show that the stress state is a powerful determinant of transport behavior: (1) An anisotropic stress state induces preferential flow paths through shear dilation; (2) An increase in geologic stress increases aperture heterogeneity that induces late-time tailing of particle breakthrough curves. Finally, we develop an effective transport model that captures the anomalous transport through the stressed fracture

Contrast-induced nephrotoxicity: possible synergistic effect of stress hyperglycemia.

LENUS (Irish Health Repository)

O'Donnell, David H

2010-07-01

Oxidative stress on the renal tubules has been implicated as a mechanism of injury in both stress hyperglycemia and contrast-induced nephrotoxicity. The purpose of this study was to determine whether the combination of these effects has a synergistic effect on accentuating renal tubular apoptosis and therefore increasing the risk of contrast-induced nephrotoxicity.

Reduced α-MSH Underlies Hypothalamic ER-Stress-Induced Hepatic Gluconeogenesis.

Science.gov (United States)

Schneeberger, Marc; Gómez-Valadés, Alicia G; Altirriba, Jordi; Sebastián, David; Ramírez, Sara; Garcia, Ainhoa; Esteban, Yaiza; Drougard, Anne; Ferrés-Coy, Albert; Bortolozzi, Analía; Garcia-Roves, Pablo M; Jones, John G; Manadas, Bruno; Zorzano, Antonio; Gomis, Ramon; Claret, Marc

2015-07-21

Alterations in ER homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here, we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (α-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic α-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective α-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress and establish α-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress

NARCIS (Netherlands)

Henckens, Marloes J. A. G.; Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C.; van Wingen, Guido A.; Fernández, Guillén

2016-01-01

Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both

Aging induced endoplasmic reticulum stress alters sleep and sleep homeostasis.

Science.gov (United States)

Brown, Marishka K; Chan, May T; Zimmerman, John E; Pack, Allan I; Jackson, Nicholas E; Naidoo, Nirinjini

2014-06-01

Alterations in the quality, quantity, and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response. The effectiveness of the adaptive unfolded protein response is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of X-box binding protein 1 and upregulation of phosphorylated elongation initiation factor 2 α, in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged or sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep or sleep debt discharge. Copyright © 2014 Elsevier Inc. All rights reserved.

Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury

Science.gov (United States)

Azzam, Edouard I.; Jay-Gerin, Jean-Paul; Pain, Debkumar

2013-01-01

Cellular exposure to ionizing radiation leads to oxidizing events that alter atomic structure through direct interactions of radiation with target macromolecules or via products of water radiolysis. Further, the oxidative damage may spread from the targeted to neighboring, non-targeted bystander cells through redox-modulated intercellular communication mechanisms. To cope with the induced stress and the changes in the redox environment, organisms elicit transient responses at the molecular, cellular and tissue levels to counteract toxic effects of radiation. Metabolic pathways are induced during and shortly after the exposure. Depending on radiation dose, dose-rate and quality, these protective mechanisms may or may not be sufficient to cope with the stress. When the harmful effects exceed those of homeostatic biochemical processes, induced biological changes persist and may be propagated to progeny cells. Physiological levels of reactive oxygen and nitrogen species play critical roles in many cellular functions. In irradiated cells, levels of these reactive species may be increased due to perturbations in oxidative metabolism and chronic inflammatory responses, thereby contributing to the long-term effects of exposure to ionizing radiation on genomic stability. Here, in addition to immediate biological effects of water radiolysis on DNA damage, we also discuss the role of mitochondria in the delayed outcomes of ionization radiation. Defects in mitochondrial functions lead to accelerated aging and numerous pathological conditions. Different types of radiation vary in their linear energy transfer (LET) properties, and we discuss their effects on various aspects of mitochondrial physiology. These include short and long-term in vitro and in vivo effects on mitochondrial DNA, mitochondrial protein import and metabolic and antioxidant enzymes. PMID:22182453

Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

International Nuclear Information System (INIS)

Qi, Xiaozhe; Yu, Tao; Zhu, Liye; Gao, Jing; He, Xiaoyun; Huang, Kunlun; Luo, Yunbo; Xu, Wentao

2014-01-01

Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected in the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation

Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

Energy Technology Data Exchange (ETDEWEB)

Qi, Xiaozhe; Yu, Tao; Zhu, Liye; Gao, Jing [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); He, Xiaoyun; Huang, Kunlun; Luo, Yunbo [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Xu, Wentao, E-mail: xuwentao@cau.edu.cn [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China)

2014-11-01

Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected in the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation.

Chlamydia trachomatis responds to heat shock, penicillin induced persistence, and IFN-gamma persistence by altering levels of the extracytoplasmic stress response protease HtrA

Directory of Open Access Journals (Sweden)

Mathews Sarah A

2008-11-01

Full Text Available Abstract Background Chlamydia trachomatis, an obligate intracellular human pathogen, is the most prevalent bacterial sexually transmitted infection worldwide and a leading cause of preventable blindness. HtrA is a virulence and stress response periplasmic serine protease and molecular chaperone found in many bacteria. Recombinant purified C. trachomatis HtrA has been previously shown to have both activities. This investigation examined the physiological role of Chlamydia trachomatis HtrA. Results The Chlamydia trachomatis htrA gene complemented the lethal high temperature phenotype of Escherichia coli htrA- (>42°C. HtrA levels were detected to increase by western blot and immunofluorescence during Chlamydia heat shock experiments. Confocal laser scanning microscopy revealed a likely periplasmic localisation of HtrA. During penicillin induced persistence of Chlamydia trachomatis, HtrA levels (as a ratio of LPS were initially less than control acute cultures (20 h post infection but increased to more than acute cultures at 44 h post infection. This was unlike IFN-γ persistence where lower levels of HtrA were observed, suggesting Chlamydia trachomatis IFN-γ persistence does not involve a broad stress response. Conclusion The heterologous heat shock protection for Escherichia coli, and increased HtrA during cell wall disruption via penicillin and heat shock, indicates an important role for HtrA during high protein stress conditions for Chlamydia trachomatis.

Shear stress-induced mitochondrial biogenesis decreases the release of microparticles from endothelial cells.

Science.gov (United States)

Kim, Ji-Seok; Kim, Boa; Lee, Hojun; Thakkar, Sunny; Babbitt, Dianne M; Eguchi, Satoru; Brown, Michael D; Park, Joon-Young

2015-08-01

The concept of enhancing structural integrity of mitochondria has emerged as a novel therapeutic option for cardiovascular disease. Flow-induced increase in laminar shear stress is a potent physiological stimulant associated with exercise, which exerts atheroprotective effects in the vasculature. However, the effect of laminar shear stress on mitochondrial remodeling within the vascular endothelium and its related functional consequences remain largely unknown. Using in vitro and in vivo complementary studies, here, we report that aerobic exercise alleviates the release of endothelial microparticles in prehypertensive individuals and that these salutary effects are, in part, mediated by shear stress-induced mitochondrial biogenesis. Circulating levels of total (CD31(+)/CD42a(-)) and activated (CD62E(+)) microparticles released by endothelial cells were significantly decreased (∼40% for both) after a 6-mo supervised aerobic exercise training program in individuals with prehypertension. In cultured human endothelial cells, laminar shear stress reduced the release of endothelial microparticles, which was accompanied by an increase in mitochondrial biogenesis through a sirtuin 1 (SIRT1)-dependent mechanism. Resveratrol, a SIRT1 activator, treatment showed similar effects. SIRT1 knockdown using small-interfering RNA completely abolished the protective effect of shear stress. Disruption of mitochondrial integrity by either antimycin A or peroxisome proliferator-activated receptor-γ coactivator-1α small-interfering RNA significantly increased the number of total, and activated, released endothelial microparticles, and shear stress restored these back to basal levels. Collectively, these data demonstrate a critical role of endothelial mitochondrial integrity in preserving endothelial homeostasis. Moreover, prolonged laminar shear stress, which is systemically elevated during aerobic exercise in the vessel wall, mitigates endothelial dysfunction by promoting

Activation of the hypothalamic-pituitary-adrenal stress axis induces cellular oxidative stress

Directory of Open Access Journals (Sweden)

Jereme G. Spiers

2015-01-01

Full Text Available Glucocorticoids released from the adrenal gland in response to stress-induced activation of the hypothalamic-pituitary-adrenal (HPA axis induce activity in the cellular reduction-oxidation (redox system. The redox system is a ubiquitous chemical mechanism allowing the transfer of electrons between donor/acceptors and target molecules during oxidative phosphorylation while simultaneously maintaining the overall cellular environment in a reduced state. The objective of this review is to present an overview of the current literature discussing the link between HPA axis-derived glucocorticoids and increased oxidative stress, particularly focussing on the redox changes observed in the hippocampus following glucocorticoid exposure.

Dynamic Behavior of Fault Slip Induced by Stress Waves

Directory of Open Access Journals (Sweden)

Guang-an Zhu

2016-01-01

Full Text Available Fault slip burst is a serious dynamic hazard in coal mining. A static and dynamic analysis for fault slip was performed to assess the risk of rock burst. A numerical model FLAC3D was established to understand the stress state and mechanical responses of fault rock system. The results obtained from the analysis show that the dynamic behavior of fault slip induced by stress waves is significantly affected by mining depth, as well as dynamic disturbance intensity and the distance between the stope and the fault. The isolation effect of the fault is also discussed based on the numerical results with the fault angle appearing to have the strongest influence on peak vertical stress and velocity induced by dynamic disturbance. By taking these risks into account, a stress-relief technology using break-tip blast was used for fault slip burst control. This technique is able to reduce the stress concentration and increase the attenuation of dynamic load by fracturing the structure of coal and rock. The adoption of this stress-relief method leads to an effective reduction of fault slip induced rock burst (FSIRB occurrence.

Omega-3 Polyunsaturated Fatty Acids Attenuate Radiation-induced Oxidative Stress and Organ Dysfunctions in Rats

International Nuclear Information System (INIS)

Abdel Aziz, N.; Yacoub, S.F.

2013-01-01

The Aim of the present study was to determine the possible protective effect of omega-3 polyunsaturated fatty acids (omega-3 PUFA) against radiation-induced oxidative stress associated with organ dysfunctions. Omega-3 PUFA was administered by oral gavages to male albino rats at a dose of 0.4 g/ kg body wt daily for 4 weeks before whole body γ-irradiation with 4Gy. Significant increase of serum lipid peroxidation end product as malondialdehyde (MDA) along with the reduction in blood glutathione (GSH) content, superoxide dismutase (SOD) and glutathione peroxidase (GPX) enzyme activities were recorded on 3rd and 8th days post-irradiation. Oxidative stress was associated with a significant increase in lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) enzyme activities, markers of heart damage, significant increases in uric acid, urea and creatinine levels, markers of kidney damage, significant increases of alkaline phosphatase (ALP) and transaminases (ALT and AST) activities, markers of liver damage. Moreover significant increases in total cholesterol and triglycerides levels were recorded. Omega-3 PUFA administration pre-irradiation significantly attenuated the radiation-induced oxidative stress and organ dysfunctions tested in this study. It could be concluded that oral supplementation of omega-3 PUFA before irradiation may afford protection against radiation-induced oxidative stress and might preserve the integrity of tissue functions of the organs under investigations.

Quantification of stress-induced damage and post-fire response of 5083 aluminum alloy

International Nuclear Information System (INIS)

Chen, Y.; Puplampu, S.B.; Summers, P.T.; Lattimer, B.Y.; Penumadu, D.; Case, S.W.

2015-01-01

One of the major concerns regarding the use of lightweight materials in ship construction is the response of those materials to fire scenarios, including the residual structural performance after a fire event. This paper presents a study on creep damage evolution in 5083 marine-grade aluminum alloy and its impact on residual mechanical behavior. Tests conducted at 400 °C and pre-selected tensile stress levels were interrupted at target amplitudes of accumulated engineering creep strains to investigate the stress-induced damage using ex-situ characterization. Two-dimensional optical and electron microscopy and three-dimensional X-ray tomography were utilized on samples extracted from these test specimens to characterize the external and internal creep damage. The stress-induced damage is primarily manifested as cavitation and dynamic microstructural evolution. Cavitation morphology, orientation and grain structure evolution were investigated on three perpendicular sample surfaces. A 3D examination of the damage state provided consistent damage information to that obtained from the 2D analysis. The post-fire mechanical properties were also evaluated and linked to the microstructural change. The competing processes of cavitation and grain structure evolution were investigated to develop an understanding of the stress-induced damage associated with high temperature creep

Quantification of stress-induced damage and post-fire response of 5083 aluminum alloy

Energy Technology Data Exchange (ETDEWEB)

Chen, Y., E-mail: yanyun@vt.edu [Department of Engineering Science & Mechanics, Virginia Tech, Blacksburg, VA 24061 (United States); Puplampu, S.B. [Department of Civil and Environmental Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Summers, P.T.; Lattimer, B.Y. [Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA 24061 (United States); Penumadu, D. [Department of Civil and Environmental Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Case, S.W. [Department of Engineering Science & Mechanics, Virginia Tech, Blacksburg, VA 24061 (United States)

2015-08-12

One of the major concerns regarding the use of lightweight materials in ship construction is the response of those materials to fire scenarios, including the residual structural performance after a fire event. This paper presents a study on creep damage evolution in 5083 marine-grade aluminum alloy and its impact on residual mechanical behavior. Tests conducted at 400 °C and pre-selected tensile stress levels were interrupted at target amplitudes of accumulated engineering creep strains to investigate the stress-induced damage using ex-situ characterization. Two-dimensional optical and electron microscopy and three-dimensional X-ray tomography were utilized on samples extracted from these test specimens to characterize the external and internal creep damage. The stress-induced damage is primarily manifested as cavitation and dynamic microstructural evolution. Cavitation morphology, orientation and grain structure evolution were investigated on three perpendicular sample surfaces. A 3D examination of the damage state provided consistent damage information to that obtained from the 2D analysis. The post-fire mechanical properties were also evaluated and linked to the microstructural change. The competing processes of cavitation and grain structure evolution were investigated to develop an understanding of the stress-induced damage associated with high temperature creep.

Social Isolation Stress Induces Anxious-Depressive-Like Behavior and Alterations of Neuroplasticity-Related Genes in Adult Male Mice

Directory of Open Access Journals (Sweden)

Alessandro Ieraci

2016-01-01

Full Text Available Stress is a major risk factor in the onset of several neuropsychiatric disorders including anxiety and depression. Although several studies have shown that social isolation stress during postweaning period induces behavioral and brain molecular changes, the effects of social isolation on behavior during adulthood have been less characterized. Aim of this work was to investigate the relationship between the behavioral alterations and brain molecular changes induced by chronic social isolation stress in adult male mice. Plasma corticosterone levels and adrenal glands weight were also analyzed. Socially isolated (SI mice showed higher locomotor activity, spent less time in the open field center, and displayed higher immobility time in the tail suspension test compared to group-housed (GH mice. SI mice exhibited reduced plasma corticosterone levels and reduced difference between right and left adrenal glands. SI showed lower mRNA levels of the BDNF-7 splice variant, c-Fos, Arc, and Egr-1 in both hippocampus and prefrontal cortex compared to GH mice. Finally, SI mice exhibited selectively reduced mGluR1 and mGluR2 levels in the prefrontal cortex. Altogether, these results suggest that anxious- and depressive-like behavior induced by social isolation stress correlates with reduction of several neuroplasticity-related genes in the hippocampus and prefrontal cortex of adult male mice.

Enhanced photosynthetic capacity and antioxidant potential mediate brassinosteriod-induced phenanthrene stress tolerance in tomato

International Nuclear Information System (INIS)

Ahammed, Golam Jalal; Li, Xin; Xia, Xiao-Jian; Shi, Kai; Zhou, Yan-Hong; Yu, Jing-Quan

2015-01-01

Photosynthesis, the basal manufacturing process in the earth is habitually restricted by airborne micropollutants such as phenanthrene (PHE). Here, we show that 24-epibrassinolide (EBR), a bioactive plant steroid is able to keep higher photosynthetic capacity consistently for a long period under a shoot-imposed PHE stress in tomato. EBR-promoted photosynthetic capacity and efficiency eventually resulted in a 37.5% increase of biomass under PHE stress. As primary response, transcripts of antioxidant genes were remarkably induced by EBR in PHE-treated plants. Activities of antioxidant and detoxification enzymes were also enhanced by EBR. Notably, EBR-induced higher antioxidant potential was associated with reduced levels of H 2 O 2 and O 2 · — , resulting in a 32.7% decrease of content of malondialdehyde in the end of experiment and relatively healthy chloroplast ultrastructure in EBR + PHE treatment compared with PHE alone. These results indicate that EBR alleviates shoot-imposed PHE phytotoxicity by maintaining a consistently higher photosynthetic capacity and antioxidant potential in tomato. - Highlights: • PHE mist spray gradually inhibits photosynthesis and eventually reduces biomass. • EBR maintains a consistently higher photosynthesis even under PHE stress. • EBR upregulates expression of antioxidant genes as initial response to PHE stress. • EBR reduces oxidative stress by constantly activating strong antioxidant potential. • EBR-induced efficient neutralization of ROS protects chloroplast ultrastructure. - 24-epibrassinolide protects tomato plants from airborne phenanthrene-induced damages by maintaining a consistently higher photosynthetic capacity and antioxidant potential

Neuroendocrine and oxidoreductive mechanisms of stress-induced cardiovascular diseases.

Science.gov (United States)

Pajović, S B; Radojcić, M B; Kanazir, D T

2008-01-01

The review concerns a number of basic molecular pathways that play a crucial role in perception, transmission, and modulation of the stress signals, and mediate the adaptation of the vital processes in the cardiovascular system (CVS). These highly complex systems for intracellular transfer of information include stress hormones and their receptors, stress-activated phosphoprotein kinases, stress-activated heat shock proteins, and antioxidant enzymes maintaining oxidoreductive homeostasis of the CVS. Failure to compensate for the deleterious effects of stress may result in the development of different pathophysiological states of the CVS, such as ischemia, hypertension, atherosclerosis and infarction. Stress-induced dysbalance in each of the CVS molecular signaling systems and their contribution to the CVS malfunctioning is reviewed. The general picture of the molecular mechanisms of the stress-induced pathophysiology in the CVS pointed out the importance of stress duration and intensity as etiological factors, and suggested that future studies should be complemented by the careful insights into the individual factors of susceptibility to stress, prophylactic effects of 'healthy' life styles and beneficial action of antioxidant-rich nutrition.

Tributyltin-induced endoplasmic reticulum stress and its Ca2+-mediated mechanism

International Nuclear Information System (INIS)

Isomura, Midori; Kotake, Yaichiro; Masuda, Kyoichi; Miyara, Masatsugu; Okuda, Katsuhiro; Samizo, Shigeyoshi; Sanoh, Seigo; Hosoi, Toru; Ozawa, Koichiro; Ohta, Shigeru

2013-01-01

Organotin compounds, especially tributyltin chloride (TBT), have been widely used in antifouling paints for marine vessels, but exhibit various toxicities in mammals. The endoplasmic reticulum (ER) is a multifunctional organelle that controls post-translational modification and intracellular Ca 2+ signaling. When the capacity of the quality control system of ER is exceeded under stress including ER Ca 2+ homeostasis disruption, ER functions are impaired and unfolded proteins are accumulated in ER lumen, which is called ER stress. Here, we examined whether TBT causes ER stress in human neuroblastoma SH-SY5Y cells. We found that 700 nM TBT induced ER stress markers such as CHOP, GRP78, spliced XBP1 mRNA and phosphorylated eIF2α. TBT also decreased the cell viability both concentration- and time-dependently. Dibutyltin and monobutyltin did not induce ER stress markers. We hypothesized that TBT induces ER stress via Ca 2+ depletion, and to test this idea, we examined the effect of TBT on intracellular Ca 2+ concentration using fura-2 AM, a Ca 2+ fluorescent probe. TBT increased intracellular Ca 2+ concentration in a TBT-concentration-dependent manner, and Ca 2+ increase in 700 nM TBT was mainly blocked by 50 μM dantrolene, a ryanodine receptor antagonist (about 70% inhibition). Dantrolene also partially but significantly inhibited TBT-induced GRP78 expression and cell death. These results suggest that TBT increases intracellular Ca 2+ concentration by releasing Ca 2+ from ER, thereby causing ER stress. - Highlights: • We established that tributyltin induces endoplasmic reticulum (ER) stress. • Tributyltin induces ER stress markers in a concentration-dependent manner. • Tributyltin increases Ca 2+ release from ER, thereby causing ER stress. • Dibutyltin and monobutyltin did not increase GRP78 or intracellular Ca 2+

Aryl hydrocarbon receptor protects lung adenocarcinoma cells against cigarette sidestream smoke particulates-induced oxidative stress

International Nuclear Information System (INIS)

Cheng, Ya-Hsin; Huang, Su-Chin; Lin, Chun-Ju; Cheng, Li-Chuan; Li, Lih-Ann

2012-01-01

Environmental cigarette smoke has been suggested to promote lung adenocarcinoma progression through aryl hydrocarbon receptor (AhR)-signaled metabolism. However, whether AhR facilitates metabolic activation or detoxification in exposed adenocarcinoma cells remains ambiguous. To address this question, we have modified the expression level of AhR in two human lung adenocarcinoma cell lines and examined their response to an extract of cigarette sidestream smoke particulates (CSSP). We found that overexpression of AhR in the CL1-5 cell line reduced CSSP-induced ROS production and oxidative DNA damage, whereas knockdown of AhR expression increased ROS level in CSSP-exposed H1355 cells. Oxidative stress sensor Nrf2 and its target gene NQO1 were insensitive to AhR expression level and CSSP treatment in human lung adenocarcinoma cells. In contrast, induction of AhR expression concurrently increased mRNA expression of xenobiotic-metabolizing genes CYP1B1, UGT1A8, and UGT1A10 in a ligand-independent manner. It appeared that AhR accelerated xenobiotic clearing and diminished associated oxidative stress by coordinate regulation of a set of phase I and II metabolizing genes. However, the AhR-signaled protection could not shield cells from constant oxidative stress. Prolonged exposure to high concentrations of CSSP induced G0/G1 cell cycle arrest via the p53–p21–Rb1 signaling pathway. Despite no effect on DNA repair rate, AhR facilitated the recovery of cells from growth arrest when CSSP exposure ended. AhR-overexpressing lung adenocarcinoma cells exhibited an increased anchorage-dependent and independent proliferation when recovery from exposure. In summary, our data demonstrated that AhR protected lung adenocarcinoma cells against CSSP-induced oxidative stress and promoted post-exposure clonogenicity. -- Highlights: ► AhR expression level influences cigarette sidestream smoke-induced ROS production. ► AhR reduces oxidative stress by coordinate regulation of

Aryl hydrocarbon receptor protects lung adenocarcinoma cells against cigarette sidestream smoke particulates-induced oxidative stress

Energy Technology Data Exchange (ETDEWEB)

Cheng, Ya-Hsin [Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung 40402, Taiwan, ROC (China); Huang, Su-Chin; Lin, Chun-Ju; Cheng, Li-Chuan [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan, ROC (China); Li, Lih-Ann, E-mail: lihann@nhri.org.tw [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan, ROC (China)

2012-03-15

Environmental cigarette smoke has been suggested to promote lung adenocarcinoma progression through aryl hydrocarbon receptor (AhR)-signaled metabolism. However, whether AhR facilitates metabolic activation or detoxification in exposed adenocarcinoma cells remains ambiguous. To address this question, we have modified the expression level of AhR in two human lung adenocarcinoma cell lines and examined their response to an extract of cigarette sidestream smoke particulates (CSSP). We found that overexpression of AhR in the CL1-5 cell line reduced CSSP-induced ROS production and oxidative DNA damage, whereas knockdown of AhR expression increased ROS level in CSSP-exposed H1355 cells. Oxidative stress sensor Nrf2 and its target gene NQO1 were insensitive to AhR expression level and CSSP treatment in human lung adenocarcinoma cells. In contrast, induction of AhR expression concurrently increased mRNA expression of xenobiotic-metabolizing genes CYP1B1, UGT1A8, and UGT1A10 in a ligand-independent manner. It appeared that AhR accelerated xenobiotic clearing and diminished associated oxidative stress by coordinate regulation of a set of phase I and II metabolizing genes. However, the AhR-signaled protection could not shield cells from constant oxidative stress. Prolonged exposure to high concentrations of CSSP induced G0/G1 cell cycle arrest via the p53–p21–Rb1 signaling pathway. Despite no effect on DNA repair rate, AhR facilitated the recovery of cells from growth arrest when CSSP exposure ended. AhR-overexpressing lung adenocarcinoma cells exhibited an increased anchorage-dependent and independent proliferation when recovery from exposure. In summary, our data demonstrated that AhR protected lung adenocarcinoma cells against CSSP-induced oxidative stress and promoted post-exposure clonogenicity. -- Highlights: ► AhR expression level influences cigarette sidestream smoke-induced ROS production. ► AhR reduces oxidative stress by coordinate regulation of

Baicalein Induces Apoptosis and Autophagy via Endoplasmic Reticulum Stress in Hepatocellular Carcinoma Cells

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Zhongxia Wang

2014-01-01

Full Text Available Background. Hepatocellular carcinoma (HCC remains a disastrous disease and the treatment for HCC is rather limited. Separation and identification of active compounds from traditionally used herbs in HCC treatment may shed light on novel therapeutic drugs for HCC. Methods. Cell viability and colony forming assay were conducted to determine anti-HCC activity. Morphology of cells and activity of caspases were analyzed. Antiapoptotic Bcl-2 family proteins and JNK were also examined. Levels of unfolded protein response (UPR markers were determined and intracellular calcium was assayed. Small interfering RNAs (siRNAs were used to investigate the role of UPR and autophagy in baicalein-induced cell death. Results. Among four studied flavonoids, only baicalein exhibited satisfactory inhibition of viability and colony formation of HCC cells within water-soluble concentration. Baicalein induced apoptosis via endoplasmic reticulum (ER stress, possibly by downregulating prosurvival Bcl-2 family, increasing intracellular calcium, and activating JNK. CHOP was the executor of cell death during baicalein-induced ER stress while eIF2α and IRE1α played protective roles. Protective autophagy was also triggered by baicalein in HCC cells. Conclusion. Baicalein exhibits prominent anti-HCC activity. This flavonoid induces apoptosis and protective autophagy via ER stress. Combination of baicalein and autophagy inhibitors may represent a promising therapy against HCC.

Maternal chewing during prenatal stress ameliorates stress-induced hypomyelination, synaptic alterations, and learning impairment in mouse offspring.

Science.gov (United States)

Suzuki, Ayumi; Iinuma, Mitsuo; Hayashi, Sakurako; Sato, Yuichi; Azuma, Kagaku; Kubo, Kin-Ya

2016-11-15

Maternal chewing during prenatal stress attenuates both the development of stress-induced learning deficits and decreased cell proliferation in mouse hippocampal dentate gyrus. Hippocampal myelination affects spatial memory and the synaptic structure is a key mediator of neuronal communication. We investigated whether maternal chewing during prenatal stress ameliorates stress-induced alterations of hippocampal myelin and synapses, and impaired development of spatial memory in adult offspring. Pregnant mice were divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube, and was initiated on day 12 of pregnancy and continued until delivery. Mice in the stress/chewing group were given a wooden stick to chew during restraint. In 1-month-old pups, spatial memory was assessed in the Morris water maze, and hippocampal oligodendrocytes and synapses in CA1 were assayed by immunohistochemistry and electron microscopy. Prenatal stress led to impaired learning ability, and decreased immunoreactivity of myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampal CA1 in adult offspring. Numerous myelin sheath abnormalities were observed. The G-ratio [axonal diameter to axonal fiber diameter (axon plus myelin sheath)] was increased and postsynaptic density length was decreased in the hippocampal CA1 region. Maternal chewing during stress attenuated the prenatal stress-induced impairment of spatial memory, and the decreased MBP and CNPase immunoreactivity, increased G-ratios, and decreased postsynaptic-density length in the hippocampal CA1 region. These findings suggest that chewing during prenatal stress in dams could be an effective coping strategy to prevent hippocampal behavioral and morphologic impairments in their offspring. Copyright © 2016 Elsevier B.V. All rights reserved.

Oxidative Stress in Fish induced by Environmental Pollutants

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Anton Kováčik

2017-05-01

Full Text Available Environmental pollutants represent a risk factor for human and animals in all areas of occurrence. Environmental pollution caused by anthropogenic activities is a major problem in many countries. Numbers of studies deals with cumulation of xenobiotics in tissues but not all respond to the real impact on living organisms. Freshwater fishes are exposed to several anthropogenic contaminants. The most commonly studied are three metals: mercury (Hg, lead (Pb, cadmium (Cd. These contaminants could have several impacts to oxidative stress. In the normal healthy cell, ROS and pro-oxidant products are detoxified by antioxidant defences. Redox-active or Redox-inactive metals may cause an increase in production of reactive oxygen species (ROS. Mercury has a high affinity for thiol groups, and can non-specifically affect several enzymes, e. g. GSH (glutathione, which can induce GSH depletion and oxidative stress in tissue, also can induce lipid peroxidation, and mitochondrial dysfunction. The toxicity of Cd to aquatic species depends on speciation, with the free ion, Cd2+ concentration being proportional to bioavailability. Cadmium toxicity worsened of Ca, Na, and Mg ions homeostasis. Lead can be toxic to nervous and skeletal systems; at cellular level can cause apoptosis, also can affect mitochondria, neurotransmitters, and can substitute for Ca.

Navigator-gated 3D blood oxygen level-dependent CMR at 3.0-T for detection of stress-induced myocardial ischemic reactions.

Science.gov (United States)

Jahnke, Cosima; Gebker, Rolf; Manka, Robert; Schnackenburg, Bernhard; Fleck, Eckart; Paetsch, Ingo

2010-04-01

This study determined the value of navigator-gated 3-dimensional blood oxygen level-dependent (BOLD) cardiac magnetic resonance (CMR) at 3.0-T for the detection of stress-induced myocardial ischemic reactions. Although BOLD CMR has been introduced for characterization of myocardial oxygenation status, previously reported CMR approaches suffered from a low signal-to-noise ratio and motion-related artifacts with impaired image quality and a limited diagnostic value in initial patient studies. Fifty patients with suspected or known coronary artery disease underwent CMR at 3.0-T followed by invasive X-ray angiography within 48 h. Three-dimensional BOLD images were acquired during free breathing with full coverage of the left ventricle in a short-axis orientation. The BOLD imaging was performed at rest and under adenosine stress, followed by stress and rest first-pass perfusion and delayed enhancement imaging. Quantitative coronary X-ray angiography (QCA) was used for coronary stenosis definition (diameter reduction > or =50%). The BOLD and first-pass perfusion images were semiquantitatively evaluated (for BOLD imaging, signal intensity differences between stress and rest [DeltaSI]; for perfusion imaging, myocardial perfusion reserve index [MPRI]). The image quality of BOLD CMR at rest and during adenosine stress was considered good to excellent in 90% and 84% of the patients, respectively. The DeltaSI measurements differed significantly between normal myocardium, myocardium supplied by a stenotic coronary artery, and infarcted myocardium (p exogenous contrast-enhancement studies. Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Cholinergic Modulation of Restraint Stress Induced Neurobehavioral ...

African Journals Online (AJOL)

The involvement of the cholinergic system in restraint stress induced neurobehavioral alterations was investigated in rodents using the hole board, elevated plus maze, the open field and the light and dark box tests. Restraint stress (3h) reduced significantly (p<0.05) the number of entries and time spent in the open arm, ...

Induced thermal stress on serotonin levels in the blue swimmer crab, Portunus pelagicus

OpenAIRE

Rajendiran, Saravanan; Muhammad Iqbal, Beema Mahin; Vasudevan, Sugumar

2016-01-01

The temperature of habitat water has a drastic influence on the behavioral, physiological and biochemical mechanisms of crustaceans. Hyperglycemia is a typical response of many aquatic animals to harmful physical and chemical environmental changes. In crustaceans increased circulating crustacean hyperglycemic hormone (CHH) and hyperglycemia are reported to occur following exposure to several environmental stress. The biogenic amine, serotonin has been found to modulate the CHH levels and oxid...

Influence of Alpha Tocopherol on Heat Stress-Induced Changes in the Reproductive Function of Swiss Albino Mice

International Nuclear Information System (INIS)

AlEnazi, Maher M.

2007-01-01

The present study was carried out to investigate the influence of vitamin E (alpha-tocopherol) on heat stress-induced changes in the reproduction of Swiss albino mice. The evaluated parameters include: the estrous cycle, fertility, post-implantation losses of fetuses and estimation of progesterone levels in the serum. Eight groups of experimental mice (10 each) were used. Groups 1-4 (24 degree C) consisted of a control and alpha-tocopherol (100, 200 and 400 mg/kg) treated groups. Groups 5-8 (42 degree C) consisted of a positive control and alpha-tocopherol (100, 200 and 400 mg/kg) treated group. Heat-stress reduced significantly (p > 0.001) the number of fetuses and corpora lutea. There was also a significant decrease in the mean weights of fetuses (p > 0.001) and placenta (p > 0.01) in the heat-stress group with a decrease in their serum progesterone levels (p > 0.01). Heat-stress groups treated with high doses of alpha-tocopherol 200 and 400 mg/kg, showed protection against heat-stress related abnormalities. The results showed that alpha-tocopherol plays a role in protection against hyperthermia induced changes in the estrous cycle length, infertility, post-implantation losses and depletion in the serum level of progesterone. (author)

Water stress induces overexpression of superoxide dismutases that ...

African Journals Online (AJOL)

SERVER

2007-09-05

Sep 5, 2007 ... Water stress is known to induce active oxygen species in plants. ... photosystem II photochemistry and whole plant growth against oxidative stress in these plants. ..... CO2. Plant Physiol. 110: 393-402. Sen Gupta A, Heinen JL, ...

Model for Stress-induced Protein Degradation in Lemna minor1

Science.gov (United States)

Cooke, Robert J.; Roberts, Keith; Davies, David D.

1980-01-01

Transfer of Lemna minor fronds to adverse or stress conditions produces a large increase in the rate of protein degradation. Cycloheximide partially inhibits stress-induced protein degradation and also partially inhibits the protein degradation which occurs in the absence of stress. The increased protein degradation does not appear to be due to an increase in activity of soluble proteolytic enzymes. Biochemical evidence indicates that stress, perhaps acting via hormones, affects the permeability of certain membranes, particularly the tonoplast. A general model for stress-induced protein degradation is presented in which changes in membrane properties allow vacuolar proteolytic enzymes increased access to cytoplasmic proteins. PMID:16661588

Correlation of oxidative stress in patients with HBV-induced liver disease with HBV genotypes and drug resistance mutations.

Science.gov (United States)

Xianyu, Jianbo; Feng, Jiafu; Yang, Yuwei; Tang, Jie; Xie, Gang; Fan, Lingying

2018-05-01

This study aims to explore the correlation of oxidative stress (OxS) in patients with chronic hepatitis B (CHB) and the disease severity with HBV genotypes and drug resistance mutations. A total of 296 patients with CHB were enrolled into the study. PCR-reverse dot-blot hybridization was used to detect the HBV genotypes (B, C, and D) and the drug resistance-causing HBV mutant genes. In addition, the total oxidative stress (TOS) and total antioxidant status (TAS) were determined, and oxidative stress index (OSI) was calculated and compared. Serum levels of TOS and OSI, the B/C ratio, and drug resistance mutation rate were increased along with the elevated disease severity degree (CHBHBV mutation had higher serum TOS and OSI levels, while lower serum TAS levels (P HBV-induced liver disease, and the damage degree is correlated with the HBV genotype and drug resistance mutation. Oxidative stress might be a useful indicator of the progression of HBV-induced liver disease in patients. Copyright © 2018. Published by Elsevier Inc.

Nitrogen Metabolism in Adaptation of Photosynthesis to Water Stress in Rice Grown under Different Nitrogen Levels

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Chu Zhong

2017-06-01

Full Text Available To investigate the role of nitrogen (N metabolism in the adaptation of photosynthesis to water stress in rice, a hydroponic experiment supplying with low N (0.72 mM, moderate N (2.86 mM, and high N (7.15 mM followed by 150 g⋅L-1 PEG-6000 induced water stress was conducted in a rainout shelter. Water stress induced stomatal limitation to photosynthesis at low N, but no significant effect was observed at moderate and high N. Non-photochemical quenching was higher at moderate and high N. In contrast, relative excessive energy at PSII level (EXC was declined with increasing N level. Malondialdehyde and hydrogen peroxide (H2O2 contents were in parallel with EXC. Water stress decreased catalase and ascorbate peroxidase activities at low N, resulting in increased H2O2 content and severer membrane lipid peroxidation; whereas the activities of antioxidative enzymes were increased at high N. In accordance with photosynthetic rate and antioxidative enzymes, water stress decreased the activities of key enzymes involving in N metabolism such as glutamate synthase and glutamate dehydrogenase, and photorespiratory key enzyme glycolate oxidase at low N. Concurrently, water stress increased nitrate content significantly at low N, but decreased nitrate content at moderate and high N. Contrary to nitrate, water stress increased proline content at moderate and high N. Our results suggest that N metabolism appears to be associated with the tolerance of photosynthesis to water stress in rice via affecting CO2 diffusion, antioxidant capacity, and osmotic adjustment.

Psychosocial Stress-Induced Analgesia: An Examination of Effects on Heat Pain Threshold and Tolerance and of Neuroendocrine Mediation.

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Gaab, Jens; Jiménez, Julia; Voneschen, Livia; Oschwald, Daniel; Meyer, Andrea H; Nater, Urs M; Krummenacher, Peter

2016-01-01

Stress-induced analgesia (SIA) is an adaptive response of reduced nociception following demanding acute internal and external stressors. Although a psychobiological understanding of this phenomenon is of importance for stress-related psychiatric and pain conditions, comparably little is known about the psychobiological mechanisms of SIA in humans. The aim of this study was to investigate the effects of acute psychosocial stress on heat pain perception and its possible neuroendocrine mediation by salivary cortisol levels and α-amylase activity in healthy men. Employing an intra-individual assessment of heat pain parameters, acute psychosocial stress did not influence heat pain threshold but significantly, albeit slightly, increased heat pain tolerance. Using linear mixed-model analysis, this effect of psychosocial stress on heat pain tolerance was not mediated by increases of salivary cortisol and state anxiety levels or by the activity of α-amylase. These results show that while psychosocial stress is selectively analgesic for heat pain tolerance, this observed effect is not mediated by stress-induced increases of salivary cortisol and α-amylase activity, as proxies of both the hypothalamus-pituitary-adrenal axis and the autonomic nervous system activation. © 2017 S. Karger AG, Basel.

Melatonin resists oxidative stress-induced apoptosis in nucleus pulposus cells.

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He, Ruijun; Cui, Min; Lin, Hui; Zhao, Lei; Wang, Jiayu; Chen, Songfeng; Shao, Zengwu

2018-04-15

Intervertebral disc degeneration (IVDD) is thought to be the major cause of low back pain (LBP), which is still in lack of effective etiological treatment. Oxidative stress has been demonstrated to participate in the impairment of nucleus pulposus cells (NPCs). As the most important neuroendocrine hormone in biological clock regulation, melatonin (MLT) is also featured by good antioxidant effect. In this study, we investigated the effect and mechanisms of melatonin on oxidative stress-induced damage in rat NPCs. Cytotoxicity of H 2 O 2 and protecting effect of melatonin were analyzed with Cell Counting kit-8 (CCK-8). Cell apoptosis rate was detected by Annexin V-FITC/PI staining. DCFH-DA probe was used for the reactive oxygen species (ROS) detection. The mitochondrial membrane potential (MMP) changes were analyzed with JC-1 probe. Intracellular oxidation product and reductants were measured through enzymatic reactions. Extracellular matrix (ECM) and apoptosis associated proteins were analyzed with Western blot assays. Melatonin preserved cell viability of NPCs under oxidative stress. The apoptosis rate, ROS level and malonaldehyde (MDA) declined with melatonin. MLT/H 2 O 2 group showed higher activities of GSH and SOD. The fall of MMP receded and the expression of ECM protein increased with treatment of melatonin. The mitochondrial pathway of apoptosis was inhibited by melatonin. Melatonin alleviated the oxidative stress-induced apoptosis of NPCs. Melatonin could be a promising alternative in treatment of IVDD. Copyright © 2018 Elsevier Inc. All rights reserved.

ROS-mediated abiotic stress-induced programmed cell death in plants

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Veselin ePetrov

2015-02-01

Full Text Available During the course of their ontogenesis, plants are continuously exposed to a large variety of abiotic stress factors which can damage tissues and jeopardize the survival of the organism unless properly countered. While animals can simply escape and thus evade stressors, plants as sessile organisms have developed complex strategies to withstand them. When the intensity of a detrimental factor is high, one of the defense programs employed by plants is the induction of programmed cell death (PCD. This is an active, genetically controlled process which is initiated to isolate and remove damaged tissues thereby ensuring the survival of the organism. The mechanism of PCD induction usually includes an increase in the levels of reactive oxygen species (ROS which are utilized as mediators of the stress signal. Abiotic stress-induced PCD is not only a process of fundamental biological importance, but also of considerable interest to agricultural practice as it has the potential to significantly influence crop yield. Therefore, numerous scientific enterprises have focused on elucidating the mechanisms leading to and controlling PCD in response to adverse conditions in plants. This knowledge may help to develop novel strategies to obtain more resilient crop varieties with improved tolerance and enhanced productivity. The aim of the present review is to summarize the recent advances in research on ROS-induced PCD related to abiotic stress and the role of the organelles in the process.

Catalase therapy corrects oxidative stress-induced pathophysiology in incipient diabetic retinopathy.

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Giordano, Courtney R; Roberts, Robin; Krentz, Kendra A; Bissig, David; Talreja, Deepa; Kumar, Ashok; Terlecky, Stanley R; Berkowitz, Bruce A

2015-05-01

Preclinical studies have highlighted retinal oxidative stress in the pathogenesis of diabetic retinopathy. We evaluated whether a treatment designed to enhance cellular catalase reduces oxidative stress in retinal cells cultured in high glucose and in diabetic mice corrects an imaging biomarker responsive to antioxidant therapy (manganese-enhanced magnetic resonance imaging [MEMRI]). Human retinal Müller and pigment epithelial cells were chronically exposed to normal or high glucose levels and treated with a cell-penetrating derivative of the peroxisomal enzyme catalase (called CAT-SKL). Hydrogen peroxide (H2O2) levels were measured using a quantitative fluorescence-based assay. For in vivo studies, streptozotocin (STZ)-induced diabetic C57Bl/6 mice were treated subcutaneously once a week for 3 to 4 months with CAT-SKL; untreated age-matched nondiabetic controls and untreated diabetic mice also were studied. MEMRI was used to analytically assess the efficacy of CAT-SKL treatment on diabetes-evoked oxidative stress-related pathophysiology in vivo. Similar analyses were performed with difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase. After catalase transduction, high glucose-induced peroxide production was significantly lowered in both human retinal cell lines. In diabetic mice in vivo, subnormal intraretinal uptake of manganese was significantly improved by catalase supplementation. In addition, in the peroxisome-rich liver of treated mice catalase enzyme activity increased and oxidative damage (as measured by lipid peroxidation) declined. On the other hand, DFMO was largely without effect in these in vitro or in vivo assays. This proof-of-concept study raises the possibility that augmentation of catalase is a therapy for treating the retinal oxidative stress associated with diabetic retinopathy.

Effects of Gladiolus dalenii on the Stress-Induced Behavioral, Neurochemical, and Reproductive Changes in Rats

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David Fotsing

2017-09-01

Full Text Available Gladiolus dalenii is a plant commonly used in many regions of Cameroon as a cure for various diseases like headaches, epilepsy, schizophrenia, and mood disorders. Recent studies have revealed that the aqueous extract of G. dalenii (AEGD exhibited antidepressant-like properties in rats. Therefore, we hypothesized that the AEGD could protect from the stress-induced behavioral, neurochemical, and reproductive changes in rats. The objective of the present study was to elucidate the effect of the AEGD on behavioral, neurochemical, and reproductive characteristics, using female rats subjected to chronic immobilization stress. The chronic immobilization stress (3 h per day for 28 days was applied to induce female reproductive and behavioral impairments in rats. The immobilization stress was provoked in rats by putting them separately inside cylindrical restrainers with ventilated doors at ambient temperature. The plant extract was given to rats orally everyday during 28 days, 5 min before induction of stress. On a daily basis, a vaginal smear was made to assess the duration of the different phases of the estrous cycle and at the end of the 28 days of chronic immobilization stress, the rat’s behavior was assessed in the elevated plus maze. They were sacrificed by cervical disruption. The organs were weighed, the ovary histology done, and the biochemical parameters assessed. The findings of this research revealed that G. dalenii increased the entries and the time of open arm exploration in the elevated plus maze. Evaluation of the biochemical parameters levels indicated that there was a significant reduction in the corticosterone, progesterone, and prolactin levels in the G. dalenii aqueous extract treated rats compared to stressed rats whereas the levels of serotonin, triglycerides, adrenaline, cholesterol, glucose estradiol, follicle stimulating hormone and luteinizing hormone were significantly increased in the stressed rats treated with, G. dalenii

3-Keto-1,5-bisphosphonates Alleviate Serum-Oxidative Stress in the High-fat Diet Induced Obesity in Rats.

Science.gov (United States)

Lahbib, Karima; Aouani, Iyadh; Cavalier, Jean-François; Touil, Soufiane

2015-09-01

Obesity has become a leading global health problem owing to its strong association with a high incidence of oxidative stress. Many epidemiologic studies showed that an antioxidant supplementation decreases the state of oxidative stress. In the present work, a HFD-induced rat obesity and oxidative stress were used to investigate the link between fat deposition and serum-oxidative stress markers. We also studied the effect of a chronic administration of 3-keto-1,5-bisphosphonates 1 (a & b) (40 μg/kg/8 weeks/i.p.). Exposure of rats to HFD during 16 weeks induced fat deposition, weight gain and metabolic disruption characterized by an increase in cholesterol, triglyceride and glycemia levels, and a decrease in ionizable calcium and free iron concentrations. HFD also induced serum-oxidative stress status vocalized by an increase in ROS (H2 O2 ), MDA and PC levels, with a decrease in antioxidant enzyme activity (CAT, GPx, SOD). Importantly, 3-keto-1,5-bisphosphonates corrected all the deleterious effects of HFD treatment in vivo, but it failed to inhibit lipases in vitro and in vivo. These studies suggest that 3-keto-1,5-bisphosphonates 1 could be considered as safe antioxidant agents that should also find other potential biological applications. © 2014 John Wiley & Sons A/S.

Sweet food improves chronic stress-induced irritable bowel syndrome-like symptoms in rats.

Science.gov (United States)

Rho, Sang-Gyun; Kim, Yong Sung; Choi, Suck Chei; Lee, Moon Young

2014-03-07

To investigate whether palatable sweet foods have a beneficial effect on chronic stress-induced colonic motility and inflammatory cytokines. Adult male rats were divided into 3 groups: control (CON, n = 5), chronic variable stress with chow (CVS-A, n = 6), and chronic variable stress with chow and sweet food (CVS-B, n = 6). The rats were fed standard rodent chow as the chow food and/or AIN-76A as the sweet food. A food preference test for AIN-76A was performed in another group of normal rats (n = 10) for twelve days. Fecal pellet output (FPO) was measured for 6 wk during water bedding stress in the CVS groups. The weight of the adrenal glands, adrenocorticotropic hormone (ACTH) and corticosterone levels in plasma were measured. The expression levels of transforming growth factor-β, interleukin (IL)-2, and interferon-gamma (IFN-γ) were measured in the distal part of colonic tissues and plasma using Western blot analysis. In sweet preference test, all rats initially preferred sweet food to chow food. However, the consumption rate of sweet food gradually decreased and reduced to below 50% of total intake eight days after sweet food feeding. Accumulated FPO was higher in the CVS-A group compared with the CVS-B group over time. All stress groups showed significant increases in the adrenal to body weight ratio (CVS-A, 0.14 ± 0.01; CVS-B, 0.14 ± 0.01) compared with the control group (0.12 ± 0.01, P food ingestion during CVS might have an effect on the reduction of stress-induced colonic hyper-motility and pro-inflammatory cytokine production in rats.

Beneficial Effect of Jojoba Seed Extracts on Hyperglycemia-Induced Oxidative Stress in RINm5f Beta Cells.

Science.gov (United States)

Belhadj, Sahla; Hentati, Olfa; Hamdaoui, Ghaith; Fakhreddine, Khaskhoussi; Maillard, Elisa; Dal, Stéphanie; Sigrist, Séverine

2018-03-20

Hyperglycemia occurs during diabetes and insulin resistance. It causes oxidative stress by increasing reactive oxygen species (ROS) levels, leading to cellular damage. Polyphenols play a central role in defense against oxidative stress. In our study, we investigated the antioxidant properties of simmondsin, a pure molecule present in jojoba seeds, and of the aqueous extract of jojoba seeds on fructose-induced oxidative stress in RINm5f beta cells. The exposure of RINm5f beta cells to fructose triggered the loss of cell viability (-48%, p jojoba seed extract makes jojoba a powerful agent to prevent the destruction of RINm5f beta cells induced by hyperglycemia.

Carnitine congener mildronate protects against stress- and haloperidol-induced impairment in memory and brain protein expression in rats.

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Beitnere, Ulrika; Dzirkale, Zane; Isajevs, Sergejs; Rumaks, Juris; Svirskis, Simons; Klusa, Vija

2014-12-15

The present study investigates the efficacy of mildronate, a carnitine congener, to protect stress and haloperidol-induced impairment of memory in rats and the expression of brain protein biomarkers involved in synaptic plasticity, such as brain-derived neurotrophic factor (BDNF), acetylcholine esterase and glutamate decarboxylase 67 (GAD67). Two amnesia models were used: 2h immobilization stress and 3-week haloperidol treatment. Stress caused memory impairment in the passive avoidance test and induced a significant 2-fold BDNF elevation in hippocampal and striatal tissues that was completely inhibited by mildronate. Mildronate decreased the level of GAD67 (but not acetylcholine esterase) expression by stress. Haloperidol decrease by a third hippocampal BDNF and acetylcholine esterase (but not GAD67) expression, which was normalized by mildronate; it also reversed the haloperidol-induced memory impairment in Barnes test. The results suggest the usefulness of mildronate as protector against neuronal disturbances caused by stress or haloperidol. Copyright © 2014 Elsevier B.V. All rights reserved.

Calcium channel blocker prevents stress-induced activation of renin and aldosterone in conscious pig

International Nuclear Information System (INIS)

Ceremuzynski, L.K.; Klos, J.; Barcikowski, B.; Herbaczynska-Cedro, K.

1991-01-01

A considerable amount of data suggest the involvement of calcium-mediated processes in the activation of the renin-angiotensin-aldosterone (RAA) cascade. To investigate the effect of calcium-channel inhibition on the RAA system, the authors studied 21 conscious pigs. Blood renin and aldosterone levels increased by subjecting animals to 24 hours of immobilization stress. Renin and aldosterone levels were repeatedly measured by radioimmunoassay in blood samples taken periodically over 24 hours from a chronically implanted arterial cannula. Pretreatment of the animals (N = 11) with nisoldipine, 2 x 20 mg p.o. daily for 2 days before and on the day of immobilization, transiently attenuated the stress-induced increase of plasma renin activity and completely prevented the rise of aldosterone, as compared to nontreated controls (N = 10). The finding that nisoldipine suppresses RAA activation induced by a nonpharmacologic stimulus in the conscious intact animal may have clinical implications

Silibinin attenuates sulfur mustard analog-induced skin injury by targeting multiple pathways connecting oxidative stress and inflammation.

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Neera Tewari-Singh

Full Text Available Chemical warfare agent sulfur mustard (HD inflicts delayed blistering and incapacitating skin injuries. To identify effective countermeasures against HD-induced skin injuries, efficacy studies were carried out employing HD analog 2-chloroethyl ethyl sulfide (CEES-induced injury biomarkers in skin cells and SKH-1 hairless mouse skin. The data demonstrate strong therapeutic efficacy of silibinin, a natural flavanone, in attenuating CEES-induced skin injury and oxidative stress. In skin cells, silibinin (10 µM treatment 30 min after 0.35/0.5 mM CEES exposure caused a significant (p90%, and activation of transcription factors NF-κB and AP-1 (complete reversal. Similarly, silibinin treatment was also effective in attenuating CEES-induced oxidative stress measured by 4-hydroxynonenal and 5,5-dimethyl-2-(8-octanoic acid-1-pyrolline N-oxide protein adduct formation, and 8-oxo-2-deoxyguanosine levels. Since our previous studies implicated oxidative stress, in part, in CEES-induced toxic responses, the reversal of CEES-induced oxidative stress and other toxic effects by silibinin in this study indicate its pleiotropic therapeutic efficacy. Together, these findings support further optimization of silibinin in HD skin toxicity model to develop a novel effective therapy for skin injuries by vesicants.

Continuous fever-range heat stress induces thermotolerance in odontoblast-lineage cells.

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Morotomi, Takahiko; Kitamura, Chiaki; Okinaga, Toshinori; Nishihara, Tatsuji; Sakagami, Ryuji; Anan, Hisashi

2014-07-01

Heat shock during restorative procedures can trigger damage to the pulpodentin complex. While severe heat shock has toxic effects, fever-range heat stress exerts beneficial effects on several cells and tissues. In this study, we examined whether continuous fever-range heat stress (CFHS) has beneficial effects on thermotolerance in the rat clonal dental pulp cell line with odontoblastic properties, KN-3. KN-3 cells were cultured at 41°C for various periods, and the expression level of several proteins was assessed by Western blot analysis. After pre-heat-treatment at 41°C for various periods, KN-3 cells were exposed to lethal severe heat shock (LSHS) at 49°C for 10min, and cell viability was examined using the MTS assay. Additionally, the expression level of odontoblast differentiation makers in surviving cells was examined by Western blot analysis. CFHS increased the expression levels of several heat shock proteins (HSPs) in KN-3 cells, and induced transient cell cycle arrest. KN-3 cells, not pre-heated or exposed to CFHS for 1 or 3h, died after exposure to LSHS. In contrast, KN-3 cells exposed to CFHS for 12h were transiently lower on day 1, but increased on day 3 after LSHS. The surviving cells expressed odontoblast differentiation markers, dentine sialoprotein and dentine matrix protein-1. These results suggest that CFHS for 12h improves tolerance to LSHS by inducing HSPs expression and cell cycle arrest in KN-3 cells. The appropriate pretreatment with continuous fever-range heat stress can provide protection against lethal heat shock in KN-3 cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

JNK and NADPH Oxidase Involved in Fluoride-Induced Oxidative Stress in BV-2 Microglia Cells

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Ling Yan

2013-01-01

Full Text Available Excessive fluoride may cause central nervous system (CNS dysfunction, and oxidative stress is a recognized mode of action of fluoride toxicity. In CNS, activated microglial cells can release more reactive oxygen species (ROS, and NADPH oxidase (NOX is the major enzyme for the production of extracellular superoxide in microglia. ROS have been characterized as an important secondary messenger and modulator for various mammalian intracellular signaling pathways, including the MAPK pathways. In this study we examined ROS production and TNF-α, IL-1β inflammatory cytokines releasing, and the expression of MAPKs in BV-2 microglia cells treated with fluoride. We found that fluoride increased JNK phosphorylation level of BV-2 cells and pretreatment with JNK inhibitor SP600125 markedly reduced the levels of intracellular and NO. NOX inhibitor apocynin and iNOS inhibitor SMT dramatically decreased NaF-induced ROS and NO generations, respectively. Antioxidant melatonin (MEL resulted in a reduction in JNK phosphorylation in fluoride-stimulated BV-2 microglia. The results confirmed that NOX and iNOS played an important role in fluoride inducing oxidative stress and NO production and JNK took part in the oxidative stress induced by fluoride and meanwhile also could be activated by ROS in fluoride-treated BV-2 cells.

JNK and NADPH Oxidase Involved in Fluoride-Induced Oxidative Stress in BV-2 Microglia Cells

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Yan, Ling; Liu, Shengnan; Wang, Chen; Wang, Fei; Song, Yingli; Yan, Nan; Xi, Shuhua; Liu, Ziyou; Sun, Guifan

2013-01-01

Excessive fluoride may cause central nervous system (CNS) dysfunction, and oxidative stress is a recognized mode of action of fluoride toxicity. In CNS, activated microglial cells can release more reactive oxygen species (ROS), and NADPH oxidase (NOX) is the major enzyme for the production of extracellular superoxide in microglia. ROS have been characterized as an important secondary messenger and modulator for various mammalian intracellular signaling pathways, including the MAPK pathways. In this study we examined ROS production and TNF-α, IL-1β inflammatory cytokines releasing, and the expression of MAPKs in BV-2 microglia cells treated with fluoride. We found that fluoride increased JNK phosphorylation level of BV-2 cells and pretreatment with JNK inhibitor SP600125 markedly reduced the levels of intracellular O2 ·− and NO. NOX inhibitor apocynin and iNOS inhibitor SMT dramatically decreased NaF-induced ROS and NO generations, respectively. Antioxidant melatonin (MEL) resulted in a reduction in JNK phosphorylation in fluoride-stimulated BV-2 microglia. The results confirmed that NOX and iNOS played an important role in fluoride inducing oxidative stress and NO production and JNK took part in the oxidative stress induced by fluoride and meanwhile also could be activated by ROS in fluoride-treated BV-2 cells. PMID:24072958

Drinking behaviors by stress level in Korean university students.

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Chung, Hye-Kyung; Lee, Hae-Young

2012-04-01

The purposes of this study are to estimate the stress level of university students, and to verify the relationships between stress level and drinking behavior. A questionnaire survey was administered to 430 university students in the Gangwon area in Korea from November 5 to November 28, 2008, and data from 391 students were used for the final statistical analysis. The most stressful factor was "Worry about academic achievements" (2.86 by Likert-type 4 point scale). The subjects were divided into two groups, a low stress group (≤ 65.0) and a high stress group (≥ 66.0), by the mean value (65.1) and median value (66.0) of the stress levels. The drinking frequency was not different between the two stress groups, but the amount of alcohol consumption was significantly different (P stress group than in the higher stress group. In addition, factor 6, "Lack of learning ability", was negatively correlated with drinking frequency and the amount of alcohol consumption (P academic achievements", was negatively correlated with the amount of drinking (P stress group showed significantly higher scores on several items in the categories of motives (P stress group. Our results imply that university students at the lower stress level may drink more from social motives in positive drinking environments, while those at the higher stress level may have more problematic-drinking despite their smaller amount of alcohol consumption.

An experimental study on effect of antioxidant vitamin E in stress and alcohol induced changes in male fertility in albino rats.

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Sanghishetti Vijay Prasad, Nayak BB, Ghongane BB, Raul AR, Vijay Kumar AN, Mutalik MM, Kapure NL.

2012-09-01

Full Text Available Introduction: Physical and Psychological stresses are believed to reduce sexual functions, resulting fromneurotransmission changes in various erectile response pathways and reduced blood flow in genital organs.Intake of alcohol depends on numerous genetic and environmental factors. Stress has long been thought to influence the alcohol drinking in humans. Forced swimming in laboratory animals has been widely used as a model of stress to study the physiological changes and the capacity of the organism in response to stress. Aim: 1. To assess the effect of forced swimming stress on seminal fluid profile, Serum testosterone level, Testicular lipid peroxidation levels. 2. To assess the effect of Vitamin E on stress induced changes. Method: Adult male albino rats weighing 200 – 220 g, aged 12-15 weeks were used in this study. The animals were randomly divided into four groups of 6 animals each. Group1 (control received distilled water, Group 2 (Forced Swimming Stress received distilled water Group 3: subjected to Forced Swimming stress with 20% alcohol intake p.o. Group 4: Swimming stress with 20% alcohol treated with Vitamin E(200mg/kg/day orally. The following parameters were studied in all groups 1. Body weight. 2. Sperm count Motility and Life /death Ratio (SLDR. 3. Serum Testosterone 4. Testicular Malondialdehyde level (MDA. Results: Forced swimming stress caused loss in body wt, reduction in sperm count, motility and SLDR in sperm analysis, reduction in serum testosterone and increase testicular MDA levels compared to control. All the changes were statistically significant. When alcohol was added along with forced swimming it caused further loss in body wt, sperm count, motility and SLDR, serum testosterone level and slightly further increase in MDA levels. These observations were also statistically significant. In case of group IV in which Vitamin E was administered long with stress with alcohol it showed a trend of reversal phenomenon of

Psychological Stress, Cocaine and Natural Reward Each Induce Endoplasmic Reticulum Stress Genes in Rat Brain

OpenAIRE

Pavlovsky, Ashly A.; Boehning, Darren; Li, Dingge; Zhang, Yafang; Fan, Xiuzhen; Green, Thomas A.

2013-01-01

Our prior research has shown that the transcription of endoplasmic reticulum (ER) stress transcription factors Activating Transcription Factor 3 (ATF3) and ATF4 are induced by amphetamine and restraint stress in rat striatum. However, presently it is unknown the full extent of ER stress responses to psychological stress or cocaine, and which of the three ER stress pathways is activated. The current study examines transcriptional responses of key ER stress target genes subsequent to psychologi...

Agmatine abolishes restraint stress-induced depressive-like behavior and hippocampal antioxidant imbalance in mice.

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Freitas, Andiara E; Bettio, Luis E B; Neis, Vivian B; Santos, Danúbia B; Ribeiro, Camille M; Rosa, Priscila B; Farina, Marcelo; Rodrigues, Ana Lúcia S

2014-04-03

Agmatine has been recently emerged as a novel candidate to assist the conventional pharmacotherapy of depression. The acute restraint stress (ARS) is an unavoidable stress situation that may cause depressive-like behavior in rodents. In this study, we investigated the potential antidepressant-like effect of agmatine (10mg/kg, administered acutely by oral route) in the forced swimming test (FST) in non-stressed mice, as well as its ability to abolish the depressive-like behavior and hippocampal antioxidant imbalance induced by ARS. Agmatine reduced the immobility time in the mouse FST (1-100mg/kg) in non-stressed mice. ARS caused an increase in the immobility time in the FST, indicative of a depressive-like behavior, as well as hippocampal lipid peroxidation, and an increase in the activity of hippocampal superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities, reduced catalase (CAT) activity and increased SOD/CAT ratio, an index of pro-oxidative conditions. Agmatine was effective to abolish the depressive-like behavior induced by ARS and to prevent the ARS-induced lipid peroxidation and changes in SOD, GR and CAT activities and in SOD/CAT activity ratio. Hippocampal levels of reduced glutathione (GSH) were not altered by any experimental condition. In conclusion, the present study shows that agmatine was able to abrogate the ARS-induced depressive-like behavior and the associated redox hippocampal imbalance observed in stressed restraint mice, suggesting that its antidepressant-like effect may be dependent on its ability to maintain the pro-/anti-oxidative homeostasis in the hippocampus. Copyright © 2013 Elsevier Inc. All rights reserved.

ROLE OF TAURINE ON THE LEVEL OF SOME ESSENTIAL ELEMENTS AND OXIDATIVE STRESS IN DIFFERENT TISSUES OF RATS EXPOSED TO GAMMA RADIATION

International Nuclear Information System (INIS)

ANIS, L.M.

2008-01-01

Whole body exposure to ionizing radiation induces the formation of reactive oxygen species (ROS) in the different tissues provoking oxidative damage and organ dysfunction. The present study was designed to determine the possible protective effect of taurine against gamma radiation-induced disorders in iron (Fe), copper (Cu), zinc (Zn) and magnesium (Mg) in parallel to radiation-induced oxidative stress in liver, spleen and heart tissues. Irradiated rats were whole body exposed to 6.5 Gy gamma radiations. Taurine treated irradiated rats received 250 mg taurine/kg body weight/day for 10 successive days before irradiation. Animals were sacrificed on 1 st , 7 th and 14 th days after irradiation. The results obtained demonstrated significant increases in Fe, Cu, Zn and Mg levels in the liver. Significant increases of Fe and Cu and significant decrease of Zn and non-significant changes in Mg were observed in the spleen. Heart tissues showed significant decrease in the level of iron and non-significant changes in the levels of Cu, Zn and Mg. Alterations in the levels of essential elements were associated with oxidative stress. Significant decreases of SOD and CAT activities along with significant increase of TBARS levels were recorded in the different tissues after irradiation. Taurine administration pre-irradiation has significantly attenuated the radiation-induced oxidative stress and alteration in the levels of essential elements. It could be concluded that taurine might protect from oxidative damage induced by gamma irradiation

Protective effect of pineapple (Ananas cosmosus peel extract on alcohol-induced oxidative stress in brain tissues of male albino rats

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Ochuko L Erukainure

2011-03-01

Full Text Available Objective: To investigate the ability of pineapple peels to protect against alcohol-induced oxidative stress in brain tissues using male albino rat models. Methods: Response surface methodology (RSM was used to design a series of experiments to optimize treatment conditions with the aim of investigating the protective effect of pineapple peel extract on alcohol-induced oxidative stress in brain tissues. Oxidative stress was induced by oral administration of ethanol (20% w/v at a dosage of 5 mL/kg bw. The treatment lasted for 28 days. At the end of the treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Tissue homogenates were used for the assessment of protein concentration, reduced glutathione (GSH content, catalase, and SOD. Results: Alcohol administration caused a significant decrease (P>0.05 in GSH level in the group which was only fed alcohol. Treatment with pineapple peel extracts caused increase in GSH level in alcohol fed groups. No significant difference (P<0.05 was observed in SOD levels of the negative control and group fed on only pineapple peel extract. Elevated level of catalase was observed in the negative control but pineapple peel extract significantly reduced the levels. Conclusions: This study indicates the protective effect of pineapple peel against alcoholinduced oxidative stress in brain tissues.

Cross-country differences in basal and stress-induced cortisol secretion in older adults.

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