Drought and Herbivory Enhance Epichloë-Mediated Resistance to Insect Herbivores via Modulation of Alkaloid Precursors and Oxidative Processes.

Fission yeast Spc1 (Sty1), a stress-activated mitogen-activated protein kinase (MAPK) homologous to human p38, orchestrates global changes in gene expression in response to diverse forms of cytotoxic stress. This control is partly mediated through Atf1, a transcription factor homologous to human ATF2. How Spc1 controls Atf1, and how the cells tailor gene expression patterns to different forms of stress, are unknown. Here we describe Csx1, a novel protein crucial for survival of oxidative but not osmotic stress. Csx1 associates with and stabilizes atf1+ mRNA in response to oxidative stress. Csx1 controls expression of the majority of the genes induced by oxidative stress, including most of the genes regulated by Spc1 and Atf1. These studies reveal a novel mechanism controlling MAPK-regulated transcription factors and suggest how gene expression patterns can be customized to specific forms of stress. Csx1-like proteins in humans may perform similar tasks.

N-Acetylcysteine Augments The Cellular Redox Changes and Cytotoxic Activity of Internalized Mycobacterium Bovis in Human Bladder Cancer Cells

The ability of fungi to sense and respond rapidly to environmental stress is crucial for their survival in the wild. One of the most important pathways involved in this response is the stress-activated MAP (mitogen-activated protein) kinase pathway. We report here on the isolation of the stress-activated MAP kinase, sakA, from the fungal endophyte Epichloë festucae. Complementation of the stress sensitivity and cell cycle defects of an Schizosaccharomyces pombe sty1Delta mutant with sakA confirmed it encodes a functional MAP kinase. Analysis of an E. festucae DeltasakA mutant revealed sakA is essential for growth under conditions of temperature and osmotic stress in culture, and for sensitivity to the fungicide fludioxonil. However, the DeltasakA mutant shows no increased sensitivity to hydrogen peroxide. Given sakA can rescue the sty1Delta mutant from sensitivity to oxidative stress, SakA has the potential to sense and transduce oxidative stress signals. The DeltasakA mutant is also defective in conidia formation, suggesting a role for SakA in asexual development of E. festucae. The detection of elevated hydrogen peroxide production in the DeltasakA mutant suggests there may be a link between MAP kinase and ROS (reactive oxygen species) signalling pathways in E. festucae.

Grasses hosting Epichloë endophytes are protected against herbivores due to the production of various fungal alkaloids. Previous research has found that high foliar phosphorus concentrations reduce the level of the alkaloid ergovaline, thereby reducing the endophyte‐mediated herbivore resistance. Yet, the impact of phosphorus on ergovaline biosynthesis versus its influence on endophyte growth and synthesis of other fungal alkaloids remains unresolved. Our objective was to elucidate these relationships. We grew endophyte‐symbiotic and non‐symbiotic Festuca arundinacea plants and fertilised them with different doses of phosphorus. Later, half of the plants from each treatment were challenged with larvae of the generalist chewing insect Spodoptera frugiperda. We assessed the relationships between foliar phosphorus levels, fungal mycelium and alkaloid concentrations, as well as their impacts on larvae performance, herbivore‐caused damage and plant biomass. Endophyte mycelial biomass in plant tissue was found to be independent of foliar phosphorus concentration. The alkaloids lolines and peramine showed a linear relationship with mycelial biomass but no correlation with foliar phosphorus. Surprisingly, high ergovaline concentrations were positively associated with an interaction between endophyte mycelial biomass and foliar phosphorus concentration. Although herbivory increased loline concentration, only high concentrations of ergovaline and peramine were related to reduced S. frugiperda larvae weight gain. However, endophyte presence did not reduce herbivory damage on plants. Contrary to expectation, we did not find a negative but a positive association between concentrations of foliar phosphorus and ergovaline alkaloid, through its interaction with endophyte mycelial biomass. Alternatively, our findings suggest that phosphorus plays a crucial role in modulating the Epichloë‐mediated defensive mutualism, primarily through its effects on ergovaline rather than on endophyte concentration or production of other alkaloids. Read the free Plain Language Summary for this article on the Journal blog.

When confronted with abiotic stress, plants actively adjust their metabolism and development. Imbalances in cellular processes are often accompanied by a change in reactive oxygen species (ROS) homeostasis. Uncontrolled accumulation of ROS will result in oxidative damage of plant tissues eventually resulting in cell death. In the last decades, it has become clear that plants exposed to abiotic stress show specific and highly dynamic signaling responses, in which ROS function as genuine signaling molecules. Here, we specifically provide an overview of recent advances and current understanding of the role of ROS signaling during the initial phase of abiotic stress. Although different molecular pathways are involved in the detection of specific forms of abiotic stress, they all share a common basic plan. This includes the production of an oxidative burst, kinase-mediated signal transduction and the activation of dormant transcription factors to initiate transcriptional reprogramming within seconds or minutes of stress detection. In this chapter, the contribution of ROS signaling in the regulation of plant adaptation during high-light, temperature, salt and low-oxygen stress will be addressed.

Reactive oxygen species (ROS) have an important role in cellular biology, being involved, in a way that depends on their levels, in cell signaling processes or in oxidative stress, probably associated with neurodegenerative and other diseases. Most of the studies about ROS formation were performed in ischemic conditions, and thus, there is limited knowledge about ROS formation in less severe hypoxic conditions. This study investigates neuronal ROS generation and autofluorescence changes in hypoxic conditions, focusing on the involvement of calcium and zinc. Using hippocampal slices from Wistar rats, ROS production was monitored by the permeant fluorescent indicator H2DCFDA under different oxygenation levels. Moderate hypoxia (40% O2) led to a small ROS increase, while severe hypoxia (0% O2) showed a more pronounced rise. KCl-induced depolarization significantly enhanced ROS formation, particularly under severe hypoxia. Inhibition of NMDA receptors reduced ROS generation without affecting autofluorescence, while chelation of zinc ions decreased ROS production and increased flavin adenine dinucleotide (FAD) autofluorescence. These findings suggest that, in hypoxic conditions, ROS formation is mediated by calcium entry through NMDA receptors and also by zinc influxes. Thus, these ions play a crucial role in oxidative stress, which may be related with neurodegenerative diseases associated with ROS dysregulation.

Alkaloids produced by endophytic fungi can have an important influence on agricultural ecology, and can often be affected by climatic factors. At present, there are no studies that have assessed the relationship between alkaloid production and elevation or climatic factors in the Qinghai-Tibetan Plateau. To address this knowledge gap, we explored ergot alkaloid and peramine production in Epichloë-infected (E+) Elymus tangutorum collected from the Qinghai-Tibetan plateau and assessed the relationship between the concentration of these alkaloids and elevation. The effects of temperature and precipitation on these relationships were also investigated. The concentrations of ergonovine, ergine, and peramine ranged from 0.47–0.84, 0.35–1.72 and 9.18–13.00 µg·g−1, respectively. Fitted cubic regression curves describing an arc-pattern across the elevational series were statistically significant for ergine and peramine concentrations. The elevational trend in peramine concentration was linked to mean daily temperature, while the ergine elevational trend was linked to mean precipitation. Our results provide a new understanding of the climatic factors that influence the alkaloid production of endophytic fungi at different elevations in the Qinghai-Tibetan plateau.

Calorie Restriction Reduces Oxidative Stress by SIRT3-Mediated SOD2 Activation

In this study, age-related changes in reactive oxygen species (ROS) production and markers of oxidative stress were investigated specifically addressing the role played by the body mass index (BMI). In two groups of healthy subjects, old (aged 72.6 ± 4.7 years) and young (aged 18.9 ± 1.6 years), ROS production rate, products of lipid peroxidation (as thiobarbituric acid-reactive substances, TBARS), protein oxidation (as total protein carbonyls, PC), and total antioxidant capacity (TAC) were assessed. BMI was also determined, and the subjects were classified into normal weight, overweight, and obese. In both groups (young and old), significant increases in ROS production rate and levels of systemic oxidative damage biomarkers (TBARS and PC) and decreases in TAC levels were shown to correlate with BMI. When comparing data in the same BMI subgroup, significant differences (lower ROS production rate, PC, and TBARS levels, and higher levels of TAC) were observed in the young group versus the old group. In conclusion, the study showed that oxidative stress biomarkers were elevated in obese subjects and old age was associated with increases in oxidative stress markers and decreases in TAC.

Do cytokinins, volatile isoprenoids and carotenoids synergically delay leaf senescence?

Oxidative stress in prostate cancer

Stroke is the second leading cause of global death and is characterized by high rates of mortality and disability. Oxidative stress is accompanied by other pathological processes that together lead to secondary brain damage in stroke. As the major component of the brain, glial cells play an important role in normal brain development and pathological injury processes. Multiple connections exist in the pathophysiological changes of reactive oxygen species (ROS) metabolism and glia cell activation. Astrocytes and microglia are rapidly activated after stroke, generating large amounts of ROS via mitochondrial and NADPH oxidase pathways, causing oxidative damage to the glial cells themselves and neurons. Meanwhile, ROS cause alterations in glial cell morphology and function, and mediate their role in pathological processes, such as neuroinflammation, excitotoxicity, and blood-brain barrier damage. In contrast, glial cells protect the Central Nervous System (CNS) from oxidative damage by synthesizing antioxidants and regulating the Nuclear factor E2-related factor 2 (Nrf2) pathway, among others. Although numerous previous studies have focused on the immune function of glial cells, little attention has been paid to the role of glial cells in oxidative stress. In this paper, we discuss the adverse consequences of ROS production and oxidative-antioxidant imbalance after stroke. In addition, we further describe the biological role of glial cells in oxidative stress after stroke, and we describe potential therapeutic tools based on glia cells.

Skin, our first interface to the external environment, is subjected to oxidative stress caused by a variety of factors such as solar ultraviolet, infrared and visible light, environmental pollution, including ozone and particulate matters, and psychological stress. Excessive reactive species, including reactive oxygen species and reactive nitrogen species, exacerbate skin pigmentation and aging, which further lead to skin tone unevenness, pigmentary disorder, skin roughness and wrinkles. Besides these, skin microbiota are also a very important factor ensuring the proper functions of skin. While environmental factors such as UV and pollutants impact skin microbiota compositions, skin dysbiosis results in various skin conditions. In this review, we summarize the generation of oxidative stress from exogenous and endogenous sources. We further introduce current knowledge on the possible roles of oxidative stress in skin pigmentation and aging, specifically with emphasis on oxidative stress and skin pigmentation. Meanwhile, we summarize the science and rationale of using three well-known antioxidants, namely vitamin C, resveratrol and ferulic acid, in the treatment of hyperpigmentation. Finally, we discuss the strategy for preventing oxidative stress-induced skin pigmentation and aging.

Radical prostectomy, radiation treatment, and/or hormone ablation therapy are the first lines of treatment for prostate cancer (CaP). Despite initial sensitivity to these treatments, CaP eventually progresses to castration-resistant CaP (CRPC), which is both aggressive and refractory to current therapeutic options. Accordingly, there is a tremendous need for a novel agent that can either retard or prevent the emergence of CRPC. Changes in reactive oxygen species (ROS) play a pivotal role in these processes. For example, a moderate increase in ROS promotes cell proliferation, but excessive amounts of ROS can induce apoptosis in cancer cells. Hence, it is possible to manipulate the redox (oxidative stress) system to selectively kill cancer cells. Psoralidin (Pso), a natural bioactive compound derived from Psoralea Corylifolia which is extensively used in Asian and African medicines, is an orally bioavailable dietary agent. We are the first group to demonstrate that Pso is non-toxic to normal prostate epithelial cells but specifically targets CaP cell lines (PC-3, DU-145, LnCaP and C4-2B) by inhibiting Akt and its downstream pro-survival signaling pathways. While dissecting the upstream events of Akt, we found that Pso generates ROS production and inhibits Akt mediated pro-survival signaling in both cell cultures and animal models of CRPC. Importantly, over expression of antioxidants, genetically (SOD/Catalase) or pharmacologically N-acetylcysteine (NAC) or treatment with ROS inhibitors Rotenone (mitochondrial) or Diphenylenel iodonium DPI (extra mitochondrial) inhibited Pso induced oxidative stress (both Intracellular and NADPH oxidase mediated) in CaP cells. Further, Pso in combination with anti-oxidants/ROS inhibitors significantly decreased the migratory and invasive property of CaP cell lines. Currently, we are delineating the role of Pso induced non-mitochondrial ROS generation, by analyzing expression patterns of NADPH oxidase and their subunits. We will apply genetic and/or pharmacological approaches to determine the key Pso target in CaP cell lines. Further, our chemopreventive and chemotherapeutic studies of Pso in both xenograft models and pilot experiments in transgenic adenocarcinoma of mouse prostate (TRAMP) model showed that Pso inhibits prostate tumor growth. These studies may suggest modulation of redox status could be a novel and powerful approach to chemoprevention and/or treatment of CaP. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-187. doi:1538-7445.AM2012-LB-187

1-Methyl-4-phenylpyridinium (MPP(+)) ion, a toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, is produced by monoamine oxidase B in astrocytes. MPP(+) causes a selective dopaminergic neurodegeneration, the pathophysiologic hallmark of Parkinson disease. However, the toxic effect of MPP(+) on astrocytes remains unclear. Here, we examined the effect of MPP(+) on human astrocytoma U373MG cells, with particular attention to the temporal interaction of glutathione (GSH) and reactive oxygen species (ROS) (H2O2 and O). MPP(+) induced astrocyte apoptosis in a dose-dependent manner 48 hr after treatment. Distinctive early (<6 hr) and late (24-48 hr) responses were observed. ROS production and the oxidized GSH (GSSG)/GSH ratio, indicators of oxidative stress, rose dramatically after 24 hr of MPP(+) exposure, whereas the H2O2 level transiently decreased at 6 hr. ROS overproduction and GSH dysfunction were concomitantly associated with caspase-3 activation and finally led to cell apoptosis. Moreover, GSH depletion by diethyl maleate, but not buthionine sulfoximine, caused cells to die quickly and potentiated the cytotoxicity of MPP(+). Co-treatment with melatonin, a known antioxidant secreted by the pineal gland, significantly prevented cell apoptosis by inhibiting oxidative stress and caspase-3 activation, but it did not affect that the early changes due to MPP(+) treatment. Our results demonstrate that in astrocytes, GSH is involved in the early decrease and late increase in ROS levels induced by MPP(+) treatment. Melatonin remedies the dysfunction of GSH system to block caspase-3 activation and cell apoptosis induced by oxidative stress during the long-term exposure of MPP(+).