Upregulation Of Antioxidant Genes Research Articles

Nrf2 Pathway Ameliorates Bladder Dysfunction in Cyclophosphamide-Induced Cystitis via Suppression of Oxidative Stress.

Objective To investigate the protective effect and molecular mechanism of nuclear factor E2-related factor 2 (Nrf2) pathway in interstitial cystitis (IC). Methods We established a mouse model of IC by cyclophosphamide (CYP) in wild-type mice and Nrf2 gene knockout mice. We examined the histological and functional alterations, the changes of oxidative stress markers, and the expression of the antioxidant genes downstream of Nrf2 pathway. Results After CYP administration, the mice showed urinary frequency and urgency, pain sensitization, decreased contractility, bladder edema, and oxidative stress disorder. Notably, the Nrf2−/− CYP mice had more severe symptoms. The mRNA and protein levels of antioxidant genes downstream of Nrf2 pathway were significantly upregulated in the Nrf2+/+ CYP mice, while there were no significant changes in the Nrf2−/− CYP mice. Conclusion Nrf2 pathway protects bladder injury and ameliorates bladder dysfunction in IC, possibly by upregulating antioxidant genes and inhibiting oxidative stress.

Physiological and molecular responses to thermal stress in red cusk-eel (Genypterus chilensis) juveniles reveals atrophy and oxidative damage in skeletal muscle.

The red cusk-eel (Genypterus chilensis) is a native species with strong potential to support Chilean aquaculture diversification. Environmental stressors, such as temperature, may generate important effects in fish physiology with negative impact. However, no information exists on the effects of thermal stress in Genypterus species or how this stressor affects the skeletal muscle. The present study evaluated for the first time the effect of high temperature stress in red cusk-eel juveniles to determine changes in plasmatic markers of stress (cortisol, glucose and lactate dehydrogenase (LDH)), the transcriptional effect in skeletal muscle genes related to (i) heat shock protein response (hsp60 and hsp70), (ii) muscle atrophy and growth (foxo1, foxo3, fbxo32, murf-1, myod1 and ddit4), and (iii) oxidative stress (cat, sod1 and gpx1), and evaluate the DNA damage (AP sites) and peroxidative damage (lipid peroxidation (HNE proteins)) in this tissue. Thermal stress generates a significant increase in plasmatic levels of cortisol, glucose and LDH activity and induced heat shock protein transcripts in muscle. We also observed an upregulation of atrophy-related genes (foxo1, foxo3 and fbxo32) and a significant modulation of growth-related genes (myod1 and ddit4). Thermal stress induced oxidative stress in skeletal muscle, as represented by the upregulation of antioxidant genes (cat and sod1) and a significant increase in DNA damage and lipid peroxidation. The present study provides the first physiological and molecular information of the effects of thermal stress on skeletal muscle in a Genypterus species, which should be considered in a climate change scenario.

Roles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer.

Prostate cancer (PCa), known as a heterogenous disease, has a high incidence and mortality rate around the world and seriously threatens public health. As an inevitable by-product of cellular metabolism, reactive oxygen species (ROS) exhibit beneficial effects by regulating signaling cascades and homeostasis. More and more evidence highlights that PCa is closely associated with age, and high levels of ROS are driven through activation of several signaling pathways with age, which facilitate the initiation, development, and progression of PCa. Nevertheless, excessive amounts of ROS result in harmful effects, such as genotoxicity and cell death. On the other hand, PCa cells adaptively upregulate antioxidant genes to detoxify from ROS, suggesting that a subtle balance of intracellular ROS levels is required for cancer cell functions. The current review discusses the generation and biological roles of ROS in PCa and provides new strategies based on the regulation of ROS for the treatment of PCa.

Antioxidant Effects of PS5, a Peptidomimetic of Suppressor of Cytokine Signaling 1, in Experimental Atherosclerosis

The chronic activation of the Janus kinase/signal transducer and activator of the transcription (JAK/STAT) pathway is linked to oxidative stress, inflammation and cell proliferation. Suppressors of cytokine signaling (SOCS) proteins negatively regulate the JAK/STAT, and SOCS1 possesses a small kinase inhibitory region (KIR) involved in the inhibition of JAK kinases. Several studies showed that KIR-SOCS1 mimetics can be considered valuable therapeutics in several disorders (e.g., diabetes, neurological disorders and atherosclerosis). Herein, we investigated the antioxidant and atheroprotective effects of PS5, a peptidomimetic of KIR-SOCS1, both in vitro (vascular smooth muscle cells and macrophages) and in vivo (atherosclerosis mouse model) by analyzing gene expression, intracellular O2•− production and atheroma plaque progression and composition. PS5 was revealed to be able to attenuate NADPH oxidase (NOX1 and NOX4) and pro-inflammatory gene expression, to upregulate antioxidant genes and to reduce atheroma plaque size, lipid content and monocyte/macrophage accumulation. These findings confirm that KIR-SOCS1-based drugs could be excellent antioxidant agents to contrast atherosclerosis.

Mitochondrial superoxide contributes to oxidative stress exacerbated by DNA damage response in RAD51-depleted ovarian cancer cells

Ovarian cancer is the most lethal gynecological malignancy. Abnormal homologous recombination repair, high level of reactive oxygen species (ROS) and upregulation of antioxidant genes are characteristic features of ovarian cancer. However, the molecular mechanisms governing the redox homeostasis in ovarian cancer cells remain to be fully elucidated. We here demonstrated a critical role of RAD51, a protein essential for homologous recombination, in the maintenance of redox homeostasis. We found that RAD51 is overexpressed in high grade serous ovarian cancer and is associated with poor prognosis. Depletion or inhibition of RAD51 results in G2/M arrest, increased production of reactive oxygen species and accumulation of oxidative DNA damage. Importantly, antioxidant N-acetylcysteine (NAC) significantly attenuated the induction of DNA damage and the perturbation of proliferation caused by RAD51 depletion. We further demonstrated that RAD51 inhibition or depletion led to elevated production of mitochondrial superoxide and increased accumulation of mitochondria. Moreover, CHK1 activation is required for the G2/M arrest and the generation of mitochondrial stress in response to RAD51 depletion. Together, our results indicate that nuclear DNA damage caused by RAD51 depletion may trigger mitochondria-originated redox dysregulation. Our findings suggest that a vicious cycle of nuclear DNA damage, mitochondrial accumulation and oxidative stress may contribute to the tumor-suppressive effects of RAD51 depletion or inhibition.

Resveratrol Protects Against Hydroquinone-Induced Oxidative Threat in Retinal Pigment Epithelial Cells.

PurposeOxidative stress in retinal pigment epithelial (RPE) cells is associated with age-related macular degeneration (AMD). Resveratrol exerts a range of protective biologic effects, but its mechanism(s) are not well understood. The aim of this study was to investigate how resveratrol could affect biologic pathways in oxidatively stressed RPE cells.MethodsCultured human RPE cells were treated with hydroquinone (HQ) in the presence or absence of resveratrol. Cell viability was determined with WST-1 reagent and trypan blue exclusion. Mitochondrial function was measured with the XFe24 Extracellular Flux Analyzer. Expression of heme oxygenase-1 (HO-1) and glutamate cysteine ligase catalytic subunit was evaluated by qPCR. Endoplasmic reticulum stress protein expression was measured by Western blot. Potential reactions between HQ and resveratrol were investigated using high-performance liquid chromatography mass spectrometry with resveratrol and additional oxidants for comparison.ResultsRPE cells treated with the combination of resveratrol and HQ had significantly increased cell viability and improved mitochondrial function when compared with HQ-treated cells alone. Resveratrol in combination with HQ significantly upregulated HO-1 mRNA expression above that of HQ-treated cells alone. Resveratrol in combination with HQ upregulated C/EBP homologous protein and spliced X-box binding protein 1. Additionally, new compounds were formed from resveratrol and HQ coincubation.ConclusionsResveratrol can ameliorate HQ-induced toxicity in RPE cells through improved mitochondrial bioenergetics, upregulated antioxidant genes, stimulated unfolded protein response, and direct oxidant interaction. This study provides insight into pathways through which resveratrol can protect RPE cells from oxidative damage, a factor thought to contribute to AMD pathogenesis.

Hydropriming and Biopriming Improve Medicago truncatula Seed Germination and Upregulate DNA Repair and Antioxidant Genes.

Seed germination is a critical parameter for the successful development of sustainable agricultural practices. While seed germination is impaired by environmental constraints emerging from the climate change scenario, several types of simple procedures, known as priming, can be used to enhance it. Seed priming is defined as the process of regulating seed germination by managing a series of parameters during the initial stages of germination. Hydropriming is a highly accessible and economic technique that involves soaking of seeds in water followed by drying. Biopriming refers to the inoculation of seeds with beneficial microorganism. The present study aims to investigate whether hydropriming and biopriming could enhance seed germination. Thereby, the germination of Medicago truncatula seeds exposed to hydropriming and/or Bacillus spp. isolates was monitored for two-weeks. The seeds were sown in trays containing two types of in situ agricultural soils collected from Northern India (Karsara, Varanasi). This region is believed to be contaminated by solid waste from a nearby power plant. Phenotypic parameters had been monitored and compared to find the most appropriate combination of treatments. Additionally, qRT-PCR was used to evaluate the expression levels of specific genes used as molecular indicators of seed quality. The results show that, while hydropriming significantly enhanced seed germination percentage, biopriming resulted in improved seedling development, represented by increased biomass rather than seedling length. At a molecular level, this is reflected by the upregulation of genes involved in DNA damage repair and antioxidant defence. In conclusion, hydropriming and biopriming are efficient to improve seed germination and seedling establishment in soils collected from damaged sites of Northern India; this is reflected by morphological parameters and molecular hallmarks of seed quality.

Towards a better understanding of Pseudomonas putida biofilm formation in the presence of ZnO nanoparticles (NPs): Role of NP concentration

Elucidating the effects of nanoparticles (NPs) on key bacterial functions not only deepens our understanding of nano-toxicity mechanisms, but also guides us in the design criteria for manufacturing safe nanomaterials. In this study, bacterial growth, biofilm development and the expression of biofilm-related genes were monitored in Pseudomonas putida KT2440, a plant-beneficial bacterium, following exposure to ZnO NPs. Low concentrations of NPs (0.5–30 mg L−1) significantly promoted bacterial growth and biofilm formation, while higher concentrations (>30 mg L−1) significantly inhibited biofilm formation. Confocal laser scanning microscopy revealed that microscope slides coated with 0.5 mg L−1 of ZnO NPs showed enhanced bacterial colonization and biomass production, but at higher concentrations (250 mg L−1), biomass production was about 11 times lower than that of the substrate without NPs. Increased protein and sugar contents of the biofilm matrix corroborated the stimulating effects of low concentrations of ZnO NPs. Physiological data were supported by changes in the expression of genes associated with oxidative stress and biofilm development. ZnO NPs at 0.5 mg L−1 stimulated the expression of quorum sensing, lipopolysaccharide biosynthesis, and antibiotic resistance genes; high concentrations of ZnO NPs (250 mg L−1) down-regulated biofilm formation-related genes and up-regulated antioxidant genes. Our results indicate that long-term release of low concentrations of ZnO NPs to the environment would promote undesired biofilm formation and increased resistance to antibiotics.

Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional Pathways

Pulmonary hypertension (PH) is a serious disorder with high morbidity and mortality rate. We analyzed the right-ventricular systolic pressure (RVSP), right-ventricular hypertrophy (RVH), lung histology, and transcriptomes of six-week-old male rats with PH induced by (1) hypoxia (HO), (2) administration of monocrotaline (CM), or (3) administration of monocrotaline and exposure to hypoxia (HM). The results in PH rats were compared to those in control rats (CO). After four weeks exposure, increased RVSP and RVH, pulmonary arterial wall thickening, and alteration of the lung transcriptome were observed in all PH groups. The HM group exhibited the largest alterations, as well as neointimal lesions and obliteration of the lumen in small arteries. We found that PH increased the expression of caveolin1, matrix metallopeptidase 2, and numerous inflammatory and cell proliferation genes. The cell cycle, vascular smooth muscle contraction, and oxidative phosphorylation pathways, as well as their interplay, were largely perturbed. Our results also suggest that the upregulated Rhoa (Ras homolog family member A) mediates its action through expression coordination with several ATPases. The upregulation of antioxidant genes and the extensive mitochondrial damage observed, especially in the HM group, indicate metabolic shift toward aerobic glycolysis.

Differential expression of antioxidant system genes in honey bee (Apis mellifera L.) caste development mitigates ROS-mediated oxidative damage in queen larvae.

The expression of morphological differences between the castes of social bees is triggered by dietary regimes that differentially activate nutrient-sensing pathways and the endocrine system, resulting in differential gene expression during larval development. In the honey bee, Apis mellifera, mitochondrial activity in the larval fat body has been postulated as a link that integrates nutrient-sensing via hypoxia signaling. To understand regulatory mechanisms in this link, we measured reactive oxygen species (ROS) levels, oxidative damage to proteins, the cellular redox environment, and the expression of genes encoding antioxidant factors in the fat body of queen and worker larvae. Despite higher mean H2O2 levels in queens, there were no differences in ROS-mediated protein carboxylation levels between the two castes. This can be explained by their higher expression of antioxidant genes (MnSOD, CuZnSOD, catalase, and Gst1) and the lower ratio between reduced and oxidized glutathione (GSH/GSSG). In worker larvae, the GSG/GSSH ratio is elevated and antioxidant gene expression is delayed. Hence, the higher ROS production resulting from the higher respiratory metabolism in queen larvae is effectively counterbalanced by the up-regulation of antioxidant genes, avoiding oxidative damage. In contrast, the delay in antioxidant gene expression in worker larvae may explain their endogenous hypoxia response.

Transcriptional, metabolic and DNA methylation changes underpinning the response of Arundo donax ecotypes to NaCl excess.

Arundo donax ecotypes react differently to salinity, partly due to differences in constitutive defences and methylome plasticity. Arundo donax L. is a C3 fast-growing grass that yields high biomass under stress. To elucidate its ability to produce biomass under high salinity, we investigated short/long-term NaCl responses of three ecotypes through transcriptional, metabolic and DNA methylation profiling of leaves and roots. Prolonged salt treatment discriminated the sensitive ecotype 'Cercola' from the tolerant 'Domitiana' and 'Canneto' in terms of biomass. Transcriptional and metabolic responses to NaCl differed between the ecotypes. In roots, constitutive expression of ion transporter and stress-related transcription factors' genes was higher in 'Canneto' and 'Domitiana' than 'Cercola' and 21-day NaCl drove strong up-regulation in all ecotypes. In leaves, unstressed 'Domitiana' confirmed higher expression of the above genes, whose transcription was repressed in 'Domitiana' but induced in 'Cercola' following NaCl treatment. In all ecotypes, salinity increased proline, ABA and leaf antioxidants, paralleled by up-regulation of antioxidant genes in 'Canneto' and 'Cercola' but not in 'Domitiana', which tolerated a higher level of oxidative damage. Changes in DNA methylation patterns highlighted a marked capacity of the tolerant 'Domitiana' ecotype to adjust DNA methylation to salt stress. The reduced salt sensitivity of 'Domitiana' and, to a lesser extent, 'Canneto' appears to rely on a complex set of constitutively activated defences, possibly due to the environmental conditions of the site of origin, and on higher plasticity of the methylome. Our findings provide insights into the mechanisms of adaptability of A. donax ecotypes to salinity, offering new perspectives for the improvement of this species for cultivation in limiting environments.

Aucubin alleviates diabetic nephropathy by inhibiting NF-κB activation and inducing SIRT1/SIRT3-FOXO3a signaling pathway in high-fat diet/streptozotocin-induced diabetic mice

Abstract Oxidative stress and inflammation are two important pathological mechanisms in diabetic nephropathy (DN). Aucubin (AU), a natural iridoid glucoside, possessing remarkable anti-inflammatory and anti-oxidation activity, has been used to treat diabetic complications. However, underlying mechanism of protective action in DN remains unclear. In the present study, AU significantly alleviated albuminuria, glomerular extracellular matrix expansion, renal fibrosis, and inflammation caused by diabetes after ten weeks of treatment. Moreover, AU significantly inhibited oxidative stress markers in kidney tissue. In addition, we demonstrated that AU promoted endogenous antioxidant defenses by triggering Nrf2 and FOXO3a nuclear translocation, respectively, and up-regulation of antioxidant genes, including NQO1, HO-1, Mn-SOD, and CAT. These effects may be, in part, mediated by inducing SIRT1 and SIRT3 activities. Furthermore, AU also attenuated pro-inflammatory cytokines in renal tissue by inhibiting the NF-κB signaling pathway. Taken together, our results suggested that AU is a potential natural agent for the prevention of diabetes-induced DN.

Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD

BackgroundPatients with chronic obstructive pulmonary disease (COPD) have high oxidative stress associated with the severity of the disease. Nuclear factor erythroid-2 related factor 2 (Nrf2)-directed stress response plays a critical role in the protection of lung cells to oxidative stress by upregulating antioxidant genes in response to tobacco smoke. There is a critical gap in our knowledge about Nrf-2 regulated genes in active smokers and former-smokers with COPD in different cell types from of lungs and surrogate peripheral tissues.MethodsWe compared the expression of Nrf2 and six of its target genes in alveolar macrophages, nasal, and bronchial epithelium and peripheral blood mononuclear cells (PBMCs) in current and former smokers with COPD. We compared cell-type specific of Nrf2 and its target genes as well as markers of oxidative and inflammatory stress.ResultsWe enrolled 89 patients; expression all Nrf2 target gene measured were significantly higher in the bronchial epithelium from smokers compared to non-smokers. None were elevated in alveolar macrophages and only one was elevated in each of the other compartments.ConclusionBronchial epithelium is the most responsive tissue for transcriptional activation of Nrf2 target genes in active smokers compared to former-smokers with COPD that correlated with oxidative stress and inflammatory markers. There were no consistent trends in gene expression in other cell types tested.Trial registrationClinicaltrials.gov: NCT01335971.

The anti-aging potential of medicinal plants in Cameroon - Harungana madagascariensis Lam. and Psorospermum aurantiacum Engl. prevent in vitro ultraviolet B light-induced skin damage

IntroductionPlants are used by the populations of Foumban (West Region) and Nkol Anga’a (Center Region) for skin care in Cameroon, Central Africa. In this study, the anti-aging potential of the medicinal plants were investigated by evaluating their in vitro antioxidant, anti-elastase and anti-tyrosinase activities followed by the analysis of their protective effect on ultraviolet B light-induced oxidative stress. MethodsAntioxidant potential to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen-hydroxyl (OH°), reduce potassium ferrocyanate and phosphomolybdenum and inhibit lipid peroxidation (LP) was assessed while the anti-elastase and anti-tyrosinase activities were determined spectrophotometrically. The protective potential of the most active extracts were determined on ultraviolet B light-induced oxidative stress in fibroblasts and melanoma cells by measuring the mRNA levels of Nrf-2 and HO-1 ResultsTwenty-six medicinal plants species belonging to sixteen families were stock-listed. The crude extracts of Harungana madagascariensis and Psorospermum aurantiacum possessed high total polyphenol content. Likewise, the antioxidant activity of both plants was comparable to that of ascorbic acid in all the studied oxidative models. Tested at 100 μg/mL, these extracts were found to inhibit the activity of elastase at 100 and 77.58% respectively. Both extracts exhibited low inhibitory activity on tyrosinase as compared to ascorbic acid while the isolated hexane and methanol fractions demonstrated strong antioxidative activities. The hexane fraction of P. aurantiacum induced significant (p < 0.01) up-regulation of antioxidant genes (Nrf-2 and HO-1). ConclusionThe above cited plants exhibited high antioxidative, anti-tyrosinase and anti-elastase activities and, their active compounds may be promising for skin care.

Redox Pioneer: Professor Hideo Kimura.

Dr. Hideo Kimura is recognized as a redox pioneer because he has published an article in the field of antioxidant and redox biology that has been cited >1000 times, and 29 articles that have been cited >100 times. Since the first description of hydrogen sulfide (H2S) as a toxic gas 300 years ago, most studies have been devoted to its toxicity. In 1996, Dr. Kimura demonstrated a physiological role of H2S as a mediator of cognitive function and cystathionine β-synthase as an H2S-producing enzyme. In the following year, he showed H2S as a vascular smooth muscle relaxant in synergy with nitric oxide and its production by cystathionine γ-lyase in vasculature. Subsequently he reported the cytoprotective effect of H2S on neurons against oxidative stress. Since then, studies on H2S have unveiled numerous physiological roles such as the regulation of inflammation, cell growth, oxygen sensing, and senescence. He also discovered polysulfides (H2Sn), which have a higher number of sulfur atoms than H2S and are one of the active forms of H2S, as potent signaling molecules produced by 3-mercaptopyruvate sulfurtransferase. H2Sn regulate ion channels and transcription factors to upregulate antioxidant genes, tumor suppressors, and protein kinases to, in turn, regulate blood pressure. These findings led to the re-evaluation of other persulfurated molecules such as cysteine persulfide and glutathione persulfide. Dr. Kimura is a pioneer of studies on H2S and H2Sn as signaling molecules.It is fortunate to come across a secret of nature and pick it up. —Prof. Hideo Kimura

Sub-acute restraint stress progressively increases oxidative/nitrosative stress and inflammatory markers while transiently upregulating antioxidant gene expression in the rat hippocampus

We have previously demonstrated that acute stress decreases neuronal nitric oxide synthase (NOS) expression in the hippocampus despite increased concentrations of nitric oxide which may indicate feedback inhibition of neuronal NOS expression via inducible NOS-derived nitric oxide. Moreover, the hippocampus undergoes an initial oxidative/nitrosative insult that is rapidly followed by upregulation of protective antioxidants, including the zinc-binding metallothioneins, in order to counter this and restore redox balance following acute stress exposure. In the present study, we have utilized indicators of oxidative/nitrosative stress, members of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, antioxidant metallothioneins, and neuroinflammatory markers to observe the changes occurring in the hippocampus following short term repeated stress exposure. Male Wistar rats were subjected to control conditions or 6 h of restraint stress applied for 1, 2, or 3 days (n = 8 per group) after which the hippocampus was isolated for redox assays and relative gene expression. The hippocampus showed increased oxidative stress, transient dys-homeostasis of total zinc, and increased expression of the Nrf2 pathway members. Moreover, repeated stress increased nitrosative status, nitric oxide metabolites, and 3-nitrotyrosine, indicative of nitrosative stress in the hippocampus. However, levels of neuronal NOS decreased over all stress treatment groups, while increases were observed in inducible NOS and xanthine dehydrogenase. In addition to inducible NOS, mRNA expression of other inflammatory markers including interleukin-6 and interleukin-1β also increased even in the presence of increased anti-inflammatory glucocorticoids. Together, these results demonstrate that despite increases in antioxidant expression, sub-acute stress causes an inflammatory phenotype in the hippocampus by inducing oxidative/nitrosative stress, zinc dys-homeostasis, and the accumulation of nitrotyrosinated proteins which is likely driven by increased inducible NOS signaling.

Gomisin N Alleviates Ethanol-Induced Liver Injury through Ameliorating Lipid Metabolism and Oxidative Stress.

Gomisin N (GN), a lignan derived from Schisandra chinensis, has been shown to possess antioxidant, anti-inflammatory, and anticancer properties. In the present study, we investigated the protective effect of GN against ethanol-induced liver injury using in vivo and in vitro experiments. Histopathological examination revealed that GN administration to chronic-binge ethanol exposure mice significantly reduced ethanol-induced hepatic steatosis through reducing lipogenesis gene expression and increasing fatty acid oxidation gene expression, and prevented liver injury by lowering the serum levels of aspartate transaminase and alanine transaminase. Further, it significantly inhibited cytochrome P450 2E1 (CYP2E1) gene expression and enzyme activity, and enhanced antioxidant genes and glutathione level in hepatic tissues, which led to decreased hepatic malondialdehyde levels. It also lowered inflammation gene expression. Finally, GN administration promoted hepatic sirtuin1 (SIRT1)-AMP-activated protein kinase (AMPK) signaling in ethanol-fed mice. Consistent with in vivo data, treatment with GN decreased lipogenesis gene expression and increased fatty acid oxidation gene expression in ethanol-treated HepG2 cells, thereby preventing ethanol-induced triglyceride accumulation. Furthermore, it inhibited reactive oxygen species generation by downregulating CYP2E1 and upregulating antioxidant gene expression, and suppressed inflammatory gene expression. Moreover, GN prevented ethanol-mediated reduction in SIRT1 and phosphorylated AMPK. These findings indicate that GN has therapeutic potential against alcoholic liver disease through inhibiting hepatic steatosis, oxidative stress and inflammation.

Immune tolerance of vector beetle to its partner plant parasitic nematode modulated by its insect parasitic nematode.

Immune response of insect vectors to transmitted pathogens or insect hosts against parasites are well studied, whereas the mechanism of tripartite interactions remains elusive. In this study, we investigated the immune interactions of the vector beetle Monochamus alternatus ( Ma) to the devastating plant parasitic nematode Bursaphelenchus xylophilus ( Bx) and the insect parasitic nematode Howardula phyllotretae ( Hp). We report the unique immune mechanism by which the vector beetle tolerates many devastating Bx in its trachea, yet that immune tolerance is compromised by the parasitic nematode Hp. Contact with either nematode species triggers epithelial reactive oxygen species (ROS) production in Ma. Only the entry of Bx, not Hp, infection, induces increased expression of antioxidative genes, through which the ROS levels are balanced in the trachea of beetles. Furthermore, we found that up-regulation of antioxidative genes was induced by the interaction of Toll receptors. In contrast, beetles infected by Hp retain high levels of oxidative stress and melanization in trachea, and as a result, decrease Bx loading. This study highlights the role of Toll receptors in mediating the activation of antioxidative genes in immune tolerance to plant parasitic nematodes, and suggests the use of insect parasites as a biologic control.-Zhou, J., Zhao, L.-L., Yu, H.-Y., Wang, Y.-H., Zhang, W., Hu, S.-N., Zou, Z., Sun, J.-H. Immune tolerance of vector beetle to its partner plant parasitic nematode modulated by its insect parasitic nematode.

Dopaminergic dysregulation and impaired associative learning behavior in zebrafish during chronic dietary exposure to selenium

A growing body of evidence indicates that exposure to selenium (Se) can cause neurotoxicity, and this can occur because of its interference with several neurotransmitter systems in humans and animals. Dopamine is a critical modulator of a variety of brain functions and a prime target for environmental neurotoxicants. However, effects of environmentally relevant concentrations of Se on dopaminergic system and its neurobehavioral effects are still largely unknown. For this purpose, we exposed zebrafish, a model organism, to different concentrations of dietary l-selenomethionine (control, 3.5, 11.1, 27.4, and 63.4 μg Se/g dry weight) for a period of 60 days. Cognitive performance of fish was evaluated using a plus maze associative learning paradigm. Oxidative stress, as the main driver of Se neurotoxicity, was assessed by measuring the ratio of reduced to oxidized glutathione (GSH:GSSG), lipid peroxidation (LPO) levels, and mRNA expression of several antioxidant enzymes in the zebrafish brain. Dopamine levels in the brain and the expression of genes involved in dopamine synthesis, storage, reuptake, metabolism, and receptor activation were examined. Moreover, transcription of several synaptic plasticity-related immediate-early and late response genes was determined. Overall, fish fed with the two highest concentrations of dietary Se displayed impaired associative learning. Se exposure also induced oxidative stress in the zebrafish brain, as indicated by a reduction in GSH:GSSG ratio, increased LPO levels, and up-regulation of antioxidant genes in fish treated with the two highest concentrations of Se. An increase in brain dopamine levels associated with altered expression of dopaminergic cell markers was evident in different treatment groups. Moreover, Se exposure led to the down-regulation of immediate-early and late response genes in fish that exhibiting learning impairment. Taken together, the results of this study imply that the induction of oxidative stress and dysregulation of dopaminergic neurotransmission may underlie Se-induced impairment of associative learning in zebrafish.

Improved salt tolerance in a wheat stay-green mutant tasg1

Salt stress inhibited the growth of both tasg1 and wild-type (WT) wheat seedlings, but the inhibition in tasg1 plants was relatively weaker than that of WT. Compared to the WT, the chlorophyll content, thylakoid membrane polypeptides, Hill reaction activity, actual photochemical efficiency of PSII (ΦPSII), and Mg2+- and Ca2+-ATPase activities were higher in tasg1 under salt stress. At the same time, the photosynthetic activity of the tasg1 was significantly higher than that of WT. In addition, tasg1 plants displayed relatively less accumulation of reactive oxygen species and oxidative damage accompanied by higher activity of some antioxidant enzymes, and the up-regulation of antioxidant genes further demonstrated the improvement of antioxidant activity in tasg1 under salt stress. Furthermore, tasg1 plants also showed relatively weaker Na+ fluorescence and lower Na+ content, but relatively higher content of K+ in their roots and shoots, and then, the roots of tasg1 plants enhanced net outward Na+ flux and a correspondingly increased net inward K+ flux during salt stress. This might be associated with the relatively higher activity of H+-ATPase in tasg1 plants. These results suggest that the improved antioxidant competence and Na+/K+ ion homeostasis play an important role in the enhanced salinity tolerance of tasg1 plants.