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Sample records for activated stress response

  1. Dynamics of active cellular response under stress

    NASA Astrophysics Data System (ADS)

    de, Rumi; Zemel, Assaf; Safran, Samuel

    2008-03-01

    Forces exerted by and on adherent cells are important for many physiological processes such as wound healing and tissue formation. In addition, recent experiments have shown that stem cell differentiation is controlled, at least in part, by the elasticity of the surrounding matrix. Using a simple theoretical model that includes the forces due to both the mechanosensitive nature of cells and the elastic response of the matrix, we predict the dynamics of orientation of cells. The model predicts many features observed in measurements of cellular forces and orientation including the increase with time of the forces generated by cells in the absence of applied stress and the consequent decrease of the force in the presence of quasi-static stresses. We also explain the puzzling observation of parallel alignment of cells for static and quasi-static stresses and of nearly perpendicular alignment for dynamically varying stresses. In addition, we predict the response of the cellular orientation to a sinusoidally varying applied stress as a function of frequency. The dependence of the cell orientation angle on the Poisson ratio of the surrounding material can be used to distinguish systems in which cell activity is controlled by stress from those where cell activity is controlled by strain. Reference: Nature Physics, vol. 3, pp 655 (2007).

  2. Cellular Stress Responses and Monitored Cellular Activities.

    PubMed

    Sawa, Teiji; Naito, Yoshifumi; Kato, Hideya; Amaya, Fumimasa

    2016-08-01

    To survive, organisms require mechanisms that enable them to sense changes in the outside environment, introduce necessary responses, and resist unfavorable distortion. Consequently, through evolutionary adaptation, cells have become equipped with the apparatus required to monitor their fundamental intracellular processes and the mechanisms needed to try to offset malfunction without receiving any direct signals from the outside environment. It has been shown recently that eukaryotic cells are equipped with a special mechanism that monitors their fundamental cellular functions and that some pathogenic proteobacteria can override this monitoring mechanism to cause harm. The monitored cellular activities involved in the stressed intracellular response have been researched extensively in Caenorhabditis elegans, where discovery of an association between key mitochondrial activities and innate immune responses was named "cellular associated detoxification and defenses (cSADD)." This cellular surveillance pathway (cSADD) oversees core cellular activities such as mitochondrial respiration and protein transport into mitochondria, detects xenobiotics and invading pathogens, and activates the endocrine pathways controlling behavior, detoxification, and immunity. The cSADD pathway is probably associated with cellular responses to stress in human inflammatory diseases. In the critical care field, the pathogenesis of lethal inflammatory syndromes (e.g., respiratory distress syndromes and sepsis) involves the disturbance of mitochondrial respiration leading to cell death. Up-to-date knowledge about monitored cellular activities and cSADD, especially focusing on mitochondrial involvement, can probably help fill a knowledge gap regarding the pathogenesis of lethal inflammatory syndromes in the critical care field. PMID:26954943

  3. Stress Reorganization and Response in Active Solids

    NASA Astrophysics Data System (ADS)

    Hawkins, Rhoda J.; Liverpool, Tanniemola B.

    2014-07-01

    We present a microscopic model of a disordered viscoelastic active solid, i.e., an active material whose long time behavior is elastic as opposed to viscous. It is composed of filaments, passive cross-links, and molecular motors powered by stored chemical energy, e.g., actomyosin powered by adenosine triphosphate. Our model allows us to study the collective behavior of contractile active elements and how their interaction with each other and the passive elastic elements determines the macroscopic mechanical properties of the active material. As a result of the (un)binding dynamics of the active elements, we find that this system provides a highly responsive material with a dynamic mechanical response strongly dependent on the amount of deformation.

  4. Dynamics of telomerase activity in response to acute psychological stress

    PubMed Central

    Epel, Elissa S.; Lin, Jue; Dhabhar, Firdaus S.; Wolkowitz, Owen M.; Puterman, E; Karan, Lori; Blackburn, Elizabeth H.

    2010-01-01

    Telomerase activity plays an essential role in cel0l survival, by lengthening telomeres and promoting cell growth and longevity. It is now possible to quantify the low levels of telomerase activity in human leukocytes. Low basal telomerase activity has been related to chronic stress in people and to chronic glucocorticoid exposure in vitro. Here we test whether leukocyte telomerase activity changes under acute psychological stress. We exposed 44 elderly women, including 22 high stress dementia caregivers and 22 matched low stress controls, to a brief laboratory psychological stressor, while examining changes in telomerase activity of peripheral blood mononuclear cells (PBMC). At baseline, caregivers had lower telomerase activity levels than controls, but during stress telomerase activity increased similarly in both groups. Across the entire sample, subsequent telomerase activity increased by 18% one hour after the end of the stressor (p<0.01). The increase in telomerase activity was independent of changes in numbers or percentages of monocytes, lymphocytes, and specific T cell types, although we cannot fully rule out some potential contribution from immune cell redistribution in the change in telomerase activity. Telomerase activity increases were associated with greater cortisol increases in response to the stressor. Lastly, psychological response to the tasks (greater threat perception) was also related to greater telomerase activity increases in controls. These findings uncover novel relationships of dynamic telomerase activity with exposure to an acute stressor, and with two classic aspects of the stress response -- perceived psychological stress and neuroendocrine (cortisol) responses to the stressor. PMID:20018236

  5. The unpredictability of prolonged activation of stress response pathways

    PubMed Central

    Lamech, Lilian T.

    2015-01-01

    In response to stress, cellular compartments activate signaling pathways that mediate transcriptional programs to promote survival and reestablish homeostasis. Manipulation of the magnitude and duration of the activation of stress responses has been proposed as a strategy to prevent or repair the damage associated with aging or degenerative diseases. However, as these pathways likely evolved to respond specifically to transient perturbations, the unpredictability of prolonged activation should be considered. PMID:26101215

  6. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

    PubMed Central

    Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

    2016-01-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage. PMID:27053445

  7. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways.

    PubMed

    Dues, Dylan J; Andrews, Emily K; Schaar, Claire E; Bergsma, Alexis L; Senchuk, Megan M; Van Raamsdonk, Jeremy M

    2016-04-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage. PMID:27053445

  8. Dynamical theory of active cellular response to external stress.

    PubMed

    De, Rumi; Safran, Samuel A

    2008-09-01

    We present a comprehensive, theoretical treatment of the orientational response to external stress of active, contractile cells embedded in a gel-like elastic medium. The theory includes both the forces that arise from the deformation of the matrix as well as forces due to the internal regulation of the stress fibers and focal adhesions of the cell. We calculate the time-dependent response of both the magnitude and the direction of the elastic dipole that characterizes the active forces exerted by the cell, for various situations. For static or quasistatic external stress, cells orient parallel to the stress while for high frequency dynamic external stress, cells orient nearly perpendicular. Both numerical and analytical calculations of these effects are presented. In addition we predict the relaxation time for the cellular response for both slowly and rapidly varying external stresses; several characteristic scaling regimes for the relaxation time as a function of applied frequency are predicted. We also treat the case of cells for which the regulation of the stress fibers and focal adhesions is controlled by strain (instead of stress) and show that the predicted dependence of the cellular orientation on the Poisson ratio of the matrix can differentiate strain vs stress regulation of cellular response. PMID:18851081

  9. Dynamical theory of active cellular response to external stress

    NASA Astrophysics Data System (ADS)

    de, Rumi; Safran, Samuel A.

    2008-09-01

    We present a comprehensive, theoretical treatment of the orientational response to external stress of active, contractile cells embedded in a gel-like elastic medium. The theory includes both the forces that arise from the deformation of the matrix as well as forces due to the internal regulation of the stress fibers and focal adhesions of the cell. We calculate the time-dependent response of both the magnitude and the direction of the elastic dipole that characterizes the active forces exerted by the cell, for various situations. For static or quasistatic external stress, cells orient parallel to the stress while for high frequency dynamic external stress, cells orient nearly perpendicular. Both numerical and analytical calculations of these effects are presented. In addition we predict the relaxation time for the cellular response for both slowly and rapidly varying external stresses; several characteristic scaling regimes for the relaxation time as a function of applied frequency are predicted. We also treat the case of cells for which the regulation of the stress fibers and focal adhesions is controlled by strain (instead of stress) and show that the predicted dependence of the cellular orientation on the Poisson ratio of the matrix can differentiate strain vs stress regulation of cellular response.

  10. Lysyl oxidase activity regulates oncogenic stress response and tumorigenesis.

    PubMed

    Wiel, C; Augert, A; Vincent, D F; Gitenay, D; Vindrieux, D; Le Calvé, B; Arfi, V; Lallet-Daher, H; Reynaud, C; Treilleux, I; Bartholin, L; Lelievre, E; Bernard, D

    2013-01-01

    Cellular senescence, a stable proliferation arrest, is induced in response to various stresses. Oncogenic stress-induced senescence (OIS) results in blocked proliferation and constitutes a fail-safe program counteracting tumorigenesis. The events that enable a tumor in a benign senescent state to escape from OIS and become malignant are largely unknown. We show that lysyl oxidase activity contributes to the decision to maintain senescence. Indeed, in human epithelial cell the constitutive expression of the LOX or LOXL2 protein favored OIS escape, whereas inhibition of lysyl oxidase activity was found to stabilize OIS. The relevance of these in vitro observations is supported by in vivo findings: in a transgenic mouse model of aggressive pancreatic ductal adenocarcinoma (PDAC), increasing lysyl oxidase activity accelerates senescence escape, whereas inhibition of lysyl oxidase activity was found to stabilize senescence, delay tumorigenesis, and increase survival. Mechanistically, we show that lysyl oxidase activity favors the escape of senescence by regulating the focal-adhesion kinase. Altogether, our results demonstrate that lysyl oxidase activity participates in primary tumor growth by directly impacting the senescence stability. PMID:24113189

  11. Stress responses in flavivirus-infected cells: activation of unfolded protein response and autophagy

    PubMed Central

    Blázquez, Ana-Belén; Escribano-Romero, Estela; Merino-Ramos, Teresa; Saiz, Juan-Carlos; Martín-Acebes, Miguel A.

    2014-01-01

    The Flavivirus is a genus of RNA viruses that includes multiple long known human, animal, and zoonotic pathogens such as Dengue virus, yellow fever virus, West Nile virus, or Japanese encephalitis virus, as well as other less known viruses that represent potential threats for human and animal health such as Usutu or Zika viruses. Flavivirus replication is based on endoplasmic reticulum-derived structures. Membrane remodeling and accumulation of viral factors induce endoplasmic reticulum stress that results in activation of a cellular signaling response termed unfolded protein response (UPR), which can be modulated by the viruses for their own benefit. Concomitant with the activation of the UPR, an upregulation of the autophagic pathway in cells infected with different flaviviruses has also been described. This review addresses the current knowledge of the relationship between endoplasmic reticulum stress, UPR, and autophagy in flavivirus-infected cells and the growing evidences for an involvement of these cellular pathways in the replication and pathogenesis of these viruses. PMID:24917859

  12. Estradiol levels modulate brain activity and negative responses to psychosocial stress across the menstrual cycle.

    PubMed

    Albert, Kimberly; Pruessner, Jens; Newhouse, Paul

    2015-09-01

    Although ovarian hormones are thought to have a potential role in the well-known sex difference in mood and anxiety disorders, the mechanisms through which ovarian hormone changes contribute to stress regulation are not well understood. One mechanism by which ovarian hormones might impact mood regulation is by mediating the effect of psychosocial stress, which often precedes depressive episodes and may have mood consequences that are particularly relevant in women. In the current study, brain activity and mood response to psychosocial stress was examined in healthy, normally cycling women at either the high or low estradiol phase of the menstrual cycle. Twenty eight women were exposed to the Montreal Imaging Stress Task (MIST), with brain activity determined through functional magnetic resonance imaging, and behavioral response assessed with subjective mood and stress measures. Brain activity responses to psychosocial stress differed between women in the low versus high estrogen phase of the menstrual cycle: women with high estradiol levels showed significantly less deactivation in limbic regions during psychosocial stress compared to women with low estradiol levels. Additionally, women with higher estradiol levels also had less subjective distress in response to the MIST than women with lower estradiol levels. The results of this study suggest that, in normally cycling premenopausal women, high estradiol levels attenuate the brain activation changes and negative mood response to psychosocial stress. Normal ovarian hormone fluctuations may alter the impact of psychosocially stressful events by presenting periods of increased vulnerability to psychosocial stress during low estradiol phases of the menstrual cycle. This menstrual cycle-related fluctuation in stress vulnerability may be relevant to the greater risk for affective disorder or post-traumatic stress disorder in women. PMID:26123902

  13. Plastid Osmotic Stress Activates Cellular Stress Responses in Arabidopsis1[C][W][OPEN

    PubMed Central

    Wilson, Margaret E.; Basu, Meera R.; Bhaskara, Govinal Badiger; Verslues, Paul E.; Haswell, Elizabeth S.

    2014-01-01

    Little is known about cytoplasmic osmoregulatory mechanisms in plants, and even less is understood about how the osmotic properties of the cytoplasm and organelles are coordinately regulated. We have previously shown that Arabidopsis (Arabidopsis thaliana) plants lacking functional versions of the plastid-localized mechanosensitive ion channels Mechanosensitive Channel of Small Conductance-Like2 (MSL2) and MSL3 contain leaf epidermal plastids under hypoosmotic stress, even during normal growth and development. Here, we use the msl2 msl3 mutant as a model to investigate the cellular response to constitutive plastid osmotic stress. Under unstressed conditions, msl2 msl3 seedlings exhibited several hallmarks of drought or environmental osmotic stress, including solute accumulation, elevated levels of the compatible osmolyte proline (Pro), and accumulation of the stress hormone abscisic acid (ABA). Furthermore, msl2 msl3 mutants expressed Pro and ABA metabolism genes in a pattern normally seen under drought or osmotic stress. Pro accumulation in the msl2 msl3 mutant was suppressed by conditions that reduce plastid osmotic stress or inhibition of ABA biosynthesis. Finally, treatment of unstressed msl2 msl3 plants with exogenous ABA elicited a much greater Pro accumulation response than in the wild type, similar to that observed in plants under drought or osmotic stress. These results suggest that osmotic imbalance across the plastid envelope can elicit a response similar to that elicited by osmotic imbalance across the plasma membrane and provide evidence for the integration of the osmotic state of an organelle into that of the cell in which it resides. PMID:24676856

  14. Transposable Elements Contribute to Activation of Maize Genes in Response to Abiotic Stress

    PubMed Central

    Makarevitch, Irina; Waters, Amanda J.; West, Patrick T.; Stitzer, Michelle; Hirsch, Candice N.; Ross-Ibarra, Jeffrey; Springer, Nathan M.

    2015-01-01

    Transposable elements (TEs) account for a large portion of the genome in many eukaryotic species. Despite their reputation as “junk” DNA or genomic parasites deleterious for the host, TEs have complex interactions with host genes and the potential to contribute to regulatory variation in gene expression. It has been hypothesized that TEs and genes they insert near may be transcriptionally activated in response to stress conditions. The maize genome, with many different types of TEs interspersed with genes, provides an ideal system to study the genome-wide influence of TEs on gene regulation. To analyze the magnitude of the TE effect on gene expression response to environmental changes, we profiled gene and TE transcript levels in maize seedlings exposed to a number of abiotic stresses. Many genes exhibit up- or down-regulation in response to these stress conditions. The analysis of TE families inserted within upstream regions of up-regulated genes revealed that between four and nine different TE families are associated with up-regulated gene expression in each of these stress conditions, affecting up to 20% of the genes up-regulated in response to abiotic stress, and as many as 33% of genes that are only expressed in response to stress. Expression of many of these same TE families also responds to the same stress conditions. The analysis of the stress-induced transcripts and proximity of the transposon to the gene suggests that these TEs may provide local enhancer activities that stimulate stress-responsive gene expression. Our data on allelic variation for insertions of several of these TEs show strong correlation between the presence of TE insertions and stress-responsive up-regulation of gene expression. Our findings suggest that TEs provide an important source of allelic regulatory variation in gene response to abiotic stress in maize. PMID:25569788

  15. An initial phase of JNK activation inhibits cell death early in the endoplasmic reticulum stress response.

    PubMed

    Brown, Max; Strudwick, Natalie; Suwara, Monika; Sutcliffe, Louise K; Mihai, Adina D; Ali, Ahmed A; Watson, Jamie N; Schröder, Martin

    2016-06-15

    Accumulation of unfolded proteins in the endoplasmic reticulum (ER) activates the unfolded protein response (UPR). In mammalian cells, UPR signals generated by several ER-membrane-resident proteins, including the bifunctional protein kinase endoribonuclease IRE1α, control cell survival and the decision to execute apoptosis. Processing of XBP1 mRNA by the RNase domain of IRE1α promotes survival of ER stress, whereas activation of the mitogen-activated protein kinase JNK family by IRE1α late in the ER stress response promotes apoptosis. Here, we show that activation of JNK in the ER stress response precedes activation of XBP1. This activation of JNK is dependent on IRE1α and TRAF2 and coincides with JNK-dependent induction of expression of several antiapoptotic genes, including cIap1 (also known as Birc2), cIap2 (also known as Birc3), Xiap and Birc6 ER-stressed Jnk1(-/-) Jnk2(-/-) (Mapk8(-/-) Mapk9(-/-)) mouse embryonic fibroblasts (MEFs) display more pronounced mitochondrial permeability transition and increased caspase 3/7 activity compared to wild-type MEFs. Caspase 3/7 activity is also elevated in ER-stressed cIap1(-/-) cIap2(-/-) and Xiap(-/-) MEFs. These observations suggest that JNK-dependent transcriptional induction of several inhibitors of apoptosis contributes to inhibiting apoptosis early in the ER stress response. PMID:27122189

  16. 25-Hydroxycholesterol Activates the Integrated Stress Response to Reprogram Transcription and Translation in Macrophages*

    PubMed Central

    Shibata, Norihito; Carlin, Aaron F.; Spann, Nathanael J.; Saijo, Kaoru; Morello, Christopher S.; McDonald, Jeffrey G.; Romanoski, Casey E.; Maurya, Mano R.; Kaikkonen, Minna U.; Lam, Michael T.; Crotti, Andrea; Reichart, Donna; Fox, Jesse N.; Quehenberger, Oswald; Raetz, Christian R. H.; Sullards, M. Cameron; Murphy, Robert C.; Merrill, Alfred H.; Brown, H. Alex; Dennis, Edward A.; Fahy, Eoin; Subramaniam, Shankar; Cavener, Douglas R.; Spector, Deborah H.; Russell, David W.; Glass, Christopher K.

    2013-01-01

    25-Hydroxycholesterol (25OHC) is an enzymatically derived oxidation product of cholesterol that modulates lipid metabolism and immunity. 25OHC is synthesized in response to interferons and exerts broad antiviral activity by as yet poorly characterized mechanisms. To gain further insights into the basis for antiviral activity, we evaluated time-dependent responses of the macrophage lipidome and transcriptome to 25OHC treatment. In addition to altering specific aspects of cholesterol and sphingolipid metabolism, we found that 25OHC activates integrated stress response (ISR) genes and reprograms protein translation. Effects of 25OHC on ISR gene expression were independent of liver X receptors and sterol-response element-binding proteins and instead primarily resulted from activation of the GCN2/eIF2α/ATF4 branch of the ISR pathway. These studies reveal that 25OHC activates the integrated stress response, which may contribute to its antiviral activity. PMID:24189069

  17. Activation of oxidative stress-responsive signaling pathways in early splenotoxic response of aniline

    SciTech Connect

    Wang Jianling; Wang Gangduo; Ansari, G.A.S.; Khan, M. Firoze

    2008-07-15

    Aniline exposure causes toxicity to the spleen, which leads to a variety of sarcomas, and fibrosis appears to be an important preneoplastic lesion. However, early molecular mechanisms in aniline-induced toxicity to the spleen are not known. Previously, we have shown that aniline exposure results in iron overload and induction of oxidative stress in the spleen, which can cause transcriptional upregulation of fibrogenic/inflammatory cytokines via activation of oxidative stress (OS)-responsive signaling pathways. To test this mechanism, male SD rats were treated with aniline (1mmol/kg/day via gavage) for 7days, an experimental condition that precedes the appearance of fibrosis. Significant increases in both NF-{kappa}B and AP-1 binding activity was observed in the nuclear extracts of splenocytes from aniline-treated rats as determined by ELISAs, and supported by Western blot data showing increases in p-I{kappa}B{alpha}, p-p65 and p-c-Jun. To understand the upstream signaling events which could account for the activation of NF-{kappa}B and AP-1, phosphorylation patterns of I{kappa}B kinases (IKK{alpha} and IKK{beta}) and mitogen-activated protein kinases (MAPKs) were pursued. Our data showed remarkable increases in both p-IKK{alpha} and p-IKK{beta} in the splenocytes from aniline-treated rats, suggesting their role in the phosphorylation of both I{kappa}B{alpha} and p65 subunits. Furthermore, aniline exposure led to activation of all three classes of MAPKs, as evident from increased phosphorylation of extracellular-signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK1/2) and p38 MAPKs, which could potentially contribute to the observed activation of both AP-1 and NF-{kappa}B. Activation of upstream signaling molecules was also associated with simultaneous increases in gene transcription of cytokines IL-1, IL-6 and TNF-{alpha}. The observed sequence of events following aniline exposure could initiate a fibrogenic and/or tumorigenic response in the spleen.

  18. S-Nitrosylation Positively Regulates Ascorbate Peroxidase Activity during Plant Stress Responses1

    PubMed Central

    Yang, Huanjie; Mu, Jinye; Chen, Lichao; Feng, Jian; Hu, Jiliang; Li, Lei; Zhou, Jian-Min; Zuo, Jianru

    2015-01-01

    Nitric oxide (NO) and reactive oxygen species (ROS) are two classes of key signaling molecules involved in various developmental processes and stress responses in plants. The burst of NO and ROS triggered by various stimuli activates downstream signaling pathways to cope with abiotic and biotic stresses. Emerging evidence suggests that the interplay of NO and ROS plays a critical role in regulating stress responses. However, the underpinning molecular mechanism remains poorly understood. Here, we show that NO positively regulates the activity of the Arabidopsis (Arabidopsis thaliana) cytosolic ascorbate peroxidase1 (APX1). We found that S-nitrosylation of APX1 at cysteine (Cys)-32 enhances its enzymatic activity of scavenging hydrogen peroxide, leading to the increased resistance to oxidative stress, whereas a substitution mutation at Cys-32 causes the reduction of ascorbate peroxidase activity and abolishes its responsiveness to the NO-enhanced enzymatic activity. Moreover, S-nitrosylation of APX1 at Cys-32 also plays an important role in regulating immune responses. These findings illustrate a unique mechanism by which NO regulates hydrogen peroxide homeostasis in plants, thereby establishing a molecular link between NO and ROS signaling pathways. PMID:25667317

  19. Beller Lectureship Talk: Active response of biological cells to mechanical stress

    NASA Astrophysics Data System (ADS)

    Safran, Samuel

    2009-03-01

    Forces exerted by and on adherent cells are important for many physiological processes such as wound healing and tissue formation. In addition, recent experiments have shown that stem cell differentiation is controlled, at least in part, by the elasticity of the surrounding matrix. We present a simple and generic theoretical model for the active response of biological cells to mechanical stress. The theory includes cell activity and mechanical forces as well as random forces as factors that determine the polarizability that relates cell orientation to stress. This allows us to explain the puzzling observation of parallel (or sometimes random) alignment of cells for static and quasi-static stresses and of nearly perpendicular alignment for dynamically varying stresses. In addition, we predict the response of the cellular orientation to a sinusoidally varying applied stress as a function of frequency and compare the theory with recent experiments. The dependence of the cell orientation angle on the Poisson ratio of the surrounding material distinguishes cells whose activity is controlled by stress from those controlled by strain. We have extended the theory to generalize the treatment of elastic inclusions in solids to ''living'' inclusions (cells) whose active polarizability, analogous to the polarizability of non-living matter, results in the feedback of cellular forces that develop in response to matrix stresses. We use this to explain recent observations of the non-monotonic dependence of stress-fiber polarization in stem cells on matrix rigidity. These findings provide a mechanical correlate for the existence of an optimal substrate elasticity for cell differentiation and function. [3pt] *In collaboration with R. De (Brown University), Y. Biton (Weizmann Institute), and A. Zemel (Hebrew University) and the experimental groups: Max Planck Institute, Stuttgart: S. Jungbauer, R. Kemkemer, J. Spatz; University of Pennsylvania: A. Brown, D. Discher, F. Rehfeldt.

  20. PIM1 destabilization activates a p53-dependent response to ribosomal stress in cancer cells.

    PubMed

    Sagar, Vinay; Caldarola, Sara; Aria, Valentina; Monteleone, Valentina; Fuoco, Claudia; Gargioli, Cesare; Cannata, Stefano; Loreni, Fabrizio

    2016-04-26

    Defects in ribosome biogenesis triggers a stress response (ribosomal stress) that can lead to growth arrest and apoptosis. Signaling pathways activated by ribosomal stress are specifically involved in the pathological mechanism of a group of disorders defined as ribosomopathies. However, more generally, the quality control of ribosome synthesis is part of the regulatory circuits that control cell metabolism. A number of studies identified tumor suppressor p53 as a central player in ribosomal stress. We have previously reported that the kinase PIM1 plays a role as a sensor for ribosome deficiency. In this report we address the relationship between PIM1 and p53 in cancer cell lines after depletion of a ribosomal protein. We identified a novel signaling pathway that includes the kinase AKT and the ubiquitin ligase MDM2. In fact, our results indicate that the lower level of PIM1, induced by ribosomal stress, causes inactivation of AKT, inhibition of MDM2 and a consequent p53 stabilization. Therefore, we propose that activation of p53 in response to ribosomal stress, is dependent on the pathway PIM1-AKT-MDM2. In addition, we report evidence that PIM1 level may be relevant to assess the sensitivity of cancer cells to chemotherapeutic drugs that induce ribosomal stress. PMID:26993775

  1. Stream mesocosm response sensitivities to simulated ion stress in produced waters from resource extraction activities

    EPA Science Inventory

    To increase the ecological relevance of laboratory exposures intent on determining species sensitivity to ion stress from resource extraction activities we have conducted several stream mesocosm dosing studies that pair single-species and community-level responses in-situ and all...

  2. Brx Mediates the Response of Lymphocytes to Osmotic Stress Through the Activation of NFAT5

    PubMed Central

    Kino, Tomoshige; Takatori, Hiroaki; Manoli, Irini; Wang, Yonghong; Tiulpakov, Anatoly; Blackman, Marc R.; Su, Yan A.; Chrousos, George P.; DeCherney, Alan H.; Segars, James H.

    2010-01-01

    Extracellular hyperosmolarity, or osmotic stress, generally caused by differences in salt and macromolecule concentrations across the plasma membrane, occurs in lymphoid organs and at inflammatory sites. The response of immune cells to osmotic stress is regulated by nuclear factor of activated T cells 5 (NFAT5), a transcription factor that induces the expression of hyperosmolarity-responsive genes and stimulates cytokine production. We report that the guanine nucleotide exchange factor (GEF) Brx [also known as protein kinase A–anchoring protein 13 (AKAP13)] is essential for the expression of nfat5 in response to osmotic stress, thus transmitting the extracellular hyperosmolarity signal and enabling differentiation of splenic B cells and production of immunoglobulin. This process required the activity of p38 mitogen-activated protein kinase (MAPK) and NFAT5 and involved a physical interaction between Brx and c-Jun N-terminal kinase (JNK)–interacting protein 4 (JIP4), a scaffold molecule specific to activation of the p38 MAPK cascade. Our results indicate that Brx integrates the responses of immune cells to osmotic stress and inflammation by elevating intracellular osmolarity and stimulating the production of cytokines. PMID:19211510

  3. HPA-Axis Hormone Modulation of Stress Response Circuitry Activity in Women with Remitted Major Depression

    PubMed Central

    Holsen, Laura M.; Lancaster, Katie; Klibanski, Anne; Whitfield-Gabrieli, Susan; Cherkerzian, Sara; Buka, Stephen; Goldstein, Jill M.

    2013-01-01

    Decades of clinical and basic research indicate significant links between altered hypothalamic-pituitary-adrenal (HPA)-axis hormone dynamics and major depressive disorder (MDD). Recent neuroimaging studies of MDD highlight abnormalities in stress response circuitry regions which play a role in the regulation of the HPA-axes. However, there is a dearth of research examining these systems in parallel, especially as related to potential trait characteristics. The current study addresses this gap by investigating neural responses to a mild visual stress challenge with real-time assessment of adrenal hormones in women with MDD in remission and controls. 15 women with recurrent MDD in remission (rMDD) and 15 healthy control women were scanned on a 3T Siemens MR scanner while viewing neutral and negative (stress-evoking) stimuli. Blood samples were obtained before, during, and after scanning for measurement of HPA-axis hormone levels. Compared to controls, rMDD women demonstrated higher anxiety ratings, increased cortisol levels, and hyperactivation in the amygdala and hippocampus, p<0.05, FWE-corrected in response to the stress challenge. Among rMDD women, amygdala activation was negatively related to cortisol changes and positively associated with duration of remission. Findings presented here provide evidence for differential effects of altered HPA-axis hormone dynamics on hyperactivity in stress response circuitry regions elicited by a well-validated stress paradigm in women with recurrent MDD in remission. PMID:23891965

  4. General stress response signaling

    PubMed Central

    Huo, Yi-Xin; Rosenthal, Adam Z.; Gralla, Jay D.

    2008-01-01

    E. coli responds to stress by a combination of specific and general transcription signaling pathways. The general pathways typically require the master stress regulator sigma38 (rpoS). Here we show that the signaling from multiple stresses that relax DNA is processed by a non-conserved 8 amino acid tail of the sigma 38 C-terminal domain (CTD). By contrast, responses to stresses that accumulate potassium glutamate do not rely on this short tail, but still require the overall CTD. In vitro transcription and footprinting studies suggest that multiple stresses can target a poised RNA polymerase and activate it by unwrapping DNA from a nucleosome-like state, allowing the RNA polymerase to escape into productive mode. This transition can be accomplished by either the DNA relaxation or potassium glutamate accumulation that characterizes many stresses. PMID:18761624

  5. Nucleolus-derived mediators in oncogenic stress response and activation of p53-dependent pathways.

    PubMed

    Stępiński, Dariusz

    2016-08-01

    Rapid growth and division of cells, including tumor ones, is correlated with intensive protein biosynthesis. The output of nucleoli, organelles where translational machineries are formed, depends on a rate of particular stages of ribosome production and on accessibility of elements crucial for their effective functioning, including substrates, enzymes as well as energy resources. Different factors that induce cellular stress also often lead to nucleolar dysfunction which results in ribosome biogenesis impairment. Such nucleolar disorders, called nucleolar or ribosomal stress, usually affect cellular functioning which in fact is a result of p53-dependent pathway activation, elicited as a response to stress. These pathways direct cells to new destinations such as cell cycle arrest, damage repair, differentiation, autophagy, programmed cell death or aging. In the case of impaired nucleolar functioning, nucleolar and ribosomal proteins mediate activation of the p53 pathways. They are also triggered as a response to oncogenic factor overexpression to protect tissues and organs against extensive proliferation of abnormal cells. Intentional impairment of any step of ribosome biosynthesis which would direct the cells to these destinations could be a strategy used in anticancer therapy. This review presents current knowledge on a nucleolus, mainly in relation to cancer biology, which is an important and extremely sensitive element of the mechanism participating in cellular stress reaction mediating activation of the p53 pathways in order to counteract stress effects, especially cancer development. PMID:27142852

  6. Thresholds for cellular disruption and activation of the stress response in renal epithelia.

    PubMed

    van Why, S K; Kim, S; Geibel, J; Seebach, F A; Kashgarian, M; Siegel, N J

    1999-08-01

    Renal ischemia causes a rapid fall in cellular ATP, increased intracellular calcium (Ca(i)), and dissociation of Na(+)-K(+)-ATPase from the cytoskeleton along with initiation of a stress response. We examined changes in Ca(i), Na(+)-K(+)-ATPase detergent solubility, and activation of heat-shock transcription factor (HSF) in relation to graded reduction of ATP in LLC-PK(1) cells to determine whether initiation of the stress response was related to any one of these perturbations alone. Ca(i) increased first at 75% of control ATP. Triton X-100 solubility of Na(+)-K(+)-ATPase increased below 70% control ATP. Reducing cellular ATP below 50% control consistently activated HSF. Stepped decrements in cellular ATP below the respective thresholds caused incremental increases in Ca(i), Na(+)-K(+)-ATPase solubility, and HSF activation. ATP depletion activated both HSF1 and HSF2. Proteasome inhibition caused activation of HSF1 and HSF2 in a pattern similar to ATP depletion. Lactate dehydrogenase release remained at control levels irrespective of the degree of ATP depletion. Progressive accumulation of nonnative proteins may be the critical signal for the adaptive induction of the stress response in renal epithelia. PMID:10444577

  7. Triptolide activates unfolded protein response leading to chronic ER stress in pancreatic cancer cells

    PubMed Central

    Mujumdar, Nameeta; Banerjee, Sulagna; Chen, Zhiyu; Sangwan, Veena; Chugh, Rohit; Dudeja, Vikas; Yamamoto, Masato; Vickers, Selwyn M.

    2014-01-01

    Pancreatic cancer is a devastating disease with a survival rate of <5%. Moreover, pancreatic cancer aggressiveness is closely related to high levels of prosurvival mediators, which can ultimately lead to rapid disease progression. One of the mechanisms that enables tumor cells to evade cellular stress and promote unhindered proliferation is the endoplasmic reticulum (ER) stress response. Disturbances in the normal functions of the ER lead to an evolutionarily conserved cell stress response, the unfolded protein response (UPR). The UPR initially compensates for damage, but it eventually triggers cell death if ER dysfunction is severe or prolonged. Triptolide, a diterpene triepoxide, has been shown to be an effective compound against pancreatic cancer. Our results show that triptolide induces the UPR by activating the PKR-like ER kinase-eukaryotic initiation factor 2α axis and the inositol-requiring enzyme 1α-X-box-binding protein 1 axis of the UPR and leads to chronic ER stress in pancreatic cancer. Our results further show that glucose-regulated protein 78 (GRP78), one of the major regulators of ER stress, is downregulated by triptolide, leading to cell death by apoptosis in MIA PaCa-2 cells and autophagy in S2-VP10 cells. PMID:24699326

  8. Inhibition of TGFbeta1 Signaling Attenutates ATM Activity inResponse to Genotoxic Stress

    SciTech Connect

    Kirshner, Julia; Jobling, Michael F.; Pajares, Maria Jose; Ravani, Shraddha A.; Glick, Adam B.; Lavin, Martin J.; Koslov, Sergei; Shiloh, Yosef; Barcellos-Hoff, Mary Helen

    2006-09-15

    Ionizing radiation causes DNA damage that elicits a cellular program of damage control coordinated by the kinase activity of ataxia telangiectasia mutated protein (ATM). Transforming growth factor {beta}1 (TGF{beta}), which is activated by radiation, is a potent and pleiotropic mediator of physiological and pathological processes. Here we show that TGF{beta} inhibition impedes the canonical cellular DNA damage stress response. Irradiated Tgf{beta}1 null murine epithelial cells or human epithelial cells treated with a small molecule inhibitor of TGF{beta} type I receptor kinase exhibit decreased phosphorylation of Chk2, Rad17 and p53, reduced {gamma}H2AX radiation-induced foci, and increased radiosensitivity compared to TGF{beta} competent cells. We determined that loss of TGF{beta} signaling in epithelial cells truncated ATM autophosphorylation and significantly reduced its kinase activity, without affecting protein abundance. Addition of TGF{beta} restored functional ATM and downstream DNA damage responses. These data reveal a heretofore undetected critical link between the microenvironment and ATM that directs epithelial cell stress responses, cell fate and tissue integrity. Thus, TGF{beta}1, in addition to its role in homoeostatic growth control, plays a complex role in regulating responses to genotoxic stress, the failure of which would contribute to the development of cancer; conversely, inhibiting TGF{beta} may be used to advantage in cancer therapy.

  9. Triterpenoid electrophiles (avicins) activate the innate stress response by redox regulation of a gene battery

    PubMed Central

    Haridas, Valsala; Hanausek, Margaret; Nishimura, Goshi; Soehnge, Holly; Gaikwad, Amos; Narog, Maciej; Spears, Erick; Zoltaszek, Robert; Walaszek, Zbigniew; Gutterman, Jordan U.

    2004-01-01

    Avicins are proapoptotic and anti-inflammatory triterpene electrophiles isolated from an Australian desert tree, Acacia victoriae. The presence of two α,β unsaturated carbonyl groups (Michael reaction sites) in the side chain of the avicin molecule prompted us to study its effects on NF-E2–related factor 2 (Nrf2), a redox-regulated transcription factor that controls the expression of a battery of detoxification and antioxidant proteins via its binding to antioxidant response element (ARE). Avicin D–treated Hep G2 cells showed translocation of Nrf2 into the nucleus and a time-dependent increase in ARE activity. These properties were sensitive to DTT, suggesting that avicins affect one or more critical cysteine residues, probably on the Keap1 molecule. Downstream of ARE, an activation of a battery of stress-induced proteins occurred. The implications of these findings were evaluated in vivo in mouse skin exposed to an ancient stressor, UV light. Avicins inhibited epidermal hyperplasia, reduced p53 mutation, enhanced apoptosis, decreased generation of 8-hydroxy-2′-deoxyguanosine, and enhanced expression of NADPH:quinone oxidoreductase 1 and heme oxygenase-1. These data, combined with our earlier published work, demonstrate that avicins represent a new class of plant stress metabolites capable of activating stress adaptation and suppressing proinflammatory components of the innate immune system in human cells by redox regulation. The relevance for treatment of clinical diseases in which stress responses are dysfunctional or deficient is discussed. PMID:14702110

  10. Diurnal cortisol amplitude and fronto-limbic activity in response to stressful stimuli.

    PubMed

    Cunningham-Bussel, Amy C; Root, James C; Butler, Tracy; Tuescher, Oliver; Pan, Hong; Epstein, Jane; Weisholtz, Daniel S; Pavony, Michelle; Silverman, Michael E; Goldstein, Martin S; Altemus, Margaret; Cloitre, Marylene; Ledoux, Joseph; McEwen, Bruce; Stern, Emily; Silbersweig, David

    2009-06-01

    The development and exacerbation of many psychiatric and neurologic conditions are associated with dysregulation of the hypothalamic pituitary adrenal (HPA) axis as measured by aberrant levels of cortisol secretion. Here we report on the relationship between the amplitude of diurnal cortisol secretion, measured across 3 typical days in 18 healthy individuals, and blood oxygen level dependant (BOLD) response in limbic fear/stress circuits, elicited by in-scanner presentation of emotionally negative stimuli, specifically, images of the World Trade Center (WTC) attack. Results indicate that subjects who secrete a greater amplitude of cortisol diurnally demonstrate less brain activation in limbic regions, including the amygdala and hippocampus/parahippocampus, and hypothalamus during exposure to traumatic WTC-related images. Such initial findings can begin to link our understanding, in humans, of the relationship between the diurnal amplitude of a hormone integral to the stress response, and those neuroanatomical regions that are implicated as both modulating and being modulated by that response. PMID:19135805

  11. Lateral prefrontal cortex activity during cognitive control of emotion predicts response to social stress in schizophrenia

    PubMed Central

    Tully, Laura M.; Lincoln, Sarah Hope; Hooker, Christine I.

    2014-01-01

    LPFC dysfunction is a well-established neural impairment in schizophrenia and is associated with worse symptoms. However, how LPFC activation influences symptoms is unclear. Previous findings in healthy individuals demonstrate that lateral prefrontal cortex (LPFC) activation during cognitive control of emotional information predicts mood and behavior in response to interpersonal conflict, thus impairments in these processes may contribute to symptom exacerbation in schizophrenia. We investigated whether schizophrenia participants show LPFC deficits during cognitive control of emotional information, and whether these LPFC deficits prospectively predict changes in mood and symptoms following real-world interpersonal conflict. During fMRI, 23 individuals with schizophrenia or schizoaffective disorder and 24 healthy controls completed the Multi-Source Interference Task superimposed on neutral and negative pictures. Afterwards, schizophrenia participants completed a 21-day online daily-diary in which they rated the extent to which they experienced mood and schizophrenia-spectrum symptoms, as well as the occurrence and response to interpersonal conflict. Schizophrenia participants had lower dorsal LPFC activity (BA9) during cognitive control of task-irrelevant negative emotional information. Within schizophrenia participants, DLPFC activity during cognitive control of emotional information predicted changes in positive and negative mood on days following highly distressing interpersonal conflicts. Results have implications for understanding the specific role of LPFC in response to social stress in schizophrenia, and suggest that treatments targeting LPFC-mediated cognitive control of emotion could promote adaptive response to social stress in schizophrenia. PMID:25379415

  12. Structure-Activity Studies of Bis-O-Arylglycolamides: Inhibitors of the Integrated Stress Response.

    PubMed

    Hearn, Brian R; Jaishankar, Priyadarshini; Sidrauski, Carmela; Tsai, Jordan C; Vedantham, Punitha; Fontaine, Shaun D; Walter, Peter; Renslo, Adam R

    2016-04-19

    The integrated stress response comprises multiple signaling pathways for detecting and responding to cellular stress that converge at a single event-the phosphorylation of Ser51 on the α-subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α-P) results in attenuation of global protein synthesis via the inhibitory effects of eIF2α-P on eIF2B, the guanine exchange factor (GEF) for eIF2. Herein we describe structure-activity relationship (SAR) studies of bis-O-arylglycolamides, first-in-class integrated stress response inhibitors (ISRIB). ISRIB analogues make cells insensitive to the effects of eIF2α-P by activating the GEF activity of eIF2B and allowing global protein synthesis to proceed with residual unphosphorylated eIF2α. The SAR studies described herein support the proposed pharmacology of ISRIB analogues as binding across a symmetrical protein-protein interface formed between protein subunits of the dimeric eIF2B heteropentamer. PMID:26789650

  13. Streptozotocin induced activation of oxidative stress responsive splenic cell signaling pathways: Protective role of arjunolic acid

    SciTech Connect

    Manna, Prasenjit; Ghosh, Jyotirmoy; Das, Joydeep

    2010-04-15

    Present study investigates the beneficial role of arjunolic acid (AA) against the alteration in the cytokine levels and simultaneous activation of oxidative stress responsive signaling pathways in spleen under hyperglycemic condition. Diabetes was induced by injection of streptozotocin (STZ) (at a dose of 70 mg/kg body weight, injected in the tail vain). STZ administration elevated the levels of IL-2 as well as IFN-gamma and attenuated the level of TNF-alpha in the sera of diabetic animals. In addition, hyperglycemia is also associated with the increased production of intracellular reactive intermediates resulting with the elevation in lipid peroxidation, protein carbonylation and reduction in intracellular antioxidant defense. Investigating the oxidative stress responsive cell signaling pathways, increased expressions (immunoreactive concentrations) of phosphorylated p65 as well as its inhibitor protein phospho IkappaBalpha and phosphorylated mitogen activated protein kinases (MAPKs) have been observed in diabetic spleen tissue. Studies on isolated splenocytes revealed that hyperglycemia caused disruption of mitochondrial membrane potential, elevation in the concentration of cytosolic cytochrome c as well as activation of caspase 3 leading to apoptotic cell death. Histological examination revealed that diabetic induction depleted the white pulp scoring which is in agreement with the reduced immunological response. Treatment with AA prevented the hyperglycemia and its associated pathogenesis in spleen tissue. Results suggest that AA might act as an anti-diabetic and immunomodulatory agent against hyperglycemia.

  14. Hyperoxia-induced activation of the integrated stress response in the newborn rat lung.

    PubMed

    Konsavage, Wesley M; Zhang, Lianqin; Wu, Yuchieh; Shenberger, Jeffrey S

    2012-01-01

    Diverse environmental stresses stimulate eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, leading to a stress-resistant state characterized by global attenuation of protein synthesis and induction of cytoprotective genes. The signal transduction network culminating in these effects is referred to as the integrated stress response (ISR) or, when initiated by misfolded proteins within the endoplasmic reticulum (ER), the unfolded protein response (UPR). Given that we previously reported that exposure of 4-day-old Sprague-Dawley rats to 95% O(2) (Ox) diminishes global pulmonary protein synthesis and increases eIF2α phosphorylation, we conducted the current study to determine whether Ox activates the ISR or UPR. We found that Ox-induced alterations in ER morphology of alveolar type II cells and interstitial fibroblasts were not associated with activation of the UPR sensors PERK or activating transcription factor (ATF) 6 or with X-box binding protein-1 mRNA splicing in whole lung extracts. Exposure to Ox enhanced ATF4 immunoreactivity and nuclear protein content, followed by a 2- and 5-fold increase in ATF3 protein and mRNA expression, respectively. The accumulation of nuclear ATF4 protein coincided with induction of glutamate-cysteine ligase catalytic subunit, an ISR-responsive gene. Immunohistochemistry revealed that changes in ATF3/4 expression were prominent in the alveolus, whereas primary cell culture implicated epithelial and endothelial cells as targets. Finally, induction of ISR intermediates in the intact lung occurred in the absence of the phosphorylation of PKR, JNK, ERK1/2, and p38 MAPK. These findings demonstrate that Ox activates the ISR within the newborn lung and highlight regional and cell-specific alterations in the expression ISR transcription factors that regulate redox balance. PMID:21984568

  15. Transdermal neuromodulation of noradrenergic activity suppresses psychophysiological and biochemical stress responses in humans

    PubMed Central

    Tyler, William J.; Boasso, Alyssa M.; Mortimore, Hailey M.; Silva, Rhonda S.; Charlesworth, Jonathan D.; Marlin, Michelle A.; Aebersold, Kirsten; Aven, Linh; Wetmore, Daniel Z.; Pal, Sumon K.

    2015-01-01

    We engineered a transdermal neuromodulation approach that targets peripheral (cranial and spinal) nerves and utilizes their afferent pathways as signaling conduits to influence brain function. We investigated the effects of this transdermal electrical neurosignaling (TEN) method on sympathetic physiology under different experimental conditions. The TEN method involved delivering high-frequency pulsed electrical currents to ophthalmic and maxillary divisions of the right trigeminal nerve and cervical spinal nerve afferents. Under resting conditions, TEN significantly suppressed basal sympathetic tone compared to sham as indicated by functional infrared thermography of facial temperatures. In a different experiment, subjects treated with TEN reported significantly lower levels of tension and anxiety on the Profile of Mood States scale compared to sham. In a third experiment when subjects were experimentally stressed TEN produced a significant suppression of heart rate variability, galvanic skin conductance, and salivary α-amylase levels compared to sham. Collectively these observations demonstrate TEN can dampen basal sympathetic tone and attenuate sympathetic activity in response to acute stress induction. Our physiological and biochemical observations are consistent with the hypothesis that TEN modulates noradrenergic signaling to suppress sympathetic activity. We conclude that dampening sympathetic activity in such a manner represents a promising approach to managing daily stress. PMID:26353920

  16. Transdermal neuromodulation of noradrenergic activity suppresses psychophysiological and biochemical stress responses in humans.

    PubMed

    Tyler, William J; Boasso, Alyssa M; Mortimore, Hailey M; Silva, Rhonda S; Charlesworth, Jonathan D; Marlin, Michelle A; Aebersold, Kirsten; Aven, Linh; Wetmore, Daniel Z; Pal, Sumon K

    2015-01-01

    We engineered a transdermal neuromodulation approach that targets peripheral (cranial and spinal) nerves and utilizes their afferent pathways as signaling conduits to influence brain function. We investigated the effects of this transdermal electrical neurosignaling (TEN) method on sympathetic physiology under different experimental conditions. The TEN method involved delivering high-frequency pulsed electrical currents to ophthalmic and maxillary divisions of the right trigeminal nerve and cervical spinal nerve afferents. Under resting conditions, TEN significantly suppressed basal sympathetic tone compared to sham as indicated by functional infrared thermography of facial temperatures. In a different experiment, subjects treated with TEN reported significantly lower levels of tension and anxiety on the Profile of Mood States scale compared to sham. In a third experiment when subjects were experimentally stressed TEN produced a significant suppression of heart rate variability, galvanic skin conductance, and salivary α-amylase levels compared to sham. Collectively these observations demonstrate TEN can dampen basal sympathetic tone and attenuate sympathetic activity in response to acute stress induction. Our physiological and biochemical observations are consistent with the hypothesis that TEN modulates noradrenergic signaling to suppress sympathetic activity. We conclude that dampening sympathetic activity in such a manner represents a promising approach to managing daily stress. PMID:26353920

  17. Activation of physiological stress responses by a natural reward: Novel vs. repeated sucrose intake.

    PubMed

    Egan, Ann E; Ulrich-Lai, Yvonne M

    2015-10-15

    Pharmacological rewards, such as drugs of abuse, evoke physiological stress responses, including increased heart rate and blood pressure, and activation of the hypothalamic-pituitary-adrenal (HPA) axis. It is not clear to what extent the natural reward of palatable foods elicits similar physiological responses. In order to address this question, HPA axis hormones, heart rate, blood pressure and brain pCREB immunolabeling were assessed following novel and repeated sucrose exposure. Briefly, adult, male rats with ad libitum food and water were given either a single (day 1) or repeated (twice-daily for 14 days) brief (up to 30 min) exposure to a second drink bottle containing 4 ml of 30% sucrose drink vs. water (as a control for bottle presentation). Sucrose-fed rats drank more than water-fed on all days of exposure, as expected. On day 1 of exposure, heart rate, blood pressure, plasma corticosterone, and locomotion were markedly increased by presentation of the second drink bottle regardless of drink type. After repeated exposure (day 14), these responses habituated to similar extents regardless of drink type and pCREB immunolabeling in the hypothalamic paraventricular nucleus (PVN) also did not vary with drink type, whereas basolateral amygdala pCREB was increased by sucrose intake. Taken together, these data suggest that while sucrose is highly palatable, physiological stress responses were evoked principally by the drink presentation itself (e.g., an unfamiliar intervention by the investigators), as opposed to the palatability of the offered drink. PMID:25747321

  18. Stress-activated signaling responses leading to apoptosis following photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Oleinick, Nancy L.; He, Jin; Xue, Liang-yan; Separovic, Duska

    1998-05-01

    Photodynamic treatment with the phthalocyanine Pc 4, a mitochondrially localizing photosensitizer, is an efficient inducer of cell death by apoptosis, a cell suicide pathway that can be triggered by physiological stimuli as well as by various types of cellular damage. Upon exposure of the dye- loaded cells to red light, several stress signalling pathways are rapidly activated. In murine L5178Y-R lymphoblasts, caspase activation and other hallmarks of the final phase of apoptosis are observed within a few minutes post-PDT. In Chinese hamster CHO-K1 cells, the first signs of apoptosis are not observed for 1 - 2 hours. The possible involvement of three parallel mitogen-activated protein kinase (MAPK) signalling pathways has been investigated. The extracellular- regulated kinases (ERK-1 and ERK-2), that are thought to promote cell growth, are not appreciably altered by PDT. However, PDT causes marked activation of the stress-activated protein kinase (SAPK) cascade in both cell types and of the p38/HOG-type kinase in CHO cells. Both of these latter pathways have been demonstrated to be associated with apoptosis. A specific inhibitor of the ERK pathway did not alter PDT-induced apoptosis; however, an inhibitor of the p38 pathway partially blocked PDT-induced apoptosis. Blockage of the SAPK pathway is being pursued by a genetic approach. It appears that the SAPK and p38 pathways may participate in signaling apoptosis in response to PDT with Pc 4.

  19. Variability in emotional responsiveness and coping style during active avoidance as a window onto psychological vulnerability to stress.

    PubMed

    Gorka, Adam X; LaBar, Kevin S; Hariri, Ahmad R

    2016-05-01

    Individual differences in coping styles are associated with psychological vulnerability to stress. Recent animal research suggests that coping styles reflect trade-offs between proactive and reactive threat responses during active avoidance paradigms, with proactive responses associated with better stress tolerance. Based on these preclinical findings, we developed a novel instructed active avoidance paradigm to characterize patterns of proactive and reactive responses using behavioral, motoric, and autonomic measures in humans. Analyses revealed significant inter-individual variability not only in the magnitude of general emotional responsiveness but also the likelihood to specifically express proactive or reactive responses. In men but not women, individual differences in general emotional responsiveness were linked to increased trait anxiety while proactive coping style was linked to increased trait aggression. These patterns are consistent with preclinical findings and suggest that instructed active avoidance paradigms may be useful in assessing psychological vulnerability to stress using objective behavioral measures. PMID:26922874

  20. Heat stroke activates a stress-induced cytokine response in skeletal muscle.

    PubMed

    Welc, Steven S; Clanton, Thomas L; Dineen, Shauna M; Leon, Lisa R

    2013-10-15

    Heat stroke (HS) induces a rapid elevation in a number of circulating cytokines. This is often attributed to the stimulatory effects of endotoxin, released from damaged intestine, on immune cells. However, parenchymal cells also produce cytokines, and skeletal muscle, comprising a large proportion of body mass, is thought to participate. We tested the hypothesis that skeletal muscle exhibits a cytokine response to HS that parallels the systemic response in conscious mice heated to a core temperature of 42.4°C (TcMax). Diaphragm and hindlimb muscles showed a rapid rise in interleukin-6 (IL-6) and interleuin-10 (IL-10) mRNA and transient inhibition of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) throughout early recovery, a pattern that parallels changes in circulating cytokines. IL-6 protein was transiently elevated in both muscles at ∼32 min after reaching TcMax. Other responses observed included an upregulation of toll-like receptor-4 (TLR-4) and heat shock protein-72 (HSP-72) mRNA but no change in TLR-2 or HSP25 mRNA. Furthermore, c-jun and c-fos mRNA increased. Together, c-jun/c-fos form the activator protein-1 (AP-1) transcription factor, critical for stress-induced regulation of IL-6. Interestingly, a second "late-phase" (24 h) cytokine response, with increases in IL-6, IL-10, IL-1β, and TNF-α protein, were observed in hindlimb but not diaphragm muscle. These results demonstrate that skeletal muscle responds to HS with a distinct "stress-induced immune response," characterized by an early upregulation of IL-6, IL-10, and TLR-4 and suppression of IL-1β and TNF-α mRNA, a pattern discrete from classic innate immune cytokine responses. PMID:23928112

  1. Mapping the crossroads of immune activation and cellular stress response pathways

    PubMed Central

    Cláudio, Nuno; Dalet, Alexandre; Gatti, Evelina; Pierre, Philippe

    2013-01-01

    The innate immune cell network detects specific microbes and damages to cell integrity in order to coordinate and polarize the immune response against invading pathogens. In recent years, a cross-talk between microbial-sensing pathways and endoplasmic reticulum (ER) homeostasis has been discovered and have attracted the attention of many researchers from the inflammation field. Abnormal accumulation of proteins in the ER can be seen as a sign of cellular malfunction and triggers a collection of conserved emergency rescue pathways. These signalling cascades, which increase ER homeostasis and favour cell survival, are collectively known as the unfolded protein response (UPR). The induction or activation by microbial stimuli of several molecules linked to the ER stress response pathway have led to the conclusion that microbe sensing by immunocytes is generally associated with an UPR, which serves as a signal amplification cascade favouring inflammatory cytokines production. Induction of the UPR alone was shown to promote inflammation in different cellular and pathological models. Here we discuss how the innate immune and ER-signalling pathways intersect. Moreover, we propose that the induction of UPR-related molecules by microbial products does not necessarily reflect ER stress, but instead is an integral part of a specific transcription programme controlled by innate immunity receptors. PMID:23584529

  2. Salt stress response triggers activation of the jasmonate signaling pathway leading to inhibition of cell elongation in Arabidopsis primary root.

    PubMed

    Valenzuela, Camilo E; Acevedo-Acevedo, Orlando; Miranda, Giovanna S; Vergara-Barros, Pablo; Holuigue, Loreto; Figueroa, Carlos R; Figueroa, Pablo M

    2016-07-01

    Salinity is a severe abiotic stress that affects irrigated croplands. Jasmonate (JA) is an essential hormone involved in plant defense against herbivory and in responses to abiotic stress. However, the relationship between the salt stress response and the JA pathway in Arabidopsis thaliana is not well understood at molecular and cellular levels. In this work we investigated the activation of JA signaling by NaCl and its effect on primary root growth. We found that JA-responsive JAZ genes were up-regulated by salt stress in a COI1-dependent manner in the roots. Using a JA-Ile sensor we demonstrated that activation of JA signaling by salt stress occurs in the meristematic zone and stele of the differentiation zone and that this activation was dependent on JAR1 and proteasome functions. Another finding is that the elongation zone (EZ) and its cortical cells were significantly longer in JA-related mutants (AOS, COI1, JAZ3 and MYC2/3/4 genes) compared with wild-type plants under salt stress, revealing the participation of the canonical JA signaling pathway. Noteworthy, osmotic stress - a component of salt stress - inhibited cell elongation in the EZ in a COI1-dependent manner. We propose that salt stress triggers activation of the JA signaling pathway followed by inhibition of cell elongation in the EZ. We have shown that salt-inhibited root growth partially involves the jasmonate signaling pathway in Arabidopsis. PMID:27217545

  3. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress

    PubMed Central

    Courchet, Julien; Lewis, Tommy L.; Losón, Oliver C.; Hellberg, Kristina; Young, Nathan P.; Chen, Hsiuchen; Polleux, Franck; Chan, David C.; Shaw, Reuben J.

    2016-01-01

    Mitochondria undergo fragmentation in response to electron transport chain (ETC) poisons and mitochondrial DNA–linked disease mutations, yet how these stimuli mechanistically connect to the mitochondrial fission and fusion machinery is poorly understood. We found that the energy-sensing adenosine monophosphate (AMP)–activated protein kinase (AMPK) is genetically required for cells to undergo rapid mitochondrial fragmentation after treatment with ETC inhibitors. Moreover, direct pharmacological activation of AMPK was sufficient to rapidly promote mitochondrial fragmentation even in the absence of mitochondrial stress. A screen for substrates of AMPK identified mitochondrial fission factor (MFF), a mitochondrial outer-membrane receptor for DRP1, the cytoplasmic guanosine triphosphatase that catalyzes mitochondrial fission. Nonphosphorylatable and phosphomimetic alleles of the AMPK sites in MFF revealed that it is a key effector of AMPK-mediated mitochondrial fission. PMID:26816379

  4. Metabolism. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress.

    PubMed

    Toyama, Erin Quan; Herzig, Sébastien; Courchet, Julien; Lewis, Tommy L; Losón, Oliver C; Hellberg, Kristina; Young, Nathan P; Chen, Hsiuchen; Polleux, Franck; Chan, David C; Shaw, Reuben J

    2016-01-15

    Mitochondria undergo fragmentation in response to electron transport chain (ETC) poisons and mitochondrial DNA-linked disease mutations, yet how these stimuli mechanistically connect to the mitochondrial fission and fusion machinery is poorly understood. We found that the energy-sensing adenosine monophosphate (AMP)-activated protein kinase (AMPK) is genetically required for cells to undergo rapid mitochondrial fragmentation after treatment with ETC inhibitors. Moreover, direct pharmacological activation of AMPK was sufficient to rapidly promote mitochondrial fragmentation even in the absence of mitochondrial stress. A screen for substrates of AMPK identified mitochondrial fission factor (MFF), a mitochondrial outer-membrane receptor for DRP1, the cytoplasmic guanosine triphosphatase that catalyzes mitochondrial fission. Nonphosphorylatable and phosphomimetic alleles of the AMPK sites in MFF revealed that it is a key effector of AMPK-mediated mitochondrial fission. PMID:26816379

  5. The stress response neuropeptide CRF increases amyloid-β production by regulating γ-secretase activity

    PubMed Central

    Park, Hyo-Jin; Ran, Yong; Jung, Joo In; Holmes, Oliver; Price, Ashleigh R; Smithson, Lisa; Ceballos-Diaz, Carolina; Han, Chul; Wolfe, Michael S; Daaka, Yehia; Ryabinin, Andrey E; Kim, Seong-Hun; Hauger, Richard L; Golde, Todd E; Felsenstein, Kevin M

    2015-01-01

    The biological underpinnings linking stress to Alzheimer's disease (AD) risk are poorly understood. We investigated how corticotrophin releasing factor (CRF), a critical stress response mediator, influences amyloid-β (Aβ) production. In cells, CRF treatment increases Aβ production and triggers CRF receptor 1 (CRFR1) and γ-secretase internalization. Co-immunoprecipitation studies establish that γ-secretase associates with CRFR1; this is mediated by β-arrestin binding motifs. Additionally, CRFR1 and γ-secretase co-localize in lipid raft fractions, with increased γ-secretase accumulation upon CRF treatment. CRF treatment also increases γ-secretase activityin vitro, revealing a second, receptor-independent mechanism of action. CRF is the first endogenous neuropeptide that can be shown to directly modulate γ-secretase activity. Unexpectedly, CRFR1 antagonists also increased Aβ. These data collectively link CRF to increased Aβ through γ-secretase and provide mechanistic insight into how stress may increase AD risk. They also suggest that direct targeting of CRF might be necessary to effectively modulate this pathway for therapeutic benefit in AD, as CRFR1 antagonists increase Aβ and in some cases preferentially increase Aβ42 via complex effects on γ-secretase. PMID:25964433

  6. Inositol pyrophosphates regulate cell growth and the environmental stress response by activating the HDAC Rpd3L.

    PubMed

    Worley, Jeremy; Luo, Xiangxia; Capaldi, Andrew P

    2013-05-30

    Cells respond to stress and starvation by adjusting their growth rate and enacting stress defense programs. In eukaryotes this involves inactivation of TORC1, which in turn triggers downregulation of ribosome and protein synthesis genes and upregulation of stress response genes. Here we report that the highly conserved inositol pyrophosphate (PP-IP) second messengers (including 1-PP-IP5, 5-PP-IP4, and 5-PP-IP5) are also critical regulators of cell growth and the general stress response, acting in parallel with the TORC1 pathway to control the activity of the class I histone deacetylase Rpd3L. In fact, yeast cells that cannot synthesize any of the PP-IPs mount little to no transcriptional response to osmotic, heat, or oxidative stress. Furthermore, PP-IP-dependent regulation of Rpd3L occurs independently of the role individual PP-IPs (such as 5-PP-IP5) play in activating specialized stress/starvation response pathways. Thus, the PP-IP second messengers simultaneously activate and tune the global response to stress and starvation signals. PMID:23643537

  7. Acute Exercise-Induced Mitochondrial Stress Triggers an Inflammatory Response in the Myocardium via NLRP3 Inflammasome Activation with Mitophagy

    PubMed Central

    Li, Haiying; Miao, Weiguo; Ma, Jingfen; Xv, Zhen; Li, Jianyu; Zhang, Yong; Ji, Li Li

    2016-01-01

    Increasing evidence has indicated that acute strenuous exercise can induce a range of adverse reactions including oxidative stress and tissue inflammation. However, little is currently known regarding the mechanisms that underlie the regulation of the inflammatory response in the myocardium during acute heavy exercise. This study evaluated the mitochondrial function, NLRP3 inflammasome activation, and mitochondrial autophagy-related proteins to investigate the regulation and mechanism of mitochondrial stress regarding the inflammatory response of the rat myocardium during acute heavy exercise. The results indicated that the mitochondrial function of the myocardium was adaptively regulated to meet the challenge of stress during acute exercise. The exercise-induced mitochondrial stress also enhanced ROS generation and triggered an inflammatory reaction via the NLRP3 inflammasome activation. Moreover, the mitochondrial autophagy-related proteins including Beclin1, LC3, and Bnip3 were all significantly upregulated during acute exercise, which suggests that mitophagy was stimulated in response to the oxidative stress and inflammatory response in the myocardium. Taken together, our data suggest that, during acute exercise, mitochondrial stress triggers the rat myocardial inflammatory response via NLRP3 inflammasome activation and activates mitophagy to minimize myocardial injury. PMID:26770647

  8. The metal-responsive transcription factor-1 contributes to HIF-1 activation during hypoxic stress

    SciTech Connect

    Murphy, Brian J. . E-mail: brian.murphy@sri.com; Sato, Barbara G.; Dalton, Timothy P.; Laderoute, Keith R.

    2005-11-25

    Hypoxia-inducible factor-1 (HIF-1), the major transcriptional regulator of the mammalian cellular response to low oxygen (hypoxia), is embedded within a complex network of signaling pathways. We have been investigating the importance of another stress-responsive transcription factor, MTF-1, for the adaptation of cells to hypoxia. This article reports that MTF-1 plays a central role in hypoxic cells by contributing to HIF-1 activity. Loss of MTF-1 in transformed Mtf1 null mouse embryonic fibroblasts (MEFs) results in an attenuation of nuclear HIF-1{alpha} protein accumulation, HIF-1 transcriptional activity, and expression of an established HIF-1 target gene, glucose transporter-1 (Glut1). Mtf1 null (Mtf1 KO) MEFs also have constitutively higher levels of both glutathione (GSH) and the rate-limiting enzyme involved in GSH synthesis-glutamate cysteine ligase catalytic subunit-than wild type cells. The altered cellular redox state arising from increased GSH may perturb oxygen-sensing mechanisms in hypoxic Mtf1 KO cells and decrease the accumulation of HIF-1{alpha} protein. Together, these novel findings define a role for MTF-1 in the regulation of HIF-1 activity.

  9. Disturbance of wildlife by outdoor winter recreation: allostatic stress response and altered activity-energy budgets.

    PubMed

    Arlettaz, Raphaël; Nusslé, Sébastien; Baltic, Marjana; Vogel, Peter; Palme, Rupert; Jenni-Eiermann, Susanne; Patthey, Patrick; Genoud, Michel

    2015-07-01

    Anthropogenic disturbance of wildlife is of growing conservation concern, but we lack comprehensive approaches of its multiple negative effects. We investigated several effects of disturbance by winter outdoor sports on free-ranging alpine Black Grouse by simultaneously measuring their physiological and behavioral responses. We experimentally flushed radio-tagged Black Grouse from their snow burrows, once a day, during several successive days, and quantified their stress hormone levels (corticosterone metabolites in feces [FCM] collected. from individual snow burrows). We also measured feeding time allocation (activity budgets reconstructed from radio-emitted signals) in response to anthropogenic disturbance. Finally, we estimated the related extra energy expenditure that may be incurred: based on activity budgets, energy expenditure was modeled from measures of metabolism obtained from captive birds subjected to different ambient temperatures. The pattern of FCM excretion indicated the existence of a funneling effect as predicted by the allostatic theory of stress: initial stress hormone concentrations showed a wide inter-individual variation, which decreased during experimental flushing. Individuals with low initial pre-flushing FCM values augmented their concentration, while individuals with high initial FCM values lowered it. Experimental disturbance resulted in an extension of feeding duration during the following evening foraging bout, confirming the prediction that Black Grouse must compensate for the extra energy expenditure elicited by human disturbance. Birds with low initial baseline FCM concentrations were those that spent more time foraging. These FCM excretion and foraging patterns suggest that birds with high initial FCM concentrations might have been experiencing a situation of allostatic overload. The energetic model provides quantitative estimates of extra energy expenditure. A longer exposure to ambient temperatures outside the shelter of snow

  10. Uterine Endoplasmic Reticulum Stress and Its Unfolded Protein Response May Regulate Caspase 3 Activation in the Pregnant Mouse Uterus

    PubMed Central

    Suresh, Arvind; Subedi, Kalpana; Kyathanahalli, Chandrashekara; Jeyasuria, Pancharatnam; Condon, Jennifer C.

    2013-01-01

    We have previously proposed that uterine caspase-3 may modulate uterine contractility in a gestationally regulated fashion. The objective of this study was to determine the mechanism by which uterine caspase-3 is activated and consequently controlled in the pregnant uterus across gestation. Utilizing the mouse uterus as our gestational model we examined the intrinsic and extrinsic apoptotic signaling pathways and the endoplasmic reticulum stress response as potential activators of uterine caspase-3 at the transcriptional and translational level. Our study revealed robust activation of the uterine myocyte endoplasmic reticulum stress response and its adaptive unfolded protein response during pregnancy coinciding respectively with increased uterine caspase-3 activity and its withdrawal to term. In contrast the intrinsic and extrinsic apoptotic signaling pathways remained inactive across gestation. We speculate that physiological stimuli experienced by the pregnant uterus likely potentiates the uterine myocyte endoplasmic reticulum stress response resulting in elevated caspase-3 activation, which is isolated to the pregnant mouse myometrium. However as term approaches, activation of an elevated adaptive unfolded protein response acts to limit the endoplasmic reticulum stress response inhibiting caspase-3 resulting in its decline towards term. We speculate that these events have the capacity to regulate gestational length in a caspase-3 dependent manner. PMID:24058658

  11. Jasmonate signaling in plant stress responses and development - active and inactive compounds.

    PubMed

    Wasternack, Claus; Strnad, Miroslav

    2016-09-25

    Jasmonates (JAs) are lipid-derived signals mediating plant responses to biotic and abiotic stresses and in plant development. Following the elucidation of each step in their biosynthesis and the important components of perception and signaling, several activators, repressors and co-repressors have been identified which contribute to fine-tuning the regulation of JA-induced gene expression. Many of the metabolic reactions in which JA participates, such as conjugation with amino acids, glucosylation, hydroxylation, carboxylation, sulfation and methylation, lead to numerous compounds with different biological activities. These metabolites may be highly active, partially active in specific processes or inactive. Hydroxylation, carboxylation and sulfation inactivate JA signaling. The precursor of JA biosynthesis, 12-oxo-phytodienoic acid (OPDA), has been identified as a JA-independent signaling compound. An increasing number of OPDA-specific processes is being identified. To conclude, the numerous JA compounds and their different modes of action allow plants to respond specifically and flexibly to alterations in the environment. PMID:26581489

  12. Deteriorated Stress Response in Stationary-Phase Yeast: Sir2 and Yap1 Are Essential for Hsf1 Activation by Heat Shock and Oxidative Stress, Respectively

    PubMed Central

    Cohen, Aviv; Bar-Nun, Shoshana

    2014-01-01

    Stationary-phase cultures have been used as an important model of aging, a complex process involving multiple pathways and signaling networks. However, the molecular processes underlying stress response of non-dividing cells are poorly understood, although deteriorated stress response is one of the hallmarks of aging. The budding yeast Saccharomyces cerevisiae is a valuable model organism to study the genetics of aging, because yeast ages within days and are amenable to genetic manipulations. As a unicellular organism, yeast has evolved robust systems to respond to environmental challenges. This response is orchestrated largely by the conserved transcription factor Hsf1, which in S. cerevisiae regulates expression of multiple genes in response to diverse stresses. Here we demonstrate that Hsf1 response to heat shock and oxidative stress deteriorates during yeast transition from exponential growth to stationary-phase, whereas Hsf1 activation by glucose starvation is maintained. Overexpressing Hsf1 does not significantly improve heat shock response, indicating that Hsf1 dwindling is not the major cause for Hsf1 attenuated response in stationary-phase yeast. Rather, factors that participate in Hsf1 activation appear to be compromised. We uncover two factors, Yap1 and Sir2, which discretely function in Hsf1 activation by oxidative stress and heat shock. In Δyap1 mutant, Hsf1 does not respond to oxidative stress, while in Δsir2 mutant, Hsf1 does not respond to heat shock. Moreover, excess Sir2 mimics the heat shock response. This role of the NAD+-dependent Sir2 is supported by our finding that supplementing NAD+ precursors improves Hsf1 heat shock response in stationary-phase yeast, especially when combined with expression of excess Sir2. Finally, the combination of excess Hsf1, excess Sir2 and NAD+ precursors rejuvenates the heat shock response. PMID:25356557

  13. Response of the nitrergic system to activation of the neuroendocrine stress axis

    PubMed Central

    Chen, Hsiao-Jou Cortina; Spiers, Jereme G.; Sernia, Conrad; Lavidis, Nickolas A.

    2015-01-01

    Exposure to stressful stimuli causes activation of the hypothalamic-pituitary-adrenal axis which rapidly releases high concentrations of glucocorticoid stress hormones, resulting in increased cellular metabolism and spontaneous oxygen and nitrogen radical formation. High concentrations of nitrogen radicals, including nitric oxide, cause damage to cellular proteins in addition to inhibiting components of the mitochondrial transport chain, leading to cellular energy deficiency. During stress exposure, pharmacological inhibition of nitric oxide production reduces indicators of anxiety- and depressive-like behavior in animal models. Therefore, the purpose of this review is to present an overview of the current literature on stress-evoked changes in the nitrergic system, particularly within neural tissue. PMID:25653586

  14. Activation of the cnidarian oxidative stress response by ultraviolet radiation, polycyclic aromatic hydrocarbons and crude oil

    PubMed Central

    Tarrant, A. M.; Reitzel, A. M.; Kwok, C. K.; Jenny, M. J.

    2014-01-01

    Organisms are continuously exposed to reactive chemicals capable of causing oxidative stress and cellular damage. Antioxidant enzymes, such as superoxide dismutases (SODs) and catalases, are present in both prokaryotes and eukaryotes and provide an important means of neutralizing such oxidants. Studies in cnidarians have previously documented the occurrence of antioxidant enzymes (transcript expression, protein expression and/or enzymatic activity), but most of these studies have not been conducted in species with sequenced genomes or included phylogenetic analyses, making it difficult to compare results across species due to uncertainties in the relationships between genes. Through searches of the genome of the sea anemone Nematostella vectensis Stephenson, one catalase gene and six SOD family members were identified, including three copper/zinc-containing SODs (CuZnSODs), two manganese-containing SODs (MnSODs) and one copper chaperone of SOD (CCS). In 24 h acute toxicity tests, juvenile N. vectensis showed enhanced sensitivity to combinations of ultraviolet radiation (UV) and polycyclic aromatic hydrocarbons (PAHs, specifically pyrene, benzo[a]pyrene and fluoranthene) relative to either stressor alone. Adult N. vectensis exhibited little or no mortality following UV, benzo[a]pyrene or crude oil exposure but exhibited changes in gene expression. Antioxidant enzyme transcripts were both upregulated and downregulated following UV and/or chemical exposure. Expression patterns were most strongly affected by UV exposure but varied between experiments, suggesting that responses vary according to the intensity and duration of exposure. These experiments provide a basis for comparison with other cnidarian taxa and for further studies of the oxidative stress response in N. vectensis. PMID:24436378

  15. Deficiency of glutathione transferase zeta causes oxidative stress and activation of antioxidant response pathways.

    PubMed

    Blackburn, Anneke C; Matthaei, Klaus I; Lim, Cindy; Taylor, Matthew C; Cappello, Jean Y; Hayes, John D; Anders, M W; Board, Philip G

    2006-02-01

    Glutathione S-transferase (GST) zeta (GSTZ1-1) plays a significant role in the catabolism of phenylalanine and tyrosine, and a deficiency of GSTZ1-1 results in the accumulation of maleylacetoacetate and its derivatives maleylacetone (MA) and succinylacetone. Induction of GST subunits was detected in the liver of Gstz1(-/-) mice by Western blotting with specific antisera and high-performance liquid chromatography analysis of glutathione affinity column-purified proteins. The greatest induction was observed in members of the mu class. Induction of NAD(P)H:quinone oxidoreductase 1 and the catalytic and modifier subunits of glutamate-cysteine ligase was also observed. Many of the enzymes that are induced in Gstz1(-/-) mice are regulated by antioxidant response elements that respond to oxidative stress via the Keap1/Nrf2 pathway. It is significant that diminished glutathione concentrations were also observed in the liver of Gstz1(-/-) mice, which supports the conclusion that under normal dietary conditions, the accumulation of electrophilic intermediates such as maleylacetoacetate and MA results in a high level of oxidative stress. Elevated GST activities in the livers of Gstz1(-/-) mice suggest that GSTZ1-1 deficiency may alter the metabolism of some drugs and xenobiotics. Gstz1(-/-) mice given acetaminophen demonstrated increased hepatotoxicity compared with wild-type mice. This toxicity may be attributed to the increased GST activity or the decreased hepatic concentrations of glutathione, or both. Patients with acquired deficiency of GSTZ1-1 caused by therapeutic exposure to dichloroacetic acid for the clinical treatment of lactic acidosis may be at increased risk of drug- and chemical-induced toxicity. PMID:16278372

  16. The Adaptogens Rhodiola and Schizandra Modify the Response to Immobilization Stress in Rabbits by Suppressing the Increase of Phosphorylated Stress-activated Protein Kinase, Nitric Oxide and Cortisol

    PubMed Central

    Panossian, Alexander; Hambardzumyan, Marina; Hovhanissyan, Areg; Wikman, Georg

    2007-01-01

    Adaptogens possess anti-fatigue and anti-stress activities that can increase mental and physical working performance against a background of fatigue or stress. The aim of the present study was to ascertain which mediators of stress response are significantly involved in the mechanisms of action of adaptogens, and to determine their relevance as biochemical markers for evaluating anti-stress effects in rabbits subjected to restraint stress. Blood levels of stress-activated protein kinase (SAPK/JNK), the phosphorylated kinase p-SAPK/p-JNK, nitric oxide (NO), cortisol, testosterone, prostaglandin E2, leukotriene B4 and thromboxane B2 were determined in groups of animals prior to daily oral administration of placebo, rhodioloside or extracts of Eleutherococcus senticosus, Schizandra chinensis, Rhodiola rosea, Bryonia alba and Panax ginseng over a 7 day period. Ten minutes after the final treatment, animals were immobilized for 2 hours and blood levels of the markers re-determined. In the placebo group, only p-SAPK/p-JNK, NO and cortisol were increased significantly (by 200–300% cf basal levels) following restraint stress, whilst in animals that had received multiple doses of adaptogens/stress-protectors, the levels of NO and cortisol remained practically unchanged after acute stress. Rhodioloside and extracts of S. chinensis and R. rosea were the most active inhibitors of stress-induced p-SAPK/p-JNK. E. senticosus, B. alba and P. ginseng exerted little effect on p-SAPK/p-JNK levels. It is suggested that the inhibitory effects of R. rosea and S. chinensis on p-SAPK/p-JNK activation may be associated with their antidepressant activity as well as their positive effects on mental performance under stress. PMID:21901061

  17. Stress response and cardiac activity of term and preterm calves in the perinatal period.

    PubMed

    Nagel, Christina; Aurich, Jörg; Trenk, Lisa; Ille, Natascha; Drillich, Marc; Pohl, Werner; Aurich, Christine

    2016-10-01

    This study tested the hypothesis of gestational age affecting fetal cardiac activity and the stress response at birth. Heart rate (HR), heart rate variability variables, SD of the beat-to-beat interval and root mean square of successive beat-to-beat differences, and postnatal salivary cortisol concentration were studied in calves born at term (Term, n = 7, gestation length 286.3 ± 2.1 days) or after induction of parturition (Preterm, n = 7, gestation length 279.6 ± 0.2 days). Observation periods covered the last month of gestation (phase A), the last hours before birth including the first stage of labor (phase B), and the neonatal period (phase C). Fetal HR decreased in phase A (P < 0.001) and did not differ between groups. During phase B, HR increased (P < 0.05) and was higher in Preterm than in Term calves in phases B (P < 0.05) and C (P < 0.01). In Term calves, heart rate variability increased from Day 6 until birth (P < 0.05). At birth, SD of the beat-to-beat interval was higher in Term than in Preterm calves (P < 0.01). On Day 1 after birth (phase C), HR accelerations were more frequent in Term than Preterm calves (P < 0.01), whereas decelerations were more frequent in Preterm calves (P < 0.05). Cortisol concentration increased postnatally (P < 0.001) and was correlated with gestation length (r ≥ 0.68, P < 0.01). Because of a certain degree of immaturity, the ability to cope with the stress of birth may be impaired in calves born 1 week before term. PMID:27312949

  18. Failure to upregulate Agrp and Orexin in response to activity based anorexia in weight loss vulnerable rats characterized by passive stress coping and prenatal stress experience.

    PubMed

    Boersma, Gretha J; Liang, Nu-Chu; Lee, Richard S; Albertz, Jennifer D; Kastelein, Anneke; Moody, Laura A; Aryal, Shivani; Moran, Timothy H; Tamashiro, Kellie L

    2016-05-01

    We hypothesize that anorexia nervosa (AN) poses a physiological stress. Therefore, the way an individual copes with stress may affect AN vulnerability. Since prenatal stress (PNS) exposure alters stress responsivity in offspring this may increase their risk of developing AN. We tested this hypothesis using the activity based anorexia (ABA) rat model in control and PNS rats that were characterized by either proactive or passive stress-coping behavior. We found that PNS passively coping rats ate less and lost more weight during the ABA paradigm. Exposure to ABA resulted in higher baseline corticosterone and lower insulin levels in all groups. However, leptin levels were only decreased in rats with a proactive stress-coping style. Similarly, ghrelin levels were increased only in proactively coping ABA rats. Neuropeptide Y (Npy) expression was increased and proopiomelanocortin (Pomc) expression was decreased in all rats exposed to ABA. In contrast, agouti-related peptide (Agrp) and orexin (Hctr) expression were increased in all but the PNS passively coping ABA rats. Furthermore, DNA methylation of the orexin gene was increased after ABA in proactive coping rats and not in passive coping rats. Overall our study suggests that passive PNS rats have innate impairments in leptin and ghrelin in responses to starvation combined with prenatal stress associated impairments in Agrp and orexin expression in response to starvation. These impairments may underlie decreased food intake and associated heightened body weight loss during ABA in the passively coping PNS rats. PMID:26907996

  19. NEFAs activate the oxidative stress-mediated NF-κB signaling pathway to induce inflammatory response in calf hepatocytes.

    PubMed

    Shi, Xiaoxia; Li, Dangdang; Deng, Qinghua; Li, Yu; Sun, Guoquan; Yuan, Xue; Song, Yuxiang; Wang, Zhe; Li, Xiaobing; Li, Xinwei; Liu, Guowen

    2015-01-01

    Non-esterified fatty acids (NEFAs) are important induction factors of inflammatory responses in some metabolic diseases. High plasma levels of NEFAs and oxidative stress exist in the dairy cows with ketosis. The aim of this study was to investigate whether high levels of NEFAs can induce inflammatory response and the specific molecular mechanism in the hepatocytes of dairy cow. In vitro, primary cultured bovine hepatocytes were treated with different concentrations of NEFAs, PDTC (an NF-κB inhibitor) and NAC (an antioxidant). NEFAs significantly activated NF-κB pathway. Activated NF-κB upregulated the release of pro-inflammatory cytokines, thereby inducing inflammatory response in bovine hepatocytes. When PDTC was added, activation of NF-κB-mediated inflammatory response induced by NEFAs was inhibited. NEFAs treatment results in the overproduction of the markers of oxidative stress, reactive oxygen species (ROS) and malondialdehyde (MDA), which were ameliorated by NAC treatment. These increased ROS and MDA were caused by decreasing activity of antioxidant system, including glutathione peroxidase, superoxide dismutase and catalase, in bovine hepatocytes treated with NEFAs. NAC also ameliorated NEFAs-mediated NF-κB activation and the release of pro-inflammatory cytokines. These results indicate that high concentrations of NEFAs can induce cattle hepatocytes inflammatory response through activating the oxidative stress-mediated NF-κB signaling pathway. PMID:25465477

  20. Neuronal responses to physiological stress.

    PubMed

    Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger

    2012-01-01

    Physiological stress can be defined as any external or internal condition that challenges the homeostasis of a cell or an organism. It can be divided into three different aspects: environmental stress, intrinsic developmental stress, and aging. Throughout life all living organisms are challenged by changes in the environment. Fluctuations in oxygen levels, temperature, and redox state for example, trigger molecular events that enable an organism to adapt, survive, and reproduce. In addition to external stressors, organisms experience stress associated with morphogenesis and changes in inner chemistry during normal development. For example, conditions such as intrinsic hypoxia and oxidative stress, due to an increase in tissue mass, have to be confronted by developing embryos in order to complete their development. Finally, organisms face the challenge of stochastic accumulation of molecular damage during aging that results in decline and eventual death. Studies have shown that the nervous system plays a pivotal role in responding to stress. Neurons not only receive and process information from the environment but also actively respond to various stresses to promote survival. These responses include changes in the expression of molecules such as transcription factors and microRNAs that regulate stress resistance and adaptation. Moreover, both intrinsic and extrinsic stresses have a tremendous impact on neuronal development and maintenance with implications in many diseases. Here, we review the responses of neurons to various physiological stressors at the molecular and cellular level. PMID:23112806

  1. Neuronal Responses to Physiological Stress

    PubMed Central

    Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger

    2012-01-01

    Physiological stress can be defined as any external or internal condition that challenges the homeostasis of a cell or an organism. It can be divided into three different aspects: environmental stress, intrinsic developmental stress, and aging. Throughout life all living organisms are challenged by changes in the environment. Fluctuations in oxygen levels, temperature, and redox state for example, trigger molecular events that enable an organism to adapt, survive, and reproduce. In addition to external stressors, organisms experience stress associated with morphogenesis and changes in inner chemistry during normal development. For example, conditions such as intrinsic hypoxia and oxidative stress, due to an increase in tissue mass, have to be confronted by developing embryos in order to complete their development. Finally, organisms face the challenge of stochastic accumulation of molecular damage during aging that results in decline and eventual death. Studies have shown that the nervous system plays a pivotal role in responding to stress. Neurons not only receive and process information from the environment but also actively respond to various stresses to promote survival. These responses include changes in the expression of molecules such as transcription factors and microRNAs that regulate stress resistance and adaptation. Moreover, both intrinsic and extrinsic stresses have a tremendous impact on neuronal development and maintenance with implications in many diseases. Here, we review the responses of neurons to various physiological stressors at the molecular and cellular level. PMID:23112806

  2. Greater amygdala activity and dorsomedial prefrontal–amygdala coupling are associated with enhanced inflammatory responses to stress

    PubMed Central

    Muscatell, Keely A.; Dedovic, Katarina; Slavich, George M.; Jarcho, Michael R.; Breen, Elizabeth C.; Bower, Julienne E.; Irwin, Michael R.; Eisenberger, Naomi I.

    2015-01-01

    Psychological stress is implicated in the etiology of many common chronic diseases and mental health disorders. Recent research suggests that inflammation may be a key biological mediator linking stress and health. Nevertheless, the neurocognitive pathways underlying stress-related increases in inflammatory activity are largely unknown. The present study thus examined associations between neural and inflammatory responses to an acute laboratory-based social stressor. Healthy female participants (n = 31) were exposed to a brief episode of stress while they underwent an fMRI scan. Blood samples were taken before and after the stressor, and plasma was assayed for markers of inflammatory activity. Exposure to the stressor was associated with significant increases in feelings of social evaluation and rejection, and with increases in levels of inflammation. Analyses linking the neural and inflammatory data revealed that heightened neural activity in the amygdala in response to the stressor was associated with greater increases in inflammation. Functional connectivity analyses indicated that individuals who showed stronger coupling between the amygdala and the dorsomedial prefrontal cortex (DMPFC) also showed a heightened inflammatory response to the stressor. Interestingly, activity in a different set of neural regions was related to increases in feelings of social rejection. These data show that greater amygdala activity in response to a stressor, as well as tighter coupling between the amygdala and the DMPFC, are associated with greater increases in inflammatory activity. Results from this study begin to identify neural mechanisms that might link stress with increased risk for inflammation-related disorders such as cardiovascular disease and depression. PMID:25016200

  3. Opioid activity in behavioral and heart rate responses of tethered pigs to acute stress.

    PubMed

    Loijens, L W S; Janssens, C J J G; Schouten, W G P; Wiegant, V M

    2002-04-15

    In a longitudinal experiment, effects of long-term tether housing on heart rate and behavioral responses to an acute stressor (a 15-min challenge with a nosesling) were investigated in pigs. The animals were challenged during loose housing and again after 10-11 weeks of tether housing. To detect possible changes in endogenous opioid systems modifying these responses, the pigs were pretreated with the opioid receptor antagonist naloxone (0.5 mg/kg body weight, iv). In response to the nosesling challenge, the animals showed pronounced resistance behavior and a sharp rise in heart rate. Following this initial phase of resistance, the heart rate dropped to prechallenge levels or below this line, and the pigs seemed to become sedated. Pretreatment with naloxone increased the heart rate response in animals that were long-term tether housed (n=12). No such effect was found in the control group (n=5) that was loose-housed during the entire experiment, indicating that the impact of endogenous opioid systems mitigating heart rate responses to acute stress had increased as a result of long-term tether housing. Changes in the effect of naloxone on the behavioral response were not found. Adaptive changes in opioid systems may prevent excessive physiological reactions to acute stress and, thus, may serve as a coping mechanism. PMID:12020727

  4. HCV induces transforming growth factor β1 through activation of endoplasmic reticulum stress and the unfolded protein response

    PubMed Central

    Chusri, Pattranuch; Kumthip, Kattareeya; Hong, Jian; Zhu, Chuanlong; Duan, Xiaoqiong; Jilg, Nikolaus; Fusco, Dahlene N.; Brisac, Cynthia; Schaefer, Esperance A.; Cai, Dachuan; Peng, Lee F.; Maneekarn, Niwat; Lin, Wenyu; Chung, Raymond T.

    2016-01-01

    HCV replication disrupts normal endoplasmic reticulum (ER) function and activates a signaling network called the unfolded protein response (UPR). UPR is directed by three ER transmembrane proteins including ATF6, IRE1, and PERK. HCV increases TGF-β1 and oxidative stress, which play important roles in liver fibrogenesis. HCV has been shown to induce TGF-β1 through the generation of reactive oxygen species (ROS) and p38 MAPK, JNK, ERK1/2, and NFκB-dependent pathways. However, the relationship between HCV-induced ER stress and UPR activation with TGF-β1 production has not been fully characterized. In this study, we found that ROS and JNK inhibitors block HCV up-regulation of ER stress and UPR activation. ROS, JNK and IRE1 inhibitors blocked HCV-activated NFκB and TGF-β1 expression. ROS, ER stress, NFκB, and TGF-β1 signaling were blocked by JNK specific siRNA. Knockdown IRE1 inhibited JFH1-activated NFκB and TGF-β1 activity. Knockdown of JNK and IRE1 blunted JFH1 HCV up-regulation of NFκB and TGF-β1 activation. We conclude that HCV activates NFκB and TGF-β1 through ROS production and induction of JNK and the IRE1 pathway. HCV infection induces ER stress and the UPR in a JNK-dependent manner. ER stress and UPR activation partially contribute to HCV-induced NF-κB activation and enhancement of TGF-β1. PMID:26927933

  5. Assessing Sources of Stress to Aquatic Ecosystems: Using Biomarkers and Bioindicators to Characterize Exodure-Response Profiles of Anthropogenic Activities

    SciTech Connect

    Adams, S.M.

    1999-03-29

    Establishing causal relationships between sources of environmental stressors and aquatic ecosystem health if difficult because of the many biotic and abiotic factors which can influence or modify responses of biological systems to stress, the orders of magnitude involved in extrapolation over both spatial and temporal scales, and compensatory mechanisms such as density-dependent responses that operate in populations. To address the problem of establishing causality between stressors and effects on aquatic systems, a diagnostic approach, based on exposure-response profiles for various anthropogenic activities, was developed to help identify sources of stress responsible for effects on aquatic systems at ecological significant levels of biological organization (individual, population, community). To generate these exposure-effects profiles, biomarkers of exposure were plotted against bioindicators of corresponding effects for several major anthropogenic activities including petrochemical , pulp and paper, domestic sewage, mining operations, land-development activities, and agricultural activities. Biomarkers of exposure to environmental stressors varied depending on the type of anthropogenic activity involved. Bioindicator effects, however, including histopathological lesions, bioenergetic status, individual growth, reproductive impairment, and community-level responses were similar among many of the major anthropogenic activities. This approach is valuable to help identify and diagnose sources of stressors in environments impacted by multiple stressors. By identifying the types and sources of environmental stressors, aquatic ecosystems can be more effectively protected and managed to maintain acceptable levels of environmental quality and ecosystem fitness.

  6. Plant responses to water stress

    PubMed Central

    Kar, Rup Kumar

    2011-01-01

    Terrestrial plants most often encounter drought stress because of erratic rainfall which has become compounded due to present climatic changes.Responses of plants to water stress may be assigned as either injurious change or tolerance index. One of the primary and cardinal changes in response to drought stress is the generation of reactive oxygen species (ROS), which is being considered as the cause of cellular damage. However, recently a signaling role of such ROS in triggering the ROS scavenging system that may confer protection or tolerance against stress is emerging. Such scavenging system consists of antioxidant enzymes like SOD, catalase and peroxidases, and antioxidant compounds like ascorbate, reduced glutathione; a balance between ROS generation and scavenging ultimately determines the oxidative load. As revealed in case of defence against pathogen, signaling via ROS is initiated by NADPH oxidase-catalyzed superoxide generation in the apoplastic space (cell wall) followed by conversion to hydrogen peroxide by the activity of cell wall-localized SOD. Wall peroxidase may also play role in ROS generation for signaling. Hydrogen peroxide may use Ca2+ and MAPK pathway as downstream signaling cascade. Plant hormones associated with stress responses like ABA and ethylene play their role possibly via a cross talk with ROS towards stress tolerance, thus projecting a dual role of ROS under drought stress. PMID:22057331

  7. [Endoplasmic reticulum stress response in osteogenesis].

    PubMed

    Saito, Atsushi; Imaizumi, Kazunori

    2013-11-01

    Various cellular conditions such as synthesis of abundant proteins, expressions of mutant proteins and oxidative stress lead to accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) lumen. This type of stress is called ER stress. The excessive ER stress causes cellular damages followed by apoptosis. When ER stress occurs, cells are activated ER stress response (unfolded protein response) to avoid cellular damages. Recently, it has been clear that ER stress response plays crucial roles not only in cell survival after ER stress but also in regulating various cellular functions and tissue formations. In particular, ER stress and ER stress response regulate protein quality control, secretory protein production, and smooth secretion of proteins in the cells such as osteoblasts which synthesize and secrete enormous matrix proteins. PMID:24162596

  8. Reduction of photosynthetic sensitivity in response to abiotic stress in tomato is mediated by a new generation plant activator

    PubMed Central

    2013-01-01

    Background Yield losses as a result of abiotic stress factors present a significant challenge for the future of global food production. While breeding technologies provide potential to combat negative stress-mediated outcomes over time, interventions which act to prime plant tolerance to stress, via the use of phytohormone-based elicitors for example, could act as a valuable tool for crop protection. However, the translation of fundamental biology into functioning solution is often constrained by knowledge-gaps. Results Photosynthetic and transcriptomic responses were characterised in young tomato (Solanum lycopersicum L.) seedlings in response to pre-treatment with a new plant health activator technology, ‘Alethea’, followed by a subsequent 100 mM salinity stress. Alethea is a novel proprietary technology composed of three key constituent compounds; the hitherto unexplored compound potassium dihydrojasmonate, an analogue of jasmonic acid; sodium benzoate, a carboxylic acid precursor to salicylic acid, and the α-amino acid L-arginine. Salinity treatment led to a maximal 47% reduction in net photosynthetic rate 8 d following NaCl treatment, yet in Alethea pre-treated seedlings, sensitivity to salinity stress was markedly reduced during the experimental period. Microarray analysis of leaf transcriptional responses showed that while salinity stress and Alethea individually impacted on largely non-overlapping, distinct groups of genes, Alethea pre-treatment substantially modified the response to salinity. Alethea affected the expression of genes related to biotic stress, ethylene signalling, cell wall synthesis, redox signalling and photosynthetic processes. Since Alethea had clear effects on photosynthesis/chloroplastic function at the physiological and molecular levels, we also investigated the ability of Alethea to protect various crop species against methyl viologen, a potent generator of oxidative stress in chloroplasts. Alethea pre-treatment produced

  9. Ethanol metabolism and oxidative stress are required for unfolded protein response activation and steatosis in zebrafish with alcoholic liver disease

    PubMed Central

    Tsedensodnom, Orkhontuya; Vacaru, Ana M.; Howarth, Deanna L.; Yin, Chunyue; Sadler, Kirsten C.

    2013-01-01

    SUMMARY Secretory pathway dysfunction and lipid accumulation (steatosis) are the two most common responses of hepatocytes to ethanol exposure and are major factors in the pathophysiology of alcoholic liver disease (ALD). However, the mechanisms by which ethanol elicits these cellular responses are not fully understood. Recent data indicates that activation of the unfolded protein response (UPR) in response to secretory pathway dysfunction can cause steatosis. Here, we examined the relationship between alcohol metabolism, oxidative stress, secretory pathway stress and steatosis using zebrafish larvae. We found that ethanol was immediately internalized and metabolized by larvae, such that the internal ethanol concentration in 4-day-old larvae equilibrated to 160 mM after 1 hour of exposure to 350 mM ethanol, with an average ethanol metabolism rate of 56 μmol/larva/hour over 32 hours. Blocking alcohol dehydrogenase 1 (Adh1) and cytochrome P450 2E1 (Cyp2e1), the major enzymes that metabolize ethanol, prevented alcohol-induced steatosis and reduced induction of the UPR in the liver. Thus, we conclude that ethanol metabolism causes ALD in zebrafish. Oxidative stress generated by Cyp2e1-mediated ethanol metabolism is proposed to be a major culprit in ALD pathology. We found that production of reactive oxygen species (ROS) increased in larvae exposed to ethanol, whereas inhibition of the zebrafish CYP2E1 homolog or administration of antioxidants reduced ROS levels. Importantly, these treatments also blocked ethanol-induced steatosis and reduced UPR activation, whereas hydrogen peroxide (H2O2) acted as a pro-oxidant that synergized with low doses of ethanol to induce the UPR. Collectively, these data demonstrate that ethanol metabolism and oxidative stress are conserved mechanisms required for the development of steatosis and hepatic dysfunction in ALD, and that these processes contribute to ethanol-induced UPR activation and secretory pathway stress in hepatocytes. PMID

  10. Stress Responses of Shewanella

    PubMed Central

    Yin, Jianhua; Gao, Haichun

    2011-01-01

    The shewanellae are ubiquitous in aquatic and sedimentary systems that are chemically stratified on a permanent or seasonal basis. In addition to their ability to utilize a diverse array of terminal electron acceptors, the microorganisms have evolved both common and unique responding mechanisms to cope with various stresses. This paper focuses on the response and adaptive mechanism of the shewanellae, largely based on transcriptional data. PMID:21912550

  11. Upregulation of the SERCA-type Ca2+ pump activity in response to endoplasmic reticulum stress in PC12 cells

    PubMed Central

    Højmann Larsen, Annette; Frandsen, Aase; Treiman, Marek

    2001-01-01

    Background Ca2+-ATPases of endoplasmic reticulum (SERCAs) are responsible for maintenance of the micro- to millimolar Ca2+ ion concentrations within the endoplasmic reticulum (ER) of eukaryotic cells. This intralumenal Ca2+ storage is important for the generation of Ca2+ signals as well as for the correct folding and posttranslational processing of proteins entering ER after synthesis. ER perturbations such as depletion of Ca2+ or abolishing the oxidative potential, inhibition of glycosylation, or block of secretory pathway, activate the Unfolded Protein Response, consisting of an upregulation of a number of ER-resident chaperones/stress proteins in an effort to boost the impaired folding capacity. Results We show here that in PC12 cells, depletion of ER Ca2+ by EGTA, as well as inhibition of disulphide bridge formation within the ER by dithiotreitol or inhibition of N-glycosylation by tunicamycin, led to a 2- to 3-fold increase of the SERCA-mediated 45Ca2+ transport to microsomes isolated from cells exposed to these stress agents. The time course of this response corresponded to that for transcriptional upregulation of ER stress proteins, as well as to the increase in the SERCA2b mRNA, as we recently observed in an independent study. Conclusions These findings provide the first functional evidence for the increase of SERCA pumping capacity in cells subjected to the ER stress. Since at least three different and unrelated mechanisms of eliciting the ER stress response were found to cause this functional upregulation of Ca2+ transport into the ER, these results support the existence of a coupling between the induction of the UPR pathway in general, and the regulation of expression of at least one of the SERCA pump isoforms. PMID:11319943

  12. Activation of Nrf2-mediated oxidative stress response in macrophages by hypochlorous acid

    SciTech Connect

    Pi Jingbo Zhang Qiang; Woods, Courtney G.; Wong, Victoria; Collins, Sheila; Andersen, Melvin E.

    2008-02-01

    Hypochlorous acid (HOCl), a potent oxidant generated when chlorine gas reacts with water, is important in the pathogenesis of many disorders. Transcription factor Nrf2-mediated antioxidant response represents a critical cellular defense mechanism that serves to maintain intracellular redox homeostasis and limit oxidative damage. In the present study, the effect of HOCl on Nrf2 activation was investigated in macrophages, one of the target cells of chlorine gas exposure. Exposure of RAW 264.7 macrophages to HOCl resulted in increased protein levels of Nrf2 in nuclear extractions, as well as a time- and dose-dependent increase in the expression of Nrf2 target genes, including heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1 (NQO-1), glutamate cysteine ligase catalytic subunit (GCLC), and glutathione synthetase (GS). Additionally, intracellular glutathione (GSH), which is the prime scavenger for HOCl in cells, decreased within the first hour of HOCl exposure. The decline was followed by a GSH rebound that surpassed the initial basal levels by up to 4-fold. This reversal in GSH levels closely correlated with the gene expression profile of GCLC and GS. To study the mechanisms of Nrf2 activation in response to HOCl exposure, we examined the effects of several antioxidants on Nrf2-mediated response. Pretreatment with cell-permeable catalase, N-acetyl-L-cysteine or GSH-monoethyl ester markedly reduced expression of NQO-1 and GCLC under HOCl challenge conditions, suggesting intracellular ROS-scavenging capacity affects HOCl-induced Nrf2 activation. Importantly, pre-activation of Nrf2 with low concentrations of pro-oxidants protected the cells against HOCl-induced cell damage. Taken together, we provide direct evidence that HOCl activates Nrf2-mediated antioxidant response, which protects cells from oxidative damage.

  13. The surgically induced stress response.

    PubMed

    Finnerty, Celeste C; Mabvuure, Nigel Tapiwa; Ali, Arham; Kozar, Rosemary A; Herndon, David N

    2013-09-01

    The stress response to surgery, critical illness, trauma, and burns encompasses derangements of metabolic and physiological processes that induce perturbations in the inflammatory, acute phase, hormonal, and genomic responses. Hypermetabolism and hypercatabolism result, leading to muscle wasting, impaired immune function and wound healing, organ failure, and death. The surgery-induced stress response is largely similar to that triggered by traumatic injuries; the duration of the stress response, however, varies according to the severity of injury (surgical or traumatic). This spectrum of injuries and insults ranges from small lacerations to severe insults such as large poly-traumatic and burn injuries. Burn injuries provide an extreme model of trauma induced stress responses that can be used to study the long-term effects of a prolonged stress response. Although the stress response to acute trauma evolved to confer improved chances of survival following injury, in modern surgical practice the stress response can be detrimental. PMID:24009246

  14. Biological Role of Trichoderma harzianum-Derived Platelet-Activating Factor Acetylhydrolase (PAF-AH) on Stress Response and Antagonism

    PubMed Central

    Yu, Chuanjin; Fan, Lili; Wu, Qiong; Fu, Kehe; Gao, Shigang; Wang, Meng; Gao, Jinxin; Li, Yaqian; Chen, Jie

    2014-01-01

    We investigated the properties of platelet-activating factor acetylhydrolase (PAF-AH) derived from Trichoderma harzianum. The enzyme, comprised of 572 amino acids, shares high homology with PAF-AH proteins from T. koningii and other microbial species. The optimum enzymatic activity of PAF-AH occurred at pH 6 in the absence of Ca2+ and it localized in the cytoplasm, and we observed the upregulation of PAF-AH expression in response to carbon starvation and strong heat shock. Furthermore, PAF-AH knockout transformant growth occurred more slowly than wild type cells and over-expression strains grown in SM medium at 37°C and 42°C. In addition, PAF-AH expression significantly increased under a series of maize root induction assay. Eicosanoic acid and ergosterol levels decreased in the PAF-AH knockouts compared to wild type cells, as revealed by GC/MS analysis. We also determined stress responses mediated by PAF-AH were related to proteins HEX1, Cu/Zn superoxide dismutase, and cytochrome c. Finally, PAF-AH exhibited antagonistic activity against Rhizoctonia solani in plate confrontation assays. Our results indicate PAF-AH may play an important role in T. harzianum stress response and antagonism under diverse environmental conditions. PMID:24964161

  15. Involvement of Clp protease activity in modulating the Bacillus subtilissigmaw stress response.

    PubMed

    Zellmeier, Stephan; Schumann, Wolfgang; Wiegert, Thomas

    2006-09-01

    The induction of Bacillus subtilis genes controlled by the extracytoplasmic function alternative sigma factor sigmaW is strongly impaired in a strain deleted for the ClpP peptidase gene and in a double knockout of the ClpX and ClpE ATPase genes. Truncated soluble forms of the sigmaW anti-sigma factor RsiW are stabilized in a clpP minus strain as revealed by the green fluorescent reporter protein fused to the N-terminus of RsiW and by pulse-chase experiments. Conserved alanine residues are present in the transmembrane region of RsiW, and mutations in these positions abolish induction of sigmaW-controlled genes. Following alkaline shock, a truncated cytoplasmic form of RsiW is detectable in a strain expressing a triple alanine mutant allele of rsiW. These data point to a mechanism where the trans-membrane segment of RsiW contains a cryptic proteolytic tag that is uncovered as a result of intramembrane proteolysis of RsiW by RasP (YluC). After RasP-clipped RsiW is detached from the membrane, this proteolytic tag becomes crucial for the complete degradation of RsiW by cytoplasmic proteases and the release of sigmaW. ClpXP plays a major role in this third proteolytic step of stress-induced degradation of RsiW. Overexpression of SsrA-tagged green fluorescent protein as a ClpXP substrate protein reduces alkali induction of a sigmaW-controlled gene by a factor of about three, indicating that a titration mechanism is able to tune the sigmaW-mediated stress response to the cellular state. PMID:16899079

  16. The stress-responsive kinases MAPKAPK2/MAPKAPK3 activate starvation-induced autophagy through Beclin 1 phosphorylation

    PubMed Central

    Zou, Zhongju; Sumpter, Rhea; Su, Minfei; Zang, Xiao; Sinha, Sangita; Gaestel, Matthias; Levine, Beth

    2015-01-01

    Autophagy is a fundamental adaptive response to amino acid starvation orchestrated by conserved gene products, the autophagy (ATG) proteins. However, the cellular cues that activate the function of ATG proteins during amino acid starvation are incompletely understood. Here we show that two related stress-responsive kinases, members of the p38 mitogen-activated protein kinase (MAPK) signaling pathway MAPKAPK2 (MK2) and MAPKAPK3 (MK3), positively regulate starvation-induced autophagy by phosphorylating an essential ATG protein, Beclin 1, at serine 90, and that this phosphorylation site is essential for the tumor suppressor function of Beclin 1. Moreover, MK2/MK3-dependent Beclin 1 phosphorylation (and starvation-induced autophagy) is blocked in vitro and in vivo by BCL2, a negative regulator of Beclin 1. Together, these findings reveal MK2/MK3 as crucial stress-responsive kinases that promote autophagy through Beclin 1 S90 phosphorylation, and identify the blockade of MK2/3-dependent Beclin 1 S90 phosphorylation as a mechanism by which BCL2 inhibits the autophagy function of Beclin 1. DOI: http://dx.doi.org/10.7554/eLife.05289.001 PMID:25693418

  17. Ethanol effect on activation and maintenance of cold stress response in immature rats.

    PubMed

    Spiers, D E; Kelleher, S A; Eichen, P A

    1996-07-01

    Rats at thermoneutral ambient temperature (Ta) exhibit change in thermoregulatory response to ethanol (EtOH) from 2 to 15 days of age. In the present study, rats at 2-3, 8-9, and 14-15 days of age were administered either saline or EtOH (4 g/kg b.wt.;IP) using two different routines to determine EtOH effect on specific cold defense mechanisms. Injection of EtOH in the first routine occurred after exposure to cold Ta, to determine effect on maintenance of cold thermogenesis. EtOH-induced metabolic depression increased from 3 to 8 days of age, with little change after this time. Injection of EtOH in the second routine was at thermoneutral Ta, followed at 20 min postinjection by rapid exposure to cold Ta to determine effect on activation of cold thermogenesis. EtOH-treatment delayed onset of cold thermogenesis at 2-3 and 14-15 days of age, and completely eliminated 8-9-day-old response to cold Ta. Rats exposed to cold Ta at 2-3 days of age exhibited a slower rate of EtOH absorption and lower blood EtOH concentration than rats in the older groups, to explain some age differences in EtOH response. PMID:8743629

  18. COP1 Controls Abiotic Stress Responses by Modulating AtSIZ1 Function through Its E3 Ubiquitin Ligase Activity.

    PubMed

    Kim, Joo Y; Jang, In-Cheol; Seo, Hak S

    2016-01-01

    Ubiquitination and sumoylation are essential post-translational modifications that regulate growth and development processes in plants, including control of hormone signaling mechanisms and responses to stress. This study showed that COP1 (Constitutive photomorphogenic 1) regulated the activity of Arabidopsis E3 SUMO (Small ubiquitin-related modifier) ligase AtSIZ1 through its E3 ubiquitin ligase activity. Yeast two hybrid analysis demonstrated that COP1 and AtSIZ1 directly interacted with one another, and subcellular localization assays indicated that COP1 and AtSIZ1 co-localized in nuclear bodies. Analysis of ubiquitination showed that AtSIZ1 was polyubiquitinated by COP1. The AtSIZ1 level was higher in cop1-4 mutants than in wild-type seedlings under light or dark conditions, and overexpression of a dominant-negative (DN)-COP1 mutant led to a substantial increase in AtSIZ1 accumulation. In addition, under drought, cold, and high salt conditions, SUMO-conjugate levels were elevated in DN-COP1-overexpressing plants and cop1-4 mutant plants compared to wild-type plants. Taken together, our results indicate that COP1 controls responses to abiotic stress by modulation of AtSIZ1 levels and activity. PMID:27536318

  19. COP1 Controls Abiotic Stress Responses by Modulating AtSIZ1 Function through Its E3 Ubiquitin Ligase Activity

    PubMed Central

    Kim, Joo Y.; Jang, In-Cheol; Seo, Hak S.

    2016-01-01

    Ubiquitination and sumoylation are essential post-translational modifications that regulate growth and development processes in plants, including control of hormone signaling mechanisms and responses to stress. This study showed that COP1 (Constitutive photomorphogenic 1) regulated the activity of Arabidopsis E3 SUMO (Small ubiquitin-related modifier) ligase AtSIZ1 through its E3 ubiquitin ligase activity. Yeast two hybrid analysis demonstrated that COP1 and AtSIZ1 directly interacted with one another, and subcellular localization assays indicated that COP1 and AtSIZ1 co-localized in nuclear bodies. Analysis of ubiquitination showed that AtSIZ1 was polyubiquitinated by COP1. The AtSIZ1 level was higher in cop1-4 mutants than in wild-type seedlings under light or dark conditions, and overexpression of a dominant-negative (DN)-COP1 mutant led to a substantial increase in AtSIZ1 accumulation. In addition, under drought, cold, and high salt conditions, SUMO-conjugate levels were elevated in DN-COP1-overexpressing plants and cop1-4 mutant plants compared to wild-type plants. Taken together, our results indicate that COP1 controls responses to abiotic stress by modulation of AtSIZ1 levels and activity. PMID:27536318

  20. NEK8 links the ATR-regulated replication stress response and S phase CDK activity to renal ciliopathies.

    PubMed

    Choi, Hyo Jei Claudia; Lin, Jia-Ren; Vannier, Jean-Baptiste; Slaats, Gisela G; Kile, Andrew C; Paulsen, Renee D; Manning, Danielle K; Beier, David R; Giles, Rachel H; Boulton, Simon J; Cimprich, Karlene A

    2013-08-22

    Renal ciliopathies are a leading cause of kidney failure, but their exact etiology is poorly understood. NEK8/NPHP9 is a ciliary kinase associated with two renal ciliopathies in humans and mice, nephronophthisis (NPHP) and polycystic kidney disease. Here, we identify NEK8 as a key effector of the ATR-mediated replication stress response. Cells lacking NEK8 form spontaneous DNA double-strand breaks (DSBs) that further accumulate when replication forks stall, and they exhibit reduced fork rates, unscheduled origin firing, and increased replication fork collapse. NEK8 suppresses DSB formation by limiting cyclin A-associated CDK activity. Strikingly, a mutation in NEK8 that is associated with renal ciliopathies affects its genome maintenance functions. Moreover, kidneys of NEK8 mutant mice accumulate DNA damage, and loss of NEK8 or replication stress similarly disrupts renal cell architecture in a 3D-culture system. Thus, NEK8 is a critical component of the DNA damage response that links replication stress with cystic kidney disorders. PMID:23973373

  1. Proteolytic activation of both components of the cation stress-responsive Slt pathway in Aspergillus nidulans.

    PubMed

    Mellado, Laura; Arst, Herbert N; Espeso, Eduardo A

    2016-08-15

    Tolerance of Aspergillus nidulans to alkalinity and elevated cation concentrations requires both SltA and SltB. Transcription factor SltA and the putative pseudokinase/protease signaling protein SltB comprise a regulatory pathway specific to filamentous fungi. In vivo, SltB is proteolytically cleaved into its two principal domains. Mutational analysis defines a chymotrypsin-like serine protease domain that mediates SltB autoproteolysis and proteolytic cleavage of SltA. The pseudokinase domain might modulate the protease activity of SltB. Three forms of the SltA transcription factor coexist in cells: a full-length, 78-kDa version and a processed, 32-kDa form, which is found in phosphorylated and unphosphorylated states. The SltA32kDa version mediates transcriptional regulation of sltB and, putatively, genes required for tolerance to cation stress and alkalinity. The full-length form, SltA78kDa, apparently has no transcriptional function. In the absence of SltB, only the primary product of SltA is detectable, and its level equals that of SltA78kDa. Mutations in sltB selected as suppressors of null vps alleles and resulting in cation/alkalinity sensitivity either reduced or eliminated SltA proteolysis. There is no evidence for cation or alkalinity regulation of SltB cleavage, but activation of sltB expression requires SltA. This work identifies the molecular mechanisms governing the Slt pathway. PMID:27307585

  2. Thinking of attachments reduces noradrenergic stress response.

    PubMed

    Bryant, Richard A; Chan, Lilian

    2015-10-01

    Although there is much evidence that activating mental representations of attachments figure is beneficial for psychological health and can reduce stress response, no research has directly investigated whether attachment activation can ameliorate hormonal stress response. This study investigated whether activating an attachment figure or a non-attachment figure following administration of a socially evaluated cold pressor test to elicit stress impacted on glucocorticoid and noradrenergic response. Participants (N = 61) provided baseline salivary samples, underwent a cold pressor test, then imagined an attachment or non-attachment figure, and finally provided subsequent saliva samples. Participants who imagined a non-attachment figure had greater noradrenergic response following the stressor than those who imagined an attachment figure. These findings highlight that activating attachment representations can ameliorate the immediate noradrenergic stress response. PMID:26115145

  3. Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response

    SciTech Connect

    Kiran, Shashi; Oddi, Vineesha; Ramakrishna, Gayatri

    2015-02-01

    Maintaining the genomic integrity is a constant challenge in proliferating cells. Amongst various proteins involved in this process, Sirtuins play a key role in DNA damage repair mechanisms in yeast as well as mammals. In the present work we report the role of one of the least explored Sirtuin viz., SIRT7, under conditions of genomic stress when treated with doxorubicin. Knockdown of SIRT7 sensitized osteosarcoma (U2OS) cells to DNA damage induced cell death by doxorubicin. SIRT7 overexpression in NIH3T3 delayed cell cycle progression by causing delay in G1 to S transition. SIRT7 overexpressing cells when treated with low dose of doxorubicin (0.25 µM) showed delayed onset of senescence, lesser accumulation of DNA damage marker γH2AX and lowered levels of growth arrest markers viz., p53 and p21 when compared to doxorubicin treated control GFP expressing cells. Resistance to DNA damage following SIRT7 overexpression was also evident by EdU incorporation studies where cellular growth arrest was significantly delayed. When treated with higher dose of doxorubicin (>1 µM), SIRT7 conferred resistance to apoptosis by attenuating stress activated kinases (SAPK viz., p38 and JNK) and p53 response thereby shifting the cellular fate towards senescence. Interestingly, relocalization of SIRT7 from nucleolus to nucleoplasm together with its co-localization with SAPK was an important feature associated with DNA damage. SIRT7 mediated resistance to doxorubicin induced apoptosis and senescence was lost when p53 level was restored by nutlin treatment. Overall, we propose SIRT7 attenuates DNA damage, SAPK activation and p53 response thereby promoting cellular survival under conditions of genomic stress. - Highlights: • Knockdown of SIRT7 sensitized cells to DNA damage induced apoptosis. • SIRT7 delayed onset of premature senescence by attenuating DNA damage response. • Overexpression of SIRT7 delayed cell cycle progression by delaying G1/S transition. • Upon DNA damage SIRT

  4. Endoplasmic reticulum stress-independent activation of unfolded protein response kinases by a small molecule ATP-mimic.

    PubMed

    Mendez, Aaron S; Alfaro, Jennifer; Morales-Soto, Marisol A; Dar, Arvin C; McCullagh, Emma; Gotthardt, Katja; Li, Han; Acosta-Alvear, Diego; Sidrauski, Carmela; Korennykh, Alexei V; Bernales, Sebastian; Shokat, Kevan M; Walter, Peter

    2015-01-01

    Two ER membrane-resident transmembrane kinases, IRE1 and PERK, function as stress sensors in the unfolded protein response. IRE1 also has an endoribonuclease activity, which initiates a non-conventional mRNA splicing reaction, while PERK phosphorylates eIF2α. We engineered a potent small molecule, IPA, that binds to IRE1's ATP-binding pocket and predisposes the kinase domain to oligomerization, activating its RNase. IPA also inhibits PERK but, paradoxically, activates it at low concentrations, resulting in a bell-shaped activation profile. We reconstituted IPA-activation of PERK-mediated eIF2α phosphorylation from purified components. We estimate that under conditions of maximal activation less than 15% of PERK molecules in the reaction are occupied by IPA. We propose that IPA binding biases the PERK kinase towards its active conformation, which trans-activates apo-PERK molecules. The mechanism by which partial occupancy with an inhibitor can activate kinases may be wide-spread and carries major implications for design and therapeutic application of kinase inhibitors. PMID:25986605

  5. Endoplasmic reticulum stress-independent activation of unfolded protein response kinases by a small molecule ATP-mimic

    PubMed Central

    Mendez, Aaron S; Alfaro, Jennifer; Morales-Soto, Marisol A; Dar, Arvin C; McCullagh, Emma; Gotthardt, Katja; Li, Han; Acosta-Alvear, Diego; Sidrauski, Carmela; Korennykh, Alexei V; Bernales, Sebastian; Shokat, Kevan M; Walter, Peter

    2015-01-01

    Two ER membrane-resident transmembrane kinases, IRE1 and PERK, function as stress sensors in the unfolded protein response. IRE1 also has an endoribonuclease activity, which initiates a non-conventional mRNA splicing reaction, while PERK phosphorylates eIF2α. We engineered a potent small molecule, IPA, that binds to IRE1's ATP-binding pocket and predisposes the kinase domain to oligomerization, activating its RNase. IPA also inhibits PERK but, paradoxically, activates it at low concentrations, resulting in a bell-shaped activation profile. We reconstituted IPA-activation of PERK-mediated eIF2α phosphorylation from purified components. We estimate that under conditions of maximal activation less than 15% of PERK molecules in the reaction are occupied by IPA. We propose that IPA binding biases the PERK kinase towards its active conformation, which trans-activates apo-PERK molecules. The mechanism by which partial occupancy with an inhibitor can activate kinases may be wide-spread and carries major implications for design and therapeutic application of kinase inhibitors. DOI: http://dx.doi.org/10.7554/eLife.05434.001 PMID:25986605

  6. Antifungal Activity of Fused Mannich Ketones Triggers an Oxidative Stress Response and Is Cap1-Dependent in Candida albicans

    PubMed Central

    Rossignol, Tristan; Kocsis, Béla; Bouquet, Orsolya; Kustos, Ildikó; Kilár, Ferenc; Nyul, Adrien; Jakus, Péter B.; Rajbhandari, Kshitij; Prókai, László; d’Enfert, Christophe; Lóránd, Tamás

    2013-01-01

    We investigated the antifungal activity of fused Mannich ketone (FMK) congeners and two of their aminoalcohol derivatives. In particular, FMKs with five-membered saturated rings were shown to have minimum inhibitory concentration (MIC90s) ranging from 0.8 to 6 µg/mL toward C. albicans and the closely related C. parapsilosis and C. krusei while having reduced efficacy toward C. glabrata and almost no efficacy against Aspergillus sp. Transcript profiling of C. albicans cells exposed for 30 or 60 min to 2-(morpholinomethyl)-1-indanone, a representative FMK with a five-membered saturated ring, revealed a transcriptional response typical of oxidative stress and similar to that of a C. albicans Cap1 transcriptional activator. Consistently, C. albicans lacking the CAP1 gene was hypersensitive to this FMK, while C. albicans strains overexpressing CAP1 had decreased sensitivity to 2-(morpholinomethyl)-1-indanone. Quantitative structure–activity relationship studies revealed a correlation of antifungal potency and the energy of the lowest unoccupied molecular orbital of FMKs and unsaturated Mannich ketones thereby implicating redox cycling-mediated oxidative stress as a mechanism of action. This conclusion was further supported by the loss of antifungal activity upon conversion of representative FMKs to aminoalcohols that were unable to participate in redox cycles. PMID:23646117

  7. Induction of a stress response in Lactococcus lactis is associated with a resistance to ribosomally active antibiotics.

    PubMed

    Dorrian, James M; Briggs, Deborah A; Ridley, Michael L; Layfield, Robert; Kerr, Ian D

    2011-11-01

    The acquisition of multidrug resistance in bacteria underlies the failure of antimicrobial therapy, and the emergence of pathogens that are resistant to almost the entire armoury of antibiotics. Among the proteins that can mediate or contribute to the drug-resistance profile in Gram-positive bacteria is a subset of ATP-binding cassette proteins that are comprised of a tandem-repeated nucleotide-binding domain. In this study, we expressed one of these NBD(2) proteins, LmrC, in an antibiotic-sensitive Gram-positive host strain (Lactococcus lactis) and demonstrated the acquisition of resistance to ribosomally active antibiotics. Mutation of key catalytic residues suggested that the resistance profile was the result of a cellular response, rather than being a function of the NBD(2) protein itself. This observation was confirmed by 2D SDS/PAGE, which demonstrated that the expression of the NBD(2) protein induced a stress response in L. lactis. A model combining this stress response induction and the acquisition of antibiotic resistance is proposed. PMID:21848804

  8. Reactive Oxygen and Nitrogen Species in Defense/Stress Responses Activated by Chitosan in Sycamore Cultured Cells

    PubMed Central

    Malerba, Massimo; Cerana, Raffaella

    2015-01-01

    Chitosan (CHT) is a non-toxic and inexpensive compound obtained by deacetylation of chitin, the main component of the exoskeleton of arthropods as well as of the cell walls of many fungi. In agriculture CHT is used to control numerous diseases on various horticultural commodities but, although different mechanisms have been proposed, the exact mode of action of CHT is still unknown. In sycamore (Acer pseudoplatanus L.) cultured cells, CHT induces a set of defense/stress responses that includes production of H2O2 and nitric oxide (NO). We investigated the possible signaling role of these reactive molecules in some CHT-induced responses by means of inhibitors of production and/or scavengers. The results show that both reactive nitrogen and oxygen species are not only a mere symptom of stress conditions but are involved in the responses induced by CHT in sycamore cells. In particular, NO appears to be involved in a cell death form induced by CHT that shows apoptotic features like DNA fragmentation, increase in caspase-3-like activity and release of cytochrome c from the mitochondrion. On the contrary, reactive oxygen species (ROS) appear involved in a cell death form induced by CHT that does not show these apoptotic features but presents increase in lipid peroxidation. PMID:25642757

  9. Reactive oxygen and nitrogen species in defense/stress responses activated by chitosan in sycamore cultured cells.

    PubMed

    Malerba, Massimo; Cerana, Raffaella

    2015-01-01

    Chitosan (CHT) is a non-toxic and inexpensive compound obtained by deacetylation of chitin, the main component of the exoskeleton of arthropods as well as of the cell walls of many fungi. In agriculture CHT is used to control numerous diseases on various horticultural commodities but, although different mechanisms have been proposed, the exact mode of action of CHT is still unknown. In sycamore (Acer pseudoplatanus L.) cultured cells, CHT induces a set of defense/stress responses that includes production of H2O2 and nitric oxide (NO). We investigated the possible signaling role of these reactive molecules in some CHT-induced responses by means of inhibitors of production and/or scavengers. The results show that both reactive nitrogen and oxygen species are not only a mere symptom of stress conditions but are involved in the responses induced by CHT in sycamore cells. In particular, NO appears to be involved in a cell death form induced by CHT that shows apoptotic features like DNA fragmentation, increase in caspase-3-like activity and release of cytochrome c from the mitochondrion. On the contrary, reactive oxygen species (ROS) appear involved in a cell death form induced by CHT that does not show these apoptotic features but presents increase in lipid peroxidation. PMID:25642757

  10. Differential coral bleaching-Contrasting the activity and response of enzymatic antioxidants in symbiotic partners under thermal stress.

    PubMed

    Krueger, Thomas; Hawkins, Thomas D; Becker, Susanne; Pontasch, Stefanie; Dove, Sophie; Hoegh-Guldberg, Ove; Leggat, William; Fisher, Paul L; Davy, Simon K

    2015-12-01

    Mass coral bleaching due to thermal stress represents a major threat to the integrity and functioning of coral reefs. Thermal thresholds vary, however, between corals, partly as a result of the specific type of endosymbiotic dinoflagellate (Symbiodinium sp.) they harbour. The production of reactive oxygen species (ROS) in corals under thermal and light stress has been recognised as one mechanism that can lead to cellular damage and the loss of their symbiont population (Oxidative Theory of Coral Bleaching). Here, we compared the response of symbiont and host enzymatic antioxidants in the coral species Acropora millepora and Montipora digitata at 28°C and 33°C. A. millepora at 33°C showed a decrease in photochemical efficiency of photosystem II (PSII) and increase in maximum midday excitation pressure on PSII, with subsequent bleaching (declining photosynthetic pigment and symbiont density). M. digitata exhibited no bleaching response and photochemical changes in its symbionts were minor. The symbiont antioxidant enzymes superoxide dismutase, ascorbate peroxidase, and catalase peroxidase showed no significant upregulation to elevated temperatures in either coral, while only catalase was significantly elevated in both coral hosts at 33°C. Increased host catalase activity in the susceptible coral after 5days at 33°C was independent of antioxidant responses in the symbiont and preceded significant declines in PSII photochemical efficiencies. This finding suggests a potential decoupling of host redox mechanisms from symbiont photophysiology and raises questions about the importance of symbiont-derived ROS in initiating coral bleaching. PMID:26310104

  11. Activation of the Nrf2-regulated antioxidant cell response inhibits HEMA-induced oxidative stress and supports cell viability.

    PubMed

    Gallorini, Marialucia; Petzel, Christine; Bolay, Carola; Hiller, Karl-Anton; Cataldi, Amelia; Buchalla, Wolfgang; Krifka, Stephanie; Schweikl, Helmut

    2015-07-01

    Oxidative stress due to increased formation of reactive oxygen species (ROS) in target cells of dental resin monomers like 2-hydroxyethyl methacrylate (HEMA) is a major mechanism underlying the disturbance of vital cell functions including mineralization and differentiation, responses of the innate immune system, and the induction of cell death via apoptosis. Although a shift in the equilibrium between cell viability and apoptosis is related to the non-enzymatic antioxidant glutathione (GSH) in HEMA-exposed cells, the major mechanisms of adaptive antioxidant cell responses to maintain cellular redox homeostasis are still unknown. The present study provides insight into the induction of a communicating network of pathways under the control of the redox-sensitive transcription factor Nrf2, a major transcriptional activator of genes coding for enzymatic antioxidants. Here, oxidative stress was indicated by DCF fluorescence in cells after a short exposure (1 h) to HEMA, while DHR123 fluorescence significantly increased about 1.8-fold after a long exposure period (24 h) showing the formation of hydrogen peroxide (H2O2). The corresponding expression of Nrf2 was activated immediately after HEMA exposure (1 h) and remained constant up to 24 h. Nrf2-regulated expression of enzymes of the glutathione metabolism (glutathione peroxidase 1/2, glutathione reductase) decreased in HEMA-exposed cells as a result of GSH depletion, and superoxide dismutase expression was downregulated after H2O2 overproduction. However, the expression of Nrf2-controlled enzymatic antioxidants (catalase, peroxiredoxin, thioredoxin 1, thioredoxin reductase, heme oxygenase-1) and the NADPH-regenerating system (glucose 6-phosphate dehydrogenase, transaldolase) was increased. Phenolic tert-butylhydroquinone (tBHQ), a classic inducer of the Nrf2 pathway, reduced oxidative stress and protected cells from HEMA-induced cell death through a shift in the number of cells in necrosis to apoptosis. The

  12. Exposure to inhaled particulate matter activates early markers of oxidative stress, inflammation and unfolded protein response in rat striatum.

    PubMed

    Guerra, R; Vera-Aguilar, E; Uribe-Ramirez, M; Gookin, G; Camacho, J; Osornio-Vargas, A R; Mugica-Alvarez, V; Angulo-Olais, R; Campbell, A; Froines, J; Kleinman, T M; De Vizcaya-Ruiz, A

    2013-10-24

    To study central nervous system airborne PM related subchronic toxicity, SD male rats were exposed for eight weeks to either coarse (32 μg/m³), fine (178 μg/m³) or ultrafine (107 μg/m³) concentrated PM or filtered air. Different brain regions (olfactory bulb, frontal cortex, striatum and hippocampus), were harvested from the rats following exposure to airborne PM. Subsequently, prooxidant (HO-1 and SOD-2), and inflammatory markers (IL-1β and TNFα), apoptotic (caspase 3), and unfolded protein response (UPR) markers (XBP-1S and BiP), were also measured using real-time PCR. Activation of nuclear transcription factors Nrf-2 and NF-κB, associated with antioxidant and inflammation processes, respectively, were also analyzed by GSMA. Ultrafine PM increased HO-1 and SOD-2 mRNA levels in the striatum and hippocampus, in the presence of Nrf-2 activation. Also, ultrafine PM activated NF-κB and increased IL-1β and TNFα in the striatum. Activation of UPR was observed after exposure to coarse PM through the increment of XBP-1S and BiP in the striatum, accompanied by an increase in antioxidant response markers HO-1 and SOD-2. Our results indicate that exposure to different size fractions of PM may induce physiological changes (in a neuroanatomical manner) in the central nervous system (CNS), specifically within the striatum, where inflammation, oxidative stress and UPR signals were effectively activated. PMID:23892126

  13. Exposure to inhaled particulate matter activates early markers of oxidative stress, inflammation and unfolded protein response in rat striatum

    PubMed Central

    Guerra, R.; Vera-Aguilar, E.; Uribe-Ramirez, M.; Gookin, G.; Camacho, J.; Osornio-Vargas, A.R.; Mugica-Alvarez, V.; Angulo-Olais, R.; Campbell, A.; Froines, J.; Kleinman, T.M.; De Vizcaya-Ruiz, A.

    2014-01-01

    To study central nervous system airborne PM related subchronic toxicity, SD male rats were exposed for eight weeks to either coarse (32 µg/m3), fine (178 µg/m3) or ultrafine (107 µg/m3) concentrated PM or filtered air. Different brain regions (olfactory bulb, frontal cortex, striatum and hippocampus), were harvested from the rats following exposure to airborne PM. Subsequently, prooxidant (HO-1 and SOD-2), and inflammatory markers (IL-1β and TNFα), apoptotic (caspase 3), and unfolded protein response (UPR) markers (XBP-1S and BiP), were also measured using real-time PCR. Activation of nuclear transcription factors Nrf-2 and NF-κB, associated with antioxidant and inflammation processes, respectively, were also analyzed by GSMA. Ultrafine PM increased HO-1 and SOD-2 mRNA levels in the striatum and hippocampus, in the presence of Nrf-2 activation. Also, ultrafine PM activated NF-κB and increased IL-1β and TNFα in the striatum. Activation of UPR was observed after exposure to coarse PM through the increment of XBP-1S and BiP in the striatum, accompanied by an increase in antioxidant response markers HO-1 and SOD-2. Our results indicate that exposure to different size fractions of PM may induce physiological changes (in a neuroanatomical manner) in the central nervous system (CNS), specifically within the striatum, where inflammation, oxidative stress and UPR signals were effectively activated. PMID:23892126

  14. Staphylococcal response to oxidative stress

    PubMed Central

    Gaupp, Rosmarie; Ledala, Nagender; Somerville, Greg A.

    2012-01-01

    Staphylococci are a versatile genus of bacteria that are capable of causing acute and chronic infections in diverse host species. The success of staphylococci as pathogens is due in part to their ability to mitigate endogenous and exogenous oxidative and nitrosative stress. Endogenous oxidative stress is a consequence of life in an aerobic environment; whereas, exogenous oxidative and nitrosative stress are often due to the bacteria's interaction with host immune systems. To overcome the deleterious effects of oxidative and nitrosative stress, staphylococci have evolved protection, detoxification, and repair mechanisms that are controlled by a network of regulators. In this review, we summarize the cellular targets of oxidative stress, the mechanisms by which staphylococci sense oxidative stress and damage, oxidative stress protection and repair mechanisms, and regulation of the oxidative stress response. When possible, special attention is given to how the oxidative stress defense mechanisms help staphylococci control oxidative stress in the host. PMID:22919625

  15. The Surgically Induced Stress Response

    PubMed Central

    Finnerty, Celeste C.; Mabvuure, Nigel Tapiwa; Ali, Arham; Kozar, Rosemary A.; Herndon, David N.

    2013-01-01

    The stress response to surgery, critical illness, trauma, and burns encompasses derangements of metabolic and physiological processes which induce perturbations in the inflammatory, acute phase, hormonal, and genomic responses. Hypermetabolism and hypercatabolism result, leading to muscle wasting, impaired immune function and wound healing, organ failure, and death. The surgery-induced stress response is largely similar to that triggered by traumatic injuries; the duration of the stress response, however, varies according to the severity of injury (surgical or traumatic). This spectrum of injuries and insults ranges from small lacerations to severe insults such as large poly-traumatic and burn injuries. Although the stress response to acute trauma evolved to improve chances of survival following injury, in modern surgical practice the stress response can be detrimental. PMID:24009246

  16. Silica nanoparticles and silver-doped silica nanoparticles induce endoplasmatic reticulum stress response and alter cytochrome P4501A activity.

    PubMed

    Christen, Verena; Fent, Karl

    2012-04-01

    Engineered silica nanoparticles (SiO(2)-NPs) find widespread application and may lead to exposure of humans and the environment. Here we compare the effects of SiO(2)-NPs and SiO(2)-NPs doped with silver (SiO(2)-Ag-NPs) on survival and cellular function of human liver cells (Huh7) and Pimephales promelas (fathead minnow) fibroblast cells (FMH). In Huh7 cells we investigate effects on the endoplasmatic reticulum (ER), including ER stress, and interactions of nanoparticles (NPs) with metabolizing enzymes and efflux transporters. The NPs formed agglomerates/aggregates in cell culture media as revealed by SEM and TEM. SiO(2) and SiO(2)-1% Ag-NPs were taken up into cells as demonstrated by agglomerates occurring in vesicular-like structures or freely dispersed in the cytosol. Cytotoxicity was more pronounced in Huh7 than in FMH cells, and increased with silver content in silver-doped NPs. Dissolved silver was the most significant factor for cytotoxicity. At toxic and non-cytotoxic concentrations SiO(2)-NPs and SiO(2)-1% Ag-NPs induced perturbations in the function of ER. In Huh7 cells NPs induced the unfolded protein response (UPR), or ER stress response, as demonstrated in induced expression of BiP and splicing of XBP1 mRNA, two selective markers of ER stress. Additionally, SiO(2)-1% Ag-NPs and AgNO(3) induced reactive oxygen species. Pre-treatment of Huh7 cells with SiO(2)-1% Ag-NPs followed by exposure to the inducer benzo(a)pyrene caused a significant reduced induction of CYP1A activity. NPs did not alter the activity of ABC transporters. These data demonstrate for the first time that SiO(2)-NPs and SiO(2)-1% Ag-NPs result in perturbations of the ER leading to the ER stress response. This represents a novel and significant cellular signalling pathway contributing to the cytotoxicity of NPs. PMID:22245057

  17. Effects of dietary yeast extract on turkey stress response and heterophil oxidative burst activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Effective nutritional approaches to counteract the negative effects of stress would both improve human health and provide food animal producers with useful alternatives to antibiotics. In this study, turkeys were fed a standard diet or the same diet supplemented with yeast extract (Alphamune™, YE), ...

  18. AMP-activated protein kinase mediates apoptosis in response to bioenergetic stress through activation of the pro-apoptotic Bcl-2 homology domain-3-only protein BMF.

    PubMed

    Kilbride, Seán M; Farrelly, Angela M; Bonner, Caroline; Ward, Manus W; Nyhan, Kristine C; Concannon, Caoimhín G; Wollheim, Claes B; Byrne, Maria M; Prehn, Jochen H M

    2010-11-12

    Heterozygous loss-of-function mutations in the hepatocyte nuclear factor 1A (HNF1A) gene result in the pathogenesis of maturity-onset diabetes-of-the-young type 3, (HNF1A-MODY). This disorder is characterized by a primary defect in metabolism-secretion coupling and decreased beta cell mass, attributed to excessive beta cell apoptosis. Here, we investigated the link between energy stress and apoptosis activation following HNF1A inactivation. This study employed single cell fluorescent microscopy, flow cytometry, gene expression analysis, and gene silencing to study the effects of overexpression of dominant-negative (DN)-HNF1A expression on cellular bioenergetics and apoptosis in INS-1 cells. Induction of DN-HNF1A expression led to reduced ATP levels and diminished the bioenergetic response to glucose. This was coupled with activation of the bioenergetic stress sensor AMP-activated protein kinase (AMPK), which preceded the onset of apoptosis. Pharmacological activation of AMPK using aminoimidazole carboxamide ribonucleotide (AICAR) was sufficient to induce apoptosis in naive cells. Conversely, inhibition of AMPK with compound C or AMPKα gene silencing protected against DN-HNF1A-induced apoptosis. Interestingly, AMPK mediated the induction of the pro-apoptotic Bcl-2 homology domain-3-only protein Bmf (Bcl-2-modifying factor). Bmf expression was also elevated in islets of DN-HNF1A transgenic mice. Furthermore, knockdown of Bmf expression in INS-1 cells using siRNA was sufficient to protect against DN-HNF1A-induced apoptosis. Our study suggests that overexpression of DN-HNF1A induces bioenergetic stress and activation of AMPK. This in turn mediates the transcriptional activation of the pro-apoptotic Bcl-2-homology protein BMF, coupling prolonged energy stress to apoptosis activation. PMID:20841353

  19. Fiber networks amplify active stress

    NASA Astrophysics Data System (ADS)

    Lenz, Martin; Ronceray, Pierre; Broedersz, Chase

    Large-scale force generation is essential for biological functions such as cell motility, embryonic development, and muscle contraction. In these processes, forces generated at the molecular level by motor proteins are transmitted by disordered fiber networks, resulting in large-scale active stresses. While fiber networks are well characterized macroscopically, this stress generation by microscopic active units is not well understood. I will present a comprehensive theoretical study of force transmission in these networks. I will show that the linear, small-force response of the networks is remarkably simple, as the macroscopic active stress depends only on the geometry of the force-exerting unit. In contrast, as non-linear buckling occurs around these units, local active forces are rectified towards isotropic contraction and strongly amplified. This stress amplification is reinforced by the networks' disordered nature, but saturates for high densities of active units. I will show that our predictions are quantitatively consistent with experiments on reconstituted tissues and actomyosin networks, and that they shed light on the role of the network microstructure in shaping active stresses in cells and tissue.

  20. General Stress Responses in the Honey Bee.

    PubMed

    Even, Naïla; Devaud, Jean-Marc; Barron, Andrew B

    2012-01-01

    The biological concept of stress originated in mammals, where a "General Adaptation Syndrome" describes a set of common integrated physiological responses to diverse noxious agents. Physiological mechanisms of stress in mammals have been extensively investigated through diverse behavioral and physiological studies. One of the main elements of the stress response pathway is the endocrine hypothalamo-pituitary-adrenal (HPA) axis, which underlies the "fight-or-flight" response via a hormonal cascade of catecholamines and corticoid hormones. Physiological responses to stress have been studied more recently in insects: they involve biogenic amines (octopamine, dopamine), neuropeptides (allatostatin, corazonin) and metabolic hormones (adipokinetic hormone, diuretic hormone). Here, we review elements of the physiological stress response that are or may be specific to honey bees, given the economical and ecological impact of this species. This review proposes a hypothetical integrated honey bee stress pathway somewhat analogous to the mammalian HPA, involving the brain and, particularly, the neurohemal organ corpora cardiaca and peripheral targets, including energy storage organs (fat body and crop). We discuss how this system can organize rapid coordinated changes in metabolic activity and arousal, in response to adverse environmental stimuli. We highlight physiological elements of the general stress responses that are specific to honey bees, and the areas in which we lack information to stimulate more research into how this fascinating and vital insect responds to stress. PMID:26466739

  1. General Stress Responses in the Honey Bee

    PubMed Central

    Even, Naïla; Devaud, Jean-Marc; Barron, Andrew B.

    2012-01-01

    The biological concept of stress originated in mammals, where a “General Adaptation Syndrome” describes a set of common integrated physiological responses to diverse noxious agents. Physiological mechanisms of stress in mammals have been extensively investigated through diverse behavioral and physiological studies. One of the main elements of the stress response pathway is the endocrine hypothalamo-pituitary-adrenal (HPA) axis, which underlies the “fight-or-flight” response via a hormonal cascade of catecholamines and corticoid hormones. Physiological responses to stress have been studied more recently in insects: they involve biogenic amines (octopamine, dopamine), neuropeptides (allatostatin, corazonin) and metabolic hormones (adipokinetic hormone, diuretic hormone). Here, we review elements of the physiological stress response that are or may be specific to honey bees, given the economical and ecological impact of this species. This review proposes a hypothetical integrated honey bee stress pathway somewhat analogous to the mammalian HPA, involving the brain and, particularly, the neurohemal organ corpora cardiaca and peripheral targets, including energy storage organs (fat body and crop). We discuss how this system can organize rapid coordinated changes in metabolic activity and arousal, in response to adverse environmental stimuli. We highlight physiological elements of the general stress responses that are specific to honey bees, and the areas in which we lack information to stimulate more research into how this fascinating and vital insect responds to stress. PMID:26466739

  2. ACTIVITY-DEPENDENT, STRESS-RESPONSIVE BDNF SIGNALING AND THE QUEST FOR OPTIMAL BRAIN HEALTH AND RESILIENCE THROUGHOUT THE LIFESPAN

    PubMed Central

    Rothman, S. M.; Mattson, M. P.

    2013-01-01

    During development of the nervous system, the formation of connections (synapses) between neurons is dependent upon electrical activity in those neurons, and neurotrophic factors produced by target cells play a pivotal role in such activity-dependent sculpting of the neural networks. A similar interplay between neurotransmitter and neurotrophic factor signaling pathways mediates adaptive responses of neural networks to environmental demands in adult mammals, with the excitatory neurotransmitter glutamate and brain-derived neurotrophic factor (BDNF) being particularly prominent regulators of synaptic plasticity throughout the central nervous system. Optimal brain health throughout the lifespan is promoted by intermittent challenges such as exercise, cognitive stimulation and dietary energy restriction, that subject neurons to activity-related metabolic stress. At the molecular level, such challenges to neurons result in the production of proteins involved in neurogenesis, learning and memory and neuronal survival; examples include proteins that regulate mitochondrial biogenesis, protein quality control, and resistance of cells to oxidative, metabolic and proteotoxic stress. BDNF signaling mediates up-regulation of several such proteins including the protein chaperone GRP-78, antioxidant enzymes, the cell survival protein Bcl-2, and the DNA repair enzyme APE1. Insufficient exposure to such challenges, genetic factors may conspire to impair BDNF production and/or signaling resulting in the vulnerability of the brain to injury and neurodegenerative disorders including Alzheimer’s, Parkinson’s and Huntington’s diseases. Further, BDNF signaling is negatively regulated by glucocorticoids. Glucocorticoids impair synaptic plasticity in the brain by negatively regulating spine density, neurogenesis and long-term potentiation, effects that are potentially linked to glucocorticoid regulation of BDNF. Findings suggest that BDNF signaling in specific brain regions mediates

  3. Cyclopentenyl cytosine induces senescence in breast cancer cells through the nucleolar stress response and activation of p53.

    PubMed

    Huang, Min; Whang, Patrick; Lewicki, Patrick; Mitchell, Beverly S

    2011-07-01

    The induction of senescence has emerged as a potentially important contributor to the effects of chemotherapeutic agents against tumors. We have demonstrated that depletion of CTP induced by cyclopentenyl cytosine (CPEC; NSC 375575), a specific inhibitor of the enzyme CTP synthetase, induces irreversible growth arrest and senescence characterized by altered morphology and expression of senescence-associated β-galactosidase activity in MCF-7 breast cancer cells expressing wild-type p53. In contrast, differentiation in the absence of senescence resulted from CPEC treatment in MDA-MB-231 breast cancer cells that express a mutated p53. Both senescence of MCF-7 cells and differentiation of MDA-MB-231 cells were prevented by repletion of CTP through the cytidine salvage pathway. Senescence in MCF-7 cells was associated with a G(2)- and S-phase arrest, whereas differentiation in MDA-MB-231 cells was associated with arrest in G(1) phase at 5 days. Mechanistic studies revealed that CTP depletion induced a rapid translocation of nucleolar proteins, including nucleostemin and nucleolin into the nucleoplasm. This nucleolar stress response resulted in a sustained elevation of p53 and the p53 target genes, p21 and Mdm2, in cells with wild-type p53. Furthermore, short interfering RNA-induced knockdown of p53 in MCF-7 cells treated with CPEC prevented cellular senescence and increased apoptotic cell death. We conclude that CTP depletion and the resulting nucleolar stress response results in a senescence-like growth arrest through activation of p53, whereas cells with mutated p53 undergo differentiation or apoptotic cell death. PMID:21464199

  4. Cyclopentenyl Cytosine Induces Senescence in Breast Cancer Cells through the Nucleolar Stress Response and Activation of p53S⃞

    PubMed Central

    Huang, Min; Whang, Patrick; Lewicki, Patrick

    2011-01-01

    The induction of senescence has emerged as a potentially important contributor to the effects of chemotherapeutic agents against tumors. We have demonstrated that depletion of CTP induced by cyclopentenyl cytosine (CPEC; NSC 375575), a specific inhibitor of the enzyme CTP synthetase, induces irreversible growth arrest and senescence characterized by altered morphology and expression of senescence-associated β-galactosidase activity in MCF-7 breast cancer cells expressing wild-type p53. In contrast, differentiation in the absence of senescence resulted from CPEC treatment in MDA-MB-231 breast cancer cells that express a mutated p53. Both senescence of MCF-7 cells and differentiation of MDA-MB-231 cells were prevented by repletion of CTP through the cytidine salvage pathway. Senescence in MCF-7 cells was associated with a G2- and S-phase arrest, whereas differentiation in MDA-MB-231 cells was associated with arrest in G1 phase at 5 days. Mechanistic studies revealed that CTP depletion induced a rapid translocation of nucleolar proteins, including nucleostemin and nucleolin into the nucleoplasm. This nucleolar stress response resulted in a sustained elevation of p53 and the p53 target genes, p21 and Mdm2, in cells with wild-type p53. Furthermore, short interfering RNA-induced knockdown of p53 in MCF-7 cells treated with CPEC prevented cellular senescence and increased apoptotic cell death. We conclude that CTP depletion and the resulting nucleolar stress response results in a senescence-like growth arrest through activation of p53, whereas cells with mutated p53 undergo differentiation or apoptotic cell death. PMID:21464199

  5. A novel pathway spatiotemporally activates Rac1 and redox signaling in response to fluid shear stress

    PubMed Central

    Liu, Yunhao; Collins, Caitlin; Kiosses, William B.; Murray, Ann M.; Joshi, Monika; Shepherd, Tyson R.; Fuentes, Ernesto J.

    2013-01-01

    Hemodynamic forces regulate embryonic organ development, hematopoiesis, vascular remodeling, and atherogenesis. The mechanosensory stimulus of blood flow initiates a complex network of intracellular pathways, including activation of Rac1 GTPase, establishment of endothelial cell (EC) polarity, and redox signaling. The activity of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase can be modulated by the GTP/GDP state of Rac1; however, the molecular mechanisms of Rac1 activation by flow are poorly understood. Here, we identify a novel polarity complex that directs localized Rac1 activation required for downstream reactive oxygen species (ROS) production. Vav2 is required for Rac1 GTP loading, whereas, surprisingly, Tiam1 functions as an adaptor in a VE-cadherin–p67phox–Par3 polarity complex that directs localized activation of Rac1. Furthermore, loss of Tiam1 led to the disruption of redox signaling both in vitro and in vivo. Our results describe a novel molecular cascade that regulates redox signaling by the coordinated regulation of Rac1 and by linking components of the polarity complex to the NADPH oxidase. PMID:23733346

  6. Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response

    PubMed Central

    Sidrauski, Carmela; Tsai, Jordan C; Kampmann, Martin; Hearn, Brian R; Vedantham, Punitha; Jaishankar, Priyadarshini; Sokabe, Masaaki; Mendez, Aaron S; Newton, Billy W; Tang, Edward L; Verschueren, Erik; Johnson, Jeffrey R; Krogan, Nevan J; Fraser, Christopher S; Weissman, Jonathan S; Renslo, Adam R; Walter, Peter

    2015-01-01

    The general translation initiation factor eIF2 is a major translational control point. Multiple signaling pathways in the integrated stress response phosphorylate eIF2 serine-51, inhibiting nucleotide exchange by eIF2B. ISRIB, a potent drug-like small molecule, renders cells insensitive to eIF2α phosphorylation and enhances cognitive function in rodents by blocking long-term depression. ISRIB was identified in a phenotypic cell-based screen, and its mechanism of action remained unknown. We now report that ISRIB is an activator of eIF2B. Our reporter-based shRNA screen revealed an eIF2B requirement for ISRIB activity. Our results define ISRIB as a symmetric molecule, show ISRIB-mediated stabilization of activated eIF2B dimers, and suggest that eIF2B4 (δ-subunit) contributes to the ISRIB binding site. We also developed new ISRIB analogs, improving its EC50 to 600 pM in cell culture. By modulating eIF2B function, ISRIB promises to be an invaluable tool in proof-of-principle studies aiming to ameliorate cognitive defects resulting from neurodegenerative diseases. DOI: http://dx.doi.org/10.7554/eLife.07314.001 PMID:25875391

  7. Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response.

    PubMed

    Sidrauski, Carmela; Tsai, Jordan C; Kampmann, Martin; Hearn, Brian R; Vedantham, Punitha; Jaishankar, Priyadarshini; Sokabe, Masaaki; Mendez, Aaron S; Newton, Billy W; Tang, Edward L; Verschueren, Erik; Johnson, Jeffrey R; Krogan, Nevan J; Fraser, Christopher S; Weissman, Jonathan S; Renslo, Adam R; Walter, Peter

    2015-01-01

    The general translation initiation factor eIF2 is a major translational control point. Multiple signaling pathways in the integrated stress response phosphorylate eIF2 serine-51, inhibiting nucleotide exchange by eIF2B. ISRIB, a potent drug-like small molecule, renders cells insensitive to eIF2α phosphorylation and enhances cognitive function in rodents by blocking long-term depression. ISRIB was identified in a phenotypic cell-based screen, and its mechanism of action remained unknown. We now report that ISRIB is an activator of eIF2B. Our reporter-based shRNA screen revealed an eIF2B requirement for ISRIB activity. Our results define ISRIB as a symmetric molecule, show ISRIB-mediated stabilization of activated eIF2B dimers, and suggest that eIF2B4 (δ-subunit) contributes to the ISRIB binding site. We also developed new ISRIB analogs, improving its EC50 to 600 pM in cell culture. By modulating eIF2B function, ISRIB promises to be an invaluable tool in proof-of-principle studies aiming to ameliorate cognitive defects resulting from neurodegenerative diseases. PMID:25875391

  8. Boron influences immune and antioxidant responses by modulating hepatic superoxide dismutase activity under calcium deficit abiotic stress in Wistar rats.

    PubMed

    Bhasker, T Vijay; Gowda, N K S; Mondal, S; Krishnamoorthy, P; Pal, D T; Mor, A; Bhat, S Karthik; Pattanaik, A K

    2016-07-01

    The influence of Boron (B) supplementation on immune and antioxidant status of rats with or without abiotic stress induced by dietary calcium (Ca) restriction was studied in a feeding trial of 90 days. Wistar strain rats (3-4 wk age, n=84) were divided into 7 dietary groups (4 replicates of 3 each) viz., normal-calcium (100%) basal diet alone (NC, control) or supplemented with B at 5 (NCB-5), 10 (NCB-10), 20 (NCB-20) and 40ppm (NCB-40) levels; low-calcium (50%) basal diet alone (LC) or supplemented with 40ppm B (LCB-40). After 75 days of experimental feeding, rats were challenged with intraperitoneal injection of sheep RBCs to assess their humoral immunity. At the end of the trial, cell-mediated immunity was assessed as foot pad reaction to sheep RBCs injected into the hind leg paws. Eight rats from each group were sacrificed to collect blood for estimation of minerals and total antioxidant activity, and liver for superoxide dismutase gene expression analysis. Supplementation of graded levels of B (5, 10, 20 and 40ppm) as borax in NC diets significantly increased (P<0.01) the footpad thickness and serum total antioxidant activity, hepatic expression levels of both Cu-Zn SOD (SOD1) and Mn-SOD (SOD2) mRNAs. The erythrocytic SOD activity and humoral response did not differ significantly among the dietary groups. In Ca restricted groups, humoral immune response was significantly decreased (P<0.01) compared to control but increased (P<0.05) with 40ppm B supplementation. Serum levels of copper (Cu) and zinc (Zn) remained similar among the dietary groups, while the manganese (Mn) content was significantly decreased (P<0.01) with increased levels of dietary B. In conclusion, B supplementation increased the hepatic mRNA expression levels of both SOD isoenzymes, thereby improving the immune and antioxidant status. PMID:27259355

  9. Victim-Offender Relationship Status Moderates the Relationships of Peritraumatic Emotional Responses, Active Resistance, and Posttraumatic Stress Symptomatology in Female Rape Survivors.

    PubMed

    Feinstein, Brian A; Humphreys, Kathryn L; Bovin, Michelle J; Marx, Brian P; Resick, Patricia A

    2011-06-01

    This study examined whether the level of victim-offender relationship (VOR) moderated the relationship between peritraumatic fear and active resistance as well as the relationship between peritraumatic fear and posttraumatic stress symptom severity in a community sample of female rape survivors. One hundred thirty-five participants were interviewed about their emotional and behavioral responses during the rape and assessed for posttraumatic stress symptomatology within one month of the assault. Results indicated that peritraumatic fear was positively associated with active resistance, but only among survivors of acquaintance rape. Additionally, peritraumatic fear was positively associated with posttraumatic stress symptom severity, but only among survivors of intimate partner rape. These results suggest that VOR may be an important contextual factor that influences emotional and behavioral responses during rape as well as posttraumatic stress symptomatology in its aftermath. PMID:21731797

  10. Victim-Offender Relationship Status Moderates the Relationships of Peritraumatic Emotional Responses, Active Resistance, and Posttraumatic Stress Symptomatology in Female Rape Survivors

    PubMed Central

    Feinstein, Brian A.; Humphreys, Kathryn L.; Bovin, Michelle J.; Marx, Brian P.; Resick, Patricia A.

    2010-01-01

    This study examined whether the level of victim-offender relationship (VOR) moderated the relationship between peritraumatic fear and active resistance as well as the relationship between peritraumatic fear and posttraumatic stress symptom severity in a community sample of female rape survivors. One hundred thirty-five participants were interviewed about their emotional and behavioral responses during the rape and assessed for posttraumatic stress symptomatology within one month of the assault. Results indicated that peritraumatic fear was positively associated with active resistance, but only among survivors of acquaintance rape. Additionally, peritraumatic fear was positively associated with posttraumatic stress symptom severity, but only among survivors of intimate partner rape. These results suggest that VOR may be an important contextual factor that influences emotional and behavioral responses during rape as well as posttraumatic stress symptomatology in its aftermath. PMID:21731797

  11. Histone acetyltransferase GCN5 is essential for heat stress-responsive gene activation and thermotolerance in Arabidopsis.

    PubMed

    Hu, Zhaorong; Song, Na; Zheng, Mei; Liu, Xinye; Liu, Zhenshan; Xing, Jiewen; Ma, Junhua; Guo, Weiwei; Yao, Yingyin; Peng, Huiru; Xin, Mingming; Zhou, Dao-Xiu; Ni, Zhongfu; Sun, Qixin

    2015-12-01

    Exposure to temperatures exceeding the normal optimum levels, or heat stress (HS), constitutes an environmental disruption for plants, resulting in severe growth and development retardation. Here we show that loss of function of the Arabidopsis histone acetyltransferase GCN5 results in serious defects in terms of thermotolerance, and considerably impairs the transcriptional activation of HS-responsive genes. Notably, expression of several key regulators such as the HS transcription factors HSFA2 and HSFA3, Multiprotein Bridging Factor 1c (MBF1c) and UV-HYPERSENSITIVE 6 (UVH6) is down-regulated in the gcn5 mutant under HS compared with the wild-type. Chromatin immunoprecipitation (ChIP) assays indicated that GCN5 protein is enriched at the promoter regions of HSFA3 and UVH6 genes, but not in HSFA2 and MBF1c, and that GCN5 facilitates H3K9 and H3K14 acetylation, which are associated with HSFA3 and UVH6 activation under HS. Moreover, constitutive expression of UVH6 in the gcn5 mutant partially restores heat tolerance. Taken together, our data indicate that GCN5 plays a key role in the preservation of thermotolerance via versatile regulation in Arabidopsis. In addition, expression of the wheat TaGCN5 gene re-establishes heat tolerance in Arabidopsis gcn5 mutant plants, suggesting that GCN5-mediated thermotolerance may be conserved between Arabidopsis and wheat. PMID:26576681

  12. Peroxidase Activity and Involvement in the Oxidative Stress Response of Roseobacter denitrificans Truncated Hemoglobin

    PubMed Central

    Wang, Yaya; Barbeau, Xavier; Bilimoria, Astha; Lagüe, Patrick; Couture, Manon; Tang, Joseph Kuo-Hsiang

    2015-01-01

    Roseobacter denitrificans is a member of the widespread marine Roseobacter genus. We report the first characterization of a truncated hemoglobin from R. denitrificans (Rd. trHb) that was purified in the heme-bound form from heterologous expression of the protein in Escherichia coli. Rd. trHb exhibits predominantly alpha-helical secondary structure and absorbs light at 412, 538 and 572 nm. The phylogenetic classification suggests that Rd. trHb falls into group II trHbs, whereas sequence alignments indicate that it shares certain important heme pocket residues with group I trHbs in addition to those of group II trHbs. The resonance Raman spectra indicate that the isolated Rd. trHb contains a ferric heme that is mostly 6-coordinate low-spin and that the heme of the ferrous form displays a mixture of 5- and 6-coordinate states. Two Fe-His stretching modes were detected, notably one at 248 cm-1, which has been reported in peroxidases and some flavohemoglobins that contain an Fe-His-Asp (or Glu) catalytic triad, but was never reported before in a trHb. We show that Rd. trHb exhibits a significant peroxidase activity with a (kcat/Km) value three orders of magnitude higher than that of bovine Hb and only one order lower than that of horseradish peroxidase. This enzymatic activity is pH-dependent with a pKa value ~6.8. Homology modeling suggests that residues known to be important for interactions with heme-bound ligands in group II trHbs from Mycobacterium tuberculosis and Bacillus subtilis are pointing toward to heme in Rd. trHb. Genomic organization and gene expression profiles imply possible functions for detoxification of reactive oxygen and nitrogen species in vivo. Altogether, Rd. trHb exhibits some distinctive features and appears equipped to help the bacterium to cope with reactive oxygen/nitrogen species and/or to operate redox biochemistry. PMID:25658318

  13. Rate of environmental change determines stress response specificity

    PubMed Central

    Young, Jonathan W.; Locke, James C. W.; Elowitz, Michael B.

    2013-01-01

    Cells use general stress response pathways to activate diverse target genes in response to a variety of stresses. However, general stress responses coexist with more specific pathways that are activated by individual stresses, provoking the fundamental question of whether and how cells control the generality or specificity of their response to a particular stress. Here we address this issue using quantitative time-lapse microscopy of the Bacillus subtilis environmental stress response, mediated by σB. We analyzed σB activation in response to stresses such as salt and ethanol imposed at varying rates of increase. Dynamically, σB responded to these stresses with a single adaptive activity pulse, whose amplitude depended on the rate at which the stress increased. This rate-responsive behavior can be understood from mathematical modeling of a key negative feedback loop in the underlying regulatory circuit. Using RNAseq we analyzed the effects of both rapid and gradual increases of ethanol and salt stress across the genome. Because of the rate responsiveness of σB activation, salt and ethanol regulons overlap under rapid, but not gradual, increases in stress. Thus, the cell responds specifically to individual stresses that appear gradually, while using σB to broaden the cellular response under more rapidly deteriorating conditions. Such dynamic control of specificity could be a critical function of other general stress response pathways. PMID:23407164

  14. The Chlamydomonas heat stress response.

    PubMed

    Schroda, Michael; Hemme, Dorothea; Mühlhaus, Timo

    2015-05-01

    Heat waves occurring at increased frequency as a consequence of global warming jeopardize crop yield safety. One way to encounter this problem is to genetically engineer crop plants toward increased thermotolerance. To identify entry points for genetic engineering, a thorough understanding of how plant cells perceive heat stress and respond to it is required. Using the unicellular green alga Chlamydomonas reinhardtii as a model system to study the fundamental mechanisms of the plant heat stress response has several advantages. Most prominent among them is the suitability of Chlamydomonas for studying stress responses system-wide and in a time-resolved manner under controlled conditions. Here we review current knowledge on how heat is sensed and signaled to trigger temporally and functionally grouped sub-responses termed response elements to prevent damage and to maintain cellular homeostasis in plant cells. PMID:25754362

  15. Transcriptional 'memory' of a stress: transient chromatin and memory (epigenetic) marks at stress-response genes.

    PubMed

    Avramova, Zoya

    2015-07-01

    Drought, salinity, extreme temperature variations, pathogen and herbivory attacks are recurring environmental stresses experienced by plants throughout their life. To survive repeated stresses, plants provide responses that may be different from their response during the first encounter with the stress. A different response to a similar stress represents the concept of 'stress memory'. A coordinated reaction at the organismal, cellular and gene/genome levels is thought to increase survival chances by improving the plant's tolerance/avoidance abilities. Ultimately, stress memory may provide a mechanism for acclimation and adaptation. At the molecular level, the concept of stress memory indicates that the mechanisms responsible for memory-type transcription during repeated stresses are not based on repetitive activation of the same response pathways activated by the first stress. Some recent advances in the search for transcription 'memory factors' are discussed with an emphasis on super-induced dehydration stress memory response genes in Arabidopsis. PMID:25788029

  16. Activation of GABAA or 5HT1A receptors in the raphé pallidus abolish the cardiovascular responses to exogenous stress in conscious rats.

    PubMed

    Pham-Le, Nhut Minh; Cockburn, Chelsea; Nowell, Katherine; Brown, Justin

    2011-11-25

    Dysfunction in serotonin (5HT) neurotransmission in the brainstem of infants may disrupt protective responses to stress and increase the risk for Sudden Infant Death Syndrome (SIDS). The raphé pallidus (NRP) and other brainstem nuclei are rich in 5HT and are thought to mediate stress responses, including increases in blood pressure (BP) and heart rate (HR). Determining how 5HT neurotransmission in the brainstem mediates responses to stress will help to explain how dysfunction in neurotransmission could increase the risk of SIDS. It was hypothesized that alterations in neurotransmission in the NRP, specifically activation of the 5HT(1A) receptor subtype, would block cardiovascular responses to various types of exogenous stress. Using aseptic techniques, male Sprague-Dawley rats were instrumented with radiotelemetry probes which enabled non-invasive measurement of BP and HR. An indwelling microinjection cannula was also stereotaxically implanted into the NRP for injection of drugs that altered local 5HT neurotransmission. Following a one week recovery period, rats were microinjected with either muscimol (GABA(A) receptor agonist), 8-OH-DPAT (agonist to the inhibitory 5HT(1A) receptor), or a vehicle control (artificial cerebral spinal fluid; ACSF) immediately prior to exposure to one of three stressors: handling, air jet, or restraint. Physical handling and restraint of the animal were designed to elicit a mild and a maximal stress response respectively; while an air jet directed at the rat's face was used to provoke a psychological stress that did not require physical contact. All three stressors elicited similar and significant elevations in HR and BP following ACSF that persisted for at least 15 min with BP and HR elevated by ∼14.0 mmHg and ∼56.3 bpm respectively. The similarity in the stress responses suggest even mild handling of a rat elicits a maximal sympathoexcitatory response. The stress response was abolished following 8-OH-DPAT or muscimol

  17. Microcystin-LR induced developmental toxicity and apoptosis in zebrafish (Danio rerio) larvae by activation of ER stress response.

    PubMed

    Qi, Mei; Dang, Yao; Xu, Qinglong; Yu, Liqin; Liu, Chunsheng; Yuan, Yongchao; Wang, Jianghua

    2016-08-01

    Recent studies have demonstrated that cyanobacteria-derived Microcystin-LR (MC-LR) can cause developmental toxicity and trigger apoptosis in zebrafish (Danio rerio) larvae, but the underlying mechanisms remain largely unknown. In this study, we tested the hypothesis that the mechanism by which MC-LR induces developmental toxicity is through activation of endoplasmic reticulum (ER) stress. MC-LR (4.0 μM) exposure through submersion caused serious developmental toxicity, such as malformation, growth delay and decreased heart rates in zebrafish larvae, which could be inhibited by ER stress blocker, tauroursodeoxycholic acid (TUDCA, 20 μM). Meanwhile, acridine orange (AO) staining showed TUDCA could rescue cell apoptosis in heart area in zebrafish larvae resulted by MC-LR exposure. Real-time polymerase chain reaction (real-time PCR) analysis demonstrated that MC-LR induced activation of ER stress which consequently triggered apoptosis in zebrafish larvae. Protein expression examined by western blot indicated that MC-LR could activate MAPK8/Bcl-2/Bax pathway and caspase-dependent apoptotic pathway in zebrafish larva and the effects were mitigated by inhibition of ER stress. Taken together, the results observed in this study suggested that ER stress plays a critical role in developmental toxicity and apoptosis in zebrafish embryos exposed to MC-LR. PMID:27219292

  18. Auxin response under osmotic stress.

    PubMed

    Naser, Victoria; Shani, Eilon

    2016-08-01

    The phytohormone auxin (indole-3-acetic acid, IAA) is a small organic molecule that coordinates many of the key processes in plant development and adaptive growth. Plants regulate the auxin response pathways at multiple levels including biosynthesis, metabolism, transport and perception. One of the most striking aspects of plant plasticity is the modulation of development in response to changing growth environments. In this review, we explore recent findings correlating auxin response-dependent growth and development with osmotic stresses. Studies of water deficit, dehydration, salt, and other osmotic stresses point towards direct and indirect molecular perturbations in the auxin pathway. Osmotic stress stimuli modulate auxin responses by affecting auxin biosynthesis (YUC, TAA1), transport (PIN), perception (TIR/AFB, Aux/IAA), and inactivation/conjugation (GH3, miR167, IAR3) to coordinate growth and patterning. In turn, stress-modulated auxin gradients drive physiological and developmental mechanisms such as stomata aperture, aquaporin and lateral root positioning. We conclude by arguing that auxin-mediated growth inhibition under abiotic stress conditions is one of the developmental and physiological strategies to acclimate to the changing environment. PMID:27052306

  19. p38α Activates Purine Metabolism to Initiate Hematopoietic Stem/Progenitor Cell Cycling in Response to Stress.

    PubMed

    Karigane, Daiki; Kobayashi, Hiroshi; Morikawa, Takayuki; Ootomo, Yukako; Sakai, Mashito; Nagamatsu, Go; Kubota, Yoshiaki; Goda, Nobuhito; Matsumoto, Michihiro; Nishimura, Emi K; Soga, Tomoyoshi; Otsu, Kinya; Suematsu, Makoto; Okamoto, Shinichiro; Suda, Toshio; Takubo, Keiyo

    2016-08-01

    Hematopoietic stem cells (HSCs) maintain quiescence by activating specific metabolic pathways, including glycolysis. We do not yet have a clear understanding of how this metabolic activity changes during stress hematopoiesis, such as bone marrow transplantation. Here, we report a critical role for the p38MAPK family isoform p38α in initiating hematopoietic stem and progenitor cell (HSPC) proliferation during stress hematopoiesis in mice. We found that p38MAPK is immediately phosphorylated in HSPCs after a hematological stress, preceding increased HSPC cycling. Conditional deletion of p38α led to defective recovery from hematological stress and a delay in initiation of HSPC proliferation. Mechanistically, p38α signaling increases expression of inosine-5'-monophosphate dehydrogenase 2 in HSPCs, leading to altered levels of amino acids and purine-related metabolites and changes in cell-cycle progression in vitro and in vivo. Our studies have therefore uncovered a p38α-mediated pathway that alters HSPC metabolism to respond to stress and promote recovery. PMID:27345838

  20. Gangliosides attenuate stress-induced changes on body weight, motor activity and on the behavioral response to 5-methoxy-N,N-dimethyltryptamine.

    PubMed

    Cancela, L M; Volosin, M; Molina, V A

    1996-01-01

    The major goal of this study was to evaluate the influence of gangliosides (GANG) treatment on the onset of adaptive changes and the sequelae induced by stress exposure. With this purpose, the behavioral response to 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 5 mg/kg, IP) and motor activity were evaluated in rats previously submitted either to a single restraint session (2 h) or to a daily restraint event for 3 consecutive days, combined or not to GANG administration (30 mg/kg IP). GANG was always injected 2 h before stress exposure. In addition, differences in body weights were recorded throughout the experiments. A similar behavioral response after 5-MeODMT was observed between saline (SAL) and GANG unstressed rats. Exposure to one or three restraint sessions did not modify the behavioral response to 5-MeODMT, whereas the association of GANG and stress during 3 consecutive days enhanced forepaw treading and hindlimb abduction. SAL-treated animals submitted to a single or to three stressful stimuli showed reduced locomotion and rearing. The combination of GANG and stress for 3 days, but not after a unique association, reversed the decrease on motor activity induced by the aversive experience. The decrease of body weights produced by one or three stress sessions was recovered only in animals treated with GANG and stress for 3 days. These findings suggest that GANG may accelerate the onset of adaptive changes on 5-HT1 sites and attenuate certain sequelae induced by previous stress experience. PMID:8724427

  1. Chk1 keeps cell cycle transcription active in response to replication stress by interfering with E2F6-dependent repression

    PubMed Central

    Bertoli, Cosetta; Klier, Steffi; McGowan, Clare; Wittenberg, Curt; de Bruin, Robertus A. M.

    2014-01-01

    Background In eukaryotic cells, detection of replication stress results in the activation of the DNA replication checkpoint, a signaling cascade whose central players are the kinases ATR and Chk1. The checkpoint response prevents the accumulation of DNA damage and ensures cell viability by delaying progression into mitosis. However, the role and mechanism of the replication checkpoint transcriptional response in human cells, which is p53-independent, is largely unknown. Results We show that, in response to DNA replication stress, the regular E2F-dependent cell cycle transcriptional program is maintained at high levels and we establish the mechanisms governing such transcriptional upregulation. E2F6, a repressor of E2F-dependent G1/S transcription, replaces the activating E2Fs at promoters to repress transcription in cells progressing into S-phase in unperturbed conditions. Following replication stress, the checkpoint kinase Chk1 phosphorylates E2F6 leading to its dissociation from promoters. This promotes E2F-dependent transcription, which mediates cell survival by preventing DNA damage and cell death. Conclusions This work reveals, for the first time, that the regular cell cycle transcriptional program is part of the DNA replication checkpoint response in human cells and establishes the molecular mechanism involved. We show that maintaining high levels of G1/S cell cycle transcription in response to replication stress contributes to two key functions of the DNA replication checkpoint response, namely preventing genomic instability and cell death. Given the critical role of replication stress in oncogene transformation, a detailed understanding of the molecular mechanisms involved in the checkpoint response will contribute to a better insight into cancer development. PMID:23954429

  2. Drought stress responses in crops.

    PubMed

    Shanker, Arun K; Maheswari, M; Yadav, S K; Desai, S; Bhanu, Divya; Attal, Neha Bajaj; Venkateswarlu, B

    2014-03-01

    Among the effects of impending climate change, drought will have a profound impact on crop productivity in the future. Response to drought stress has been studied widely, and the model plant Arabidopsis has guided the studies on crop plants with genome sequence information viz., rice, wheat, maize and sorghum. Since the value of functions of genes, dynamics of pathways and interaction of networks for drought tolerance in plants can only be judged by evidence from field performance, this mini-review provides a research update focussing on the current developments on the response to drought in crop plants. Studies in Arabidopsis provide the basis for interpreting the available information in a systems biology perspective. In particular, the elucidation of the mechanism of drought stress response in crops is considered from evidence-based outputs emerging from recent omic studies in crops. PMID:24408129

  3. Plant Responses to Nanoparticle Stress

    PubMed Central

    Hossain, Zahed; Mustafa, Ghazala; Komatsu, Setsuko

    2015-01-01

    With the rapid advancement in nanotechnology, release of nanoscale materials into the environment is inevitable. Such contamination may negatively influence the functioning of the ecosystems. Many manufactured nanoparticles (NPs) contain heavy metals, which can cause soil and water contamination. Proteomic techniques have contributed substantially in understanding the molecular mechanisms of plant responses against various stresses by providing a link between gene expression and cell metabolism. As the coding regions of genome are responsible for plant adaptation to adverse conditions, protein signatures provide insights into the phytotoxicity of NPs at proteome level. This review summarizes the recent contributions of plant proteomic research to elaborate the complex molecular pathways of plant response to NPs stress. PMID:26561803

  4. Homologous pairs of regulatory proteins control activity of Bacillus subtilis transcription factor sigma(b) in response to environmental stress.

    PubMed Central

    Kang, C M; Brody, M S; Akbar, S; Yang, X; Price, C W

    1996-01-01

    In Bacillus subtilis, activity of the general stress transcription factor sigma B is controlled posttranslationally by a regulatory network that transmits signals of environmental and metabolic stress. These signals include heat, ethanol, or osmotic challenge, or a sharp decrease in cellular energy levels, and all ultimately control sigma B activity by influencing the binding decision of the RsbW anti-sigma factor. In the absence of stress, RsbW binds to sigma B and prevents its association with RNA polymerase core enzyme. However, following stress, RsbW binds instead to the RsbV anti-anti-sigma factor, thereby releasing sigma B to direct transcription of its target genes. These two principal regulators of sigmaB activity are encoded in the eight-gene sigB operon, which has the gene order rsbR-rsbS-rsbT-rsbU-rsbV-rsbW-sig B-rsbX (where rsb stands for regulator of sigma B). Notably, the predicted rsbS product has significant amino acid identity to the RsbV anti-anti-sigma factor and the predicted rsbT product resembles the RsbW anti-sigma factor. To determine the roles of rsbS and rsbT, null or missense mutations were constructed in the chromosomal copies or each and tested for their effects on expression of a sigma B-dependent reporter fusion. On the basis of this genetic analysis, our principal conclusions are that (i) the rsbS product is a negative regulator of or" activity, (ii) the rsbT product is a positive regulator, (iii) RsbS requires RsbT for function, and (iv) the RsbS-RsbT and RsbV-RsbW pairs act hierarchically by a common mechanism in which key protein-protein interactions are controlled by phosphorylation events. PMID:8682789

  5. Experimentally Induced Stress Validated by EMG Activity

    PubMed Central

    Luijcks, Rosan; Hermens, Hermie J.; Bodar, Lonneke; Vossen, Catherine J.; Os, Jim van.; Lousberg, Richel

    2014-01-01

    Experience of stress may lead to increased electromyography (EMG) activity in specific muscles compared to a non-stressful situation. The main aim of this study was to develop and validate a stress-EMG paradigm in which a single uncontrollable and unpredictable nociceptive stimulus was presented. EMG activity of the trapezius muscles was the response of interest. In addition to linear time effects, non-linear EMG time courses were also examined. Taking into account the hierarchical structure of the dataset, a multilevel random regression model was applied. The stress paradigm, executed in N = 70 subjects, consisted of a 3-minute baseline measurement, a 3-minute pre-stimulus stress period and a 2-minute post-stimulus phase. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. EMG activity during the entire experiment was conform a priori expectations: the pre-stimulus phase showed a significantly higher mean EMG activity level compared to the other two phases, and an immediate EMG response to the stimulus was demonstrated. In addition, the analyses revealed significant non-linear EMG time courses in all three phases. Linear and quadratic EMG time courses were significantly modified by subjective anticipatory stress level, measured just before the start of the stress task. Linking subjective anticipatory stress to EMG stress reactivity revealed that subjects with a high anticipatory stress level responded with more EMG activity during the pre-stimulus stress phase, whereas subjects with a low stress level showed an inverse effect. Results suggest that the stress paradigm presented here is a valid test to quantify individual differences in stress susceptibility. Further studies with this paradigm are required to demonstrate its potential use in mechanistic clinical studies. PMID:24736740

  6. GhMPK17, a Cotton Mitogen-Activated Protein Kinase, Is Involved in Plant Response to High Salinity and Osmotic Stresses and ABA Signaling

    PubMed Central

    Li, Yang; Sun, Xiang; Wang, Na-Na; Gong, Si-Ying; Zheng, Yong; Li, Xue-Bao

    2014-01-01

    Mitogen-activated protein kinase (MAPK) cascades play pivotal roles in mediating biotic and abiotic stress responses. Cotton (Gossypium hirsutum) is the most important textile crop in the world, and often encounters abiotic stress during its growth seasons. In this study, a gene encoding a mitogen-activated protein kinase (MAPK) was isolated from cotton, and designated as GhMPK17. The open reading frame (ORF) of GhMPK17 gene is 1494 bp in length and encodes a protein with 497 amino acids. Quantitative RT-PCR analysis indicated that GhMPK17 expression was up-regulated in cotton under NaCl, mannitol and ABA treatments. The transgenic Arabidopsis plants expressing GhMPK17 gene showed higher seed germination, root elongation and cotyledon greening/expansion rates than those of the wild type on MS medium containing NaCl, mannitol and exogenous ABA, suggesting that overexpression of GhMPK17 in Arabidopsis increased plant ABA-insensitivity, and enhanced plant tolerance to salt and osmotic stresses. Furthermore, overexpression of GhMPK17 in Arabidopsis reduced H2O2 level and altered expression of ABA- and abiotic stress-related genes in the transgenic plants. Collectively, these data suggested that GhMPK17 gene may be involved in plant response to high salinity and osmotic stresses and ABA signaling. PMID:24743296

  7. Inhibition of Transforming Growth Factor-Beta1 SignalingAttenuates Ataxia Telangiectasia Mutated Activity in Response toGenotoxic Stress

    SciTech Connect

    Kirshner, Julia; Jobling, Michael F.; Pajares, Maria Jose; Ravani, Shraddha A.; Glick, Adam; Lavin, Martin F.; Koslov, Sergei; Shiloh, Yosef; Barcellos-Hoff, Mary Helen

    2006-01-01

    Ionizing radiation causes DNA damage that elicits a cellular program of damage control coordinated by the kinase activity of ataxia telangiectasia mutated protein (ATM). Transforming growth factor {beta} (TGF{beta})-1, which is activated by radiation, is a potent and pleiotropic mediator of physiologic and pathologic processes. Here we show that TGF{beta} inhibition impedes the canonical cellular DNA damage stress response. Irradiated Tgf{beta}I null murine epithelial cells or human epithelial cells treated with a small-molecule inhibitor of TGF{beta} type I receptor kinase exhibit decreased phosphorylation of Chk2, Rad17, and p53; reduced H2AX radiation-induced foci; and increased radiosensitivity compared with TGF{beta} competent cells. We determined that loss of TGF{beta} signaling in epithelial cells truncated ATM autophosphorylation and significantly reduced its kinase activity, without affecting protein abundance. Addition of TGF{beta} restored functional ATM and downstream DNA damage responses. These data reveal a heretofore undetected critical link between the microenvironment and ATM, which directs epithelial cell stress responses, cell fate, and tissue integrity. Thus, Tgf{beta}I, in addition to its role in homoeostatic growth control, plays a complex role in regulating responses to genotoxic stress, the failure of which would contribute to the development of cancer; conversely, inhibiting TGF{beta} may be used to advantage in cancer therapy.

  8. Hypothalamus-pituitary-adrenal axis activity and the subsequent response to chronic stress differ depending upon life history stage.

    PubMed

    Lattin, Christine R; Bauer, Carolyn M; de Bruijn, Robert; Michael Romero, L

    2012-09-15

    The hypothalamus-pituitary-adrenal (HPA) axis is modulated seasonally in many species, and chronic stress can alter HPA functioning. However, it is not known how these two factors interact - are there particular life history stages when animals are more or less vulnerable to chronic stress? We captured wild house sparrows (Passer domesticus) in Massachusetts during six different life history stages: early and late winter, pre-laying, breeding, late breeding, and molt. At each time point, we tested HPA function by measuring baseline and stress-induced corticosterone (CORT), negative feedback in response to an injection of dexamethasone, and maximum adrenal response through an injection of adrenocorticotropic hormone. We then brought birds into captivity as a model for chronic stress, and repeated the four tests 5 days later. At capture, all HPA variables varied seasonally. Birds showed increased negative feedback during breeding and late winter compared to pre-laying. Furthermore, birds during the late breeding period had down-regulated their HPA axis, perhaps in preparation for molt. After 5 days of captivity, house sparrows lost ∼11% of initial body mass, although birds lost more weight during molt and early winter. Overall, captive sparrows showed elevated baseline CORT and increased negative feedback, although negative feedback did not show a significant increase during any individual life history stage. During most of the year, adrenal sensitivity was unaffected by captivity. However, during late breeding and molt, adrenal sensitivity increased during captivity. Taken together, these data provide further support that HPA function naturally varies throughout the year, with the interesting consequence that molting birds may potentially be more vulnerable to a chronic stressor such as captivity. PMID:22841762

  9. Platycodin D induces reactive oxygen species-mediated apoptosis signal-regulating kinase 1 activation and endoplasmic reticulum stress response in human breast cancer cells.

    PubMed

    Yu, Ji Sun; Kim, An Keun

    2012-08-01

    Platycodin D (PD), a natural compound found in Platycodon grandiflorum, induces apoptotic cell death in various carcinoma cells. One mechanism of PD-mediated cell death is by activation of mitogen-activated protein kinases, as suggested in a recent report. In this study, we further examined upstream signal pathways and the relationship between these signals and reactive oxygen species (ROS). Using immunoblotting assays, we found that PD activated apoptosis signal-regulating kinase 1 (ASK1) through phosphorylation of ASK1 at threonine and dephosphorylation of ASK1 at serine. We also showed that PD caused activation of the endoplasmic reticulum (ER) stress response. This was supported by observations showing that treatment with PD induces phosphorylation of PKR-like ER kinase (PERK) and eukaryotic initiation factor 2 α (eIF 2α), up-regulating expression of glucose-regulated protein 78/immunoglobulin heavy chain binding protein (GRP78/Bip) and CCAAT/enhancer-binding protein homologous protein/growth arrest and DNA damage-inducible gene 153 (CHOP/GADD153) and activation of caspase-4. Furthermore, PD-induced ASK1 and ER stress responses were inhibited by the antioxidant N-acetyl-l-cysteine. These results suggest that ROS play a critical role for activation of ASK1 and ER stress in PD-treated cancer cells. PMID:22784044

  10. The bacterial translation stress response

    PubMed Central

    Starosta, Agata L.; Lassak, Jürgen; Jung, Kirsten; Wilson, Daniel N.

    2014-01-01

    Throughout their life, bacteria need to sense and respond to environmental stress. Thus, such stress responses can require dramatic cellular reprogramming, both at the transcriptional as well as the translational level. This review focuses on the protein factors that interact with the bacterial translational apparatus in order to respond to and cope with different types of environmental stress. For example, the stringent factor RelA interacts with the ribosome to generate ppGpp under nutrient deprivation, whereas a variety of factors have been identified that bind to the ribosome under unfavorable growth conditions to shut-down (RelE, pY, RMF, HPF and EttA) or re-program (MazF, EF4 and BipA) translation. Additional factors have been identified that rescue ribosomes stalled due to stress-induced mRNA truncation (tmRNA, ArfA, ArfB), translation of unfavorable protein sequences (EF-P), heat shock induced subunit dissociation (Hsp15) or antibiotic inhibition (TetM, FusB). Understanding the mechanism of how the bacterial cell responds to stress will not only provide fundamental insight into translation regulation, but will also be an important step to identifying new targets for the development of novel antimicrobial agents. PMID:25135187

  11. Regulated cell death and adaptive stress responses.

    PubMed

    Galluzzi, Lorenzo; Bravo-San Pedro, José Manuel; Kepp, Oliver; Kroemer, Guido

    2016-06-01

    Eukaryotic cells react to potentially dangerous perturbations of the intracellular or extracellular microenvironment by activating rapid (transcription-independent) mechanisms that attempt to restore homeostasis. If such perturbations persist, cells may still try to cope with stress by activating delayed and robust (transcription-dependent) adaptive systems, or they may actively engage in cellular suicide. This regulated form of cell death can manifest with various morphological, biochemical and immunological correlates, and constitutes an ultimate attempt of stressed cells to maintain organismal homeostasis. Here, we dissect the general organization of adaptive cellular responses to stress, their intimate connection with regulated cell death, and how the latter operates for the preservation of organismal homeostasis. PMID:27048813

  12. Expression of xCT and activity of system xc(-) are regulated by NRF2 in human breast cancer cells in response to oxidative stress.

    PubMed

    Habib, Eric; Linher-Melville, Katja; Lin, Han-Xin; Singh, Gurmit

    2015-08-01

    Cancer cells adapt to high levels of oxidative stress in order to survive and proliferate by activating key transcription factors. One such master regulator, the redox sensitive transcription factor NF E2 Related Factor 2 (NRF2), controls the expression of cellular defense genes including those encoding intracellular redox-balancing proteins involved in glutathione (GSH) synthesis. Under basal conditions, Kelch-like ECH-associated protein 1 (KEAP1) targets NRF2 for ubiquitination. In response to oxidative stress, NRF2 dissociates from KEAP1, entering the nucleus and binding to the antioxidant response element (ARE) in the promoter of its target genes. Elevated reactive oxygen species (ROS) production may deplete GSH levels within cancer cells. System xc(-), an antiporter that exports glutamate while importing cystine to be converted into cysteine for GSH synthesis, is upregulated in cancer cells in response to oxidative stress. Here, we provided evidence that the expression of xCT, the light chain subunit of system xc(-), is regulated by NRF2 in representative human breast cancer cells. Hydrogen peroxide (H2O2) treatment increased nuclear translocation of NRF2, also increasing levels of xCT mRNA and protein and extracellular glutamate release. Overexpression of NRF2 up-regulated the activity of the xCT promoter, which contains a proximal ARE. In contrast, overexpression of KEAP1 repressed promoter activity and decreased xCT protein levels, while siRNA knockdown of KEAP1 up-regulated xCT protein levels and transporter activity. These results demonstrate the importance of the KEAP1/NRF2 pathway in balancing oxidative stress in breast cancer cells through system xc(-). We have previously shown that xCT is upregulated in various cancer cell lines under oxidative stress. In the current investigation, we focused on MCF-7 cells as a model for mechanistic studies. PMID:25827424

  13. Mitogen-activated Protein Kinase (MAPK) Activated by Prostaglandin E2 Phosphorylates Connexin 43 and Closes Osteocytic Hemichannels in Response to Continuous Flow Shear Stress.

    PubMed

    Riquelme, Manuel A; Burra, Sirisha; Kar, Rekha; Lampe, Paul D; Jiang, Jean X

    2015-11-20

    Cx43 hemichannels serve as a portal for the release of prostaglandins, a critical process in mediating biological responses of mechanical loading on bone formation and remodeling. We have previously observed that fluid flow shear stress (FFSS) opens hemichannels; however, sustained FFSS results in hemichannel closure, as continuous opening of hemichannels is detrimental to cell viability and bone remodeling. However, the mechanism that regulates the closure of the hemichannels is unknown. Here, we show that activation of p44/42 ERK upon continuous FFSS leads to Cx43 phosphorylation at Ser(279)-Ser(282), sites known to be phosphorylated sites by p44/42 MAPK. Incubation of osteocytic MLO-Y4 cells with conditioned media (CM) collected after continuous FFSS increased MAPK-dependent phosphorylation of Cx43. CM treatment inhibited hemichannel opening and this inhibition was reversed when cells were pretreated with the MAPK pathway inhibitor. We found that prostaglandin E2 (PGE2) accumulates in the CM in a time-dependent manner. Treatment with PGE2 increased phospho-p44/42 ERK levels and also Cx43 phosphorylation at Ser(279)-Ser(282) sites. Depletion of PGE2 from CM, and pre-treatment with a p44/42 ERK pathway-specific inhibitor, resulted in a complete inhibition of ERK-dependent Cx43 phosphorylation and attenuated the inhibition of hemichannels by CM and PGE2. Consistently, the opening of hemichannels by FFSS was blocked by PGE2 and CM and this blockage was reversed by U0126 and the CM depleted of PGE2. A similar observation was also obtained in isolated primary osteocytes. Together, results from this study suggest that extracellular PGE2 accumulated after continuous FFSS is responsible for activation of p44/42 ERK signaling and subsequently, direct Cx43 phosphorylation by activated ERK leads to hemichannel closure. PMID:26442583

  14. Human Cardiovascular Responses to Passive Heat Stress

    PubMed Central

    Crandall, Craig G.; Wilson, Thad E.

    2016-01-01

    Heat stress increases human morbidity and mortality compared to normothermic conditions. Many occupations, disease states, as well as stages of life are especially vulnerable to the stress imposed on the cardiovascular system during exposure to hot ambient conditions. This review focuses on the cardiovascular responses to heat stress that are necessary for heat dissipation. To accomplish this regulatory feat requires complex autonomic nervous system control of the heart and various vascular beds. For example, during heat stress cardiac output increases up to twofold, by increases in heart rate and an active maintenance of stroke volume via increases in inotropy in the presence of decreases in cardiac preload. Baroreflexes retain the ability to regulate blood pressure in many, but not all, heat stress conditions. Central hypovolemia is another cardiovascular challenge brought about by heat stress, which if added to a subsequent central volumetric stress, such as hemorrhage, can be problematic and potentially dangerous, as syncope and cardiovascular collapse may ensue. These combined stresses can compromise blood flow and oxygenation to important tissues such as the brain. It is notable that this compromised condition can occur at cardiac outputs that are adequate during normothermic conditions but are inadequate in heat because of the increased systemic vascular conductance associated with cutaneous vasodilation. Understanding the mechanisms within this complex regulatory system will allow for the development of treatment recommendations and countermeasures to reduce risks during the ever-increasing frequency of severe heat events that are predicted to occur. PMID:25589263

  15. Human cardiovascular responses to passive heat stress.

    PubMed

    Crandall, Craig G; Wilson, Thad E

    2015-01-01

    Heat stress increases human morbidity and mortality compared to normothermic conditions. Many occupations, disease states, as well as stages of life are especially vulnerable to the stress imposed on the cardiovascular system during exposure to hot ambient conditions. This review focuses on the cardiovascular responses to heat stress that are necessary for heat dissipation. To accomplish this regulatory feat requires complex autonomic nervous system control of the heart and various vascular beds. For example, during heat stress cardiac output increases up to twofold, by increases in heart rate and an active maintenance of stroke volume via increases in inotropy in the presence of decreases in cardiac preload. Baroreflexes retain the ability to regulate blood pressure in many, but not all, heat stress conditions. Central hypovolemia is another cardiovascular challenge brought about by heat stress, which if added to a subsequent central volumetric stress, such as hemorrhage, can be problematic and potentially dangerous, as syncope and cardiovascular collapse may ensue. These combined stresses can compromise blood flow and oxygenation to important tissues such as the brain. It is notable that this compromised condition can occur at cardiac outputs that are adequate during normothermic conditions but are inadequate in heat because of the increased systemic vascular conductance associated with cutaneous vasodilation. Understanding the mechanisms within this complex regulatory system will allow for the development of treatment recommendations and countermeasures to reduce risks during the ever-increasing frequency of severe heat events that are predicted to occur. PMID:25589263

  16. Dysfunctional stress responses in chronic pain.

    PubMed

    Woda, Alain; Picard, Pascale; Dutheil, Frédéric

    2016-09-01

    Many dysfunctional and chronic pain conditions overlap. This review describes the different modes of chronic deregulation of the adaptive response to stress which may be a common factor for these conditions. Several types of dysfunction can be identified within the hypothalamo-pituitary-adrenal axis: basal hypercortisolism, hyper-reactivity, basal hypocortisolism and hypo-reactivity. Neuroactive steroid synthesis is another component of the adaptive response to stress. Dehydroepiandrosterone (DHEA) and its sulfated form DHEA-S, and progesterone and its derivatives are synthetized in cutaneous, nervous, and adipose cells. They are neuroactive factors that act locally. They may have a role in the localization of the symptoms and their levels can vary both in the central nervous system and in the periphery. Persistent changes in neuroactive steroid levels or precursors can induce localized neurodegeneration. The autonomic nervous system is another component of the stress response. Its dysfunction in chronic stress responses can be expressed by decreased basal parasympathethic activity, increased basal sympathetic activity or sympathetic hyporeactivity to a stressful stimulus. The immune and genetic systems also participate. The helper-T cells Th1 secrete pro-inflammatory cytokines such as IL-1-β, IL-2, IL-6, IL-8, IL-12, IFN-γ, and TNF-α, whereas Th2 secrete anti-inflammatory cytokines: IL-4, IL-10, IGF-10, IL-13. Chronic deregulation of the Th1/Th2 balance can occur in favor of anti- or pro-inflammatory direction, locally or systemically. Individual vulnerability to stress can be due to environmental factors but can also be genetically influenced. Genetic polymorphisms and epigenetics are the main keys to understanding the influence of genetics on the response of individuals to constraints. PMID:27262345

  17. Combined therapeutic effects of bortezomib and anacardic acid on multiple myeloma cells via activation of the endoplasmic reticulum stress response.

    PubMed

    Dong, Xiaoxian; Liao, Yuning; Liu, Ningning; Hua, Xianliang; Cai, Jianyu; Liu, Jinbao; Huang, Hongbiao

    2016-09-01

    Bortezomib (Bor), a proteasome inhibitor, has marked therapeutic effects in multiple myeloma (MM), and its synergistic effects with other anticancer agents have been widely investigated. In the present study, endoplasmic reticulum (ER) stress was the target of the treatment strategy; anacardic acid (AA) and Bor induce ER stress, resulting in apoptosis of multiple myeloma cells. AA/Bor combination therapy exhibited overt cytotoxicity in MM cells, by synergistically reducing cell growth and promoting cell death. Notably, expression levels of the stress‑associated molecules binding protein, phosphorylated eukaryotic initiation factor 2α, activating transcription factor 4 (ATF4) and CCAAT‑enhancer binding protein homologous protein (CHOP) were increased following treatment. AA/Bor combination therapy‑induced U266 cell cytotoxicity was partially reversed by ATF4 gene silencing and slightly enhanced by CHOP knockdown. The results of the present study suggest that AA/Bor combination may be a potential therapeutic strategy for MM treatment. PMID:27430733

  18. Cardiovascular reactivity, stress, and physical activity

    PubMed Central

    Huang, Chun-Jung; Webb, Heather E.; Zourdos, Michael C.; Acevedo, Edmund O.

    2013-01-01

    Psychological stress has been proposed as a major contributor to the progression of cardiovascular disease (CVD). Acute mental stress can activate the sympathetic-adrenal-medullary (SAM) axis, eliciting the release of catecholamines (NE and EPI) resulting in the elevation of heart rate (HR) and blood pressure (BP). Combined stress (psychological and physical) can exacerbate these cardiovascular responses, which may partially contribute to the elevated risk of CVD and increased proportionate mortality risks experienced by some occupations (e.g., firefighting and law enforcement). Studies have supported the benefits of physical activity on physiological and psychological health, including the cardiovascular response to acute stress. Aerobically trained individuals exhibit lower sympathetic nervous system (e.g., HR) reactivity and enhanced cardiovascular efficiency (e.g., lower vascular reactivity and decreased recovery time) in response to physical and/or psychological stress. In addition, resistance training has been demonstrated to attenuate cardiovascular responses and improve mental health. This review will examine stress-induced cardiovascular reactivity and plausible explanations for how exercise training and physical fitness (aerobic and resistance exercise) can attenuate cardiovascular responses to stress. This enhanced functionality may facilitate a reduction in the incidence of stroke and myocardial infarction. Finally, this review will also address the interaction of obesity and physical activity on cardiovascular reactivity and CVD. PMID:24223557

  19. Assessment of Antioxidant Enzyme Activity and Mineral Nutrients in Response to NaCl Stress and its Amelioration Through Glutathione in Chickpea.

    PubMed

    Shankar, Vinay; Kumar, Dinesh; Agrawal, Veena

    2016-01-01

    Salinity stress has been reckoned as one of the major threat towards crop productivity as it causes significant decline in the yield. The impact of NaCl stress (0, 1, 10, 50, 100 and 200 mg L(-1)) as well as glutathione (10 mg L(-1)) either alone or in combination has been evaluated on the induction of multiple shoots, antioxidant enzymes' activity, lipid peroxidation, relative permeability, concentration of nutrients, photosynthetic pigments, protein and proline content of nodal segments of chickpea after 14 days of culture. The antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (GPX) and glutathione reductase (GR) were found to be increased under salt stress as well as glutathione-supplemented medium. A significant decrease in the concentrations of chlorophylls a, b, total chlorophyll and carotenoid was observed under salt stress. Concentrations of nitrogen, phosphorus, potassium, calcium, carbon, magnesium and sulphur showed an initial increase up to 10 mg L(-1) NaCl, but a decline was seen at higher NaCl levels. Proline content and malondialdehyde concentration were found to be increased under salt stress. Three isoforms of SOD, one of CAT and four of GPX were expressed during native polyacrylamide gel electrophoresis (PAGE) analysis. However, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of the stressed nodal explants revealed the over-expression of several polypeptide bands related to NaCl stress. These findings for the first time suggest that glutathione (GSH) helps in ameliorating NaCl stress in nodal explants of chickpea by manipulating various biochemical and physiological responses of plants. PMID:26440314

  20. Protein kinase B/Akt activates c-Jun NH(2)-terminal kinase by increasing NO production in response to shear stress

    NASA Technical Reports Server (NTRS)

    Go, Y. M.; Boo, Y. C.; Park, H.; Maland, M. C.; Patel, R.; Pritchard, K. A. Jr; Fujio, Y.; Walsh, K.; Darley-Usmar, V.; Jo, H.

    2001-01-01

    Laminar shear stress activates c-Jun NH(2)-terminal kinase (JNK) by the mechanisms involving both nitric oxide (NO) and phosphatidylinositide 3-kinase (PI3K). Because protein kinase B (Akt), a downstream effector of PI3K, has been shown to phosphorylate and activate endothelial NO synthase, we hypothesized that Akt regulates shear-dependent activation of JNK by stimulating NO production. Here, we examined the role of Akt in shear-dependent NO production and JNK activation by expressing a dominant negative Akt mutant (Akt(AA)) and a constitutively active mutant (Akt(Myr)) in bovine aortic endothelial cells (BAEC). As expected, pretreatment of BAEC with the PI3K inhibitor (wortmannin) prevented shear-dependent stimulation of Akt and NO production. Transient expression of Akt(AA) in BAEC by using a recombinant adenoviral construct inhibited the shear-dependent stimulation of NO production and JNK activation. However, transient expression of Akt(Myr) by using a recombinant adenoviral construct did not induce JNK activation. This is consistent with our previous finding that NO is required, but not sufficient on its own, to activate JNK in response to shear stress. These results and our previous findings strongly suggest that shear stress triggers activation of PI3K, Akt, and endothelial NO synthase, leading to production of NO, which (along with O(2-), which is also produced by shear) activates Ras-JNK pathway. The regulation of Akt, NO, and JNK by shear stress is likely to play a critical role in its antiatherogenic effects.

  1. Evolutionarily conserved IMPACT impairs various stress responses that require GCN1 for activating the eIF2 kinase GCN2.

    PubMed

    Cambiaghi, Tavane D; Pereira, Catia M; Shanmugam, Renuka; Bolech, Michael; Wek, Ronald C; Sattlegger, Evelyn; Castilho, Beatriz A

    2014-01-10

    In response to a range of environmental stresses, phosphorylation of the alpha subunit of the translation initiation factor 2 (eIF2α) represses general protein synthesis coincident with increased translation of specific mRNAs, such as those encoding the transcription activators GCN4 and ATF4. The eIF2α kinase GCN2 is activated by amino acid starvation by a mechanism involving GCN2 binding to an activator protein GCN1, along with association with uncharged tRNA that accumulates during nutrient deprivation. We previously showed that mammalian IMPACT and its yeast ortholog YIH1 bind to GCN1, thereby preventing GCN1 association with GCN2 and stimulation of this eIF2α kinase during amino acid depletion. GCN2 activity is also enhanced by other stresses, including proteasome inhibition, UV irradiation and lack of glucose. Here, we provide evidence that IMPACT affects directly and specifically the activation of GCN2 under these stress conditions in mammalian cells. We show that activation of mammalian GCN2 requires its interaction with GCN1 and that IMPACT promotes the dissolution of the GCN2-GCN1 complex. To a similar extent as the overexpression of YIH1, overexpression of IMPACT in yeast cells inhibited growth under all stress conditions that require GCN2 and GCN1 for cell survival, including exposure to acetic acid, high levels of NaCl, H₂O₂ or benomyl. This study extends our understanding of the roles played by GCN1 in GCN2 activation induced by a variety of stress arrangements and suggests that IMPACT and YIH1 use similar mechanisms for regulating this eIF2α kinase. PMID:24333428

  2. Styrene induces an inflammatory response in human lung epithelial cells via oxidative stress and NF-{kappa}B activation

    SciTech Connect

    Roeder-Stolinski, Carmen Fischaeder, Gundula Oostingh, Gertie Janneke Feltens, Ralph Kohse, Franziska; Bergen, Martin von Moerbt, Nora Eder, Klaus Duschl, Albert Lehmann, Irina

    2008-09-01

    Styrene is a volatile organic compound (VOC) that is widely used as a solvent in many industrial settings. Chronic exposure to styrene can result in irritation of the mucosa of the upper respiratory tract. Contact of styrene with epithelial cells stimulates the expression of a variety of inflammatory mediators, including the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1). To characterise the underlying mechanisms of the induction of inflammatory signals by styrene, we investigated the influence of this compound on the induction of oxidative stress and the activation of the nuclear factor-kappa B (NF-{kappa}B) signalling pathway in human lung epithelial cells (A549). The results demonstrate that styrene-induced MCP-1 expression, as well as the expression of the oxidative stress marker glutathione S-transferase (GST), is associated with a concentration dependent pattern of NF-{kappa}B activity. An inhibitor of NF-{kappa}B, IKK-NBD, and the anti-inflammatory antioxidant N-acetylcysteine (NAC) were both effective in suppressing styrene-induced MCP-1 secretion. In addition, NAC was capable of inhibiting the upregulation of GST expression. Our findings suggest that the activation of the NF-{kappa}B signalling pathway by styrene is mediated via a redox-sensitive mechanism.

  3. Nitric oxide and iron modulate heme oxygenase activity as a long distance signaling response to salt stress in sunflower seedling cotyledons.

    PubMed

    Singh, Neha; Bhatla, Satish C

    2016-02-29

    Nitric oxide is a significant component of iron signaling in plants. Heme is one of the iron sensors in plants. Free heme is highly toxic and can cause cell damage as it catalyzes the formation of reactive oxygen species (ROS). Its catabolism is carried out by heme oxygenase (HOs; EC 1.14.99.3) which uses heme both as a prosthetic group and as a substrate. Two significant events, which accompany adaptation to salt stress in sunflower seedlings, are accumulation of ROS and enhanced production of nitric oxide (NO) in roots and cotyledons. Present investigations on the immunolocalization of heme oxygenase distribution in sunflower seedling cotyledons by confocal laser scanning microscopic (CLSM) imaging provide new information on the differential spatial distribution of the inducible form of HO (HO-1) as a long distance in response to NaCl stress. The enzyme is abundantly distributed in the specialized cells around the secretory canals (SCs) in seedling cotyledons. Abundance of tyrosine nitrated proteins has also been observed in the specialized cells around the secretory canals in cotyledons derived from salt stressed seedlings. The spatial distribution of tyrosine nitrated proteins and HO-1 expression further correlates with the abundance of mitochondria in these cells. Present findings, thus, highlight a link among distribution of HO-1 expression, abundance of tyrosine nitrated proteins and mitochondria in specialized cells around the secretory canal as a long distance mechanism of salt stress tolerance in sunflower seedlings. Enhanced spatial distribution of HO-1 in response to NaCl stress in seedling cotyledons is in congruence with the observed increase in specific activity of HO-1 in NaCl stressed conditions. The enzyme activity is further enhanced by hemin (HO-1 inducer) both in the absence or presence of NaCl stress and inhibited by zinc protoporphyrin. Western blot analysis of cotyledon homogenates using anti-HO-1 polyclonal antibody shows one major band (29

  4. Gamma-glutamyl transpeptidase activity alters the T cell response to oxidative stress and Fas-induced apoptosis.

    PubMed

    Carlisle, Margaret L; King, Miranda R; Karp, David R

    2003-01-01

    The ectoenzyme gamma-glutamyl transpeptidase (GGT) is absent on resting naive peripheral blood T cells, highly expressed upon stimulation and intermediate on resting memory T cells. In other tissues, GGT is essential for the recapture of the antioxidant glutathione (GSH). T cells with different levels of GGT activity were examined for their ability to withstand oxidative stress. To create a model system that reflected the level of GGT seen on naive and memory T cells, Jurkat T cells were cloned by limiting dilution and their GGT expression analyzed. Jurkat expressing GGT at levels comparable to resting memory T cells have levels of intracellular reactive oxygen species (ROS) that are only 65% that seen in Jurkat that have low levels of GGT (similar to naive T cells). Treatment of the cells with H(2)O(2) increases ROS in both cells, although the level seen in the GGT(high) Jurkat is less than half that in the GGT(low) variant. Despite protection from oxidative stress, the GGT(high) Jurkat were found to be 2- to 3-fold more sensitive to Fas-induced apoptosis. The redox-regulated NF-kappaB pathway is activated in GGT(low) cells, resulting in higher levels of cIAP-1/2 proteins that limit caspase activity. The GGT(low) cells were found to have higher levels of NF-kappaB in the nucleus as well as lower levels of IkappaB-alpha. The GGT(low) cells also express higher levels of the caspase inhibitors cIAP-1/2 and have lower levels of caspase activity. These findings suggest that GGT expression regulates ROS in T lymphocytes and modulates Fas-induced killing by altering NF-kappaB activity. PMID:12502722

  5. Induction of ER stress in response to oxygen-glucose deprivation of cortical cultures involves the activation of the PERK and IRE-1 pathways and of caspase-12

    PubMed Central

    Badiola, N; Penas, C; Miñano-Molina, A; Barneda-Zahonero, B; Fadó, R; Sánchez-Opazo, G; Comella, J X; Sabriá, J; Zhu, C; Blomgren, K; Casas, C; Rodríguez-Alvarez, J

    2011-01-01

    Disturbance of calcium homeostasis and accumulation of misfolded proteins in the endoplasmic reticulum (ER) are considered contributory components of cell death after ischemia. However, the signal-transducing events that are activated by ER stress after cerebral ischemia are incompletely understood. In this study, we show that caspase-12 and the PERK and IRE pathways are activated following oxygen-glucose deprivation (OGD) of mixed cortical cultures or neonatal hypoxia–ischemia (HI). Activation of PERK led to a transient phosphorylation of eIF2α, an increase in ATF4 levels and the induction of gadd34 (a subunit of an eIF2α-directed phosphatase). Interestingly, the upregulation of ATF4 did not lead to an increase in the levels of CHOP. Additionally, IRE1 activation was mediated by the increase in the processed form of xbp1, which would be responsible for the observed expression of edem2 and the increased levels of the chaperones GRP78 and GRP94. We were also able to detect caspase-12 proteolysis after HI or OGD. Processing of procaspase-12 was mediated by NMDA receptor and calpain activation. Moreover, our data suggest that caspase-12 activation is independent of the unfolded protein response activated by ER stress. PMID:21525936

  6. Responses to Fiscal Stress in Higher Education.

    ERIC Educational Resources Information Center

    Wilson, Robert A., Ed.

    Proceedings of the 1981 University of Arizona conference on responses to fiscal stress in higher education are presented. Topics include the impact of the federal government on higher education, state and institutional responses to new federal policies, developing responses to fiscal stress, alternate perspectives on fiscal stress, and tactical…

  7. Arabidopsis FHY3 and FAR1 Regulate Light-Induced myo-Inositol Biosynthesis and Oxidative Stress Responses by Transcriptional Activation of MIPS1.

    PubMed

    Ma, Lin; Tian, Tian; Lin, Rongcheng; Deng, Xing-Wang; Wang, Haiyang; Li, Gang

    2016-04-01

    myo-Inositol-1-phosphate synthase (MIPS) catalyzes the limiting step of inositol biosynthesis and has crucial roles in plant growth and development. In response to stress, the transcription of MIPS1 is induced and the biosynthesis of inositol or inositol derivatives is promoted by unknown mechanisms. Here, we found that the light signaling protein FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and its homolog FAR-RED IMPAIRED RESPONSE1 (FAR1) regulate light-induced inositol biosynthesis and oxidative stress responses by activating the transcription of MIPS1. Disruption of FHY3 and FAR1 caused light-induced cell death after dark-light transition, precocious leaf senescence, and increased sensitivity to oxidative stress. Reduction of salicylic acid (SA) accumulation by overexpression of SALICYLIC ACID 3-HYDROXYLASE largely suppressed the cell death phenotype of fhy3 far1 mutant plants, suggesting that FHY3- and FAR1-mediated cell death is dependent on SA. Furthermore, comparative analysis of chromatin immunoprecipitation sequencing and microarray results revealed that FHY3 and FAR1 directly target both MIPS1 and MIPS2. The fhy3 far1 mutant plants showed severely decreased MIPS1/2 transcript levels and reduced inositol levels. Conversely, constitutive expression of MIPS1 partially rescued the inositol contents, caused reduced transcript levels of SA-biosynthesis genes, and prevented oxidative stress in fhy3 far1. Taken together, our results indicate that the light signaling proteins FHY3 and FAR1 directly bind the promoter of MIPS1 to activate its expression and thereby promote inositol biosynthesis to prevent light-induced oxidative stress and SA-dependent cell death. PMID:26714049

  8. Fiber networks amplify active stress.

    PubMed

    Ronceray, Pierre; Broedersz, Chase P; Lenz, Martin

    2016-03-15

    Large-scale force generation is essential for biological functions such as cell motility, embryonic development, and muscle contraction. In these processes, forces generated at the molecular level by motor proteins are transmitted by disordered fiber networks, resulting in large-scale active stresses. Although these fiber networks are well characterized macroscopically, this stress generation by microscopic active units is not well understood. Here we theoretically study force transmission in these networks. We find that collective fiber buckling in the vicinity of a local active unit results in a rectification of stress towards strongly amplified isotropic contraction. This stress amplification is reinforced by the networks' disordered nature, but saturates for high densities of active units. Our predictions are quantitatively consistent with experiments on reconstituted tissues and actomyosin networks and shed light on the role of the network microstructure in shaping active stresses in cells and tissue. PMID:26921325

  9. Acute Activation of Oxidative Pentose Phosphate Pathway as First-Line Response to Oxidative Stress in Human Skin Cells.

    PubMed

    Kuehne, Andreas; Emmert, Hila; Soehle, Joern; Winnefeld, Marc; Fischer, Frank; Wenck, Horst; Gallinat, Stefan; Terstegen, Lara; Lucius, Ralph; Hildebrand, Janosch; Zamboni, Nicola

    2015-08-01

    Integrity of human skin is endangered by exposure to UV irradiation and chemical stressors, which can provoke a toxic production of reactive oxygen species (ROS) and oxidative damage. Since oxidation of proteins and metabolites occurs virtually instantaneously, immediate cellular countermeasures are pivotal to mitigate the negative implications of acute oxidative stress. We investigated the short-term metabolic response in human skin fibroblasts and keratinocytes to H2O2 and UV exposure. In time-resolved metabolomics experiments, we observed that within seconds after stress induction, glucose catabolism is routed to the oxidative pentose phosphate pathway (PPP) and nucleotide synthesis independent of previously postulated blocks in glycolysis (i.e., of GAPDH or PKM2). Through ultra-short (13)C labeling experiments, we provide evidence for multiple cycling of carbon backbones in the oxidative PPP, potentially maximizing NADPH reduction. The identified metabolic rerouting in oxidative and non-oxidative PPP has important physiological roles in stabilization of the redox balance and ROS clearance. PMID:26190262

  10. The SrkA Kinase Is Part of the SakA Mitogen-Activated Protein Kinase Interactome and Regulates Stress Responses and Development in Aspergillus nidulans

    PubMed Central

    Jaimes-Arroyo, Rafael; Lara-Rojas, Fernando; Bayram, Özgür; Valerius, Oliver; Braus, Gerhard H.

    2015-01-01

    Fungi and many other eukaryotes use specialized mitogen-activated protein kinases (MAPK) of the Hog1/p38 family to transduce environmental stress signals. In Aspergillus nidulans, the MAPK SakA and the transcription factor AtfA are components of a central multiple stress-signaling pathway that also regulates development. Here we characterize SrkA, a putative MAPK-activated protein kinase, as a novel component of this pathway. ΔsrkA and ΔsakA mutants share a derepressed sexual development phenotype. However, ΔsrkA mutants are not sensitive to oxidative stress, and in fact, srkA inactivation partially suppresses the sensitivity of ΔsakA mutant conidia to H2O2, tert-butyl-hydroperoxide (t-BOOH), and menadione. In the absence of stress, SrkA shows physical interaction with nonphosphorylated SakA in the cytosol. We show that H2O2 induces a drastic change in mitochondrial morphology consistent with a fission process and the relocalization of SrkA to nuclei and mitochondria, depending on the presence of SakA. SakA-SrkA nuclear interaction is also observed during normal asexual development in dormant spores. Using SakA and SrkA S-tag pulldown and purification studies coupled to mass spectrometry, we found that SakA interacts with SrkA, the stress MAPK MpkC, the PPT1-type phosphatase AN6892, and other proteins involved in cell cycle regulation, DNA damage response, mRNA stability and protein synthesis, mitochondrial function, and other stress-related responses. We propose that oxidative stress induces DNA damage and mitochondrial fission and that SakA and SrkA mediate cell cycle arrest and regulate mitochondrial function during stress. Our results provide new insights into the mechanisms by which SakA and SrkA regulate the remodelling of cell physiology during oxidative stress and development. PMID:25820520

  11. 78 FR 16536 - Agency Information Collection Activities; Proposed New Collection; Comments Requested: Stress...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-15

    ... Information Collection Activities; Proposed New Collection; Comments Requested: Stress Resiliency Study... new collection; comments requested. (2) Title of the Form/Collection: Stress Resiliency Study... MPD officers' perceived stress, responses to stressful experiences, stress and its relationship...

  12. Sustained stress response after oxidative stress in trabecular meshwork cells

    PubMed Central

    Li, Guorong; Luna, Coralia; Liton, Paloma B.; Navarro, Iris; Epstein, David L.

    2007-01-01

    Purpose To investigate the mechanisms by which chronic oxidative stress may lead to a sustained stress response similar to that previously observed in the trabecular meshwork (TM) of glaucoma donors. Methods Porcine TM cells were treated with 200 μM H2O2 twice a day for four days and were allowed to recover for three additional days. After the treatment, TM cells were analyzed for generation of intracellular reactive oxygen species (iROS), mitochondrial potential, activation of NF-κB, and the expression of inflammatory markers IL-1α, IL-6, IL-8, and ELAM-1. Potential sources of iROS were evaluated using inhibitors for nitric oxide, nitric oxide synthetase, cyclooxygenase, xanthine oxidase, NADPH oxidase, mitochondrial ROS, and PKC. The role of NF-κB activation in the induction of inflammatory markers was evaluated using the inhibitors Lactacystin and BAY11–7082. Results Chronic oxidative stress simulated by H2O2 exposure of porcine TM cells resulted in the sustained production of iROS by the mitochondria. Inhibition of mitochondrial iROS had a significant inhibitory effect on the activation of NF-κB and the induction of IL-1α, IL-6, IL-8, and ELAM-1 triggered by chronic oxidative stress. Inhibition of NF-κB partially prevented the induction of IL-1α, IL-8, and ELAM-1, but not IL-6. Conclusions Chronic oxidative stress in TM cells induced iROS production in mitochondria. This increase in iROS may contribute to the pathogenesis of the TM in glaucoma by inducing the expression of inflammatory mediators previously observed in glaucoma donors as well as the levels of oxidative damage in the tissue. PMID:18199969

  13. Enzyme activities associated with oxidative stress in Metarhizium anisopliae during germination, mycelial growth, and conidiation and in response to near-UV irradiation.

    PubMed

    Miller, Charles D; Rangel, Drauzio; Braga, Gilberto U L; Flint, Stephan; Kwon, Sun-Il; Messias, Claudio L; Roberts, Donald W; Anderson, Anne J

    2004-01-01

    Metarhizium anisopliae isolates have a wide insect host range, but an impediment to their commercial use as a biocontrol agent of above-ground insects is the high susceptibility of spores to the near-UV present in solar irradiation. To understand stress responses in M. anisopliae, we initiated studies of enzymes that protect against oxidative stress in two strains selected because their spores differed in sensitivity to UV-B. Spores of the more near-UV resistant strain in M. anisopliae 324 displayed different isozyme profiles for catalase-peroxidase, glutathione reductase, and superoxide dismutase when compared with the less resistant strain 2575. A transient loss in activity of catalase-peroxidase and glutathione reductase was observed during germination of the spores, whereas the intensity of isozymes displaying superoxide dismutase did not change as the mycelium developed. Isozyme composition for catalase-peroxidases and glutathione reductase in germlings changed with growth phase. UV-B exposure from lamps reduced the activity of isozymes displaying catalase-peroxidase and glutathione reductase activities in 2575 more than in 324. The major effect of solar UV-A plus UV-B also was a reduction in catalase-peroxidases isozyme level, a finding confirmed by measurement of catalase specific activity. Impaired growth of M. anisopliae after near-UV exposure may be related to reduced abilities to handle oxidative stress. PMID:15052320

  14. Physiological responses of biomass allocation, root architecture, and invertase activity to copper stress in young seedlings from two populations of Kummerowia stipulacea (maxim.) Makino.

    PubMed

    Zhang, Luan; Pan, Yuxue; Lv, Wei; Xiong, Zhi-ting

    2014-06-01

    In the current study, we hypothesize that mine (metallicolous) populations of metallophytes form a trade-off between the roots and shoots when under copper (Cu) stress to adapt themselves to heavy metal contaminated habitats, and thus, differ from normal (non-metallicolous) populations in biomass allocation. To test the hypothesis, two populations of the metallophyte Kummerowia stipulacea, one from an ancient Cu mine (MP) and the other from a non-contaminated site (NMP), were treated with Cu(2+) in hydroponic conditions. The results showed that MP plants had higher root/shoot biomass allocation and more complicated root system architecture compared to those of the NMP plants when under Cu stress. The net photosynthetic capacity was more inhibited in the NMP plants than in the MP plants when under Cu stress. The sugar (sucrose and hexose) contents and acid invertase activities of MP plants were elevated while those in NMP plants were inhibited after Cu treatment. The neutral/alkaline invertase activities and sucrose synthase level showed no significant differences between the two populations when under Cu stress. The results showed that acid invertase played an important role in biomass allocation and that the physiological responses were beneficial for the high root/shoot biomass allocation, which were advantageous during adaptive evolution to Cu-enriched mine soils. PMID:24726940

  15. Biological responses of audiogenic stress

    NASA Astrophysics Data System (ADS)

    Mathur, R.; Behari, J.; Sharma, K. N.

    1986-12-01

    Biological effects of prolonged exposure to sound waves (˜17 kHz) on developing female rats were examined. Rat pups of day 80 were grouped into two. Experimental group was exposed to sound waves and control group, who were not so exposed. Daily food, water intake were measured in developing animals and spontaneous motor activity, electrocardiogram and blood sugar were studied in adults. It was found that the experimental group of animals behaved differently from the control group. It is concluded that the sound waves produced changes in the animals which were within the physiological limits but were suggestive of development of stress.

  16. Condition-specific genetic interaction maps reveal crosstalk between the cAMP/PKA and the HOG MAPK pathways in the activation of the general stress response

    PubMed Central

    Gutin, Jenia; Sadeh, Amit; Rahat, Ayelet; Aharoni, Amir; Friedman, Nir

    2015-01-01

    Cells must quickly respond and efficiently adapt to environmental changes. The yeast Saccharomyces cerevisiae has multiple pathways that respond to specific environmental insults, as well as a generic stress response program. The later is regulated by two transcription factors, Msn2 and Msn4, that integrate information from upstream pathways to produce fast, tunable, and robust response to different environmental changes. To understand this integration, we employed a systematic approach to genetically dissect the contribution of various cellular pathways to Msn2/4 regulation under a range of stress and growth conditions. We established a high-throughput liquid handling and automated flow cytometry system and measured GFP levels in 68 single-knockout and 1,566 double-knockout strains that carry an HSP12-GFP allele as a reporter for Msn2/4 activity. Based on the expression of this Msn2/4 reporter in five different conditions, we identified numerous genetic and epistatic interactions between different components in the network upstream to Msn2/4. Our analysis gains new insights into the functional specialization of the RAS paralogs in the repression of stress response and identifies a three-way crosstalk between the Mediator complex, the HOG MAPK pathway, and the cAMP/PKA pathway. PMID:26446933

  17. Condition-specific genetic interaction maps reveal crosstalk between the cAMP/PKA and the HOG MAPK pathways in the activation of the general stress response.

    PubMed

    Gutin, Jenia; Sadeh, Amit; Rahat, Ayelet; Aharoni, Amir; Friedman, Nir

    2015-10-01

    Cells must quickly respond and efficiently adapt to environmental changes. The yeast Saccharomyces cerevisiae has multiple pathways that respond to specific environmental insults, as well as a generic stress response program. The later is regulated by two transcription factors, Msn2 and Msn4, that integrate information from upstream pathways to produce fast, tunable, and robust response to different environmental changes. To understand this integration, we employed a systematic approach to genetically dissect the contribution of various cellular pathways to Msn2/4 regulation under a range of stress and growth conditions. We established a high-throughput liquid handling and automated flow cytometry system and measured GFP levels in 68 single-knockout and 1,566 double-knockout strains that carry an HSP12-GFP allele as a reporter for Msn2/4 activity. Based on the expression of this Msn2/4 reporter in five different conditions, we identified numerous genetic and epistatic interactions between different components in the network upstream to Msn2/4. Our analysis gains new insights into the functional specialization of the RAS paralogs in the repression of stress response and identifies a three-way crosstalk between the Mediator complex, the HOG MAPK pathway, and the cAMP/PKA pathway. PMID:26446933

  18. Biological Stress Response Terminology: Integrating the Concepts of Adaptive Response and Preconditioning Stress Within a Hormetic Dose-Response Framework

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stres...

  19. Understanding the responses of rice to environmental stress using proteomics.

    PubMed

    Singh, Raksha; Jwa, Nam-Soo

    2013-11-01

    Diverse abiotic and biotic stresses have marked effects on plant growth and productivity. To combat such stresses, plants have evolved complex but not well understood responses. Common effects upon perception of environmental stress are differential expression of the plant proteome and the synthesis of novel regulatory proteins for protection from and acclimation to stress conditions. Plants respond differently in terms of activation of stress-responsive signaling pathways depending upon the type and nature of the stresses to which they are exposed. Progress in proteomics and systems biology approaches has made it possible to identify the novel proteins and their interactions that function in abiotic stress responses. This will enable elucidation of the functions of individual proteins and their roles in signaling networks. Proteomic analysis of the responses to various stress conditions is performed most commonly using 2D gel electrophoresis and high-throughput identification by LC-MS/MS. Because of recent developments in proteomics techniques, numerous proteomics studies of rice under abiotic stress conditions have been performed. In this review, proteomics studies addressing rice responses to the major environmental stresses--including cold, heat, drought, salt, heavy metals, minerals, UV radiation, and ozone--are discussed. Unique or common protein responses to these stress conditions are summarized and interpreted according to their possible physiological responses in each stress. Additionally, proteomics studies on various plant systems under various abiotic stress conditions are compared to provide deeper understanding of specific and common proteome responses in rice and other plant systems, which will further contribute to the identification of abiotic stress tolerance factor at protein level. Functional analysis of stress-responsive proteins will provide new research objectives with the aim of achieving stable crop productivity in the face of the

  20. Role of the PFXFATG[G/Y] Motif in the Activation of SdrG, a Response Regulator Involved in the Alphaproteobacterial General Stress Response.

    PubMed

    Campagne, Sébastien; Dintner, Sebastian; Gottschlich, Lisa; Thibault, Maxence; Bortfeld-Miller, Miriam; Kaczmarczyk, Andreas; Francez-Charlot, Anne; Allain, Frédéric H-T; Vorholt, Julia A

    2016-08-01

    Two-component systems are major signal transduction pathways, which consist of histidine kinases and response regulators that communicate through phosphorylation. Here, we highlight a distinct class of single-domain response regulators containing the PFXFATG[G/Y] motif that are activated by a mechanism distinct from the Y-T coupling described for prototypical receiver domains. We first solved the structures of inactive and active SdrG, a representative of the FAT GUY family, and then biochemically and genetically characterized variants in which residues in this motif were mutated. Our results support a model of activation mainly driven by a conserved lysine and reveal that the rotation of the threonine induces the reorganization of several aromatic residues in and around the PFXFATG[G/Y] motif to generate intermediates resembling those occurring during classical Y-T coupling. Overall, this helps define a new subfamily of response regulators that emerge as important players in physiological adaptation. PMID:27396826

  1. Ferritin and the response to oxidative stress.

    PubMed Central

    Orino, K; Lehman, L; Tsuji, Y; Ayaki, H; Torti, S V; Torti, F M

    2001-01-01

    Iron is required for normal cell growth and proliferation. However, excess iron is potentially harmful, as it can catalyse the formation of toxic reactive oxygen species (ROS) via Fenton chemistry. For this reason, cells have evolved highly regulated mechanisms for controlling intracellular iron levels. Chief among these is the sequestration of iron in ferritin. Ferritin is a 24 subunit protein composed of two subunit types, termed H and L. The ferritin H subunit has a potent ferroxidase activity that catalyses the oxidation of ferrous iron, whereas ferritin L plays a role in iron nucleation and protein stability. In the present study we report that increased synthesis of both subunits of ferritin occurs in HeLa cells exposed to oxidative stress. An increase in the activity of iron responsive element binding proteins in response to oxidative stress was also observed. However, this activation was transient, allowing ferritin protein induction to subsequently proceed. To assess whether ferritin induction reduced the accumulation of ROS, and to test the relative contribution of ferritin H and L subunits in this process, we prepared stable transfectants that overexpressed either ferritin H or ferritin L cDNA under control of a tetracycline-responsive promoter. We observed that overexpression of either ferritin H or ferritin L reduced the accumulation of ROS in response to oxidant challenge. PMID:11415455

  2. Cancer Microenvironment and Endoplasmic Reticulum Stress Response

    PubMed Central

    Giampietri, Claudia; Petrungaro, Simonetta; Conti, Silvia; Facchiano, Antonio; Filippini, Antonio; Ziparo, Elio

    2015-01-01

    Different stressful conditions such as hypoxia, nutrient deprivation, pH changes, or reduced vascularization, potentially able to act as growth-limiting factors for tumor cells, activate the unfolded protein response (UPR). UPR is therefore involved in tumor growth and adaptation to severe environments and is generally cytoprotective in cancer. The present review describes the molecular mechanisms underlying UPR and able to promote survival and proliferation in cancer. The critical role of UPR activation in tumor growth promotion is discussed in detail for a few paradigmatic tumors such as prostate cancer and melanoma. PMID:26491226

  3. Evolutionarily conserved IMPACT impairs various stress responses that require GCN1 for activating the eIF2 kinase GCN2

    SciTech Connect

    Cambiaghi, Tavane D.; Pereira, Catia M.; Shanmugam, Renuka; Bolech, Michael; Wek, Ronald C.; Sattlegger, Evelyn; Castilho, Beatriz A.

    2014-01-10

    Highlights: •GCN1 is required for mammalian and yeast GCN2 function in a variety of conditions. •Mammalian IMPACT competes with GCN2 for GCN1 binding. •IMPACT and its yeast counterpart YIH1 downregulate GCN1-dependent GCN2 activation. -- Abstract: In response to a range of environmental stresses, phosphorylation of the alpha subunit of the translation initiation factor 2 (eIF2α) represses general protein synthesis coincident with increased translation of specific mRNAs, such as those encoding the transcription activators GCN4 and ATF4. The eIF2α kinase GCN2 is activated by amino acid starvation by a mechanism involving GCN2 binding to an activator protein GCN1, along with association with uncharged tRNA that accumulates during nutrient deprivation. We previously showed that mammalian IMPACT and its yeast ortholog YIH1 bind to GCN1, thereby preventing GCN1 association with GCN2 and stimulation of this eIF2α kinase during amino acid depletion. GCN2 activity is also enhanced by other stresses, including proteasome inhibition, UV irradiation and lack of glucose. Here, we provide evidence that IMPACT affects directly and specifically the activation of GCN2 under these stress conditions in mammalian cells. We show that activation of mammalian GCN2 requires its interaction with GCN1 and that IMPACT promotes the dissolution of the GCN2–GCN1 complex. To a similar extent as the overexpression of YIH1, overexpression of IMPACT in yeast cells inhibited growth under all stress conditions that require GCN2 and GCN1 for cell survival, including exposure to acetic acid, high levels of NaCl, H{sub 2}O{sub 2} or benomyl. This study extends our understanding of the roles played by GCN1 in GCN2 activation induced by a variety of stress arrangements and suggests that IMPACT and YIH1 use similar mechanisms for regulating this eIF2α kinase.

  4. The nuclear protein GmbZIP110 has transcription activation activity and plays important roles in the response to salinity stress in soybean

    PubMed Central

    Xu, Zhaolong; Ali, Zulfiqar; Xu, Ling; He, Xiaolan; Huang, Yihong; Yi, Jinxin; Shao, Hongbo; Ma, Hongxiang; Zhang, Dayong

    2016-01-01

    Plant basic-leucine zipper (bZIP) transcription factors play important roles in many biological processes and are involved in the regulation of salt stress tolerance. Previously, our lab generated digital gene expression profiling (DGEP) data to identify differentially expressed genes in a salt-tolerant genotype of Glycine soja (STGoGS) and a salt-sensitive genotype of Glycine max (SSGoGM). This DGEP data revealed that the expression (log2 ratio) of GmbZIP110 was up-regulated 2.76-fold and 3.38-fold in SSGoGM and STGoGS, respectively. In the present study, the salt inducible gene GmbZIP110 was cloned and characterized through phylogenetic analysis, subcellular localization and in silico transcript abundance analysis in different tissues. The functional role of this gene in salt tolerance was studied through transactivation analysis, DNA binding ability, expression in soybean composite seedlings and transgenic Arabidopsis, and the effect of GmbZIP110 on the expression of stress-related genes in transgenic Arabidopsis was investigated. We found that GmbZIP110 could bind to the ACGT motif, impact the expression of many stress-related genes and the accumulation of proline, Na+ and K+, and enhanced the salt tolerance of composite seedlings and transgenic Arabidopsis. Integrating all these results, we propose that GmbZIP110 plays a critical role in the response to salinity stress in soybean and has high potential usefulness in crop improvement. PMID:26837841

  5. The nuclear protein GmbZIP110 has transcription activation activity and plays important roles in the response to salinity stress in soybean.

    PubMed

    Xu, Zhaolong; Ali, Zulfiqar; Xu, Ling; He, Xiaolan; Huang, Yihong; Yi, Jinxin; Shao, Hongbo; Ma, Hongxiang; Zhang, Dayong

    2016-01-01

    Plant basic-leucine zipper (bZIP) transcription factors play important roles in many biological processes and are involved in the regulation of salt stress tolerance. Previously, our lab generated digital gene expression profiling (DGEP) data to identify differentially expressed genes in a salt-tolerant genotype of Glycine soja (STGoGS) and a salt-sensitive genotype of Glycine max (SSGoGM). This DGEP data revealed that the expression (log2 ratio) of GmbZIP110 was up-regulated 2.76-fold and 3.38-fold in SSGoGM and STGoGS, respectively. In the present study, the salt inducible gene GmbZIP110 was cloned and characterized through phylogenetic analysis, subcellular localization and in silico transcript abundance analysis in different tissues. The functional role of this gene in salt tolerance was studied through transactivation analysis, DNA binding ability, expression in soybean composite seedlings and transgenic Arabidopsis, and the effect of GmbZIP110 on the expression of stress-related genes in transgenic Arabidopsis was investigated. We found that GmbZIP110 could bind to the ACGT motif, impact the expression of many stress-related genes and the accumulation of proline, Na(+) and K(+), and enhanced the salt tolerance of composite seedlings and transgenic Arabidopsis. Integrating all these results, we propose that GmbZIP110 plays a critical role in the response to salinity stress in soybean and has high potential usefulness in crop improvement. PMID:26837841

  6. Physiological Responses to Thermal Stress and Exercise

    NASA Astrophysics Data System (ADS)

    Iyota, Hiroyuki; Ohya, Akira; Yamagata, Junko; Suzuki, Takashi; Miyagawa, Toshiaki; Kawabata, Takashi

    The simple and noninvasive measuring methods of bioinstrumentation in humans is required for optimization of air conditioning and management of thermal environments, taking into consideration the individual specificity of the human body as well as the stress conditions affecting each. Changes in human blood circulation were induced with environmental factors such as heat, cold, exercise, mental stress, and so on. In this study, the physiological responses of human body to heat stress and exercise were investigated in the initial phase of the developmental research. We measured the body core and skin temperatures, skin blood flow, and pulse wave as the indices of the adaptation of the cardiovascular system. A laser Doppler skin blood flowmetry using an optical-sensor with a small portable data logger was employed for the measurement. These results reveal the heat-stress and exercise-induced circulatory responses, which are under the control of the sympathetic nerve system. Furthermore, it was suggested that the activity of the sympathetic nervous system could be evaluated from the signals of the pulse wave included in the signals derived from skin blood flow by means of heart rate variability assessments and detecting peak heights of velocity-plethysmogram.

  7. Medial hypothalamic 5-hydroxytryptamine (5-HT)1A receptors regulate neuroendocrine responses to stress and exploratory locomotor activity: application of recombinant adenovirus containing 5-HT1A sequences.

    PubMed

    Li, Qian; Holmes, Andrew; Ma, Li; Van de Kar, Louis D; Garcia, Francisca; Murphy, Dennis L

    2004-12-01

    Our previous studies found that serotonin transporter (SERT) knock-out mice showed increased sensitivity to minor stress and increased anxiety-like behavior but reduced locomotor activity. These mice also showed decreased density of 5-hydroxytryptamine (5-HT1A) receptors in the hypothalamus, amygdala, and dorsal raphe. To evaluate the contribution of hypothalamic 5-HT1A receptors to these phenotypes of SERT knock-out mice, two studies were conducted. Recombinant adenoviruses containing 5-HT1A sense and antisense sequences (Ad-1AP-sense and Ad-1AP-antisense) were used to manipulate 5-HT1A receptors in the hypothalamus. The expression of the 5-HT1A genes is controlled by the 5-HT1A promoter, so that they are only expressed in 5-HT1A receptor-containing cells. (1) Injection of Ad-1AP-sense into the hypothalamus of SERT knock-out mice restored 5-HT1A receptors in the medial hypothalamus; this effect was accompanied by elimination of the exaggerated adrenocorticotropin responses to a saline injection (minor stress) and reduced locomotor activity but not by a change in increased exploratory anxiety-like behavior. (2) To further confirm the observation in SERT-/- mice, Ad-1AP-antisense was injected into the hypothalamus of normal mice. The density and the function of 5-HT1A receptors in the medial hypothalamus were significantly reduced in Ad-1AP-antisense-treated mice. Compared with the control group (injected with Ad-track), Ad-1A-antisense-treated mice showed a significant reduction in locomotor activity, but again no changes in exploratory anxiety-like behaviors, tested by elevated plus-maze and open-field tests. Thus, the present results demonstrate that medial hypothalamic 5-HT1A receptors regulate stress responses and locomotor activity but may not regulate exploratory anxiety-like behaviors. PMID:15574737

  8. ZnO Nanoparticles Impose a Panmetabolic Toxic Effect Along with Strong Necrosis, Inducing Activation of the Envelope Stress Response in Salmonella enterica Serovar Enteritidis

    PubMed Central

    Vidovic, Sinisa; Elder, Jeff; Medihala, Prabhakara; Lawrence, John R.; Predicala, Bernardo; Zhang, Haixia

    2015-01-01

    In this study, we tested the antimicrobial activity of three metal nanoparticles (NPs), ZnO, MgO, and CaO NPs, against Salmonella enterica serovar Enteritidis in liquid medium and on solid surfaces. Out of the three tested metal NPs, ZnO NPs exhibited the most significant antimicrobial effect both in liquid medium and when embedded on solid surfaces. Therefore, we focused on revealing the mechanisms of surface-associated ZnO biocidal activity. Using the global proteome approach, we report that a great majority (79%) of the altered proteins in biofilms formed by Salmonella enterica serovar Enteritidis were downregulated, whereas a much smaller fraction (21%) of proteins were upregulated. Intriguingly, all downregulated proteins were enzymes involved in a wide range of the central metabolic pathways, including translation; amino acid biosynthetic pathways; nucleobase, nucleoside, and nucleotide biosynthetic processes; ATP synthesis-coupled proton transport; the pentose phosphate shunt; and carboxylic acid metabolic processes, indicating that ZnO NPs exert a panmetabolic toxic effect on this prokaryotic organism. In addition to their panmetabolic toxicity, ZnO NPs induced profound changes in cell envelope morphology, imposing additional necrotic effects and triggering the envelope stress response of Salmonella serovar Enteritidis. The envelope stress response effect activated periplasmic chaperones and proteases, transenvelope complexes, and regulators, thereby facilitating protection of this prokaryotic organism against ZnO NPs. PMID:25801570

  9. ZnO nanoparticles impose a panmetabolic toxic effect along with strong necrosis, inducing activation of the envelope stress response in Salmonella enterica serovar Enteritidis.

    PubMed

    Vidovic, Sinisa; Elder, Jeff; Medihala, Prabhakara; Lawrence, John R; Predicala, Bernardo; Zhang, Haixia; Korber, Darren R

    2015-01-01

    In this study, we tested the antimicrobial activity of three metal nanoparticles (NPs), ZnO, MgO, and CaO NPs, against Salmonella enterica serovar Enteritidis in liquid medium and on solid surfaces. Out of the three tested metal NPs, ZnO NPs exhibited the most significant antimicrobial effect both in liquid medium and when embedded on solid surfaces. Therefore, we focused on revealing the mechanisms of surface-associated ZnO biocidal activity. Using the global proteome approach, we report that a great majority (79%) of the altered proteins in biofilms formed by Salmonella enterica serovar Enteritidis were downregulated, whereas a much smaller fraction (21%) of proteins were upregulated. Intriguingly, all downregulated proteins were enzymes involved in a wide range of the central metabolic pathways, including translation; amino acid biosynthetic pathways; nucleobase, nucleoside, and nucleotide biosynthetic processes; ATP synthesis-coupled proton transport; the pentose phosphate shunt; and carboxylic acid metabolic processes, indicating that ZnO NPs exert a panmetabolic toxic effect on this prokaryotic organism. In addition to their panmetabolic toxicity, ZnO NPs induced profound changes in cell envelope morphology, imposing additional necrotic effects and triggering the envelope stress response of Salmonella serovar Enteritidis. The envelope stress response effect activated periplasmic chaperones and proteases, transenvelope complexes, and regulators, thereby facilitating protection of this prokaryotic organism against ZnO NPs. PMID:25801570

  10. A Chaperone Function of NO CATALASE ACTIVITY1 Is Required to Maintain Catalase Activity and for Multiple Stress Responses in Arabidopsis

    PubMed Central

    Li, Jing; Liu, Juntao; Wang, Guoqiang; Cha, Joon-Yung; Li, Guannan; Chen, She; Li, Zhen; Guo, Jinghua; Zhang, Caiguo; Yang, Yongqing; Kim, Woe-Yeon; Yun, Dae-Jin; Schumaker, Karen S.; Chen, Zhongzhou; Guo, Yan

    2015-01-01

    Catalases are key regulators of reactive oxygen species homeostasis in plant cells. However, the regulation of catalase activity is not well understood. In this study, we isolated an Arabidopsis thaliana mutant, no catalase activity1-3 (nca1-3) that is hypersensitive to many abiotic stress treatments. The mutated gene was identified by map-based cloning as NCA1, which encodes a protein containing an N-terminal RING-finger domain and a C-terminal tetratricopeptide repeat-like helical domain. NCA1 interacts with and increases catalase activity maximally in a 240-kD complex in planta. In vitro, NCA1 interacts with CATALASE2 (CAT2) in a 1:1 molar ratio, and the NCA1 C terminus is essential for this interaction. CAT2 activity increased 10-fold in the presence of NCA1, and zinc ion binding of the NCA1 N terminus is required for this increase. NCA1 has chaperone protein activity that may maintain the folding of catalase in a functional state. NCA1 is a cytosol-located protein. Expression of NCA1 in the mitochondrion of the nca1-3 mutant does not rescue the abiotic stress phenotypes of the mutant, while expression in the cytosol or peroxisome does. Our results suggest that NCA1 is essential for catalase activity. PMID:25700484

  11. Activation of the endoplasmic reticulum stress response in skeletal muscle of G93A*SOD1 amyotrophic lateral sclerosis mice

    PubMed Central

    Chen, Dapeng; Wang, Yan; Chin, Eva R.

    2015-01-01

    Mutations in Cu/Zn superoxide dismutase (SOD1) are one of the genetic causes of Amyotrophic Lateral Sclerosis (ALS). Although the primary symptom of ALS is muscle weakness, the link between SOD1 mutations, cellular dysfunction and muscle atrophy and weakness is not well understood. The purpose of this study was to characterize cellular markers of ER stress in skeletal muscle across the lifespan of G93A*SOD1 (ALS-Tg) mice. Muscles were obtained from ALS-Tg and age-matched wild type (WT) mice at 70d (pre-symptomatic), 90d and 120–140d (symptomatic) and analyzed for ER stress markers. In white gastrocnemius (WG) muscle, ER stress sensors PERK and IRE1α were upregulated ~2-fold at 70d and remained (PERK) or increased further (IRE1α) at 120–140d. Phospho-eIF2α, a downstream target of PERK and an inhibitor of protein translation, was increased by 70d and increased further to 12.9-fold at 120–140d. IRE1α upregulation leads to increased splicing of X-box binding protein 1 (XBP-1) to the XBP-1s isoform. XBP-1s transcript was increased at 90d and 120–140d indicating activation of IRE1α signaling. The ER chaperone/heat shock protein Grp78/BiP was upregulated 2-fold at 70d and 90d and increased to 6.1-fold by 120–140d. The ER-stress-specific apoptotic signaling protein CHOP was upregulated 2-fold at 70d and 90d and increased to 13.3-fold at 120–140d indicating progressive activation of an apoptotic signal in muscle. There was a greater increase in Grp78/BiP and CHOP in WG vs. the more oxidative red gastrocnemius (RG) ALS-Tg at 120–140d indicating greater ER stress and apoptosis in fast glycolytic muscle. These data show that the ER stress response is activated in skeletal muscle of ALS-Tg mice by an early pre-symptomatic age and increases with disease progression. These data suggest a mechanism by which myocellular ER stress leads to reduced protein translation and contributes to muscle atrophy and weakness in ALS. PMID:26041991

  12. The role of biological activity of hydrohumate, produced from peat, in formation of adaptive response of rats under influence of chronic stress

    NASA Astrophysics Data System (ADS)

    Lyanna, O. L.; Chorna, V. I.; Stepchenko, L. M.

    2009-04-01

    It is well known that humic compounds are the most distributed in nature among the organic matter. It is believed that humic polyphenol preparations, produced from the peat, represent adaptogenes and immunomodulators. But the total mechanism of their adaptogenic action is still completely unclear. In response to extraordinary irritant action, one of the most sensitive to stress and highly reactive systems of organism, endosomal-lysosomal cellular apparatus takes part. It is believed that humic compounds are able to penetrate through plasmatic membrane and by this way to affect on lysosomal proteases function. Among the wide range of lysosomal proteases, cysteine cathepsin L (EC 3.4.22.15) was in interest due to its powerful endopeptidase activity and widespread localization. Purpose. The aim of the work was to investigate the influence of humic acids on intracellular proteolysis in blood plasma and heart muscle of rats in adaptive-restorative processes developing in rat organisms as a result of chronic stress action. The experiment was held on Wistar's rats (160-200 g weight) which were divided into 4 groups: 1 - the control group; 2 - the animals which were received the hydrohumate with water (10 mg hydrohumate (0,1% solution) per 1 kg of weight) during 3 weeks; 3 - the group of stressed rats (test "forced swimming" for 2 hours); 4 - the stressed rats which received the hydrohumate. The activity of lysosomal cysteine cathepsin L was determined spectrophotometrically by usage 1% azocasein, denaturated by 3 M urea, as substrate. It was obtained that under hydrohumate influence the activity of lysosomal cysteine cathepsin L in rat blood plasma changed on 20% in comparison with control group that is suggested to be caused by leakage of tissue cathepsins from organs and tissues and kidneys' filtration of these cysteine enzymes in urine. In rat heart tissues it was obtained that cathepsin L activity level was on 26,8% higher in rats which were under stress influence in

  13. ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2α kinases

    PubMed Central

    Kline, C. Leah B.; Van den Heuvel, A. Pieter J.; Allen, Joshua E.; Prabhu, Varun V.; Dicker, David T.; El-Deiry, Wafik S.

    2016-01-01

    ONC201 (also called TIC10) is a small molecule that inactivates the cell proliferation- and cell survival-promoting kinases AKT and ERK and induces cell death through the pro-apoptotic protein TRAIL. ONC201 is currently in early phase clinical testing for various malignancies. Here, we found through gene expression and protein analyses that ONC201 triggered an increase in TRAIL abundance and cell death through an integrated stress response (ISR) involving the transcription factor ATF4, the transactivator CHOP, and the TRAIL receptor DR5. ATF4 was not activated in ONC201-resistant cancer cells, and in ONC201-sensitive cells, knockdown of ATF4 or CHOP partially abrogated ONC201-induced cytotoxicity and diminished the ONC201-stimulated increase in DR5 abundance. The activation of ATF4 in response to ONC201 required the kinases HRI and PKR, which phosphorylate and activate the translation initiation factor eIF2α. ONC201 rapidly triggered cell cycle arrest, which was associated with decreased abundance of cyclin D1, decreased activity of the kinase complex mTORC1, and dephosphorylation of the retinoblastoma (Rb) protein. The abundance of X-linked inhibitor of apoptosis protein (XIAP) negatively correlated with the extent of apoptosis in response to ONC201. These effects of ONC201 were independent of whether cancer cells had normal or mutant p53. Thus, ONC201 induces cell death through the coordinated induction of TRAIL by an ISR pathway. PMID:26884600

  14. Oxidative stress in deep scattering layers: Heat shock response and antioxidant enzymes activities of myctophid fishes thriving in oxygen minimum zones

    NASA Astrophysics Data System (ADS)

    Lopes, Ana Rita; Trübenbach, Katja; Teixeira, Tatiana; Lopes, Vanessa M.; Pires, Vanessa; Baptista, Miguel; Repolho, Tiago; Calado, Ricardo; Diniz, Mário; Rosa, Rui

    2013-12-01

    Diel vertical migrators, such as myctophid fishes, are known to encounter oxygen minimum zones (OMZ) during daytime in the Eastern Pacific Ocean and, therefore, have to cope with temperature and oxidative stress that arise while ascending to warmer, normoxic surface waters at night-time. The aim of this study was to investigate the antioxidant defense strategies and heat shock response (HSR) in two myctophid species, namely Triphoturus mexicanus and Benthosema panamense, at shallow and warm surface waters (21 kPa, 20-25 °C) and at hypoxic, cold (≤1 kPa, 10 °C) mesopelagic depths. More specifically, we quantified (i) heat shock protein concentrations (HSP70/HSC70) (ii) antioxidant enzyme activities [including superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST)], and (iii) lipid peroxidation [malondialdehyde (MDA) levels]. HSP70/HSC70 levels increased in both myctophid species at warmer, well-oxygenated surface waters probably to prevent cellular damage (oxidative stress) due to increased oxygen demand under elevated temperatures and reactive oxygen species (ROS) formation. On the other hand, CAT and GST activities were augmented under hypoxic conditions, probably as preparatory response to a burst of oxyradicals during the reoxygenation phase (while ascending). SOD activity decreased under hypoxia in B. panamense, but was kept unchanged in T. mexicanus. MDA levels in B. panamense did not change between the surface and deep-sea conditions, whereas T. mexicanus showed elevated MDA and HSP70/HSC70 concentrations at warmer surface waters. This indicated that T. mexicanus seems to be not so well tuned to temperature and oxidative stress associated to diel vertical migrations. The understanding of such physiological strategies that are linked to oxygen deprivation and reoxygenation phases may provide valuable information about how different species might respond to the impacts of environmental stressors (e.g. expanding mesopelagic hypoxia

  15. The early stress responses in fish larvae.

    PubMed

    Pederzoli, Aurora; Mola, Lucrezia

    2016-05-01

    During the life cycle of fish the larval stages are the most interesting and variable. Teleost larvae undergo a daily increase in adaptability and many organs differentiate and become active. These processes are concerted and require an early neuro-immune-endocrine integration. In larvae communication among the nervous, endocrine and immune systems utilizes several known signal molecule families which could be different from those of the adult fish. The immune-neuroendocrine system was studied in several fish species, among which in particular the sea bass (Dicentrarchus labrax), that is a species of great commercial interest, very important in aquaculture and thus highly studied. Indeed the immune system of this species is the best known among marine teleosts. In this review the data on main signal molecules of stress carried out on larvae of fish are considered and discussed. For sea bass active roles in the early immunological responses of some well-known molecules involved in the stress, such as ACTH, nitric oxide, CRF, HSP-70 and cortisol have been proposed. These molecules and/or their receptors are biologically active mainly in the gut before complete differentiation of gut-associated lymphoid tissue (GALT), probably acting in an autocrine/paracrine way. An intriguing idea emerges from all results of these researches; the molecules involved in stress responses, expressed in the adult cells of the hypothalamic-pituitary axis, during the larval life of fish are present in several other localizations, where they perform probably the same role. It may be hypothesized that the functions performed by hypothalamic-pituitary system are particularly important for the survival of the larva and therefore they comprises several other localizations of body. Indeed the larval stages of fish are very crucial phases that include many physiological changes and several possible stress both internal and environmental. PMID:26968620

  16. Hormonal, cardiovascular, and subjective responses to acute stress in smokers

    PubMed Central

    de Wit, Harriet

    2009-01-01

    Rationale There are complex relationships between stress and smoking; smoking may reduce the emotional discomfort of stress, yet nicotine activates stress systems and may alter responses to acute stress. It is important to understand how smoking affects physiological and psychological outcomes after stress and how these may interact to motivate smoking. Objectives This study aimed to examine the magnitude and time course of hormonal, cardiovascular, and psychological responses to acute psychosocial stress in smokers and non-smokers to investigate whether responses to acute stress are altered in smokers. Materials and methods Healthy male non-smokers (n=20) and smokers (n=15) participated in two experimental sessions involving a standardized public speaking stress procedure and a control non-stressful task. The outcome measures included self-reported mood, cardiovascular measures (heart rate and blood pressure), and plasma hormone levels (noradrenaline, cortisol, progesterone, and allopregnanolone). Results Smokers exhibited blunted increases in cortisol after the Trier Social Stress Test, and they reported greater and more prolonged subjective agitation than non-smokers. Stress-induced changes in progesterone were similar between smokers and non-smokers, although responses overall were smaller among smokers. Stress did not significantly alter levels of allopregnanolone, but smokers exhibited lower plasma concentrations of this neurosteroid. Conclusions These findings suggest that smoking dampens hormonal responses to stress and prolongs subjective discomfort. Dysregulated stress responses may represent a breakdown in the body’s ability to cope efficiently and effectively with stress and may contribute to smokers’ susceptibility to acute stress, especially during abstinence. PMID:18936915

  17. Computations of uncertainty mediate acute stress responses in humans

    PubMed Central

    de Berker, Archy O.; Rutledge, Robb B.; Mathys, Christoph; Marshall, Louise; Cross, Gemma F.; Dolan, Raymond J.; Bestmann, Sven

    2016-01-01

    The effects of stress are frequently studied, yet its proximal causes remain unclear. Here we demonstrate that subjective estimates of uncertainty predict the dynamics of subjective and physiological stress responses. Subjects learned a probabilistic mapping between visual stimuli and electric shocks. Salivary cortisol confirmed that our stressor elicited changes in endocrine activity. Using a hierarchical Bayesian learning model, we quantified the relationship between the different forms of subjective task uncertainty and acute stress responses. Subjective stress, pupil diameter and skin conductance all tracked the evolution of irreducible uncertainty. We observed a coupling between emotional and somatic state, with subjective and physiological tuning to uncertainty tightly correlated. Furthermore, the uncertainty tuning of subjective and physiological stress predicted individual task performance, consistent with an adaptive role for stress in learning under uncertain threat. Our finding that stress responses are tuned to environmental uncertainty provides new insight into their generation and likely adaptive function. PMID:27020312

  18. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework

    SciTech Connect

    Calabrese, Edward J. . E-mail: edwardc@schoolph.umass.edu; Bachmann, Kenneth A.; Bailer, A. John; Bolger, P. Michael; Borak, Jonathan; Cai, Lu; Cedergreen, Nina; Cherian, M. George; Chiueh, Chuang C.; Clarkson, Thomas W.; Cook, Ralph R.; Diamond, David M.; Doolittle, David J.; Dorato, Michael A.; Duke, Stephen O.; Feinendegen, Ludwig; Gardner, Donald E.; Hart, Ronald W.; Hastings, Kenneth L.; Hayes, A. Wallace; Hoffmann, George R.; Ives, John A.; Jaworowski, Zbigniew; Johnson, Thomas E.; Jonas, Wayne B.; Kaminski, Norbert E.

    2007-07-01

    Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines.

  19. Prostaglandin F2a activates stress response signaling and induces expression of activating transcription factor 3 (ATF3) in bovine large luteal cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pulsatile uterine secretion of prostaglandin F2 alpha (PGF) triggers the regression of the corpus luteum (CL). Recent studies have explored global changes in gene expression in response to PGF that may contribute to structural and functional regression of the CL. Activating transcription facto...

  20. The Ferrous Iron-Responsive BqsRS Two-Component System Activates Genes That Promote Cationic Stress Tolerance

    PubMed Central

    Kreamer, Naomi N.; Costa, Flavia

    2015-01-01

    ABSTRACT The physiological resistance of pathogens to antimicrobial treatment is a severe problem in the context of chronic infections. For example, the mucus-filled lungs of cystic fibrosis (CF) patients are readily colonized by diverse antibiotic-resistant microorganisms, including Pseudomonas aeruginosa. Previously, we showed that bioavailable ferrous iron [Fe(II)] is present in CF sputum at all stages of infection and constitutes a significant portion of the iron pool at advanced stages of lung function decline [R. C. Hunter et al., mBio 4(4):e00557-13, 2013]. P. aeruginosa, a dominant CF pathogen, senses Fe(II) using a two-component signal transduction system, BqsRS, which is transcriptionally active in CF sputum [R. C. Hunter et al., mBio 4(4):e00557-13, 2013; N. N. Kreamer, J. C. Wilks, J. J. Marlow, M. L. Coleman, and D. K. Newman, J Bacteriol 194:1195–1204, 2012]. Here, we show that an RExxE motif in BqsS is required for BqsRS activation. Once Fe(II) is sensed, BqsR binds a tandem repeat DNA sequence, activating transcription. The BqsR regulon—defined through iterative bioinformatic predictions and experimental validation—includes several genes whose products are known to drive antibiotic resistance to aminoglycosides and polymyxins. Among them are genes encoding predicted determinants of polyamine transport and biosynthesis. Compared to the wild type, bqsS and bqsR deletion mutants are sensitive to high levels of Fe(II), produce less spermidine in high Fe(II), and are more sensitive to tobramycin and polymyxin B but not arsenate, chromate, or cefsulodin. BqsRS thus mediates a physiological response to Fe(II) that guards the cell against positively charged molecules but not negatively charged stressors. These results suggest Fe(II) is an important environmental signal that, via BqsRS, bolsters tolerance of a variety of cationic stressors, including clinically important antimicrobial agents. PMID:25714721

  1. Prenatal stress enhances responsiveness to cocaine.

    PubMed

    Kippin, Tod E; Szumlinski, Karen K; Kapasova, Zuzana; Rezner, Betsy; See, Ronald E

    2008-03-01

    Early environmental events have profound influences on a wide range of adult behavior. In the current study, we assessed the influence of maternal stress during gestation on psychostimulant and neurochemical responsiveness to cocaine, cocaine self-administration, and reinstatement of cocaine-seeking in adult offspring. Pregnant, female Sprague-Dawley rats were subjected to either no treatment or to restraint stress three times per day for the last 7 days of gestation and cocaine-related behavior was assessed in offspring at 10 weeks of age. Relative to controls, a noncontingent cocaine injection elevated locomotor activity as well as nucleus accumbens levels of extracellular dopamine and glutamate to a greater extent in both cocaine-naive and cocaine-experienced prenatal stress (PNS) rats and elevated prefrontal cortex dopamine in cocaine-experienced PNS rats. To assess the impact of PNS on cocaine addiction-related behavior, rats were trained to lever press for intravenous (i.v.) infusions of cocaine (0.25, 0.5, or 1 mg/kg/infusion), with each infusion paired with a light+tone-conditioned stimulus. Lever-pressing was extinguished and cocaine-seeking reinstated by re-exposure to the conditioned cues or by intraperitoneal cocaine-priming injections (5 or 10 mg/kg). PNS elevated active lever responding both during extinction and cocaine-primed reinstatement, but not during self-administration or conditioned-cued reinstatement. PNS also did not alter intake during self-administration. These findings demonstrate that PNS produces enduring nervous system alterations that increase the psychomotor stimulant, motivational, and neurochemical responsiveness to noncontingent cocaine. Thus, early environmental factors contribute to an individual's initial responsiveness to cocaine and propensity to relapse to cocaine-seeking. PMID:17487224

  2. The mitogen-activated protein kinase gene, VdHog1, regulates osmotic stress response, microsclerotia formation and virulence in Verticillium dahliae.

    PubMed

    Wang, Yonglin; Tian, Longyan; Xiong, Dianguang; Klosterman, Steven J; Xiao, Shuxiao; Tian, Chengming

    2016-03-01

    The fungus Verticillium dahliae has gained worldwide notoriety as a destructive plant pathogen, causing vascular wilt diseases on diverse plant species. V. dahliae produces melanized resting bodies, known as microsclerotia, which can survive for 15years in the soil, and are thus critically important in its disease cycle. However, the molecular mechanisms that underpin microsclerotia formation, survival, and germination remain poorly understood. In this study, we observed that deletion of VdHog1 (ΔVdHog1), encoding a homolog of a high-osmolarity glycerol (HOG) response mitogen-activated protein kinase, displayed decreased numbers of melanized microsclerotia in culture, heightened sensitivity to hyperosmotic stress, and increased resistance to the fungicide fludioxonil. Through RNA-Seq analysis, we identified 221 genes differentially expressed in the ΔVdHog1 strain. Interestingly, the expression levels of genes involved in melanin biosynthesis, as well as the hydrophobin gene VDH1, involved in the early stage of microsclerotia formation, were significantly decreased in the ΔVdHog1 strains relative to the wild-type expression levels. The ΔVdHog1 strains exhibited decreased virulence relative to the wild type strain on smoke tree seedlings. These results indicate that VdHog1 regulates hyperosmotic stress responses in V. dahliae, and establishes the Hog1-mediated pathway as a target to further probe the up- and downstream processes that regulate asexual development in this fungus. PMID:26812120

  3. Oleate protects beta-cells from the toxic effect of palmitate by activating pro-survival pathways of the ER stress response.

    PubMed

    Sargsyan, Ernest; Artemenko, Konstantin; Manukyan, Levon; Bergquist, Jonas; Bergsten, Peter

    2016-09-01

    Long-term exposure of beta cells to saturated fatty acids impairs insulin secretion and increases apoptosis. In contrast, unsaturated fatty acids protect beta-cells from the long-term negative effects of saturated fatty acids. We aimed to identify the mechanisms underlying this protective action of unsaturated fatty acids. To address the aim, insulin-secreting MIN6 cells were exposed to palmitate in the absence or presence of oleate and analyzed by using nano-LC MS/MS based proteomic approach. Important findings were validated by using alternative approaches. Proteomic analysis identified 34 proteins differentially expressed in the presence of palmitate compared to control samples. These proteins play a role in insulin processing, mitochondrial function, metabolism of biomolecules, calcium homeostasis, exocytosis, receptor signaling, ER protein folding, antioxidant activity and anti-apoptotic function. When oleate was also present during culture, expression of 15 proteins was different from the expression in the presence of palmitate alone. Most of the proteins affected by oleate are targets of the ER stress response and play a pro-survival role in beta cells such as protein folding and antioxidative defence. We conclude that restoration of pro-survival pathways of the ER stress response is a major mechanism underlying the protective effect of unsaturated fatty acids in beta-cells treated with saturated fatty acids. PMID:27344025

  4. The Arabidopsis Stress Responsive Gene Database

    PubMed Central

    Borkotoky, Subhomoi; Saravanan, Vijayakumar; Jaiswal, Amit; Das, Bipul; Selvaraj, Suresh; Murali, Ayaluru; Lakshmi, P. T. V.

    2013-01-01

    Plants in nature may face a wide range of favorable or unfavorable biotic and abiotic factors during their life cycle. Any of these factors may cause stress in plants; therefore, they have to be more adaptable to stressful environments and must acquire greater response to different stresses. The objective of this study is to retrieve and arrange data from the literature in a standardized electronic format for the development of information resources on potential stress responsive genes in Arabidopsis thaliana. This provides a powerful mean for manipulation, comparison, search, and retrieval of records describing the nature of various stress responsive genes in Arabidopsis thaliana. The database is based exclusively on published stress tolerance genes associated with plants. PMID:23573074

  5. Stress-inducible phosphoprotein 1 has unique cochaperone activity during development and regulates cellular response to ischemia via the prion protein.

    PubMed

    Beraldo, Flavio H; Soares, Iaci N; Goncalves, Daniela F; Fan, Jue; Thomas, Anu A; Santos, Tiago G; Mohammad, Amro H; Roffé, Martin; Calder, Michele D; Nikolova, Simona; Hajj, Glaucia N; Guimaraes, Andre L; Massensini, Andre R; Welch, Ian; Betts, Dean H; Gros, Robert; Drangova, Maria; Watson, Andrew J; Bartha, Robert; Prado, Vania F; Martins, Vilma R; Prado, Marco A M

    2013-09-01

    Stress-inducible phosphoprotein 1 (STI1) is part of the chaperone machinery, but it also functions as an extracellular ligand for the prion protein. However, the physiological relevance of these STI1 activities in vivo is unknown. Here, we show that in the absence of embryonic STI1, several Hsp90 client proteins are decreased by 50%, although Hsp90 levels are unaffected. Mutant STI1 mice showed increased caspase-3 activation and 50% impairment in cellular proliferation. Moreover, placental disruption and lack of cellular viability were linked to embryonic death by E10.5 in STI1-mutant mice. Rescue of embryonic lethality in these mutants, by transgenic expression of the STI1 gene, supported a unique role for STI1 during embryonic development. The response of STI1 haploinsufficient mice to cellular stress seemed compromised, and mutant mice showed increased vulnerability to ischemic insult. At the cellular level, ischemia increased the secretion of STI1 from wild-type astrocytes by 3-fold, whereas STI1 haploinsufficient mice secreted half as much STI1. Interesting, extracellular STI1 prevented ischemia-mediated neuronal death in a prion protein-dependent way. Our study reveals essential roles for intracellular and extracellular STI1 in cellular resilience. PMID:23729591

  6. The Reductase Activity of the Arabidopsis Caleosin RESPONSIVE TO DESSICATION20 Mediates Gibberellin-Dependent Flowering Time, Abscisic Acid Sensitivity, and Tolerance to Oxidative Stress1[W

    PubMed Central

    Blée, Elizabeth; Boachon, Benoît; Burcklen, Michel; Le Guédard, Marina; Hanano, Abdulsamie; Heintz, Dimitri; Ehlting, Jürgen; Herrfurth, Cornelia; Feussner, Ivo; Bessoule, Jean-Jacques

    2014-01-01

    Contrasting with the wealth of information available on the multiple roles of jasmonates in plant development and defense, knowledge about the functions and the biosynthesis of hydroxylated oxylipins remains scarce. By expressing the caleosin RESPONSIVE TO DESSICATION20 (RD20) in Saccharomyces cerevisiae, we show that the recombinant protein possesses an unusual peroxygenase activity with restricted specificity toward hydroperoxides of unsaturated fatty acid. Accordingly, Arabidopsis (Arabidopsis thaliana) plants overexpressing RD20 accumulate the product 13-hydroxy-9,11,15-octadecatrienoic acid, a linolenate-derived hydroxide. These plants exhibit elevated levels of reactive oxygen species (ROS) associated with early gibberellin-dependent flowering and abscisic acid hypersensitivity at seed germination. These phenotypes are dependent on the presence of active RD20, since they are abolished in the rd20 null mutant and in lines overexpressing RD20, in which peroxygenase was inactivated by a point mutation of a catalytic histidine residue. RD20 also confers tolerance against stress induced by Paraquat, Rose Bengal, heavy metal, and the synthetic auxins 1-naphthaleneacetic acid and 2,4-dichlorophenoxyacetic acid. Under oxidative stress, 13-hydroxy-9,11,15-octadecatrienoic acid still accumulates in RD20-overexpressing lines, but this lipid oxidation is associated with reduced ROS levels, minor cell death, and delayed floral transition. A model is discussed where the interplay between fatty acid hydroxides generated by RD20 and ROS is counteracted by ethylene during development in unstressed environments. PMID:25056921

  7. The reductase activity of the Arabidopsis caleosin RESPONSIVE TO DESSICATION20 mediates gibberellin-dependent flowering time, abscisic acid sensitivity, and tolerance to oxidative stress.

    PubMed

    Blée, Elizabeth; Boachon, Benoît; Burcklen, Michel; Le Guédard, Marina; Hanano, Abdulsamie; Heintz, Dimitri; Ehlting, Jürgen; Herrfurth, Cornelia; Feussner, Ivo; Bessoule, Jean-Jacques

    2014-09-01

    Contrasting with the wealth of information available on the multiple roles of jasmonates in plant development and defense, knowledge about the functions and the biosynthesis of hydroxylated oxylipins remains scarce. By expressing the caleosin RESPONSIVE TO DESSICATION20 (RD20) in Saccharomyces cerevisiae, we show that the recombinant protein possesses an unusual peroxygenase activity with restricted specificity toward hydroperoxides of unsaturated fatty acid. Accordingly, Arabidopsis (Arabidopsis thaliana) plants overexpressing RD20 accumulate the product 13-hydroxy-9,11,15-octadecatrienoic acid, a linolenate-derived hydroxide. These plants exhibit elevated levels of reactive oxygen species (ROS) associated with early gibberellin-dependent flowering and abscisic acid hypersensitivity at seed germination. These phenotypes are dependent on the presence of active RD20, since they are abolished in the rd20 null mutant and in lines overexpressing RD20, in which peroxygenase was inactivated by a point mutation of a catalytic histidine residue. RD20 also confers tolerance against stress induced by Paraquat, Rose Bengal, heavy metal, and the synthetic auxins 1-naphthaleneacetic acid and 2,4-dichlorophenoxyacetic acid. Under oxidative stress, 13-hydroxy-9,11,15-octadecatrienoic acid still accumulates in RD20-overexpressing lines, but this lipid oxidation is associated with reduced ROS levels, minor cell death, and delayed floral transition. A model is discussed where the interplay between fatty acid hydroxides generated by RD20 and ROS is counteracted by ethylene during development in unstressed environments. PMID:25056921

  8. Activation of the Classical Mitogen-Activated Protein Kinases Is Part of the Shiga Toxin-Induced Ribotoxic Stress Response and May Contribute to Shiga Toxin-Induced Inflammation

    PubMed Central

    Ahluwalia, Amrita; Schimmel, Jennifer J.; Rogers, Arlin B.; Leong, John M.; Thorpe, Cheleste M.

    2015-01-01

    Infection with enterohemorrhagic Escherichia coli (EHEC) can result in severe disease, including hemorrhagic colitis and the hemolytic uremic syndrome. Shiga toxins (Stx) are the key EHEC virulence determinant contributing to severe disease. Despite inhibiting protein synthesis, Shiga toxins paradoxically induce the expression of proinflammatory cytokines from various cell types in vitro, including intestinal epithelial cells (IECs). This effect is mediated in large part by the ribotoxic stress response (RSR). The Shiga toxin-induced RSR is known to involve the activation of the stress-activated protein kinases (SAPKs) p38 and JNK. In some cell types, Stx also can induce the classical mitogen-activated protein kinases (MAPKs) or ERK1/2, but the mechanism(s) by which this activation occurs is unknown. In this study, we investigated the mechanism by which Stx activates ERK1/2s in IECs and the contribution of ERK1/2 activation to interleukin-8 (IL-8) expression. We demonstrate that Stx1 activates ERK1/2 in a biphasic manner: the first phase occurs in response to StxB1 subunit, while the second phase requires StxA1 subunit activity. We show that the A subunit-dependent ERK1/2 activation is mediated through ZAK-dependent signaling, and inhibition of ERK1/2 activation via the MEK1/2 inhibitors U0126 and PD98059 results in decreased Stx1-mediated IL-8 mRNA. Finally, we demonstrate that ERK1/2 are activated in vivo in the colon of Stx2-intoxicated infant rabbits, a model in which Stx2 induces a primarily neutrophilic inflammatory response. Together, our data support a role for ERK1/2 activation in the development of Stx-mediated intestinal inflammation. PMID:26483408

  9. Oxidative stress contributes to autophagy induction in response to endoplasmic reticulum stress in Chlamydomonas reinhardtii.

    PubMed

    Pérez-Martín, Marta; Pérez-Pérez, María Esther; Lemaire, Stéphane D; Crespo, José L

    2014-10-01

    The accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER) results in the activation of stress responses, such as the unfolded protein response or the catabolic process of autophagy to ultimately recover cellular homeostasis. ER stress also promotes the production of reactive oxygen species, which play an important role in autophagy regulation. However, it remains unknown whether reactive oxygen species are involved in ER stress-induced autophagy. In this study, we provide evidence connecting redox imbalance caused by ER stress and autophagy activation in the model unicellular green alga Chlamydomonas reinhardtii. Treatment of C. reinhardtii cells with the ER stressors tunicamycin or dithiothreitol resulted in up-regulation of the expression of genes encoding ER resident endoplasmic reticulum oxidoreductin1 oxidoreductase and protein disulfide isomerases. ER stress also triggered autophagy in C. reinhardtii based on the protein abundance, lipidation, cellular distribution, and mRNA levels of the autophagy marker ATG8. Moreover, increases in the oxidation of the glutathione pool and the expression of oxidative stress-related genes were detected in tunicamycin-treated cells. Our results revealed that the antioxidant glutathione partially suppressed ER stress-induced autophagy and decreased the toxicity of tunicamycin, suggesting that oxidative stress participates in the control of autophagy in response to ER stress in C. reinhardtii In close agreement, we also found that autophagy activation by tunicamycin was more pronounced in the C. reinhardtii sor1 mutant, which shows increased expression of oxidative stress-related genes. PMID:25143584

  10. Transgenerational response to stress in Arabidopsis thaliana.

    PubMed

    Boyko, Alex; Kovalchuk, Igor

    2010-08-01

    Plants exposed to stress pass the memory of exposure to stress to the progeny. Previously, we showed that the phenomenon of transgenerational memory of stress is of epigenetic nature and depends on the function of Dicer-like (DCL) 2 and DCL3 proteins. Here, we discuss a possible role of DNA methylation and function of small RNAs in establishing and maintaining transgenerational responses to stress. Our new data report that memory of stress is passed to the progeny predominantly through the female rather than male gamete. Possible evolutionary advantages of this mechanism are also discussed. PMID:20724818

  11. Regulation of the hypothalamic-pituitary-adrenocortical stress response

    PubMed Central

    Herman, James P.; McKlveen, Jessica M.; Ghosal, Sriparna; Kopp, Brittany; Wulsin, Aynara; Makinson, Ryan; Scheimann, Jessie; Myers, Brent

    2016-01-01

    The hypothalamo-pituitary-adrenocortical (HPA axis) is required for stress adaptation. Activation of the HPA axis causes secretion of glucocorticoids, which act on multiple organ systems to redirect energy resources to meet real or anticipated demand. The HPA stress response is driven primarily by neural mechanisms, invoking corticotrophin releasing hormone (CRH) release from hypothalamic paraventricular nucleus (PVN) neurons. Pathways activating CRH release are stressor dependent: reactive responses to homeostatic disruption frequently involve direct noradrenergic or peptidergic drive of PVN neurons by sensory relays, whereas anticipatory responses use oligosynaptic pathways originating in upstream limbic structures. Anticipatory responses are driven largely by disinhibition, mediated by trans-synaptic silencing of tonic PVN inhibition via GABAergic neurons in the amygdala. Stress responses are inhibited by negative feedback mechanisms, whereby glucocorticoids act to diminish drive (brainstem), promote trans-synaptic inhibition by limbic structures (e.g, hippocampus). Glucocorticoids also act at the PVN to rapidly inhibit CRH neuronal activity via membrane glucocorticoid receptors. Chronic stress-induced activation of the HPA axis takes many forms (chronic basal hypersecretion, sensitized stress responses, even adrenal exhaustion), with manifestation dependent upon factors such as stressor chronicity, intensity, frequency and modality. Neural mechanisms driving chronic stress responses can be distinct from those controlling acute reactions, including recruitment of novel limbic, hypothalamic and brainstem circuits. Importantly, an individual’s response to acute or chronic stress is determined by numerous factors, including genetics, early life experience, environmental conditions, sex and age. The context in which stressors occur will determine whether an individual’s acute or chronic stress responses are adaptive or maladaptive (pathological). PMID:27065163

  12. HPA axis responsiveness to stress: Implications for healthy aging

    PubMed Central

    Aguilera, Greti

    2010-01-01

    The major neuroendocrine response mediating stress adaptation is activation of the hypothalamic pituitary adrenal axis, with stimulation of corticotropin releasing hormone (CRH) and vasopressin (VP) from parvocellular neurons of the hypothalamic paraventricular nucleus, leading to stimulation of pituitary ACTH secretion and increases in glucocorticoid secretion from the adrenal cortex. Basal production and transient increases during stress of glucocorticoids and its hypothalamic regulators are essential for neuronal plasticity and normal brain function. While activation of the HPA axis is essential for survival during stress, chronic exposure to stress hormones can predispose to psychological, metabolic and immune alterations. Thus, prompt termination of the stress response is essential to prevent negative effects of inappropriate levels of CRH and glucocorticoids. This review addresses the regulation of HPA axis activity with emphasis on the mechanisms of termination of CRH transcription, which is a critical step in this process. In addition, the actions by which glucocorticoids, CRH and VP can affect the aging process will be discussed. PMID:20833240

  13. Heat shock protein 90 (HSP90) inhibitors activate the heat shock factor 1 (HSF1) stress response pathway and improve glucose regulation in diabetic mice.

    PubMed

    Lee, Jee-Hyung; Gao, Jiaping; Kosinski, Penelope A; Elliman, Stephen J; Hughes, Thomas E; Gromada, Jesper; Kemp, Daniel M

    2013-01-18

    The cytoprotective stress response factor HSF1 regulates the transcription of the chaperone HSP70, which exhibits anti-inflammatory effects and improves insulin sensitivity. We tested the therapeutic potential of this pathway in rodent models of diabetes using pharmacological tools. Activation of the HSF1 pathway was achieved using potent inhibitors of the upstream regulatory protein, HSP90. Treatment with AUY922, a selective HSP90 inhibitor led to robust inhibition of JNK1 phosphorylation, cytoprotection and improved insulin signaling in cells, consistent with effects observed with HSP70 treatment. Chronic dosing with HSP90 inhibitors reversed hyperglycemia in the diabetic db/db mouse model, and improved insulin sensitivity in the diet-induced obese mouse model of insulin resistance, further supporting the concept that the HSF1 pathway is a potentially viable anti-diabetes target. PMID:23261432

  14. Stress Response and Perinatal Reprogramming: Unraveling (Mal)adaptive Strategies.

    PubMed

    Musazzi, Laura; Marrocco, Jordan

    2016-01-01

    Environmental stressors induce coping strategies in the majority of individuals. The stress response, involving the activation of the hypothalamic-pituitary-adrenocortical axis and the consequent release of corticosteroid hormones, is indeed aimed at promoting metabolic, functional, and behavioral adaptations. However, behavioral stress is also associated with fast and long-lasting neurochemical, structural, and behavioral changes, leading to long-term remodeling of glutamate transmission, and increased susceptibility to neuropsychiatric disorders. Of note, early-life events, both in utero and during the early postnatal life, trigger reprogramming of the stress response, which is often associated with loss of stress resilience and ensuing neurobehavioral (mal)adaptations. Indeed, adverse experiences in early life are known to induce long-term stress-related neuropsychiatric disorders in vulnerable individuals. Here, we discuss recent findings about stress remodeling of excitatory neurotransmission and brain morphology in animal models of behavioral stress. These changes are likely driven by epigenetic factors that lie at the core of the stress-response reprogramming in individuals with a history of perinatal stress. We propose that reprogramming mechanisms may underlie the reorganization of excitatory neurotransmission in the short- and long-term response to stressful stimuli. PMID:27057367

  15. Stress Response and Perinatal Reprogramming: Unraveling (Mal)adaptive Strategies

    PubMed Central

    Musazzi, Laura; Marrocco, Jordan

    2016-01-01

    Environmental stressors induce coping strategies in the majority of individuals. The stress response, involving the activation of the hypothalamic-pituitary-adrenocortical axis and the consequent release of corticosteroid hormones, is indeed aimed at promoting metabolic, functional, and behavioral adaptations. However, behavioral stress is also associated with fast and long-lasting neurochemical, structural, and behavioral changes, leading to long-term remodeling of glutamate transmission, and increased susceptibility to neuropsychiatric disorders. Of note, early-life events, both in utero and during the early postnatal life, trigger reprogramming of the stress response, which is often associated with loss of stress resilience and ensuing neurobehavioral (mal)adaptations. Indeed, adverse experiences in early life are known to induce long-term stress-related neuropsychiatric disorders in vulnerable individuals. Here, we discuss recent findings about stress remodeling of excitatory neurotransmission and brain morphology in animal models of behavioral stress. These changes are likely driven by epigenetic factors that lie at the core of the stress-response reprogramming in individuals with a history of perinatal stress. We propose that reprogramming mechanisms may underlie the reorganization of excitatory neurotransmission in the short- and long-term response to stressful stimuli. PMID:27057367

  16. Low-stress and high-stress singing have contrasting effects on glucocorticoid response.

    PubMed

    Fancourt, Daisy; Aufegger, Lisa; Williamon, Aaron

    2015-01-01

    Performing music in public is widely recognized as a potentially stress-inducing activity. However, despite the interest in music performance as an acute psychosocial stressor, there has been relatively little research on the effects of public performance on the endocrine system. This study examined the impact of singing in a low-stress performance situation and a high-stress live concert on levels of glucocorticoids (cortisol and cortisone) in 15 professional singers. The results showed a significant decrease in both cortisol and cortisone across the low-stress condition, suggesting that singing in itself is a stress-reducing (and possibly health-promoting) activity, but significant increases across the high-stress condition. This is the first study to demonstrate that singing affects cortisol as well as cortisone responses and that these responses are modulated by the conditions of performance. PMID:26388794

  17. Low-stress and high-stress singing have contrasting effects on glucocorticoid response

    PubMed Central

    Fancourt, Daisy; Aufegger, Lisa; Williamon, Aaron

    2015-01-01

    Performing music in public is widely recognized as a potentially stress-inducing activity. However, despite the interest in music performance as an acute psychosocial stressor, there has been relatively little research on the effects of public performance on the endocrine system. This study examined the impact of singing in a low-stress performance situation and a high-stress live concert on levels of glucocorticoids (cortisol and cortisone) in 15 professional singers. The results showed a significant decrease in both cortisol and cortisone across the low-stress condition, suggesting that singing in itself is a stress-reducing (and possibly health-promoting) activity, but significant increases across the high-stress condition. This is the first study to demonstrate that singing affects cortisol as well as cortisone responses and that these responses are modulated by the conditions of performance. PMID:26388794

  18. Process Control Minitoring by Stress Response

    SciTech Connect

    Hazen, Terry C.; Stahl, David A.

    2006-04-17

    Environmental contamination with a variety of pollutants hasprompted the development of effective bioremediation strategies. But howcan these processes be best monitored and controlled? One avenue underinvestigation is the development of stress response systems as tools foreffective and general process control. Although the microbial stressresponse has been the subject of intensive laboratory investigation, theenvironmental reflection of the laboratory response to specific stresseshas been little explored. However, it is only within an environmentalcontext, in which microorganisms are constantly exposed to multiplechanging environmental stresses, that there will be full understanding ofmicrobial adaptive resiliency. Knowledge of the stress response in theenvironment will facilitate the control of bioremediation and otherprocesses mediated by complex microbial communities.

  19. Subjective Stress, Salivary Cortisol, and Electrophysiological Responses to Psychological Stress

    PubMed Central

    Qi, Mingming; Gao, Heming; Guan, Lili; Liu, Guangyuan; Yang, Juan

    2016-01-01

    The present study aimed to investigate the subjective stress, salivary cortisol, and electrophysiological responses to psychological stress induced by a modified version of a mental arithmetic task. Fifteen participants were asked to estimate whether the multiplication product of two-decimal numbers was above 10 or not either with a time limit (the stress condition) or without a time limit (the control condition). The results showed that participants reported higher levels of stress, anxiety, and negative affect in the stress condition than they did in the control condition. Moreover, the salivary cortisol level continued to increase after the stress condition but exhibited a sharp decrease after the control condition. In addition, the electrophysiological data showed that the amplitude of the frontal-central N1 component was larger for the stress condition than it was for the control condition, while the amplitude of the frontal-central P2 component was larger for the control condition than it was for the stress condition. Our study suggests that the psychological stress characteristics of time pressure and social-evaluative threat caused dissociable effects on perception and on the subsequent attentional resource allocation of visual information. PMID:26925026

  20. Arctigenin alleviates ER stress via activating AMPK

    PubMed Central

    Gu, Yuan; Sun, Xiao-xiao; Ye, Ji-ming; He, Li; Yan, Shou-sheng; Zhang, Hao-hao; Hu, Li-hong; Yuan, Jun-ying; Yu, Qiang

    2012-01-01

    Aim: To investigate the protective effects of arctigenin (ATG), a phenylpropanoid dibenzylbutyrolactone lignan from Arctium lappa L (Compositae), against ER stress in vitro and the underlying mechanisms. Methods: A cell-based screening assay for ER stress regulators was established. Cell viability was measured using MTT assay. PCR and Western blotting were used to analyze gene and protein expression. Silencing of the CaMKKβ, LKB1, and AMPKα1 genes was achieved by RNA interference (RNAi). An ATP bioluminescent assay kit was employed to measure the intracellular ATP levels. Results: ATG (2.5, 5 and 10 μmol/L) inhibited cell death and unfolded protein response (UPR) in a concentration-dependent manner in cells treated with the ER stress inducer brefeldin A (100 nmol/L). ATG (1, 5 and 10 μmol/L) significantly attenuated protein synthesis in cells through inhibiting mTOR-p70S6K signaling and eEF2 activity, which were partially reversed by silencing AMPKα1 with RNAi. ATG (1-50 μmol/L) reduced intracellular ATP level and activated AMPK through inhibiting complex I-mediated respiration. Pretreatment of cells with the AMPK inhibitor compound C (25 μmol/L) rescued the inhibitory effects of ATG on ER stress. Furthermore, ATG (2.5 and 5 μmol/L) efficiently activated AMPK and reduced the ER stress and cell death induced by palmitate (2 mmol/L) in INS-1 β cells. Conclusion: ATG is an effective ER stress alleviator, which protects cells against ER stress through activating AMPK, thus attenuating protein translation and reducing ER load. PMID:22705729

  1. Inhibition of the oxidative stress response by heat stress in Caenorhabditis elegans.

    PubMed

    Crombie, Timothy A; Tang, Lanlan; Choe, Keith P; Julian, David

    2016-07-15

    It has long been recognized that simultaneous exposure to heat stress and oxidative stress shows a synergistic interaction that reduces organismal fitness, but relatively little is known about the mechanisms underlying this interaction. We investigated the role of molecular stress responses in driving this synergistic interaction using the nematode Caenorhabditis elegans To induce oxidative stress, we used the pro-oxidant compounds acrylamide, paraquat and juglone. As expected, we found that heat stress and oxidative stress interact synergistically to reduce survival. Compared with exposure to each stressor alone, during simultaneous sublethal exposure to heat stress and oxidative stress the normal induction of key oxidative-stress response (OxSR) genes was generally inhibited, whereas the induction of key heat-shock response (HSR) genes was not. Genetically activating the SKN-1-dependent OxSR increased a marker for protein aggregation and decreased whole-worm survival during heat stress alone, with the latter being independent of HSF-1. In contrast, compared with wild-type worms, inactivating the HSR by HSF-1 knockdown, which would be expected to decrease basal heat shock protein expression, increased survival during oxidative stress alone. Taken together, these data suggest that, in C. elegans, the HSR and OxSR cannot be simultaneously activated to the same extent that each can be activated during a single stressor exposure. We conclude that the observed synergistic reduction in survival during combined exposure to heat stress and oxidative stress is due, at least in part, to inhibition of the OxSR during activation of the HSR. PMID:27207646

  2. Potentiation of Aminoglycoside Activity in Pseudomonas aeruginosa by Targeting the AmgRS Envelope Stress-Responsive Two-Component System.

    PubMed

    Poole, Keith; Gilmour, Christie; Farha, Maya A; Mullen, Erin; Lau, Calvin Ho-Fung; Brown, Eric D

    2016-06-01

    A screen for agents that potentiated the activity of paromomycin (PAR), a 4,5-linked aminoglycoside (AG), against wild-type Pseudomonas aeruginosa identified the RNA polymerase inhibitor rifampin (RIF). RIF potentiated additional 4,5-linked AGs, such as neomycin and ribostamycin, but not the clinically important 4,6-linked AGs amikacin and gentamicin. Potentiation was absent in a mutant lacking the AmgRS envelope stress response two-component system (TCS), which protects the organism from AG-generated membrane-damaging aberrant polypeptides and, thus, promotes AG resistance, an indication that RIF was acting via this TCS in potentiating 4,5-linked AG activity. Potentiation was also absent in a RIF-resistant RNA polymerase mutant, consistent with its potentiation of AG activity being dependent on RNA polymerase perturbation. PAR-inducible expression of the AmgRS-dependent genes htpX and yccA was reduced by RIF, suggesting that AG activation of this TCS was compromised by this agent. Still, RIF did not compromise the membrane-protective activity of AmgRS, an indication that it impacted some other function of this TCS. RIF potentiated the activities of 4,5-linked AGs against several AG-resistant clinical isolates, in two cases also potentiating the activity of the 4,6-linked AGs. These cases were, in one instance, explained by an observed AmgRS-dependent expression of the MexXY multidrug efflux system, which accommodates a range of AGs, with RIF targeting of AmgRS undermining mexXY expression and its promotion of resistance to 4,5- and 4,6-linked AGs. Given this link between AmgRS, MexXY expression, and pan-AG resistance in P. aeruginosa, RIF might be a useful adjuvant in the AG treatment of P. aeruginosa infections. PMID:27021319

  3. ENHANCED ACTIVITY OF STROBILURIN AND FLUDIOXONIL BY TARGETING FUNGAL ANTIOXIDATIVE STRESS RESPONSE WITH BERBERINE AND PHENOLIC SYNERGISTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antifungal activity of strobilurins was tested using berberine hemisulfate and different phenolic compounds. With berberine, the most effective phenolic was veratraldehyde. The sod2delta mutant of Saccharomyces cerevisiae was highly sensitive to berberine and veratraldehyde. Functional complementati...

  4. Cis-element of the rice PDIL2-3 promoter is responsible for inducing the endoplasmic reticulum stress response.

    PubMed

    Takahashi, Hideyuki; Wang, Shuyi; Hayashi, Shimpei; Wakasa, Yuhya; Takaiwa, Fumio

    2014-05-01

    A protein disulfide isomerase (PDI) family oxidoreductase, PDIL2-3, is involved in endoplasmic reticulum (ER) stress responses in rice. We identified a critical cis-element required for induction of the ER stress response. The activation of PDIL2-3 in response to ER stress strongly depends on the IRE1-OsbZIP50 signaling pathway. PMID:24315532

  5. Stress, stress-induced cortisol responses, and eyewitness identification performance.

    PubMed

    Sauerland, Melanie; Raymaekers, Linsey H C; Otgaar, Henry; Memon, Amina; Waltjen, Thijs T; Nivo, Maud; Slegers, Chiel; Broers, Nick J; Smeets, Tom

    2016-07-01

    In the eyewitness identification literature, stress and arousal at the time of encoding are considered to adversely influence identification performance. This assumption is in contrast with findings from the neurobiology field of learning and memory, showing that stress and stress hormones are critically involved in forming enduring memories. This discrepancy may be related to methodological differences between the two fields of research, such as the tendency for immediate testing or the use of very short (1-2 hours) retention intervals in eyewitness research, while neurobiology studies insert at least 24 hours. Other differences refer to the extent to which stress-responsive systems (i.e., the hypothalamic-pituitary-adrenal axis) are stimulated effectively under laboratory conditions. The aim of the current study was to conduct an experiment that accounts for the contemporary state of knowledge in both fields. In all, 123 participants witnessed a live staged theft while being exposed to a laboratory stressor that reliably elicits autonomic and glucocorticoid stress responses or while performing a control task. Salivary cortisol levels were measured to control for the effectiveness of the stress induction. One week later, participants attempted to identify the thief from target-present and target-absent line-ups. According to regression and receiver operating characteristic analyses, stress did not have robust detrimental effects on identification performance. Copyright © 2016 John Wiley & Sons, Ltd. © 2016 The Authors Behavioral Sciences & the Law Published by John Wiley & Sons Ltd. PMID:27417874

  6. The hyperosmotic stress response of Campylobacter jejuni

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The hyperosmotic stress response of Campylobacter jejuni: The diarrheal pathogen Campylobacter jejuni and other gastrointestinal bacteria encounter changes in osmolarity in the environment, through exposure to food processing, or upon entering host organisms, where osmotic adaptation can be associa...

  7. Motor/autonomic stress responses in a competitive piano performance.

    PubMed

    Yoshie, Michiko; Kudo, Kazutoshi; Ohtsuki, Tatsuyuki

    2009-07-01

    The present study examined the effects of psychological stress on performance quality, autonomic responses, and upper extremity muscle activity in skilled pianists through comparisons between stressful (competition) and nonstressful (rehearsal) conditions. We observed increased levels of subjective anxiety, autonomic arousal, and electromyographic activity in the competition condition, which could contribute to the impairment of performance quality. The results provide important practical implications for enhancing performance quality as well as preventing playing-related musculoskeletal disorders in musicians. PMID:19673810

  8. Effect of simulated microgravity on nitric oxide synthase activity of osteocyte-like cell line MLO-Y4 in response to fluid shear stress

    NASA Astrophysics Data System (ADS)

    Sun, Lian-Wen; Yang, Xiao; Fan, Yu-Bo

    It is well known that microgravity could induce bone loss. However, the mechanism remains poorly understood. Osteocytes are extremely sensitive to fluid shear stress, even more than osteobleasts. The effect of simulated microgravity on osteocytes in response to fluid shear was investigated in this study in order to see if the mechanosensibility of osteocytes changed under simulated microgravity. The osteocyte-like cell line, MLO-Y4, was cultured and divided into four groups, including control (CON), control and shear (CONS), rotary (RT), rotary and shear (RTS). In RT and RTS, the cells were cultured in the rotary cell culture system to simulate microgravity condition. After 5 days, the cells in RTS and CONS were subjected to flow shear for 15 min. Then nitric oxide synthase (NOS) activity in the cells was measured using assay kit. The results showed that NOS activity in respond to fluid shear decreased significantly in RTS compared with CONS. In addition, there was significant difference in NOS activity between CONS and CON while no significant difference between RTS and RT. These indicates that the mechanosensibility of osteocytes decreased under simulated microgravity and this maybe the partly causes of the poor effect of exercise to counter microgravity-induced-bone loss. However, further research need to be done to support this finding.

  9. Estimation of restraint stress in rats using salivary amylase activity.

    PubMed

    Matsuura, Tetsuya; Takimura, Ryo; Yamaguchi, Masaki; Ichinose, Mitsuyuki

    2012-09-01

    The rat is an ideal model animal for studying physical and psychological stresses. Recent human studies have shown that salivary amylase activity is a useful biomarker of stress in our social life. To estimate the usefulness of amylase activity as a biomarker of stress in rats, we analyzed changes in physiological parameters including amylase activity and anatomical variables, which were induced by a mild restraint of paws (10 min, 3 times/week, 9 weeks). The quantities of food and water intake and excretion amount of the stress rats were smaller than those of the control rats during the experimental period (5-13 weeks). The body weight of the stress rats decreased compared with that of the control rats. Moreover, the enlargement of the adrenal gland was confirmed in the stress rats, indicating that the mild restraint caused a chronic stress response. The amylase activities of the stress rats were significantly greater than those of the control rats at 5 weeks of age. However, the amylase activity of the stress rats decreased compared with that of the control rats after 6 weeks of age. These results indicate that amylase activity is increased by acute stress and reduced by chronic stress, which is caused by repeated restraint stress. In conclusion, amylase activity is a useful biomarker of acute and chronic stresses in rats. PMID:22753135

  10. Context and strain-dependent behavioral response to stress

    PubMed Central

    Nosek, Katarzyna; Dennis, Kristen; Andrus, Brian M; Ahmadiyeh, Nasim; Baum, Amber E; Woods, Leah C Solberg; Redei, Eva E

    2008-01-01

    Background This study posed the question whether strain differences in stress-reactivity lead to differential behavioral responses in two different tests of anxiety. Strain differences in anxiety-measures are known, but strain differences in the behavioral responses to acute prior stress are not well characterized. Methods We studied male Fisher 344 (F344) and Wistar Kyoto (WKY) rats basally and immediately after one hour restraint stress. To distinguish between the effects of novelty and prior stress, we also investigated behavior after repeated exposure to the test chamber. Two behavioral tests were explored; the elevated plus maze (EPM) and the open field (OFT), both of which are thought to measure activity, exploration and anxiety-like behaviors. Additionally, rearing, a voluntary behavior, and grooming, a relatively automatic, stress-responsive stereotyped behavior were measured in both tests. Results Prior exposure to the test environment increased anxiety-related measures regardless of prior stress, reflecting context-dependent learning process in both tests and strains. Activity decreased in response to repeated testing in both tests and both strains, but prior stress decreased activity only in the OFT which was reversed by repeated testing. Prior stress decreased anxiety-related measures in the EPM, only in F344s, while in the OFT, stress led to increased freezing mainly in WKYs. Conclusion Data suggest that differences in stressfulness of these tests predict the behavior of the two strains of animals according to their stress-reactivity and coping style, but that repeated testing can overcome some of these differences. PMID:18518967

  11. Suppression of the HSF1-mediated proteotoxic stress response by the metabolic stress sensor AMPK

    PubMed Central

    Dai, Siyuan; Tang, Zijian; Cao, Junyue; Zhou, Wei; Li, Huawen; Sampson, Stephen; Dai, Chengkai

    2015-01-01

    Numerous extrinsic and intrinsic insults trigger the HSF1-mediated proteotoxic stress response (PSR), an ancient transcriptional program that is essential to proteostasis and survival under such conditions. In contrast to its well-recognized mobilization by proteotoxic stress, little is known about how this powerful adaptive mechanism reacts to other stresses. Surprisingly, we discovered that metabolic stress suppresses the PSR. This suppression is largely mediated through the central metabolic sensor AMPK, which physically interacts with and phosphorylates HSF1 at Ser121. Through AMPK activation, metabolic stress represses HSF1, rendering cells vulnerable to proteotoxic stress. Conversely, proteotoxic stress inactivates AMPK and thereby interferes with the metabolic stress response. Importantly, metformin, a metabolic stressor and popular anti-diabetic drug, inactivates HSF1 and provokes proteotoxic stress within tumor cells, thereby impeding tumor growth. Thus, these findings uncover a novel interplay between the metabolic stress sensor AMPK and the proteotoxic stress sensor HSF1 that profoundly impacts stress resistance, proteostasis, and malignant growth. PMID:25425574

  12. Bacterial Stress Responses during Host Infection.

    PubMed

    Fang, Ferric C; Frawley, Elaine R; Tapscott, Timothy; Vázquez-Torres, Andrés

    2016-08-10

    Pathogenic bacteria must withstand diverse host environments during infection. Environmental signals, such as pH, temperature, nutrient limitation, etc., not only trigger adaptive responses within bacteria to these specific stress conditions but also direct the expression of virulence genes at an appropriate time and place. An appreciation of stress responses and their regulation is therefore essential for an understanding of bacterial pathogenesis. This review considers specific stresses in the host environment and their relevance to pathogenesis, with a particular focus on the enteric pathogen Salmonella. PMID:27512901

  13. Resveratrol Inhibits Paraquat-Induced Oxidative Stress and Fibrogenic Response by Activating the Nuclear Factor Erythroid 2-Related Factor 2 Pathway

    PubMed Central

    He, Xiaoqing; Wang, Liping; Szklarz, Grazyna; Bi, Yongyi; Ma, Qiang

    2015-01-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2) is an antioxidant-activated transcription factor that recently emerged as a critical regulator of cellular defense against oxidative and inflammatory lesions. Resveratrol (Res) is a natural phytoalexin that exhibits multiple therapeutic potentials, including antioxidative and anti-inflammatory effects in animals. Paraquat (PQ) is the second most widely used herbicide worldwide, but it selectively accumulates in human lungs to cause oxidative injury and fibrosis with high mortality. Here, we analyzed the molecular mechanism of the fibrogenic response to PQ and its inhibition by Res and Nrf2. PQ dose-dependently caused toxicity in normal human bronchial epithelial cells (BEAS-2B), resulting in mitochondrial damage, oxidative stress, and cell death. Res at 10 µM markedly inhibited PQ toxicity. PQ at 10 µM stimulated production of inflammatory and profibrogenic factors (tumor necrosis factor α, interleukin 6, and transforming growth factor β1) and induced the transformation of normal human lung fibroblasts (WI38-VA13) to myofibroblasts; both effects were inhibited by Res. Res strongly activated the Nrf2 signaling pathway and induced antioxidant response elementdependent cytoprotective genes. On the other hand, knockout or knockdown of Nrf2 markedly increased PQ-induced cytotoxicity, cytokine production, and myofibroblast transformation and abolished protection by Res. The findings demonstrate that Res attenuates PQ-induced reactive oxygen species production, inflammation, and fibrotic reactions by activating Nrf2 signaling. The study reveals a new pathway for molecular intervention against pulmonary oxidative injury and fibrosis. PMID:22493042

  14. Protein Degradation and the Stress Response

    PubMed Central

    Flick, Karin; Kaiser, Peter

    2012-01-01

    Environmental stresses are manifold and so are the responses they elicit. This is particularly true for higher eukaryotes where various tissues and cell types are differentially affected by the insult. Type and scope of the stress response can therefore differ greatly among cell types. Given the importance of the Ubiquitin Proteasome System (UPS) for most cellular processes, it comes as no surprise that the UPR plays a pivotal role in counteracting the effects of stressors. Here we outline contributions of the UPS to stress sensing, signaling, and response pathways. We make no claim to comprehensiveness but choose selected examples to illustrate concepts and mechanisms by which protein modification with ubiquitin and proteasomal degradation of key regulators ensures cellular integrity during stress situations. PMID:22414377

  15. Inhibition of helicase activity by a small molecule impairs Werner syndrome helicase (WRN) function in the cellular response to DNA damage or replication stress.

    PubMed

    Aggarwal, Monika; Sommers, Joshua A; Shoemaker, Robert H; Brosh, Robert M

    2011-01-25

    Modulation of DNA repair proteins by small molecules has attracted great interest. An in vitro helicase activity screen was used to identify molecules that modulate DNA unwinding by Werner syndrome helicase (WRN), mutated in the premature aging disorder Werner syndrome. A small molecule from the National Cancer Institute Diversity Set designated NSC 19630 [1-(propoxymethyl)-maleimide] was identified that inhibited WRN helicase activity but did not affect other DNA helicases [Bloom syndrome (BLM), Fanconi anemia group J (FANCJ), RECQ1, RecQ, UvrD, or DnaB). Exposure of human cells to NSC 19630 dramatically impaired growth and proliferation, induced apoptosis in a WRN-dependent manner, and resulted in elevated γ-H2AX and proliferating cell nuclear antigen (PCNA) foci. NSC 19630 exposure led to delayed S-phase progression, consistent with the accumulation of stalled replication forks, and to DNA damage in a WRN-dependent manner. Exposure to NSC 19630 sensitized cancer cells to the G-quadruplex-binding compound telomestatin or a poly(ADP ribose) polymerase (PARP) inhibitor. Sublethal dosage of NSC 19630 and the chemotherapy drug topotecan acted synergistically to inhibit cell proliferation and induce DNA damage. The use of this WRN helicase inhibitor molecule may provide insight into the importance of WRN-mediated pathway(s) important for DNA repair and the replicational stress response. PMID:21220316

  16. Direct Activation of Ribosome-Associated Double-Stranded RNA-Dependent Protein Kinase (PKR) by Deoxynivalenol, Anisomycin and Ricin: A New Model for Ribotoxic Stress Response Induction

    PubMed Central

    Zhou, Hui-Ren; He, Kaiyu; Landgraf, Jeff; Pan, Xiao; Pestka, James J.

    2014-01-01

    Double-stranded RNA (dsRNA)-activated protein kinase (PKR) is a critical upstream mediator of the ribotoxic stress response (RSR) to the trichothecene deoxynivalenol (DON) and other translational inhibitors. Here, we employed HeLa cell lysates to: (1) characterize PKR’s interactions with the ribosome and ribosomal RNA (rRNA); (2) demonstrate cell-free activation of ribosomal-associated PKR and (3) integrate these findings in a unified model for RSR. Robust PKR-dependent RSR was initially confirmed in intact cells. PKR basally associated with 40S, 60S, 80S and polysome fractions at molar ratios of 7, 2, 23 and 3, respectively. Treatment of ATP-containing HeLa lysates with DON or the ribotoxins anisomycin and ricin concentration-dependently elicited phosphorylation of PKR and its substrate eIF2α. These phosphorylations could be blocked by PKR inhibitors. rRNA immunoprecipitation (RNA-IP) of HeLa lysates with PKR-specific antibody and sequencing revealed that in the presence of DON or not, the kinase associated with numerous discrete sites on both the 18S and 28S rRNA molecules, a number of which contained double-stranded hairpins. These findings are consistent with a sentinel model whereby multiple PKR molecules basally associate with the ribosome positioning them to respond to ribotoxin-induced alterations in rRNA structure by dimerizing, autoactivating and, ultimately, evoking RSR. PMID:25521494

  17. Glaucomatous MYOC mutations activate the IL-1/NF-κB inflammatory stress response and the glaucoma marker SELE in trabecular meshwork cells

    PubMed Central

    Itakura, Tatsuo; Peters, Donna M.

    2015-01-01

    Purpose Activation of the IL-1/NF-κB inflammatory stress pathway and induction of SELE expression in the trabecular meshwork (TBM) is a marker for high-tension glaucomas of diverse etiology. Pathway activation stimulates aqueous outflow and protects against oxidative stress, but may be damaging in the long-term. MYOC mutations have been causally linked to high-tension forms of primary open angle glaucoma (POAG). This study investigated a possible link between MYOC mutations and activation of the IL-1/NF-κB pathway and expression of SELE. Methods We constructed MYOC expression vectors with mutations at sites that cause POAG. Mutations (Q368X, Y437H, A427T) were selected to represent proteins with differing POAG-causing potency (Q368X > Y437H > A427T) and intracellular retention behavior (Q368X and Y437H retained, A427T released). The constructs were made in two different kinds of vectors; one a plasmid designed for transient transfection (pCMV6), and one a doxycycline-inducible lentiviral vector (pSLIK) for stable cell transduction. The immortalized human trabecular meshwork line TM-1 was used for all expression studies. Expression of IL1A mRNA was determined by reverse transcription (RT)–PCR, as well as a set of five other genes associated with signaling pathways linked to glaucoma: IL1B and IL6 (NF-κB pathway), TGFB2 and ACTA2 (TGF-β pathway) and FOXO1 (E2F1 apoptotic pathway). An ELISA was used to quantify IL1A protein released into culture media. To quantify intracellular NF-κB activity, we transiently transfected stably transduced cell lines with a luciferase expression vector under control of the IL8 promoter (containing an NF-κB response element). Results Transiently expressed wild-type MYOC was released into cell culture media, whereas mutant MYOCs Q368X and Y437H remained within cells. Both mutant MYOCs activated the IL-1/ NF-κB pathway, significantly stimulating expression of IL1A and IL1B. However Y437H, which causes a severe glaucoma phenotype

  18. Effects of regional analgesia on stress responses to pediatric surgery.

    PubMed

    Wolf, Andrew R

    2012-01-01

    Invasive surgery induces a combination of local response to tissue injury and generalized activation of systemic metabolic and hormonal pathways via afferent nerve pathways and the central nervous system. The local inflammatory responses and the parallel neurohumoral responses are not isolated but linked through complex signaling networks, some of which remain poorly understood. The magnitude of the response is broadly related to the site of injury (greater in regions with visceral pain afferents such as abdomen and thorax) and the extent of the trauma. The changes include alterations in metabolic, hormonal, inflammatory, and immune systems that can be collectively termed the stress response. Integral to the stress responses are the effects of nociceptive afferent stimuli on systemic and pulmonary vascular resistance, heart rate, and blood pressure, which are a combination of efferent autonomic response and catecholamine release via the adrenal medulla. Therefore, pain responses, cardiovascular responses, and stress responses need to be considered as different aspects of a combined bodily reaction to surgery and trauma. It is important at the outset to understand that not all components of the stress response are suppressed together and that this is important when discussing different analgesic modalities (i.e. opioids vs regional anesthesia). For example, in terms of the use of fentanyl in the infant, the dose required to provide analgesia (1-5 mcg·kg(-1)) is less than that required for hemodynamic stability in response to stimuli (5-10 mcg·kg(-1)) (1) and that this in turn is less than that required to suppress most aspects of the stress response (25-50 mcg·kg(-1)) (2). In contrast to this considerable dose dependency, central local anesthetic blocks allow blockade of the afferent and efferent sympathetic pathways at relatively low doses resulting in profound suppression of hemodynamic and stress responses to surgery. PMID:21999144

  19. Response of Desulfovibrio vulgaris to Alkaline Stress

    SciTech Connect

    Stolyar, S.; He, Q.; He, Z.; Yang, Z.; Borglin, S.E.; Joyner, D.; Huang, K.; Alm, E.; Hazen, T.C.; Zhou, J.; Wall, J.D.; Arkin, A.P.; Stahl, D.A.

    2007-11-30

    The response of exponentially growing Desulfovibrio vulgarisHildenborough to pH 10 stress was studied using oligonucleotidemicroarrays and a study set of mutants with genes suggested by microarraydata to be involved in the alkaline stress response deleted. The datashowed that the response of D. vulgaris to increased pH is generallysimilar to that of Escherichia coli but is apparently controlled byunique regulatory circuits since the alternative sigma factors (sigma Sand sigma E) contributing to this stress response in E. coli appear to beabsent in D. vulgaris. Genes previously reported to be up-regulated in E.coli were up-regulated in D. vulgaris; these genes included three ATPasegenes and a tryptophan synthase gene. Transcription of chaperone andprotease genes (encoding ATP-dependent Clp and La proteases and DnaK) wasalso elevated in D. vulgaris. As in E. coli, genes involved in flagellumsynthesis were down-regulated. The transcriptional data also identifiedregulators, distinct from sigma S and sigma E, that are likely part of aD. vulgaris Hildenborough-specific stress response system.Characterization of a study set of mutants with genes implicated inalkaline stress response deleted confirmed that there was protectiveinvolvement of the sodium/proton antiporter NhaC-2, tryptophanase A, andtwo putative regulators/histidine kinases (DVU0331 andDVU2580).

  20. Divergent functions of the Arabidopsis mitochondrial SCO proteins: HCC1 is essential for COX activity while HCC2 is involved in the UV-B stress response

    PubMed Central

    Steinebrunner, Iris; Gey, Uta; Andres, Manuela; Garcia, Lucila; Gonzalez, Daniel H.

    2014-01-01

    The two related putative cytochrome c oxidase (COX) assembly factors HCC1 and HCC2 from Arabidopsis thaliana are Homologs of the yeast Copper Chaperones Sco1p and Sco2p. The hcc1 null mutation was previously shown to be embryo lethal while the disruption of the HCC2 gene function had no obvious effect on plant development, but increased the expression of stress-responsive genes. Both HCC1 and HCC2 contain a thioredoxin domain, but only HCC1 carries a Cu-binding motif also found in Sco1p and Sco2p. In order to investigate the physiological implications suggested by this difference, various hcc1 and hcc2 mutants were generated and analyzed. The lethality of the hcc1 knockout mutation was rescued by complementation with the HCC1 gene under the control of the embryo-specific promoter ABSCISIC ACID INSENSITIVE 3. However, the complemented seedlings did not grow into mature plants, underscoring the general importance of HCC1 for plant growth. The HCC2 homolog was shown to localize to mitochondria like HCC1, yet the function of HCC2 is evidently different, because two hcc2 knockout lines developed normally and exhibited only mild growth suppression compared with the wild type (WT). However, hcc2 knockouts were more sensitive to UV-B treatment than the WT. Complementation of the hcc2 knockout with HCC2 rescued the UV-B-sensitive phenotype. In agreement with this, exposure of wild-type plants to UV-B led to an increase of HCC2 transcripts. In order to corroborate a function of HCC1 and HCC2 in COX biogenesis, COX activity of hcc1 and hcc2 mutants was compared. While the loss of HCC2 function had no significant effect on COX activity, the disruption of one HCC1 gene copy was enough to suppress respiration by more than half compared with the WT. Therefore, we conclude that HCC1 is essential for COX function, most likely by delivering Cu to the catalytic center. HCC2, on the other hand, seems to be involved directly or indirectly in UV-B-stress responses. PMID:24723925

  1. High activity of the stress promoter contributes to susceptibility to stress in the tree shrew.

    PubMed

    Fang, Hui; Sun, Yun-Jun; Lv, Yan-Hong; Ni, Rong-Jun; Shu, Yu-Mian; Feng, Xiu-Yu; Wang, Yu; Shan, Qing-Hong; Zu, Ya-Nan; Zhou, Jiang-Ning

    2016-01-01

    Stress is increasingly present in everyday life in our fast-paced society and involved in the pathogenesis of many psychiatric diseases. Corticotrophin-releasing-hormone (CRH) plays a pivotal role in regulating the stress responses. The tree shrews are highly vulnerable to stress which makes them the promising animal models for studying stress responses. However, the mechanisms underlying their high stress-susceptibility remained unknown. Here we confirmed that cortisol was the dominate corticosteroid in tree shrew and was significantly increased after acute stress. Our study showed that the function of tree shrew CRH - hypothalamic-pituitary-adrenal (HPA) axis was nearly identical to human that contributed little to their hyper-responsiveness to stress. Using CRH transcriptional regulation analysis we discovered a peculiar active glucocorticoid receptor response element (aGRE) site within the tree shrew CRH promoter, which continued to recruit co-activators including SRC-1 (steroid receptor co-activator-1) to promote CRH transcription under basal or forskolin/dexamethasone treatment conditions. Basal CRH mRNA increased when the aGRE was knocked into the CRH promoter in human HeLa cells using CAS9/CRISPR. The aGRE functioned critically to form the "Stress promoter" that contributed to the higher CRH expression and susceptibility to stress. These findings implicated novel molecular bases of the stress-related diseases in specific populations. PMID:27125313

  2. High activity of the stress promoter contributes to susceptibility to stress in the tree shrew

    PubMed Central

    Fang, Hui; Sun, Yun-Jun; Lv, Yan-Hong; Ni, Rong-Jun; Shu, Yu-Mian; Feng, Xiu-Yu; Wang, Yu; Shan, Qing-Hong; Zu, Ya-Nan; Zhou, Jiang-Ning

    2016-01-01

    Stress is increasingly present in everyday life in our fast-paced society and involved in the pathogenesis of many psychiatric diseases. Corticotrophin-releasing-hormone (CRH) plays a pivotal role in regulating the stress responses. The tree shrews are highly vulnerable to stress which makes them the promising animal models for studying stress responses. However, the mechanisms underlying their high stress-susceptibility remained unknown. Here we confirmed that cortisol was the dominate corticosteroid in tree shrew and was significantly increased after acute stress. Our study showed that the function of tree shrew CRH - hypothalamic-pituitary-adrenal (HPA) axis was nearly identical to human that contributed little to their hyper-responsiveness to stress. Using CRH transcriptional regulation analysis we discovered a peculiar active glucocorticoid receptor response element (aGRE) site within the tree shrew CRH promoter, which continued to recruit co-activators including SRC-1 (steroid receptor co-activator-1) to promote CRH transcription under basal or forskolin/dexamethasone treatment conditions. Basal CRH mRNA increased when the aGRE was knocked into the CRH promoter in human HeLa cells using CAS9/CRISPR. The aGRE functioned critically to form the “Stress promoter” that contributed to the higher CRH expression and susceptibility to stress. These findings implicated novel molecular bases of the stress-related diseases in specific populations. PMID:27125313

  3. EATING BEHAVIOR IN RESPONSE TO ACUTE STRESS.

    PubMed

    Mocanu, Veronica; Bontea, Amalia; Anton-Păduraru, Dana-teodora

    2016-01-01

    Obesity is a medical and social problem with a dramatically increasing prevalence. It is important to take action since childhood to prevent and treat obesity and metabolic syndrome. Infantile obesity affects all body systems starting in childhood and continuing to adulthood. Understanding the impact of stressors on weight status may be especially important for preventing obesity. The relationship between stress, eating behavior and obesity is not fully understood. However, there is evidence that stress causes disorders in hypothalamic-pituitary-adrenal (HPA) axis, system that regulates both stress and feeding responses. Also, the response is different depending on the type of stressors. Chronic stress, especially when people live in a palatable food environment, induces HPA stimulation, excess glucocorticoids, insulin resistance, which lead to inhibition of lipid mobilization, accumulation of triglyceride and retention of abdominal fat. PMID:27483696

  4. Dynamic neural activity during stress signals resilient coping.

    PubMed

    Sinha, Rajita; Lacadie, Cheryl M; Constable, R Todd; Seo, Dongju

    2016-08-01

    Active coping underlies a healthy stress response, but neural processes supporting such resilient coping are not well-known. Using a brief, sustained exposure paradigm contrasting highly stressful, threatening, and violent stimuli versus nonaversive neutral visual stimuli in a functional magnetic resonance imaging (fMRI) study, we show significant subjective, physiologic, and endocrine increases and temporally related dynamically distinct patterns of neural activation in brain circuits underlying the stress response. First, stress-specific sustained increases in the amygdala, striatum, hypothalamus, midbrain, right insula, and right dorsolateral prefrontal cortex (DLPFC) regions supported the stress processing and reactivity circuit. Second, dynamic neural activation during stress versus neutral runs, showing early increases followed by later reduced activation in the ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dACC), left DLPFC, hippocampus, and left insula, suggested a stress adaptation response network. Finally, dynamic stress-specific mobilization of the ventromedial prefrontal cortex (VmPFC), marked by initial hypoactivity followed by increased VmPFC activation, pointed to the VmPFC as a key locus of the emotional and behavioral control network. Consistent with this finding, greater neural flexibility signals in the VmPFC during stress correlated with active coping ratings whereas lower dynamic activity in the VmPFC also predicted a higher level of maladaptive coping behaviors in real life, including binge alcohol intake, emotional eating, and frequency of arguments and fights. These findings demonstrate acute functional neuroplasticity during stress, with distinct and separable brain networks that underlie critical components of the stress response, and a specific role for VmPFC neuroflexibility in stress-resilient coping. PMID:27432990

  5. Transcript changes in Vibrio cholerae in response to salt stress.

    PubMed

    Fu, Xiuping; Liang, Weili; Du, Pengcheng; Yan, Meiying; Kan, Biao

    2014-01-01

    Vibrio cholerae, which is a serious human intestinal pathogen, often resides and thrives in estuaries but requires major self-regulation to overcome intestinal hyperosmotic stress or high salt stress in water and food. In the present study, we selected multiple O1 and O139 group V. cholerae strains that were isolated from different regions and during different years to study their salt tolerance. Based on the mechanisms that other bacteria use to respond to high salt stress, we selected salt stress-response related genes to study the mechanisms which V. cholerae responds to high salt stress. V. cholerae strains showed salt-resistance characteristics that varied in salt concentrations from 4% to 6%. However, group O1 and group O139 showed no significant difference in the degree of salt tolerance. The primary responses of bacteria to salt stress, including Na(+) exclusion, K(+) uptake and glutamate biosynthesis, were observed in V. cholerae strains. In addition, some sigma factors were up-regulated in V. cholerae strains, suggesting that V. cholerae may recruit common sigma factors to achieve an active salt stress response. However, some changes in gene transcript levels in response to salt stress in V. cholerae were strain-specific. In particular, hierarchical clustering of differentially expressed genes indicated that transcript levels of these genes were correlated with the degree of salt tolerance. Therefore, elevated transcript levels of some genes, including sigma factors and genes involved in peptidoglycan biosynthesis, may be due to the salt tolerance of strains. In addition, high salt-tolerant strains may recruit common as well as additional sigma factors to activate the salt stress response. PMID:25589902

  6. 78 FR 1250 - Agency Information Collection Activities: Proposed New Collection; Comments Requested; Stress...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-08

    ... Information Collection Activities: Proposed New Collection; Comments Requested; Stress Resiliency Study... Form/Collection: Stress Resiliency Study Questionnaires for Milwaukee Police Department. (3) Agency... MPD. These surveys will be used to collect data on MPD officers' perceived stress, responses...

  7. Juvenile stress impairs body temperature regulation and augments anticipatory stress-induced hyperthermia responses in rats.

    PubMed

    Yee, Nicole; Plassmann, Kerstin; Fuchs, Eberhard

    2011-09-01

    Clinical studies have implicated adolescence as an important and vulnerable period during which traumatic experiences can predispose individuals to anxiety and mood disorders. As such, a stress model in juvenile rats (age 27-29 d) was previously developed to investigate the long-term effects of stress exposure during adolescence on behavior and physiology. This paradigm involves exposing rats to different stressors on consecutive days over a 3-day period. Here, we studied the effects of juvenile stress on long-term core body temperature regulation and acute stress-induced hyperthermia (SIH) responses using telemetry. We found no differences between control and juvenile stress rats in anxiety-related behavior on the elevated plus maze, which we attribute to stress associated with surgical implantation of telemetry devices. This highlights the severe impact of surgical stress on the results of subsequent behavioral measurements. Nonetheless, juvenile stress disrupted the circadian rhythmicity of body temperature and decreased circadian amplitude. It also induced chronic hypothermia during the dark phase of the day, when rats are most active. When subjected to acute social defeat stress as adults, juvenile stress had no impact on the SIH response relative to controls. However, 24 h later, juvenile stress rats displayed an elevated SIH response in anticipation of social defeat when re-exposed to the social defeat environment. Taken together, our findings indicate that juvenile stress can induce long-term alterations in body temperature regulation and heighten the increase in temperature associated with anticipation of social defeat. The outcomes of behavioral measurements in these experiments, however, are severely affected by surgical stress. PMID:21557956

  8. Molecular and biochemical responses of Volvox carteri to oxidative stress

    NASA Astrophysics Data System (ADS)

    Lingappa, U.; Rankin-Gee, E. K.; Lera, M.; Bebour, B.; Marcu, O.

    2014-03-01

    Understanding the intracellular response to environmental stresses is a key aspect to understanding the limits of habitability for life as we know it. A wide range of relevant stressors, from heat shock to radiation, result in the intracellular production of reactive oxygen species (ROS). ROS are used physiologically as signaling molecules to cause changes in gene expression and metabolism. However, ROS, including superoxide (O2-) and peroxides, are also highly reactive molecules that cause oxidative damage to proteins, lipids and DNA. Here we studied stress response in the multicellular, eukaryotic green alga Volvox carteri, after exposure to heat shock conditions. We show that the ROS response to heat stress is paralleled by changes in photosynthetic metabolism, antioxidant enzyme activity and gene expression, and fluctuations in the elemental composition of cells. Metabolism, as measured by pulse amplitude modulated (PAM) fluorometry over two hours of heat stress, showed a linear decrease in the photosynthetic efficiency of Volvox. ROS quantification uncovered an increase in ROS in the culture medium, paralleled by a decrease in ROS within the Volvox colonies, suggesting an export mechanism is utilized to mitigate stress. Enzyme kinetics indicated an increase in superoxide dismutase (SOD) activity over the heat stress timecourse. Using X-ray fluorescence (XRF) at the Stanford Synchrotron Radiation Lightsource, we show that these changes coincide with cell-specific import/export and intracellular redistribution of transition elements and halides, suggesting that the cellular metallome is also engaged in mediating oxidative stress in Volvox.

  9. Thiol specific oxidative stress response in Mycobacteria.

    PubMed

    Dosanjh, Nirpjit S; Rawat, Mamta; Chung, Ji-Hae; Av-Gay, Yossef

    2005-08-01

    The cellular response of mycobacteria to thiol specific oxidative stress was studied in Mycobacterium bovis BCG cultures. Two-dimensional gel electrophoresis revealed that upon diamide treatment at least 60 proteins were upregulated. Fourteen of these proteins were identified by MALDI-MS; four proteins, AhpC, Tpx, GroEL2, and GroEL1 are functionally related to oxidative stress response; eight proteins, LeuC, LeuD, Rv0224c, Rv3029c, AsnB, Rv2971, PheA and HisH are classified as part of the bacterial intermediary metabolism and respiration pathways; protein EchA14 belong to lipid metabolism, and NrdE, belongs to the mycobacterial information pathway category. Reverse transcription followed by quantitative real time PCR in response to diamide stress demonstrated that protein expression is directly proportional to the corresponding gene transcription. PMID:16006064

  10. Modulation of immune responses in stress by Yoga

    PubMed Central

    Arora, Sarika; Bhattacharjee, Jayashree

    2008-01-01

    Stress is a constant factor in today's fastpaced life that can jeopardize our health if left unchecked. It is only in the last half century that the role of stress in every ailment from the common cold to AIDS has been emphasized, and the mechanisms involved in this process have been studied. Stress influences the immune response presumably through the activation of the hypothalamic-pituitary adrenal axis, hypothalamic pituitary-gonadal axis, and the sympathetic-adrenal-medullary system. Various neurotransmitters, neuropeptides, hormones, and cytokines mediate these complex bidirectional interactions between the central nervous system (CNS) and the immune system. The effects of stress on the immune responses result in alterations in the number of immune cells and cytokine dysregulation. Various stress management strategies such as meditation, yoga, hypnosis, and muscle relaxation have been shown to reduce the psychological and physiological effects of stress in cancers and HIV infection. This review aims to discuss the effect of stress on the immune system and examine how relaxation techniques such as Yoga and meditation could regulate the cytokine levels and hence, the immune responses during stress. PMID:21829284

  11. ROS Regulation During Abiotic Stress Responses in Crop Plants

    PubMed Central

    You, Jun; Chan, Zhulong

    2015-01-01

    Abiotic stresses such as drought, cold, salt and heat cause reduction of plant growth and loss of crop yield worldwide. Reactive oxygen species (ROS) including hydrogen peroxide (H2O2), superoxide anions (O2•-), hydroxyl radical (OH•) and singlet oxygen (1O2) are by-products of physiological metabolisms, and are precisely controlled by enzymatic and non-enzymatic antioxidant defense systems. ROS are significantly accumulated under abiotic stress conditions, which cause oxidative damage and eventually resulting in cell death. Recently, ROS have been also recognized as key players in the complex signaling network of plants stress responses. The involvement of ROS in signal transduction implies that there must be coordinated function of regulation networks to maintain ROS at non-toxic levels in a delicate balancing act between ROS production, involving ROS generating enzymes and the unavoidable production of ROS during basic cellular metabolism, and ROS-scavenging pathways. Increasing evidence showed that ROS play crucial roles in abiotic stress responses of crop plants for the activation of stress-response and defense pathways. More importantly, manipulating ROS levels provides an opportunity to enhance stress tolerances of crop plants under a variety of unfavorable environmental conditions. This review presents an overview of current knowledge about homeostasis regulation of ROS in crop plants. In particular, we summarize the essential proteins that are involved in abiotic stress tolerance of crop plants through ROS regulation. Finally, the challenges toward the improvement of abiotic stress tolerance through ROS regulation in crops are discussed. PMID:26697045

  12. Reactive oxygen species in response of plants to gravity stress

    NASA Astrophysics Data System (ADS)

    Jadko, Sergiy

    2016-07-01

    Reactive oxygen species (ROS) as second messengers can induce stress response of plants. Thioredoxins (Trx) and peroxiredoxins (Prx) can function as sensors and transmitters of the ROS in stress signaling and antioxidant response. 12-14 days old tissue culture of Arabidopsis thaliana have been investigated. Hypergravity stress was induced by centrifugation at 10 and 20 g during 30 and 90 min and than intensity of spontaneous chemiluminescence (SChL/ROS content), Trx and Prx activities were determined. All experiments were repeated from 3 to 5 times and the obtained data were statistically treated. In the tissue culture under development of the stress there were an increase in intensity of SChL and Trx and Prx activities. Thus, under hypergravity stress in the plant occurred early increase in the ROS level and the ROS induced the increase in the Trx and Prx activities. Prx and Trx can also participate in the formation of stress respons as acceptors and transducers of the redox signals. Increase in the activity of these enzymes primarily aimed at increasing of the total antioxidant activity in the cells to prevent of the plant to development of oxidative degradation by ROS.

  13. The transcriptional regulator megakaryoblastic leukemia-1 mediates serum response factor-independent activation of tenascin-C transcription by mechanical stress.

    PubMed

    Asparuhova, Maria B; Ferralli, Jacqueline; Chiquet, Matthias; Chiquet-Ehrismann, Ruth

    2011-10-01

    The extracellular matrix protein tenascin-C (TNC) is up-regulated in processes influenced by mechanical stress, such as inflammation, tissue remodeling, wound healing, and tumorigenesis. Cyclic strain-induced TNC expression depends on RhoA-actin signaling, the pathway that regulates transcriptional activity of serum response factor (SRF) by its coactivator megakaryoblastic leukemia-1 (MKL1). Therefore, we tested whether MKL1 controls TNC transcription. We demonstrate that overexpression of MKL1 strongly induces TNC expression in mouse NIH3T3 fibroblasts and normal HC11 and transformed 4T1 mammary epithelial cells. Part of the induction was dependant on SRF and a newly identified atypical CArG box in the TNC promoter. Another part was independent of SRF but required the SAP domain of MKL1. An MKL1 mutant incapable of binding to SRF still strongly induced TNC, while induction of the SRF target c-fos was abolished. Cyclic strain failed to induce TNC in MKL1-deficient but not in SRF-deficient fibroblasts, and strain-induced TNC expression strongly depended on the SAP domain of MKL1. Promoter-reporter and chromatin immunoprecipitation experiments unraveled a SAP-dependent, SRF-independent interaction of MKL1 with the proximal promoter region of TNC, attributing for the first time a functional role to the SAP domain of MKL1 in regulating gene expression. PMID:21705668

  14. Nitric oxide triggers a concentration-dependent differential modulation of superoxide dismutase (FeSOD and Cu/ZnSOD) activity in sunflower seedling roots and cotyledons as an early and long distance signaling response to NaCl stress.

    PubMed

    Arora, Dhara; Bhatla, Satish C

    2015-01-01

    Dark-grown sunflower (Helianthus annuus L.) seedlings exhibit modulation of total superoxide dismutase (SOD;EC 1.15.1.1) activity in roots and cotyledons (10,000g supernatant) in response to salt stress (NaCl; 120 mM) through a differential, zymographically detectable, whole tissue activity of FeSOD and Cu/ZnSOD. Confocal laser scanning microscopic imaging (CLSM) has further shown that NaCl stress significantly influences differential spatial distribution of Cu/ZnSOD and MnSOD isoforms in an inverse manner. Dual action of nitric oxide (NO) is evident in its crosstalk with FeSOD and Cu/ZnSOD in seedling roots and cotyledons in control and NaCl(-) stress conditions. Cu/ZnSOD activity in the roots of 2 d old NaCl(-) stressed seedlings is enhanced in the presence of 125-1000 µM of NO donor (sodium nitroprusside; SNP) indicating salt sensitivity of the enzyme activity. Quenching of endogenous NO by cPTIO treatment (500, 1000 µM) lowers FeSOD activity in roots (-NaCl). Cotyledons from control seedlings show an upregulation of FeSOD activity with increasing availability of SNP (125-1000 µM) in the Hoagland irrigation medium. Quenching of NO by cPTIO provides evidence for an inverse correlation between NO availability and FeSOD activity in seedling cotyledons irrespective of NaCl stress. Variable response due to NO on SOD isoforms in sunflower seedlings reflects its concentration-dependent biphasic (pro- and antioxidant) nature of action. Differential induction of SOD isoforms by NO indicates separate intracellular signaling pathways (associated with their respective functional separation) operative in seedling roots as an early salt stress mechanism and in cotyledons as an early long-distance NaCl stress sensing mechanism. PMID:26339977

  15. Nitric oxide triggers a concentration-dependent differential modulation of superoxide dismutase (FeSOD and Cu/ZnSOD) activity in sunflower seedling roots and cotyledons as an early and long distance signaling response to NaCl stress

    PubMed Central

    Arora, Dhara; Bhatla, Satish C

    2015-01-01

    Dark-grown sunflower (Helianthus annuus L.) seedlings exhibit modulation of total superoxide dismutase (SOD;EC 1.15.1.1) activity in roots and cotyledons (10,000g supernatant) in response to salt stress (NaCl; 120 mM) through a differential, zymographically detectable, whole tissue activity of FeSOD and Cu/ZnSOD. Confocal laser scanning microscopic imaging (CLSM) has further shown that NaCl stress significantly influences differential spatial distribution of Cu/ZnSOD and MnSOD isoforms in an inverse manner. Dual action of nitric oxide (NO) is evident in its crosstalk with FeSOD and Cu/ZnSOD in seedling roots and cotyledons in control and NaCl− stress conditions. Cu/ZnSOD activity in the roots of 2 d old NaCl− stressed seedlings is enhanced in the presence of 125–1000 µM of NO donor (sodium nitroprusside; SNP) indicating salt sensitivity of the enzyme activity. Quenching of endogenous NO by cPTIO treatment (500, 1000 µM) lowers FeSOD activity in roots (-NaCl). Cotyledons from control seedlings show an upregulation of FeSOD activity with increasing availability of SNP (125–1000 µM) in the Hoagland irrigation medium. Quenching of NO by cPTIO provides evidence for an inverse correlation between NO availability and FeSOD activity in seedling cotyledons irrespective of NaCl stress. Variable response due to NO on SOD isoforms in sunflower seedlings reflects its concentration-dependent biphasic (pro- and antioxidant) nature of action. Differential induction of SOD isoforms by NO indicates separate intracellular signaling pathways (associated with their respective functional separation) operative in seedling roots as an early salt stress mechanism and in cotyledons as an early long-distance NaCl stress sensing mechanism. PMID:26339977

  16. Proteolytic regulation of stress response pathways in Escherichia coli.

    PubMed

    Micevski, Dimce; Dougan, David A

    2013-01-01

    Maintaining correct cellular function is a fundamental biological process for all forms of life. A critical aspect of this process is the maintenance of protein homeostasis (proteostasis) in the cell, which is largely performed by a group of proteins, referred to as the protein quality control (PQC) network. This network of proteins, comprised of chaperones and proteases, is critical for maintaining proteostasis not only during favourable growth conditions, but also in response to stress. Indeed proteases play a crucial role in the clearance of unwanted proteins that accumulate during stress, but more importantly, in the activation of various different stress response pathways. In bacteria, the cells response to stress is usually orchestrated by a specific transcription factor (sigma factor). In Escherichia coli there are seven different sigma factors, each of which responds to a particular stress, resulting in the rapid expression of a specific set of genes. The cellular concentration of each transcription factor is tightly controlled, at the level of transcription, translation and protein stability. Here we will focus on the proteolytic regulation of two sigma factors (σ(32) and σ(S)), which control the heat and general stress response pathways, respectively. This review will also briefly discuss the role proteolytic systems play in the clearance of unwanted proteins that accumulate during stress. PMID:23479439

  17. Thermodynamic Modeling and Analysis of Human Stress Response

    NASA Technical Reports Server (NTRS)

    Boregowda, S. C.; Tiwari, S. N.

    1999-01-01

    A novel approach based on the second law of thermodynamics is developed to investigate the psychophysiology and quantify human stress level. Two types of stresses (thermal and mental) are examined. A Unified Stress Response Theory (USRT) is developed under the new proposed field of study called Engineering Psychophysiology. The USRT is used to investigate both thermal and mental stresses from a holistic (human body as a whole) and thermodynamic viewpoint. The original concepts and definitions are established as postulates which form the basis for thermodynamic approach to quantify human stress level. An Objective Thermal Stress Index (OTSI) is developed by applying the second law of thermodynamics to the human thermal system to quantify thermal stress or dis- comfort in the human body. The human thermal model based on finite element method is implemented. It is utilized as a "Computational Environmental Chamber" to conduct series of simulations to examine the human thermal stress responses under different environmental conditions. An innovative hybrid technique is developed to analyze human thermal behavior based on series of human-environment interaction simulations. Continuous monitoring of thermal stress is demonstrated with the help of OTSI. It is well established that the human thermal system obeys the second law of thermodynamics. Further, the OTSI is validated against the experimental data. Regarding mental stress, an Objective Mental Stress Index (OMSI) is developed by applying the Maxwell relations of thermodynamics to the combined thermal and cardiovascular system in the human body. The OMSI is utilized to demonstrate the technique of monitoring mental stress continuously and is validated with the help of series of experimental studies. Although the OMSI indicates the level of mental stress, it provides a strong thermodynamic and mathematical relationship between activities of thermal and cardiovascular systems of the human body.

  18. Orientational Polarizability and Stress Response of Biological Cells

    NASA Astrophysics Data System (ADS)

    Safran, S. A.; de, R.; Zemel, A.

    We present a theoretical treatment of the orientational response to external stress of active, contractile cells embedded in a gel-like elastic medium. The theory includes random forces as well as forces that arise from the deformation of the matrix and those due to the internal regulation of the stress fibers and focal adhesions of the cell. We calculate both the static and high frequency limits of the orientational response in terms of the cellular polarizability. For systems in which the forces due to regulation and activity dominate the mechanical forces, we show that there is a non-linear dynamical response which, in the high frequency limit, causes the cell to orient nearly perpendicular to the direction of the applied stress.

  19. Stress in Atlantic salmon: response to unpredictable chronic stress.

    PubMed

    Madaro, Angelico; Olsen, Rolf E; Kristiansen, Tore S; Ebbesson, Lars O E; Nilsen, Tom O; Flik, Gert; Gorissen, Marnix

    2015-08-01

    Combinations of stressors occur regularly throughout an animal's life, especially in agriculture and aquaculture settings. If an animal fails to acclimate to these stressors, stress becomes chronic, and a condition of allostatic overload arises with negative results for animal welfare. In the current study, we describe effects of exposing Atlantic salmon parr to an unpredictable chronic stressor (UCS) paradigm for 3 weeks. The paradigm involves exposure of fish to seven unpredictable stressors three times a day. At the end of the trial, experimental and control fish were challenged with yet another novel stressor and sampled before and 1 h after that challenge. Plasma cortisol decreased steadily over time in stressed fish, indicative of exhaustion of the endocrine stress axis. This was confirmed by a lower cortisol response to the novel stressor at the end of the stress period in chronically stressed fish compared with the control group. In the preoptic area (POA) and pituitary gland, chronic stress resulted in decreased gene expression of 11βhsd2, gr1 and gr2 in the POA and increased expression of those genes in the pituitary gland. POA crf expression and pituitary expression of pomcs and mr increased, whereas interrenal gene expression was unaffected. Exposure to the novel stressor had no effect on POA and interrenal gene expression. In the pituitary, crfr1, pomcs, 11βhsd2, grs and mr were down-regulated. In summary, our results provide a novel overview of the dynamic changes that occur at every level of the hypothalamic-pituitary gland-interrenal gland (HPI) axis as a result of chronic stress in Atlantic salmon. PMID:26056242

  20. Chloroplast Retrograde Regulation of Heat Stress Responses in Plants.

    PubMed

    Sun, Ai-Zhen; Guo, Fang-Qing

    2016-01-01

    It is well known that intracellular signaling from chloroplast to nucleus plays a vital role in stress responses to survive environmental perturbations. The chloroplasts were proposed as sensors to heat stress since components of the photosynthetic apparatus housed in the chloroplast are the major targets of thermal damage in plants. Thus, communicating subcellular perturbations to the nucleus is critical during exposure to extreme environmental conditions such as heat stress. By coordinating expression of stress specific nuclear genes essential for adaptive responses to hostile environment, plants optimize different cell functions and activate acclimation responses through retrograde signaling pathways. The efficient communication between plastids and the nucleus is highly required for such diverse metabolic and biosynthetic functions during adaptation processes to environmental stresses. In recent years, several putative retrograde signals released from plastids that regulate nuclear genes have been identified and signaling pathways have been proposed. In this review, we provide an update on retrograde signals derived from tetrapyrroles, carotenoids, reactive oxygen species (ROS) and organellar gene expression (OGE) in the context of heat stress responses and address their roles in retrograde regulation of heat-responsive gene expression, systemic acquired acclimation, and cellular coordination in plants. PMID:27066042

  1. Chloroplast Retrograde Regulation of Heat Stress Responses in Plants

    PubMed Central

    Sun, Ai-Zhen; Guo, Fang-Qing

    2016-01-01

    It is well known that intracellular signaling from chloroplast to nucleus plays a vital role in stress responses to survive environmental perturbations. The chloroplasts were proposed as sensors to heat stress since components of the photosynthetic apparatus housed in the chloroplast are the major targets of thermal damage in plants. Thus, communicating subcellular perturbations to the nucleus is critical during exposure to extreme environmental conditions such as heat stress. By coordinating expression of stress specific nuclear genes essential for adaptive responses to hostile environment, plants optimize different cell functions and activate acclimation responses through retrograde signaling pathways. The efficient communication between plastids and the nucleus is highly required for such diverse metabolic and biosynthetic functions during adaptation processes to environmental stresses. In recent years, several putative retrograde signals released from plastids that regulate nuclear genes have been identified and signaling pathways have been proposed. In this review, we provide an update on retrograde signals derived from tetrapyrroles, carotenoids, reactive oxygen species (ROS) and organellar gene expression (OGE) in the context of heat stress responses and address their roles in retrograde regulation of heat-responsive gene expression, systemic acquired acclimation, and cellular coordination in plants. PMID:27066042

  2. Stress Responses from the Endoplasmic Reticulum in Cancer

    PubMed Central

    Kato, Hironori; Nishitoh, Hideki

    2015-01-01

    The endoplasmic reticulum (ER) is a dynamic organelle that is essential for multiple cellular functions. During cellular stress conditions, including nutrient deprivation and dysregulation of protein synthesis, unfolded/misfolded proteins accumulate in the ER lumen, resulting in activation of the unfolded protein response (UPR). The UPR also contributes to the regulation of various intracellular signaling pathways such as calcium signaling and lipid signaling. More recently, the mitochondria-associated ER membrane (MAM), which is a site of close contact between the ER and mitochondria, has been shown to function as a platform for various intracellular stress responses including apoptotic signaling, inflammatory signaling, the autophagic response, and the UPR. Interestingly, in cancer, these signaling pathways from the ER are often dysregulated, contributing to cancer cell metabolism. Thus, the signaling pathway from the ER may be a novel therapeutic target for various cancers. In this review, we discuss recent research on the roles of stress responses from the ER, including the MAM. PMID:25941664

  3. Nrf2 activators modulate oxidative stress responses and bioenergetic profiles of human retinal epithelial cells cultured in normal or high glucose conditions.

    PubMed

    Foresti, Roberta; Bucolo, Claudio; Platania, Chiara Maria Bianca; Drago, Filippo; Dubois-Randé, Jean-Luc; Motterlini, Roberto

    2015-09-01

    Retinal pigment epithelial cells exert an important supporting role in the eye and develop adaptive responses to oxidative stress or high glucose levels, as observed during diabetes. Endogenous antioxidant defences are mainly regulated by Nrf2, a transcription factor that is activated by naturally-derived and electrophilic compounds. Here we investigated the effect of the Nrf2 activators dimethylfumarate (DMF) and carnosol on antioxidant pathways, oxygen consumption rate and wound healing in human retinal pigment epithelial cells (ARPE-19) cultured in medium containing normal (NG, 5mM) or high (HG, 25 mM) glucose levels. We also assessed wound healing using an in vivo corneal epithelial injury model. We found that Nrf2 nuclear translocation and heme oxygenase activity increased in ARPE cells treated with 10 μM DMF or carnosol irrespective of glucose culture conditions. However, HG rendered retinal cells more sensitive to regulators of glutathione synthesis or inhibition and caused a decrease of both cellular and mitochondrial reactive oxygen species. Culture in HG also reduced ATP production and mitochondrial function as measured with the Seahorse XF analyzer and electron microscopy analysis revealed morphologically damaged mitochondria. Acute treatment with DMF or carnosol did not restore mitochondrial function in HG cells; conversely, the compounds reduced cellular maximal respiratory and reserve capacity, which were completely prevented by N-acetylcysteine thus suggesting the involvement of thiols in this effect. Interestingly, the scratch assay showed that wound closure was faster in cells cultured in HG than NG and was accelerated by carnosol. This effect was reversed by an inhibitor of heme oxygenase activity. Moreover, topical application of carnosol to the cornea of diabetic rats significantly accelerated wound healing. In summary, these data indicate that culture of retinal epithelial cells in HG does not affect the activation of the Nrf2/heme oxygenase

  4. Environmental Change, the Stress Response, and Neurogenesis.

    PubMed

    LaDage, Lara D

    2015-09-01

    Previous to the 1980's, the prevailing neuroscience dogma held that no new neurons were produced in the brains of adult mammals. Now, we understand that the production of new neurons, or neurogenesis, is a common and plastic process in the adult brain. To date, however, researchers have not come to a unified understanding of the functional significance of neurogenesis. Several factors have been shown to modulate hippocampal neurogenesis including spatial learning, stress, and aspects of environmental change, but questions still remain. How do these modulating factors overlap? Which aspects of environmental change induce a stress response? Is there a relationship between hippocampal neurogenesis, the stress response, and environmental change? Can this relationship be altered when taking into consideration other factors such as perception and predictability of the environment? Finally, do results from neurobiological research on laboratory rodents translate to wild systems? This review attempts to address these questions and synthesize research from the fields of ecology, psychology, and behavioral neuroscience. PMID:25980567

  5. Hyperosmotic Stress Response of Campylobacter jejuni

    PubMed Central

    Cameron, Andrew; Frirdich, Emilisa; Huynh, Steven; Parker, Craig T.

    2012-01-01

    The diarrheal pathogen Campylobacter jejuni and other gastrointestinal bacteria encounter changes in osmolarity in the environment, through exposure to food processing, and upon entering host organisms, where osmotic adaptation can be associated with virulence. In this study, growth profiles, transcriptomics, and phenotypic, mutant, and single-cell analyses were used to explore the effects of hyperosmotic stress exposure on C. jejuni. Increased growth inhibition correlated with increased osmotic concentration, with both ionic and nonionic stressors inhibiting growth at 0.620 total osmol liter−1. C. jejuni adaptation to a range of osmotic stressors and concentrations was accompanied by severe filamentation in subpopulations, with microscopy indicating septum formation and phenotypic diversity between individual cells in a filament. Population heterogeneity was also exemplified by the bifurcation of colony morphology into small and large variants on salt stress plates. Flow cytometry of C. jejuni harboring green fluorescent protein (GFP) fused to the ATP synthase promoter likewise revealed bimodal subpopulations under hyperosmotic stress. We also identified frequent hyperosmotic stress-sensitive variants within the clonal wild-type population propagated on standard laboratory medium. Microarray analysis following hyperosmotic upshift revealed enhanced expression of heat shock genes and genes encoding enzymes for synthesis of potential osmoprotectants and cross-protective induction of oxidative stress genes. The capsule export gene kpsM was also upregulated, and an acapsular mutant was defective for growth under hyperosmotic stress. For C. jejuni, an organism lacking most conventional osmotic response factors, these data suggest an unusual hyperosmotic stress response, including likely “bet-hedging” survival strategies relying on the presence of stress-fit individuals in a heterogeneous population. PMID:22961853

  6. Mechanisms of Cell Propulsion by Active Stresses.

    PubMed

    Carlsson, A E

    2011-07-01

    The mechanisms by which cytoskeletal flows and cell-substrate interactions interact to generate cell motion are explored using a simplified model of the cytoskeleton as a viscous gel containing active stresses. This model yields explicit general results relating cell speed and traction forces to the distributions of active stress and cell-substrate friction. It is found that 1) the cell velocity is given by a function that quantifies the asymmetry of the active-stress distribution, 2) gradients in cell-substrate friction can induce motion even when the active stresses are symmetrically distributed, 3) the traction-force dipole is enhanced by protrusive stresses near the cell edges or contractile stresses near the center of the cell, and 4) the cell velocity depends biphasically on the cell-substrate adhesion strength if active stress is enhanced by adhesion. Specific experimental tests of the calculated dependences are proposed. PMID:21804763

  7. Mechanisms of Cell Propulsion by Active Stresses

    PubMed Central

    Carlsson, A. E.

    2011-01-01

    The mechanisms by which cytoskeletal flows and cell-substrate interactions interact to generate cell motion are explored using a simplified model of the cytoskeleton as a viscous gel containing active stresses. This model yields explicit general results relating cell speed and traction forces to the distributions of active stress and cell-substrate friction. It is found that 1) the cell velocity is given by a function that quantifies the asymmetry of the active-stress distribution, 2) gradients in cell-substrate friction can induce motion even when the active stresses are symmetrically distributed, 3) the traction-force dipole is enhanced by protrusive stresses near the cell edges or contractile stresses near the center of the cell, and 4) the cell velocity depends biphasically on the cell-substrate adhesion strength if active stress is enhanced by adhesion. Specific experimental tests of the calculated dependences are proposed. PMID:21804763

  8. The Adaptive Calibration Model of stress responsivity

    PubMed Central

    Ellis, Bruce J.; Shirtcliff, Elizabeth A.

    2010-01-01

    This paper presents the Adaptive Calibration Model (ACM), an evolutionary-developmental theory of individual differences in the functioning of the stress response system. The stress response system has three main biological functions: (1) to coordinate the organism’s allostatic response to physical and psychosocial challenges; (2) to encode and filter information about the organism’s social and physical environment, mediating the organism’s openness to environmental inputs; and (3) to regulate the organism’s physiology and behavior in a broad range of fitness-relevant areas including defensive behaviors, competitive risk-taking, learning, attachment, affiliation and reproductive functioning. The information encoded by the system during development feeds back on the long-term calibration of the system itself, resulting in adaptive patterns of responsivity and individual differences in behavior. Drawing on evolutionary life history theory, we build a model of the development of stress responsivity across life stages, describe four prototypical responsivity patterns, and discuss the emergence and meaning of sex differences. The ACM extends the theory of biological sensitivity to context (BSC) and provides an integrative framework for future research in the field. PMID:21145350

  9. Phospholipid Signaling Responses in Salt-Stressed Rice Leaves

    PubMed Central

    Darwish, Essam; Testerink, Christa; Khalil, Mohamed; El-Shihy, Osama; Munnik, Teun

    2009-01-01

    Salinity is one of the major environmental factors limiting growth and productivity of rice plants. In this study, the effect of salt stress on phospholipid signaling responses in rice leaves was investigated. Leaf cuts were radiolabeled with 32P-orthophosphate and the lipids extracted and analyzed by thin-layer chromatography, autoradiography and phosphoimaging. Phospholipids were identified by co-migration of known standards. Results showed that 32Pi was rapidly incorporated into the minor lipids, phos-phatidylinositol bisphosphate (PIP2) and phosphatidic acid (PA) and, interestingly, also into the structural lipids phosphatidylethanolamine (PE) and phosphatidylglycerol (PG), which normally label relatively slowly, like phosphatidylcholine (PC) and phosphatidylinositol (PI). Only very small amounts of PIP2 were found. However, in response to salt stress (NaCl), PIP2 levels rapidly (<30 min) increased up to 4-fold, in a time- and dose-dependent manner. PA and its phosphorylated product, diacylglyc-erolpyrophosphate (DGPP), also increased upon NaCl stress, while cardiolipin (CL) levels decreased. All other phospholipid levels remained unchanged. PA signaling can be generated via the combined action of phospholipase C (PLC) and diacylglycerol kinase (DGK) or directly via phospholipase D (PLD). The latter can be measured in vivo, using a transphosphatidylation assay. Interestingly, these measurements revealed that salt stress inhibited PLD activity, indicating that the salt stress-induced PA response was not due to PLD activity. Comparison of the 32P-lipid responses in salt-tolerant and salt-sensitive cultivars revealed no significant differences. Together these results show that salt stress rapidly activates several lipid responses in rice leaves but that these responses do not explain the difference in salt tolerance between sensitive and tolerant cultivars. PMID:19369274

  10. Plant Heat Adaptation: priming in response to heat stress

    PubMed Central

    Bäurle, Isabel

    2016-01-01

    Abiotic stress is a major threat to crop yield stability. Plants can be primed by heat stress, which enables them to subsequently survive temperatures that are lethal to a plant in the naïve state. This is a rapid response that has been known for many years and that is highly conserved across kingdoms. Interestingly, recent studies in Arabidopsis and rice show that this thermo-priming lasts for several days at normal growth temperatures and that it is an active process that is genetically separable from the priming itself. This is referred to as maintenance of acquired thermotolerance or heat stress memory. Such a memory conceivably has adaptive advantages under natural conditions, where heat stress often is chronic or recurring. In this review, I will focus on recent advances in the mechanistic understanding of heat stress memory. PMID:27134736

  11. Gene 33/Mig-6, a transcriptionally inducible adapter protein that binds GTP-Cdc42 and activates SAPK/JNK. A potential marker transcript for chronic pathologic conditions, such as diabetic nephropathy. Possible role in the response to persistent stress.

    PubMed

    Makkinje, A; Quinn, D A; Chen, A; Cadilla, C L; Force, T; Bonventre, J V; Kyriakis, J M

    2000-06-01

    Chronic stresses, including the mechanical strain caused by hypertension or excess pulmonary ventilation pressure, lead to important clinical consequences, including hypertrophy and acute respiratory distress syndrome. Pathologic hypertrophy contributes to decreased organ function and, ultimately, organ failure; and cardiac and diabetic renal hypertrophy are major causes of morbidity and morality in the developed world. Likewise, acute respiratory distress syndrome is a serious potential side effect of mechanical pulmonary ventilation. Whereas the deleterious effects of chronic stress are well established, the molecular mechanisms by which these stresses affect cell function are still poorly characterized. gene 33 (also called mitogen-inducible gene-6, mig-6) is an immediate early gene that is transcriptionally induced by a divergent array of extracellular stimuli. The physiologic function of Gene 33 is unknown. Here we show that gene 33 mRNA levels increase sharply in response to a set of commonly occurring chronic stress stimuli: mechanical strain, vasoactive peptides, and diabetic nephropathy. Induction of gene 33 requires the stress-activated protein kinases (SAPKs)/c-Jun NH(2)-terminal kinases. This expression pattern suggests that gene 33 is a potential marker for diabetic nephropathy and other pathologic responses to persistent sublethal stress. The structure of Gene 33 indicates an adapter protein capable of binding monomeric GTPases of the Rho subfamily. Consistent with this, Gene 33 interacts in vivo and, in a GTP-dependent manner, in vitro with Cdc42Hs; and transient expression of Gene 33 results in the selective activation of the SAPKs. These results imply a reciprocal, positive feedback relationship between Gene 33 expression and SAPK activation. Expression of Gene 33 at sufficient levels may enable a compensatory reprogramming of cellular function in response to chronic stress, which may have pathophysiological consequences. PMID:10749885

  12. Adaptive Patterns of Stress Responsivity: A Preliminary Investigation

    ERIC Educational Resources Information Center

    Del Giudice, Marco; Hinnant, J. Benjamin; Ellis, Bruce J.; El-Sheikh, Mona

    2012-01-01

    The adaptive calibration model (ACM) is an evolutionary-developmental theory of individual differences in stress responsivity. In this article, we tested some key predictions of the ACM in a middle childhood sample (N = 256). Measures of autonomic nervous system activity across the sympathetic and parasympathetic branches validated the 4-pattern…

  13. Endoplasmic Reticulum Stress Sensing in the Unfolded Protein Response

    PubMed Central

    Gardner, Brooke M.; Pincus, David; Gotthardt, Katja; Gallagher, Ciara M.; Walter, Peter

    2013-01-01

    Secretory and transmembrane proteins enter the endoplasmic reticulum (ER) as unfolded proteins and exit as either folded proteins in transit to their target organelles or as misfolded proteins targeted for degradation. The unfolded protein response (UPR) maintains the protein-folding homeostasis within the ER, ensuring that the protein-folding capacity of the ER meets the load of client proteins. Activation of the UPR depends on three ER stress sensor proteins, Ire1, PERK, and ATF6. Although the consequences of activation are well understood, how these sensors detect ER stress remains unclear. Recent evidence suggests that yeast Ire1 directly binds to unfolded proteins, which induces its oligomerization and activation. BiP dissociation from Ire1 regulates this oligomeric equilibrium, ultimately modulating Ire1’s sensitivity and duration of activation. The mechanistic principles of ER stress sensing are the focus of this review. PMID:23388626

  14. Multiple Envelope Stress Response Pathways Are Activated in an Escherichia coli Strain with Mutations in Two Members of the DedA Membrane Protein Family

    PubMed Central

    Sikdar, Rakesh; Simmons, Angelica R.

    2013-01-01

    We have reported that simultaneous deletion of two Escherichia coli genes, yqjA and yghB, encoding related and conserved inner membrane proteins belonging to the DedA protein family results in a number of intriguing phenotypes, including temperature sensitivity at 42°C, altered membrane lipid composition, and cell division defects. We sought to characterize these and other phenotypes in an effort to establish a function for this protein family in E. coli. Here, using reporter assays, we show that the major envelope stress response pathways Cpx, Psp, Bae, and Rcs are activated in strain BC202 (W3110; ΔyqjA ΔyghB) at the permissive growth temperature of 30°C. We previously demonstrated that 10 mM Mg2+, 400 mM NaCl, and overexpression of tatABC are capable of restoring normal growth to BC202 at elevated growth temperatures. Deletion of the cpxR gene from BC202 results in the loss of the ability of these supplements to restore growth at 42°C. Additionally, we report that the membrane potential of BC202 is significantly reduced and that cell division and growth can be restored either by expression of the multidrug transporter MdfA from a multicopy plasmid or by growth at pH 6.0. Together, these results suggest that the DedA family proteins YqjA and YghB are required for general envelope maintenance and homeostasis of the proton motive force under a variety of growth conditions. PMID:23042993

  15. Chk1 inhibition after replicative stress activates a double strand break response mediated by ATM and DNA-dependent protein kinase.

    PubMed

    McNeely, Samuel; Conti, Chiara; Sheikh, Tahir; Patel, Himali; Zabludoff, Sonya; Pommier, Yves; Schwartz, Gary; Tse, Archie

    2010-03-01

    Checkpoint kinase 1 (Chk1) regulates cell cycle checkpoints and DNA damage repair in response to genotoxic stress. Inhibition of Chk1 is an emerging strategy for potentiating the cytotoxicity of chemotherapeutic drugs. Here, we demonstrate that AZD7762, an ATP -competitive Chk1/2 inhibitor induces gammaH2AX in gemcitabine-treated cells by altering both dynamics and stability of replication forks, allowing the firing of suppressed replication origins as measured by DNA fiber combing and causing a dramatic increase in DNA breaks as measured by comet assay. Furthermore, we identify ATM and DNA-PK, rather than ATR, as the kinases mediating gammaH2AX induction, suggesting AZD7762 converts stalled forks into double strand breaks (DSBs). Consistent with DSB formation upon fork collapse, cells deficient in DSB repair by lack of BRCA2, XRCC3 or DNA-PK were selectively more sensitive to combined AZD7762 and gemcitabine. Checkpoint abrogation by AZD7762 also caused premature mitosis in gemcitabine-treated cells arrested in G(1)/early S-phase. Prevention of premature mitotic entry via Cdk1 siRNA knockdown suppressed apoptosis. These results demonstrate that chemosensitization of gemcitabine by Chk1 inhibition results from at least three cellular events, namely, activation of origin firing, destabilization of stalled replication forks and entry of cells with damaged DNA into lethal mitosis. Additionally, the current study indicates that the combination of Chk1 inhibitor and gemcitabine may be particularly effective in targeting tumors with specific DNA repair defects. PMID:20160494

  16. Integrator of Stress Responses Calmodulin Binding Transcription Activator 1 (Camta1) Regulates miR-212/miR-132 Expression and Insulin Secretion.

    PubMed

    Mollet, Inês Guerra; Malm, Helena Anna; Wendt, Anna; Orho-Melander, Marju; Eliasson, Lena

    2016-08-26

    Altered microRNA profiles have been demonstrated in experimental models of type 2 diabetes, including in islets of the diabetic Goto-Kakizaki (GK) rat. Our bioinformatic analysis of conserved sequences in promoters of microRNAs, previously observed to be up-regulated in GK rat islets, revealed putative CGCG-core motifs on the promoter of the miR-212/miR-132 cluster, overexpression of which has been shown to increase insulin secretion. These motifs are possible targets of calmodulin binding transcription activators Camta1 and Camta2 that have been recognized as integrators of stress responses. We also identified putative NKE elements, possible targets of NK2 homeobox proteins like the essential islet transcription factor Nkx2-2. As Camtas can function as co-activators with NK2 proteins in other tissues, we explored the role of Camta1, Camta2, and Nkx2-2 in the regulation of the miR-212/miR-132 cluster and insulin secretion. We demonstrate that exposure of control Wistar or GK rat islets to 16.7 mm glucose increases miR-212/miR-132 expression but significantly less so in the GK rat. In addition, Camta1, Camta2, and Nkx2-2 were down-regulated in GK rat islets, and knockdown of Camta1 reduced miR-212/miR-132 promoter activity and miR-212/miR-132 expression, even under cAMP elevation. Knockdown of Camta1 decreased insulin secretion in INS-1 832/13 cells and Wistar rat islets but increased insulin content. Furthermore, knockdown of Camta1 reduced K(+)-induced insulin secretion and voltage-dependent Ca(2+) currents. We also demonstrate Camta1 and Nkx2-2 protein interaction. These results indicate that Camta1 is required not only for expression of the miR-212/miR-132 cluster but at multiple levels for regulating beta cell insulin content and secretion. PMID:27402838

  17. Lipid Biosynthesis Coordinates a Mitochondrial-to-Cytosolic Stress Response.

    PubMed

    Kim, Hyun-Eui; Grant, Ana Rodrigues; Simic, Milos S; Kohnz, Rebecca A; Nomura, Daniel K; Durieux, Jenni; Riera, Celine E; Sanchez, Melissa; Kapernick, Erik; Wolff, Suzanne; Dillin, Andrew

    2016-09-01

    Defects in mitochondrial metabolism have been increasingly linked with age-onset protein-misfolding diseases such as Alzheimer's, Parkinson's, and Huntington's. In response to protein-folding stress, compartment-specific unfolded protein responses (UPRs) within the ER, mitochondria, and cytosol work in parallel to ensure cellular protein homeostasis. While perturbation of individual compartments can make other compartments more susceptible to protein stress, the cellular conditions that trigger cross-communication between the individual UPRs remain poorly understood. We have uncovered a conserved, robust mechanism linking mitochondrial protein homeostasis and the cytosolic folding environment through changes in lipid homeostasis. Metabolic restructuring caused by mitochondrial stress or small-molecule activators trigger changes in gene expression coordinated uniquely by both the mitochondrial and cytosolic UPRs, protecting the cell from disease-associated proteins. Our data suggest an intricate and unique system of communication between UPRs in response to metabolic changes that could unveil new targets for diseases of protein misfolding. PMID:27610574

  18. Pharmacological modification of the perioperative stress response in noncardiac surgery.

    PubMed

    Priebe, Hans-Joachim

    2016-06-01

    The perioperative period is associated with alterations in the neuroendocrine, metabolic, and immune systems, referred to as "stress response." The resultant increased sympathetic activity and elevated serum concentrations of catecholamines may adversely affect the cardiovascular system, resulting in cardiovascular instability (hypertension, tachycardia, and arrhythmia), morbidity (myocardial ischemia, myocardial infarction, and stroke), and mortality (cardiac death and fatal stroke), particularly in patients at an elevated cardiovascular risk and with reduced cardiovascular reserve. Various strategies have been used to ameliorate the adverse perioperative cardiovascular sequelae of the perioperative stress response. Effective pharmacologic blunting of the stress response plays a crucial role in perioperative cardiac risk reduction strategies. In this context, the role of beta-adrenoceptor blockers, alpha2-adrenoceptor agonists, and statins has been extensively examined. This chapter evaluates the available evidence with respect to treatment efficacy of these commonly prescribed drugs in patients undergoing noncardiac surgery. PMID:27396805

  19. Adaptive Patterns of Stress Responsivity: A Preliminary Investigation

    PubMed Central

    Del Giudice, Marco; Hinnant, J. Benjamin; Ellis, Bruce J.; El-Sheikh, Mona

    2014-01-01

    The adaptive calibration model (ACM) is an evolutionary–developmental theory of individual differences in stress responsivity. In this article, we tested some key predictions of the ACM in a middle childhood sample (N = 256). Measures of autonomic nervous system activity across the sympathetic and parasympathetic branches validated the 4-pattern taxonomy of the ACM via finite mixture modeling. Moreover, the 4 patterns of responsivity showed the predicted associations with family stress levels but no association with measures of ecological stress. Our hypotheses concerning sex differences in responsivity were only partly confirmed. This preliminary study provides initial support for the key predictions of the ACM and highlights some of the methodological challenges that will need to be considered in future research on this topic. PMID:22148947

  20. Comparative transcriptome analysis of grapevine in response to copper stress.

    PubMed

    Leng, Xiangpeng; Jia, Haifeng; Sun, Xin; Shangguan, Lingfei; Mu, Qian; Wang, Baoju; Fang, Jinggui

    2015-01-01

    Grapevine is one of the most economically important and widely cultivated fruit crop worldwide. With the industrialization and the popular application of cupric fungicides in grape industry, copper stress and copper pollution are also the factors affecting grape production and berry and wine quality. Here, 3,843 transcripts were significantly differently expressed genes in response to Cu stress by RNA-seq, which included 1,892 up-regulated and 1,951 down-regulated transcripts. During this study we found many known and novel Cu-induced and -repressed genes. Biological analysis of grape samples were indicated that exogenous Cu can influence chlorophylls metabolism and photosynthetic activities of grapevine. Most ROS detoxification systems, including antioxidant enzyme, stress-related proteins and secondary metabolites were strongly induced. Concomitantly, abscisic acid functioned as a negative regulator in Cu stress, in opposite action to ethylene, auxin, jasmonic acid, and brassinolide. This study also identified a set of Cu stress specifically activated genes coding copper transporter, P1B-type ATPase, multidrug transporters. Overall, this work was carried out to gain insights into the copper-regulated and stress-responsive mechanisms in grapevine at transcriptome level. This research can also provide some genetic information that can help us in better vinery management and breeding Cu-resistant grape cultivars. PMID:26673527

  1. Comparative transcriptome analysis of grapevine in response to copper stress

    PubMed Central

    Leng, Xiangpeng; Jia, Haifeng; Sun, Xin; Shangguan, Lingfei; Mu, Qian; Wang, Baoju; Fang, Jinggui

    2015-01-01

    Grapevine is one of the most economically important and widely cultivated fruit crop worldwide. With the industrialization and the popular application of cupric fungicides in grape industry, copper stress and copper pollution are also the factors affecting grape production and berry and wine quality. Here, 3,843 transcripts were significantly differently expressed genes in response to Cu stress by RNA-seq, which included 1,892 up-regulated and 1,951 down-regulated transcripts. During this study we found many known and novel Cu-induced and -repressed genes. Biological analysis of grape samples were indicated that exogenous Cu can influence chlorophylls metabolism and photosynthetic activities of grapevine. Most ROS detoxification systems, including antioxidant enzyme, stress-related proteins and secondary metabolites were strongly induced. Concomitantly, abscisic acid functioned as a negative regulator in Cu stress, in opposite action to ethylene, auxin, jasmonic acid, and brassinolide. This study also identified a set of Cu stress specifically activated genes coding copper transporter, P1B-type ATPase, multidrug transporters. Overall, this work was carried out to gain insights into the copper-regulated and stress-responsive mechanisms in grapevine at transcriptome level. This research can also provide some genetic information that can help us in better vinery management and breeding Cu-resistant grape cultivars. PMID:26673527

  2. Stress Sensitive Healthy Females Show Less Left Amygdala Activation in Response to Withdrawal-Related Visual Stimuli under Passive Viewing Conditions

    ERIC Educational Resources Information Center

    Baeken, Chris; Van Schuerbeek, Peter; De Raedt, Rudi; Vanderhasselt, Marie-Anne; De Mey, Johan; Bossuyt, Axel; Luypaert, Robert

    2012-01-01

    The amygdalae are key players in the processing of a variety of emotional stimuli. Especially aversive visual stimuli have been reported to attract attention and activate the amygdalae. However, as it has been argued that passively viewing withdrawal-related images could attenuate instead of activate amygdalae neuronal responses, its role under…

  3. ERK2 Mediates Metabolic Stress Response to Regulate Cell Fate.

    PubMed

    Shin, Sejeong; Buel, Gwen R; Wolgamott, Laura; Plas, David R; Asara, John M; Blenis, John; Yoon, Sang-Oh

    2015-08-01

    Insufficient nutrients disrupt physiological homeostasis, resulting in diseases and even death. Considering the physiological and pathological consequences of this metabolic stress, the adaptive responses that cells utilize under this condition are of great interest. We show that under low-glucose conditions, cells initiate adaptation followed by apoptosis responses using PERK/Akt and MEK1/ERK2 signaling, respectively. For adaptation, cells engage the ER stress-induced unfolded protein response, which results in PERK/Akt activation and cell survival. Sustained and extreme energetic stress promotes a switch to isoform-specific MEK1/ERK2 signaling, induction of GCN2/eIF2α phosphorylation, and ATF4 expression, which overrides PERK/Akt-mediated adaptation and induces apoptosis through ATF4-dependent expression of pro-apoptotic factors including Bid and Trb3. ERK2 activation during metabolic stress contributes to changes in TCA cycle and amino acid metabolism, and cell death, which is suppressed by glutamate and α-ketoglutarate supplementation. Taken together, our results reveal promising targets to protect cells or tissues from metabolic stress. PMID:26190261

  4. Psychological hardiness predicts neuroimmunological responses to stress.

    PubMed

    Sandvik, Asle M; Bartone, Paul T; Hystad, Sigurd William; Phillips, Terry M; Thayer, Julian F; Johnsen, Bjørn Helge

    2013-01-01

    Psychological hardiness characterizes people who remain healthy under psychosocial stress. The present exploratory study investigates possible links between hardiness and several immune and neuroendocrine markers: IL-6, IL-12, IL-4, IL-10, & neuropeptide-Y. A total of 21 Norwegian navy cadets were studied in the context of a highly stressful military field exercise. Blood samples were collected midway, and again late in the exercise when stress levels were highest. Psychological hardiness (including commitment, control, and challenge) was measured two days before the exercise. While all subjects scored high in hardiness, some were high only in commitment and control, but relatively low in challenge. These "unbalanced" hardiness subjects were also more stress reactive, showing suppressed proinflammatory cytokines (IL-12), increased anti-inflammatory cytokines (IL-4, IL-10), and lower neuropeptide-Y levels as compared to the hardiness-balanced group. This study thus shows that being high in hardiness with a balanced profile is linked to more moderate and healthy immune and neuroendocrine responses to stress. PMID:23458268

  5. Quorum sensing regulates the osmotic stress response in Vibrio harveyi.

    PubMed

    van Kessel, Julia C; Rutherford, Steven T; Cong, Jian-Ping; Quinodoz, Sofia; Healy, James; Bassler, Bonnie L

    2015-01-01

    Bacteria use a chemical communication process called quorum sensing to monitor cell density and to alter behavior in response to fluctuations in population numbers. Previous studies with Vibrio harveyi have shown that LuxR, the master quorum-sensing regulator, activates and represses >600 genes. These include six genes that encode homologs of the Escherichia coli Bet and ProU systems for synthesis and transport, respectively, of glycine betaine, an osmoprotectant used during osmotic stress. Here we show that LuxR activates expression of the glycine betaine operon betIBA-proXWV, which enhances growth recovery under osmotic stress conditions. BetI, an autorepressor of the V. harveyi betIBA-proXWV operon, activates the expression of genes encoding regulatory small RNAs that control quorum-sensing transitions. Connecting quorum-sensing and glycine betaine pathways presumably enables V. harveyi to tune its execution of collective behaviors to its tolerance to stress. PMID:25313392

  6. Quorum Sensing Regulates the Osmotic Stress Response in Vibrio harveyi

    PubMed Central

    Rutherford, Steven T.; Cong, Jian-Ping; Quinodoz, Sofia; Healy, James

    2014-01-01

    Bacteria use a chemical communication process called quorum sensing to monitor cell density and to alter behavior in response to fluctuations in population numbers. Previous studies with Vibrio harveyi have shown that LuxR, the master quorum-sensing regulator, activates and represses >600 genes. These include six genes that encode homologs of the Escherichia coli Bet and ProU systems for synthesis and transport, respectively, of glycine betaine, an osmoprotectant used during osmotic stress. Here we show that LuxR activates expression of the glycine betaine operon betIBA-proXWV, which enhances growth recovery under osmotic stress conditions. BetI, an autorepressor of the V. harveyi betIBA-proXWV operon, activates the expression of genes encoding regulatory small RNAs that control quorum-sensing transitions. Connecting quorum-sensing and glycine betaine pathways presumably enables V. harveyi to tune its execution of collective behaviors to its tolerance to stress. PMID:25313392

  7. Salt stress induced lipid accumulation in heterotrophic culture cells of Chlorella protothecoides: Mechanisms based on the multi-level analysis of oxidative response, key enzyme activity and biochemical alteration.

    PubMed

    Wang, Tao; Ge, Haiyan; Liu, Tingting; Tian, Xiwei; Wang, Zejian; Guo, Meijin; Chu, Ju; Zhuang, Yingping

    2016-06-20

    Salt stress as an effective stress factor that could improve the lipid content and lipid yield of glucose in the heterotrophic culture cells of Chlorella protothecoides was demonstrated in this study. The highest lipid content of 41.2% and lipid yield of 185.8mg/g were obtained when C. protothecoides was stressed under 30g/L NaCl condition at its late logarithmic growth phase. Moreover, the effects of salt and osmotic stress on lipid accumulation were comparatively analyzed, and it was found that the effects of NaCl and KCl stress had no significant differences at the same osmolarity level of 1150mOsm/kg with lipid contents of 41.7 and 40.8% as well as lipid yields of 192.9 and 186.8mg/g, respectively, whereas these results were obviously higher than those obtained under the iso-osmotic glycerol and sorbitol stresses. Furthermore, basing on the multi-level analysis of oxidative response, key enzyme activity and biochemical alteration, the superior performance of salt stress driving lipid over-synthesis was probably ascribed to the more ROS production as a result of additional ion effect besides the osmotic effect, subsequently mediating the alteration from carbohydrate storage to lipid accumulation in signal transduction process of C. protothecoides. PMID:27085889

  8. Activity of antioxidant enzymes in response to atmospheric pressure induced physiological stress in deep-sea hydrothermal vent mussel Bathymodiolus azoricus.

    PubMed

    Martins, Inês; Romão, Célia V; Goulart, Joana; Cerqueira, Teresa; Santos, Ricardo S; Bettencourt, Raul

    2016-03-01

    Deep sea hydrothermal Bathymodiolus azoricus mussels from Portuguese EEZ Menez Gwen hydrothermal field possess the remarkable ability to overcome decompression and survive successfully at atmospheric pressure conditions. We investigated the potential use of antioxidant defense enzymes in mussel B. azoricus as biomarkers of oxidative stress induced by long term acclimatization to atmospheric pressure conditions. Mussels collected at Menez Gwen hydrothermal field were acclimatized for two weeks in three distinct conditions suitable of promoting physiological stress, (i) in plain seawater for concomitant endosymbiont bacteria loss, (ii) in plain seawater under metal iron exposure, (iii) constant bubbling methane and pumped sulfide for endosymbiont bacteria survival. The enzymatic activities of superoxide dismutase (SOD), catalase (CAT), and iron storage proteins in addition to electrophoretic profiles were examined in vent mussel gills and digestive gland. Gills showed approximately 3 times more SOD specific activity than digestive glands. On the other hand, digestive glands showed approximately 6 times more CAT specific activity than gills. Iron storage proteins were identified in gill extracts from all experimental conditions mussels. However, in digestive gland extracts only fresh collected mussels and after 2 weeks in FeSO4 showed the presence of iron storage proteins. The differences between SOD, CAT specific activities and the presence of iron storage proteins in the examined tissues reflect dissimilar metabolic and antioxidant activities, as a result of tissue specificities and acclimatization conditions influences on the organism. PMID:26790096

  9. Transcriptional responses of Arabidopsis thaliana plants to As (V) stress

    PubMed Central

    Abercrombie, Jason M; Halfhill, Matthew D; Ranjan, Priya; Rao, Murali R; Saxton, Arnold M; Yuan, Joshua S; Stewart, C Neal

    2008-01-01

    Background Arsenic is toxic to plants and a common environmental pollutant. There is a strong chemical similarity between arsenate [As (V)] and phosphate (Pi). Whole genome oligonucleotide microarrays were employed to investigate the transcriptional responses of Arabidopsis thaliana plants to As (V) stress. Results Antioxidant-related genes (i.e. coding for superoxide dismutases and peroxidases) play prominent roles in response to arsenate. The microarray experiment revealed induction of chloroplast Cu/Zn superoxide dismutase (SOD) (at2g28190), Cu/Zn SOD (at1g08830), as well as an SOD copper chaperone (at1g12520). On the other hand, Fe SODs were strongly repressed in response to As (V) stress. Non-parametric rank product statistics were used to detect differentially expressed genes. Arsenate stress resulted in the repression of numerous genes known to be induced by phosphate starvation. These observations were confirmed with qRT-PCR and SOD activity assays. Conclusion Microarray data suggest that As (V) induces genes involved in response to oxidative stress and represses transcription of genes induced by phosphate starvation. This study implicates As (V) as a phosphate mimic in the cell by repressing genes normally induced when available phosphate is scarce. Most importantly, these data reveal that arsenate stress affects the expression of several genes with little or unknown biological functions, thereby providing new putative gene targets for future research. PMID:18684332

  10. Brain activation induced by psychological stress in patients with schizophrenia.

    PubMed

    Castro, M N; Villarreal, M F; Bolotinsky, N; Papávero, E; Goldschmidt, M G; Costanzo, E Y; Drucaroff, L; Wainsztein, A; de Achával, D; Pahissa, J; Bär, K-J; Nemeroff, C B; Guinjoan, S M

    2015-10-01

    Environmental influences are critical for the expression of genes putatively related to the behavioral and cognitive phenotypes of schizophrenia. Among such factors, psychosocial stress has been proposed to play a major role in the expression of symptoms. However, it is unsettled how stress interacts with pathophysiological pathways to produce the disease. We studied 21 patients with schizophrenia and 21 healthy controls aged 18 to 50years with 3T-fMRI, in which a period of 6min of resting state acquisition was followed by a block design, with three blocks of 1-min control-task, 1-min stress-task and 1-min rest after-task. Self-report of stress and PANSS were measured. Limbic structures were activated in schizophrenia patients by simple tasks and remained active during, and shortly after stress. In controls, stress-related brain activation was more time-focused, and restricted to the stressful task itself. Negative symptom severity was inversely related to activation of anterior cingulum and orbitofrontal cortex. Results might represent the neurobiological aspect of hyper-reactivity to normal stressful situations previously described in schizophrenia, thus providing evidence on the involvement of limbic areas in the response to stress in schizophrenia. Patients present a pattern of persistent limbic activation probably contributing to hypervigilance and subsequent psychotic thought distortions. PMID:26190301

  11. Erythropoietin Action in Stress Response, Tissue Maintenance and Metabolism

    PubMed Central

    Zhang, Yuanyuan; Wang, Li; Dey, Soumyadeep; Alnaeeli, Mawadda; Suresh, Sukanya; Rogers, Heather; Teng, Ruifeng; Noguchi, Constance Tom

    2014-01-01

    Erythropoietin (EPO) regulation of red blood cell production and its induction at reduced oxygen tension provides for the important erythropoietic response to ischemic stress. The cloning and production of recombinant human EPO has led to its clinical use in patients with anemia for two and half decades and has facilitated studies of EPO action. Reports of animal and cell models of ischemic stress in vitro and injury suggest potential EPO benefit beyond red blood cell production including vascular endothelial response to increase nitric oxide production, which facilitates oxygen delivery to brain, heart and other non-hematopoietic tissues. This review discusses these and other reports of EPO action beyond red blood cell production, including EPO response affecting metabolism and obesity in animal models. Observations of EPO activity in cell and animal model systems, including mice with tissue specific deletion of EPO receptor (EpoR), suggest the potential for EPO response in metabolism and disease. PMID:24918289

  12. Erythropoietin action in stress response, tissue maintenance and metabolism.

    PubMed

    Zhang, Yuanyuan; Wang, Li; Dey, Soumyadeep; Alnaeeli, Mawadda; Suresh, Sukanya; Rogers, Heather; Teng, Ruifeng; Noguchi, Constance Tom

    2014-01-01

    Erythropoietin (EPO) regulation of red blood cell production and its induction at reduced oxygen tension provides for the important erythropoietic response to ischemic stress. The cloning and production of recombinant human EPO has led to its clinical use in patients with anemia for two and half decades and has facilitated studies of EPO action. Reports of animal and cell models of ischemic stress in vitro and injury suggest potential EPO benefit beyond red blood cell production including vascular endothelial response to increase nitric oxide production, which facilitates oxygen delivery to brain, heart and other non-hematopoietic tissues. This review discusses these and other reports of EPO action beyond red blood cell production, including EPO response affecting metabolism and obesity in animal models. Observations of EPO activity in cell and animal model systems, including mice with tissue specific deletion of EPO receptor (EpoR), suggest the potential for EPO response in metabolism and disease. PMID:24918289

  13. Dopamine signaling promotes the xenobiotic stress response and protein homeostasis.

    PubMed

    Joshi, Kishore K; Matlack, Tarmie L; Rongo, Christopher

    2016-09-01

    Multicellular organisms encounter environmental conditions that adversely affect protein homeostasis (proteostasis), including extreme temperatures, toxins, and pathogens. It is unclear how they use sensory signaling to detect adverse conditions and then activate stress response pathways so as to offset potential damage. Here, we show that dopaminergic mechanosensory neurons in C. elegans release the neurohormone dopamine to promote proteostasis in epithelia. Signaling through the DA receptor DOP-1 activates the expression of xenobiotic stress response genes involved in pathogenic resistance and toxin removal, and these genes are required for the removal of unstable proteins in epithelia. Exposure to a bacterial pathogen (Pseudomonas aeruginosa) results in elevated removal of unstable proteins in epithelia, and this enhancement requires DA signaling. In the absence of DA signaling, nematodes show increased sensitivity to pathogenic bacteria and heat-shock stress. Our results suggest that dopaminergic sensory neurons, in addition to slowing down locomotion upon sensing a potential bacterial feeding source, also signal to frontline epithelia to activate the xenobiotic stress response so as to maintain proteostasis and prepare for possible infection. PMID:27261197

  14. Methylation of NR3C1 is related to maternal PTSD, parenting stress and maternal medial prefrontal cortical activity in response to child separation among mothers with histories of violence exposure

    PubMed Central

    Schechter, Daniel S.; Moser, Dominik A.; Paoloni-Giacobino, Ariane; Stenz, Ludwig; Gex-Fabry, Marianne; Aue, Tatjana; Adouan, Wafae; Cordero, María I.; Suardi, Francesca; Manini, Aurelia; Sancho Rossignol, Ana; Merminod, Gaëlle; Ansermet, Francois; Dayer, Alexandre G.; Rusconi Serpa, Sandra

    2015-01-01

    Prior research has shown that mothers with Interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) report greater difficulty in parenting their toddlers. Relative to their frequent early exposure to violence and maltreatment, these mothers display dysregulation of their hypothalamic pituitary adrenal axis (HPA-axis), characterized by hypocortisolism. Considering methylation of the promoter region of the glucocorticoid receptor gene NR3C1 as a marker for HPA-axis functioning, with less methylation likely being associated with less circulating cortisol, the present study tested the hypothesis that the degree of methylation of this gene would be negatively correlated with maternal IPV-PTSD severity and parenting stress, and positively correlated with medial prefrontal cortical (mPFC) activity in response to video-stimuli of stressful versus non-stressful mother–child interactions. Following a mental health assessment, 45 mothers and their children (ages 12–42 months) participated in a behavioral protocol involving free-play and laboratory stressors such as mother–child separation. Maternal DNA was extracted from saliva. Interactive behavior was rated on the CARE-Index. During subsequent fMRI scanning, mothers were shown films of free-play and separation drawn from this protocol. Maternal PTSD severity and parenting stress were negatively correlated with the mean percentage of methylation of NR3C1. Maternal mPFC activity in response to video-stimuli of mother–child separation versus play correlated positively to NR3C1 methylation, and negatively to maternal IPV-PTSD and parenting stress. Among interactive behavior variables, child cooperativeness in play was positively correlated with NR3C1 methylation. Thus, the present study is the first published report to our knowledge, suggesting convergence of behavioral, epigenetic, and neuroimaging data that form a psychobiological signature of parenting-risk in the context of early life stress and PTSD

  15. Stressed out? Associations between perceived and physiological stress responses in adolescents: the TRAILS study.

    PubMed

    Oldehinkel, Albertine J; Ormel, Johan; Bosch, Nienke M; Bouma, Esther M C; Van Roon, Arie M; Rosmalen, Judith G M; Riese, Harriëtte

    2011-04-01

    Studies regarding the interrelation of perceived and physiological stress indices have shown diverging results. Using a population sample of adolescents (N=715, 50.9% girls, mean age 16.11 years, SD=0.59), we tested three hypotheses: (1) perceived responses during social stress covary with concurrent physiological stress responses; (2) high pretest levels of perceived stress predict large physiological responses; and (3) large physiological responses to social stress predict low posttest perceived stress levels. Perceived arousal, unpleasantness, and dominance were related to heart rate, respiratory sinus arrhythmia, and cortisol responses to a laboratory social stress test. Although effect sizes were small, the results suggest covariation of perceived stress and concurrent physiological stress responses in both the ANS and the HPA axis, as well as inverse associations between heart rate responsiveness and the subsequent appraisal of stress. PMID:21361964

  16. Enterovirus Control of Translation and RNA Granule Stress Responses

    PubMed Central

    Lloyd, Richard E.

    2016-01-01

    Enteroviruses such as poliovirus (PV) and coxsackievirus B3 (CVB3) have evolved several parallel strategies to regulate cellular gene expression and stress responses to ensure efficient expression of the viral genome. Enteroviruses utilize their encoded proteinases to take over the cellular translation apparatus and direct ribosomes to viral mRNAs. In addition, viral proteinases are used to control and repress the two main types of cytoplasmic RNA granules, stress granules (SGs) and processing bodies (P-bodies, PBs), which are stress-responsive dynamic structures involved in repression of gene expression. This review discusses these processes and the current understanding of the underlying mechanisms with respect to enterovirus infections. In addition, the review discusses accumulating data suggesting linkage exists between RNA granule formation and innate immune sensing and activation. PMID:27043612

  17. Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish.

    PubMed

    Christen, Verena; Capelle, Martinus; Fent, Karl

    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 6h and 24h 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 5mg/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 24h at 0.1 and 5mg/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. PMID:23800688

  18. Exploiting the yeast stress-activated signaling network to inform on stress biology and disease signaling

    PubMed Central

    Ho, Yi-Hsuan

    2016-01-01

    Healthy cells utilize intricate systems to monitor their environment and mount robust responses in the event of cellular stress. Whether stress arises from external insults or defects due to mutation and disease, cells must be able to respond precisely to mount the appropriate defenses. Multi-faceted stress responses are generally coupled with arrest of growth and cell-cycle progression, which both limits the transmission of damaged materials and serves to reallocate limited cellular resources toward defense. Therefore, stress defense versus rapid growth represent competing interests in the cell. How eukaryotic cells set the balance between defense versus proliferation, and in particular knowledge of the regulatory networks that control this decision, are poorly understood. In this perspective, we expand upon our recent work inferring the stress-activated signaling network in budding yeast, which captures pathways controlling stress defense and regulators of growth and cell-cycle progression. We highlight similarities between the yeast and mammalian stress responses and explore how stress-activated signaling networks in yeast can inform on signaling defects in human cancers. PMID:25957506

  19. Anger responses to psychosocial stress predict heart rate and cortisol stress responses in men but not women

    PubMed Central

    Lupis, Sarah B.; Lerman, Michelle; Wolf, Jutta M.

    2014-01-01

    While previous research has suggested that anger and fear responses to stress are linked to distinct sympathetic nervous system (SNS) stress responses, little is known about how these emotions predict hypothalamus-pituitary-adrenal (HPA) axis reactivity. Further, earlier research primarily relied on retrospective self-report of emotion. The current study aimed at addressing both issues in male and female individuals by assessing the role of anger and fear in predicting heart rate and cortisol stress responses using both self-report and facial coding analysis to assess emotion responses. We exposed 32 healthy students (18 female; 19.6+/−1.7 yrs.) to an acute psychosocial stress paradigm (TSST) and measured heart rate and salivary cortisol levels throughout the protocol. Anger and fear before and after stress exposure was assessed by self-report, and video recordings of the TSST were assessed by a certified facial coder to determine emotion expression (FACS). Self-reported emotions and emotion expressions did not correlate (all p > .23). Increases in self-reported fear predicted blunted cortisol responses in men (β = 0.41, p = .04). Also for men, longer durations of anger expression predicted exaggerated cortisol responses (β = 0.67 p = .004), and more anger incidences predicted exaggerated cortisol and heart rate responses (β = 0.51, p = .033; β = 0.46, p = .066, resp.). Anger and fear did not predict SNS or HPA activity for females (all p > .23). The current differential self-report and facial coding findings support the use of multiple modes of emotion assessment. Particularly, FACS but not self-report revealed a robust anger-stress association that could have important downstream health effects for men. For women, future research may clarify the role of other emotions, such as self-conscious expressions of shame, for physiological stress responses. A better understanding of the emotion-stress link may contribute to behavioral interventions targeting health

  20. Alternative strategy for Alzheimer's disease: stress response triggers.

    PubMed

    Smith Sonneborn, Joan

    2012-01-01

    Stress resistance capacity is a hallmark of longevity protection and survival throughout the plant and animal kingdoms. Latent pathway activation of protective cascades, triggered by environmental challenges to tolerate heat, oxygen deprivation, reactive oxygen species (ROS), diet restriction, and exercise provides tolerance to these stresses. Age-related changes and disease vulnerability mark an increase in damage, like damage induced by environmental challenges. An alternative approach to immunotherapy intervention in Alzheimer's Disease is the use of mimetics of stress to upregulate endogenous protective cascades to repair age damage, shift the balance of apoptosis to regeneration to promote delay of onset, and even progression of Alzheimer's disease memory dysfunction. Mimetics of environmental stress, hormetic agents, and triggers, endogenous or engineered, can "trick" activation of expression patterns of repair and rejuvenation. Examples of known candidate triggers of heat response, endogenous antioxidants, DNA repair, exercise, hibernation, and telomeres are available for AD intervention trials. Telomeres and telomerase emerge as major regulators in crossroads of senescence, cancer, and rejuvenation responsive to mimetics of telomeres. Lessons emerge from transgenic rodent models, the long-lived mole rat, clinical studies, and conserved innate pathways of stress resistance. Cross-reaction of benefits of different triggers promises intervention into seemingly otherwise unrelated diseases. PMID:22655213

  1. LTR retrotransposons, handy hitchhikers of plant regulation and stress response.

    PubMed

    Grandbastien, Marie-Angèle

    2015-04-01

    LTR retrotransposons are major components of plant genomes. They are regulated by a diverse array of external stresses and tissue culture conditions, displaying finely tuned responses to these stimuli, mostly in the form of upregulation. Second to stress conditions and tissue culture, meristems are also permissive for LTR retrotransposon expression, suggesting that a dedifferentiated cell status may represent a frequent activating condition. LTR regions are highly plastic and contain regulatory motifs similar to those of cellular genes. The activation of LTR retrotransposons results from interplay between the release of epigenetic silencing and the recruitment by LTRs of specific regulatory factors. Despite the role of LTR retrotransposons in driving plant genome diversification, convincing evidence for major mobilizations of LTR retrotransposons remains much rarer than observations of massive bursts of transcriptional upregulation. Current evidence suggests that LTR retrotransposon expression may be involved in host functional plasticity, acting as dispersed regulatory modules able to redirect stress stimuli to adjacent plant genes. This may be of crucial importance for plants that cannot escape stress, and have evolved complex and highly coordinated responses to external challenges. This article is part of a Special Issue entitled: Stress as a fundamental theme in cell plasticity. PMID:25086340

  2. Social stress, autonomic neural activation, and cardiac activity in rats.

    PubMed

    Sgoifo, A; Koolhaas, J; De Boer, S; Musso, E; Stilli, D; Buwalda, B; Meerlo, P

    1999-11-01

    Animal models of social stress represent a useful experimental tool to investigate the relationship between psychological stress, autonomic neural activity and cardiovascular disease. This paper summarizes the results obtained in a series of experiments performed on rats and aimed at verifying whether social challenges produce specific modifications in the autonomic neural control of heart rate and whether these changes can be detrimental for cardiac electrical stability. Short-term electrocardiographic recordings were performed via radiotelemetry and the autonomic input to the heart evaluated by means of time-domain heart rate variability measures. Compared to other stress contexts, a social defeat experience produces a strong shift of autonomic balance toward sympathetic dominance, poorly antagonized by vagal rebound, and associated with the occurrence of cardiac tachyarrhythmias. These effects were particularly severe when a wild-type strain of rats was studied. The data also suggest that the cardiac autonomic responses produced by different types of social contexts (dominant-subordinate interaction, dominant-dominant confrontation, social defeat) are related to different degrees of emotional activation, which in turn are likely modulated by the social rank of the experimental animal and the opponent, the prior experience with the stressor, and the level of controllability over the stimulus. PMID:10580306

  3. The Cold Signaling Attenuator HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1 Activates FLOWERING LOCUS C Transcription via Chromatin Remodeling under Short-Term Cold Stress in Arabidopsis[C][W

    PubMed Central

    Jung, Jae-Hoon; Park, Ju-Hyung; Lee, Sangmin; To, Taiko Kim; Kim, Jong-Myong; Seki, Motoaki; Park, Chung-Mo

    2013-01-01

    Exposure to short-term cold stress delays flowering by activating the floral repressor FLOWERING LOCUS C (FLC) in Arabidopsis thaliana. The cold signaling attenuator HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1 (HOS1) negatively regulates cold responses. Notably, HOS1-deficient mutants exhibit early flowering, and FLC expression is suppressed in the mutants. However, it remains unknown how HOS1 regulates FLC expression. Here, we show that HOS1 induces FLC expression by antagonizing the actions of FVE and its interacting partner histone deacetylase 6 (HDA6) under short-term cold stress. HOS1 binds to FLC chromatin in an FVE-dependent manner, and FVE is essential for the HOS1-mediated activation of FLC transcription. HOS1 also interacts with HDA6 and inhibits the binding of HDA6 to FLC chromatin. Intermittent cold treatments induce FLC expression by activating HOS1, which attenuates the activity of HDA6 in silencing FLC chromatin, and the effects of intermittent cold are diminished in hos1 and fve mutants. These observations indicate that HOS1 acts as a chromatin remodeling factor for FLC regulation under short-term cold stress. PMID:24220632

  4. A Trichoderma atroviride stress-activated MAPK pathway integrates stress and light signals.

    PubMed

    Esquivel-Naranjo, Edgardo Ulises; García-Esquivel, Mónica; Medina-Castellanos, Elizabeth; Correa-Pérez, Víctor Alejandro; Parra-Arriaga, Jorge Luis; Landeros-Jaime, Fidel; Cervantes-Chávez, José Antonio; Herrera-Estrella, Alfredo

    2016-06-01

    Cells possess stress-activated protein kinase (SAPK) signalling pathways, which are activated practically in response to any cellular insult, regulating responses for survival and adaptation to harmful environmental changes. To understand the function of SAPK pathways in T. atroviride, mutants lacking the MAPKK Pbs2 and the MAPK Tmk3 were analysed under several cellular stresses, and in their response to light. All mutants were highly sensitive to cellular insults such as osmotic and oxidative stress, cell wall damage, high temperature, cadmium, and UV irradiation. Under oxidative stress, the Tmk3 pathway showed specific roles during development, which in conidia are essential for tolerance to oxidant agents and appear to play a minor role in mycelia. The function of this pathway was more evident in Δpbs2 and Δtmk3 mutant strains when combining oxidative stress or cell wall damage with light. Light stimulates tolerance to osmotic stress through Tmk3 independently of the photoreceptor Blr1. Strikingly, photoconidiation and expression of blue light regulated genes was severally affected in Δtmk3 and Δpbs2 strains, indicating that this pathway regulates light responses. Furthermore, Tmk3 was rapidly phosphorylated upon light exposure. Thus, our data indicate that Tmk3 signalling cooperates with the Blr photoreceptor complex in the activation of gene expression. PMID:26878111

  5. Aldehyde dehydrogenases in cellular responses to oxidative/electrophilic stress.

    PubMed

    Singh, Surendra; Brocker, Chad; Koppaka, Vindhya; Chen, Ying; Jackson, Brian C; Matsumoto, Akiko; Thompson, David C; Vasiliou, Vasilis

    2013-03-01

    Reactive oxygen species (ROS) are continuously generated within living systems and the inability to manage ROS load leads to elevated oxidative stress and cell damage. Oxidative stress is coupled to the oxidative degradation of lipid membranes, also known as lipid peroxidation. This process generates over 200 types of aldehydes, many of which are highly reactive and toxic. Aldehyde dehydrogenases (ALDHs) metabolize endogenous and exogenous aldehydes and thereby mitigate oxidative/electrophilic stress in prokaryotic and eukaryotic organisms. ALDHs are found throughout the evolutionary gamut, from single-celled organisms to complex multicellular species. Not surprisingly, many ALDHs in evolutionarily distant, and seemingly unrelated, species perform similar functions, including protection against a variety of environmental stressors such as dehydration and ultraviolet radiation. The ability to act as an "aldehyde scavenger" during lipid peroxidation is another ostensibly universal ALDH function found across species. Upregulation of ALDHs is a stress response in bacteria (environmental and chemical stress), plants (dehydration, salinity, and oxidative stress), yeast (ethanol exposure and oxidative stress), Caenorhabditis elegans (lipid peroxidation), and mammals (oxidative stress and lipid peroxidation). Recent studies have also identified ALDH activity as an important feature of cancer stem cells. In these cells, ALDH expression helps abrogate oxidative stress and imparts resistance against chemotherapeutic agents such as oxazaphosphorine, taxane, and platinum drugs. The ALDH superfamily represents a fundamentally important class of enzymes that contributes significantly to the management of electrophilic/oxidative stress within living systems. Mutations in various ALDHs are associated with a variety of pathological conditions in humans, highlighting the fundamental importance of these enzymes in physiological and pathological processes. PMID:23195683

  6. Cannibalism stress response in Bacillus subtilis.

    PubMed

    Höfler, Carolin; Heckmann, Judith; Fritsch, Anne; Popp, Philipp; Gebhard, Susanne; Fritz, Georg; Mascher, Thorsten

    2016-01-01

    When faced with carbon source limitation, the Gram-positive soil organism Bacillus subtilis initiates a survival strategy called sporulation, which leads to the formation of highly resistant endospores that allow B. subtilis to survive even long periods of starvation. In order to avoid commitment to this energy-demanding and irreversible process, B. subtilis employs another strategy called 'cannibalism' to delay sporulation as long as possible. Cannibalism involves the production and secretion of two cannibalism toxins, sporulation delaying protein (SDP) and sporulation killing factor (SKF), which are able to lyse sensitive siblings. The lysed cells are thought to then provide nutrients for the cannibals to slow down or even prevent them from entering sporulation. In this study, we uncovered the role of the cell envelope stress response (CESR), especially the Bce-like antimicrobial peptide detoxification modules, in the cannibalism stress response during the stationary phase. SDP and SKF specifically induce Bce-like systems and some extracytoplasmic function σ factors in stationary-phase cultures, but only the latter provide some degree of protection. A full Bce response is only triggered by mature toxins, and not by toxin precursors. Our study provides insights into the close relationship between stationary-phase survival and the CESR of B. subtilis. PMID:26364265

  7. Molecular characterization and expression of AMP-activated protein kinase in response to low-salinity stress in the Pacific white shrimp Litopenaeus vannamei.

    PubMed

    Xu, Chang; Li, Erchao; Xu, Zhixin; Wang, Shifeng; Chen, Ke; Wang, Xiaodan; Li, Tongyu; Qin, Jian G; Chen, Liqiao

    2016-08-01

    AMP-activated protein kinase (AMPK) serves as a major regulator of cellular energy metabolism by activating ATP production pathways and blocking ATP consumption. However, information on AMPK genes in aquatic animals is limited. In this study, three subunits of AMPK were cloned from the Pacific white shrimp Litopenaeus vannamei. The full-length cDNAs of the α, β and γ subunits were 1617, 1243 and 3467bp long, respectively, with open reading frames of 1566, 873 and 2988bp encoding for 521, 290 and 996 amino acids, respectively. Amino acid sequence alignments of the three subunits showed that the functional domains in the L. vannamei proteins retained the highest similarity with those of other animals, at 89%, 58%, and 75%, respectively. The expression levels of the three subunits were higher in the muscle and gills than in the eyestalk and hepatopancreas. The mRNA levels of AMPK-α and AMPK-β were up-regulated in the hepatopancreas and muscle after acute low-salinity stress at 3psu for 6h compared with control salinity at 20psu. After 8-week salinity stress at 3psu, AMPK-α and AMPK-β mRNA levels in the hepatopancreas were significantly higher than those of the control at 30psu. However, in the muscle only AMPK-γ mRNA was significantly up-regulated at low salinity relative to controls. Muscle and hepatopancreas showed increases in AMPK protein after 6h exposure to low salinity, but there were no differences seen after long term acclimation. The change patterns of protein were slightly differing from the mRNA patterns due to the distinguishing function of individual subunits of AMPK. These findings confirm that three AMPK subunits are present in L. vannamei and that all encode proteins with conserved functional domains. The three AMPK subunits are all regulated at the transcriptional and protein levels to manage excess energy expenditure during salinity stress. PMID:27095693

  8. Waterborne Risperidone Decreases Stress Response in Zebrafish

    PubMed Central

    Kalichak, Fabiana; Rosa, João Gabriel Santos; de Oliveira, Tiago Acosta; Koakoski, Gessi; Gusso, Darlan; de Abreu, Murilo Sander; Giacomini, Ana Cristina Varrone; Barcellos, Heloísa Helena de Alcântara

    2015-01-01

    The presence of drugs and their metabolites in surface waters and municipal effluents has been reported in several studies, but its impacts on aquatic organisms are not yet well understood. This study investigated the effects of acute exposure to the antipsychotic risperidone on the stress and behavioral responses in zebrafish. It became clear that intermediate concentration of risperidone inhibited the hypothalamic-pituitary-interrenal axis and displayed anxiolytic-like effects in zebrafish. The data presented here suggest that the presence of this antipsychotic in aquatic environments can alter neuroendocrine and behavior profiles in zebrafish. PMID:26473477

  9. Oxidative Stress Contributes to Autophagy Induction in Response to Endoplasmic Reticulum Stress in Chlamydomonas reinhardtii1[W

    PubMed Central

    Pérez-Martín, Marta; Pérez-Pérez, María Esther; Lemaire, Stéphane D.; Crespo, José L.

    2014-01-01

    The accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER) results in the activation of stress responses, such as the unfolded protein response or the catabolic process of autophagy to ultimately recover cellular homeostasis. ER stress also promotes the production of reactive oxygen species, which play an important role in autophagy regulation. However, it remains unknown whether reactive oxygen species are involved in ER stress-induced autophagy. In this study, we provide evidence connecting redox imbalance caused by ER stress and autophagy activation in the model unicellular green alga Chlamydomonas reinhardtii. Treatment of C. reinhardtii cells with the ER stressors tunicamycin or dithiothreitol resulted in up-regulation of the expression of genes encoding ER resident endoplasmic reticulum oxidoreductin1 oxidoreductase and protein disulfide isomerases. ER stress also triggered autophagy in C. reinhardtii based on the protein abundance, lipidation, cellular distribution, and mRNA levels of the autophagy marker ATG8. Moreover, increases in the oxidation of the glutathione pool and the expression of oxidative stress-related genes were detected in tunicamycin-treated cells. Our results revealed that the antioxidant glutathione partially suppressed ER stress-induced autophagy and decreased the toxicity of tunicamycin, suggesting that oxidative stress participates in the control of autophagy in response to ER stress in C. reinhardtii In close agreement, we also found that autophagy activation by tunicamycin was more pronounced in the C. reinhardtii sor1 mutant, which shows increased expression of oxidative stress-related genes. PMID:25143584

  10. Cloning of PEPC-1 from a C4 halophyte Suaeda aralocaspica without Kranz anatomy and its recombinant enzymatic activity in responses to abiotic stresses.

    PubMed

    Cheng, Gang; Wang, Lu; Lan, Haiyan

    2016-02-01

    Phosphoenolpyruvate carboxylase (PEPC) is a key enzyme of C4 photosynthetic pathway and plays an important biochemical role in higher plants and micro organisms. To gain understanding of the role of PEPC in stress adaptation in plant, we cloned PEPC gene from Suaeda aralocaspica, a C4 species without Kranz anatomy, and performed a series of experiments with PEPC gene expressed in Escherichia coli under various abiotic stresses. Results showed that, based on the homology cloning and 5'-RACE technique, the full-length cDNA sequence of PEPC (2901 bp) from S. aralocaspica was obtained, which shares the typical conserved domains to documented PEPCs and was identified as PEPC-1 in accord to the reported partial sequence (ppc-1) in S. aralocaspica. qRT-PCR analysis revealed the expression patterns of PEPC-1 and PEPC-2 (known as ppc-2, another plant type of PEPC) in S. aralocaspica, suggesting that PEPC-1 was up-regulated during seed germination and under NaCl stress, and presented higher level in chlorenchyma than other tissues, which were significantly different with PEPC-2. Afterwards, PEPC-1 was recombinant in E. coli (pET-28a-PEPC) and expressed as an approximate 110 kDa protein. Under various abiotic stresses, the recombinant E. coli strain harboring with PEPC-1 showed significant advantage in growth at 400-800 mmol L(-1) NaCl, 10-20% PEG6000, 25 and 30 °C lower temperature, 50-200 μmol L(-1) methyl viologen, and pH 5.0 and 9.0 condition, compared to control. Further analysis of the enzymatic characteristics of the recombinant PEPC-1 suggests that it was the higher enzyme activity of PEPC-1 which might confer the stress tolerance to E. coli. We speculate that over expression of PEPC-1 is probably related to regulation of oxaloacetate (OAA) in tricarboxylic acid (TCA) cycle in E. coli, which may contribute to further understanding of the physiological function of PEPC in S. aralocaspica. PMID:26777251

  11. Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish

    SciTech Connect

    Christen, Verena; Capelle, Martinus; Fent, Karl

    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.

  12. Chronic psychological stress activates BMP4-dependent extramedullary erythropoiesis.

    PubMed

    Vignjević, Sanja; Budeč, Mirela; Marković, Dragana; Dikić, Dragoslava; Mitrović, Olivera; Mojsilović, Slavko; Durić, Sanja Vranješ; Koko, Vesna; Cokić, Bojana Beleslin; Cokić, Vladan; Jovčić, Gordana

    2014-01-01

    Psychological stress affects different physiological processes including haematopoiesis. However, erythropoietic effects of chronic psychological stress remain largely unknown. The adult spleen contains a distinct microenvironment favourable for rapid expansion of erythroid progenitors in response to stressful stimuli, and emerging evidence suggests that inappropriate activation of stress erythropoiesis may predispose to leukaemic transformation. We used a mouse model to study the influence of chronic psychological stress on erythropoiesis in the spleen and to investigate potential mediators of observed effects. Adult mice were subjected to 2 hrs daily restraint stress for 7 or 14 consecutive days. Our results showed that chronic exposure to restraint stress decreased the concentration of haemoglobin in the blood, elevated circulating levels of erythropoietin and corticosterone, and resulted in markedly increased number of erythroid progenitors and precursors in the spleen. Western blot analysis revealed significantly decreased expression of both erythropoietin receptor and glucocorticoid receptor in the spleen of restrained mice. Furthermore, chronic stress enhanced the expression of stem cell factor receptor in the red pulp. Moreover, chronically stressed animals exhibited significantly increased expression of bone morphogenetic protein 4 (BMP4) in the red pulp as well as substantially enhanced mRNA expression levels of its receptors in the spleen. These findings demonstrate for the first time that chronic psychological stress activates BMP4-dependent extramedullary erythropoiesis and leads to the prolonged activation of stress erythropoiesis pathways. Prolonged activation of these pathways along with an excessive production of immature erythroid cells may predispose chronically stressed subjects to a higher risk of leukaemic transformation. PMID:24283209

  13. Left brain cortical activity modulates stress effects on social behavior.

    PubMed

    Lee, Eunee; Hong, Jiso; Park, Young-Gyun; Chae, Sujin; Kim, Yong; Kim, Daesoo

    2015-01-01

    When subjected to stress, some individuals develop maladaptive symptoms whereas others retain normal behavior. The medial prefrontal cortex (mPFC) is known to control these adaptive responses to stress. Here, we show that mPFC neurons in the left hemisphere control stress effects on social behavior. Mice made socially avoidant by the stress of chronic social defeats showed depressed neural activity in the left mPFC. Photoactivation of these neurons reversed social avoidance and restored social activity. Despite social defeats, resilient mice with normal sociability showed normal firing rates in the left mPFC; however, photoinhibition of these neurons induced social avoidance. The same photomodulation administered to the right mPFC caused no significant effects. These results explain how stressed individuals develop maladaptive behaviors through left cortical depression, as reported in mood and anxiety disorders. PMID:26302668

  14. Left brain cortical activity modulates stress effects on social behavior

    PubMed Central

    Lee, Eunee; Hong, Jiso; Park, Young-Gyun; Chae, Sujin; Kim, Yong; Kim, Daesoo

    2015-01-01

    When subjected to stress, some individuals develop maladaptive symptoms whereas others retain normal behavior. The medial prefrontal cortex (mPFC) is known to control these adaptive responses to stress. Here, we show that mPFC neurons in the left hemisphere control stress effects on social behavior. Mice made socially avoidant by the stress of chronic social defeats showed depressed neural activity in the left mPFC. Photoactivation of these neurons reversed social avoidance and restored social activity. Despite social defeats, resilient mice with normal sociability showed normal firing rates in the left mPFC; however, photoinhibition of these neurons induced social avoidance. The same photomodulation administered to the right mPFC caused no significant effects. These results explain how stressed individuals develop maladaptive behaviors through left cortical depression, as reported in mood and anxiety disorders. PMID:26302668

  15. Xenohormesis: health benefits from an eon of plant stress response evolution

    PubMed Central

    Hooper, Paul L.; Tytell, Michael; Vígh, Lászlo

    2010-01-01

    Xenohormesis is a biological principle that explains how environmentally stressed plants produce bioactive compounds that can confer stress resistance and survival benefits to animals that consume them. Animals can piggyback off products of plants' sophisticated stress response which has evolved as a result of their stationary lifestyle. Factors eliciting the plant stress response can judiciously be employed to maximize yield of health-promoting plant compounds. The xenohormetic plant compounds can, when ingested, improve longevity and fitness by activating the animal's cellular stress response and can be applied in drug discovery, drug production, and nutritional enhancement of diet. PMID:20524162

  16. Role of various hormones in photosynthetic responses of green plants under environmental stresses.

    PubMed

    Poonam; Bhardwaj, Renu; Kaur, Ravdeep; Bali, Shagun; Kaur, Parminder; Sirhindi, Geetika; Thukral, Ashwani K; Ohri, Puja; Vig, Adarsh P

    2015-01-01

    Environmental stress includes adverse factors like water deficit, high salinity, enhanced temperature and heavy metals etc. These stresses alter the normal growth and metabolic processes of plants including photosynthesis. Major photosynthetic responses under various stresses include inhibition of photosystems (I and II), changes in thylakoid complexes, decreased photosynthetic activity and modifications in structure and functions of chloroplasts etc. Various defense mechanisms are triggered inside the plants in response to these stresses that are regulated by plant hormones or plant growth regulators. These phytohormones include abscisic acid, auxins, cytokinins, ethylene, brassinosteroids, jasmonates and salicylic acid etc. The present review focuses on stress protective effects of plants hormones on the photosynthetic responses. PMID:25824389

  17. Chromatin changes in response to drought, salinity, heat, and cold stresses in plants

    PubMed Central

    Kim, Jong-Myong; Sasaki, Taku; Ueda, Minoru; Sako, Kaori; Seki, Motoaki

    2015-01-01

    Chromatin regulation is essential to regulate genes and genome activities. In plants, the alteration of histone modification and DNA methylation are coordinated with changes in the expression of stress-responsive genes to adapt to environmental changes. Several chromatin regulators have been shown to be involved in the regulation of stress-responsive gene networks under abiotic stress conditions. Specific histone modification sites and the histone modifiers that regulate key stress-responsive genes have been identified by genetic and biochemical approaches, revealing the importance of chromatin regulation in plant stress responses. Recent studies have also suggested that histone modification plays an important role in plant stress memory. In this review, we summarize recent progress on the regulation and alteration of histone modification (acetylation, methylation, phosphorylation, and SUMOylation) in response to the abiotic stresses, drought, high-salinity, heat, and cold in plants. PMID:25784920

  18. Cytokinin cross-talking during biotic and abiotic stress responses

    PubMed Central

    O’Brien, José A.; Benková, Eva

    2013-01-01

    As sessile organisms, plants have to be able to adapt to a continuously changing environment. Plants that perceive some of these changes as stress signals activate signaling pathways to modulate their development and to enable them to survive. The complex responses to environmental cues are to a large extent mediated by plant hormones that together orchestrate the final plant response. The phytohormone cytokinin is involved in many plant developmental processes. Recently, it has been established that cytokinin plays an important role in stress responses, but does not act alone. Indeed, the hormonal control of plant development and stress adaptation is the outcome of a complex network of multiple synergistic and antagonistic interactions between various hormones. Here, we review the recent findings on the cytokinin function as part of this hormonal network. We focus on the importance of the crosstalk between cytokinin and other hormones, such as abscisic acid, jasmonate, salicylic acid, ethylene, and auxin in the modulation of plant development and stress adaptation. Finally, the impact of the current research in the biotechnological industry will be discussed. PMID:24312105

  19. Contributions of Socialization of Coping to Physiological Responses to Stress

    PubMed Central

    Monti, Jennifer D.; Abaied, Jamie L.; Rudolph, Karen D.

    2015-01-01

    The messages mothers communicate to their children about coping may play an important role in children’s emotional development by shaping children’s responses to stress. Building on prior research demonstrating associations between maternal socialization of coping (SOC) and children’s self-reported coping and emotional functioning (Abaied & Rudolph, 2010; 2011), we examined the contribution of SOC to children’s physiological responses to stress. Mothers completed a measure of SOC with peer victimization. Children (N = 118; M age = 9.46 years, SD = 0.33) completed a measure of peer victimization and participated in a laboratory social challenge task. Saliva samples were collected prior to and following the task and were assayed for alpha-amylase (sAA), a marker of autonomic nervous system (ANS) activation. Hierarchical linear modeling analyses revealed that SOC contributed to sAA reactivity. Peer victimization predicted greater sAA reactivity when mothers made few engagement suggestions (orienting toward stress and associated emotions and cognitions) but not when mothers made many engagement suggestions. Mothers’ distress responses predicted greater sAA reactivity. These findings provide novel evidence that the messages parents communicate about coping have implications for children’s physiological reactivity to stress during middle childhood. PMID:26973351

  20. The Role of Mitogen-Activated Protein (MAP) Kinase Signaling Components in the Fungal Development, Stress Response and Virulence of the Fungal Cereal Pathogen Bipolaris sorokiniana

    PubMed Central

    Leng, Yueqiang; Zhong, Shaobin

    2015-01-01

    Mitogen-activated protein kinases (MAPKs) have been demonstrated to be involved in fungal development, sexual reproduction, pathogenicity and/or virulence in many filamentous plant pathogenic fungi, but genes for MAPKs in the fungal cereal pathogen Bipolaris sorokiniana have not been characterized. In this study, orthologues of three MAPK genes (CsSLT2, CsHOG1 and CsFUS3) and one MAPK kinase kinase (MAPKKK) gene (CsSTE11) were identified in the whole genome sequence of the B. sorokiniana isolate ND90Pr, and knockout mutants were generated for each of them. The ∆Csfus3 and ∆Csste11 mutants were defective in conidiation and formation of appressoria-like structures, showed hypersensitivity to oxidative stress and lost pathogenicity on non-wounded leaves of barley cv. Bowman. When inoculated on wounded leaves of Bowman, the ∆Csfus3 and ∆Csste11 mutants were reduced in virulence compared to the wild type. No morphological changes were observed in the ∆Cshog1 mutants in comparison with the wild type; however, they were slightly reduced in growth under oxidative stress and were hypersensitive to hyperosmotic stress. The ∆Cshog1 mutants formed normal appressoria-like structures but were reduced in virulence when inoculated on Bowman leaves. The ∆Csslt2 mutants produced more vegetative hyphae, had lighter pigmentation, were more sensitive to cell wall degrading enzymes, and were reduced in virulence on Bowman leaves, although they formed normal appressoria like the wild type. Root infection assays indicated that the ∆Cshog1 and ∆Csslt2 mutants were able to infect barley roots while the ∆Csfus3 and ∆Csste11 failed to cause any symptoms. However, no significant difference in virulence was observed for ∆Cshog1 mutants while ∆Csslt2 mutants showed significantly reduced virulence on barley roots in comparison with the wild type. Our results indicated that all of these MAPK and MAPKKK genes are involved in the regulation of fungal development under

  1. Mammalian autophagy degrades nuclear constituents in response to tumorigenic stress.

    PubMed

    Dou, Zhixun; Ivanov, Andrejs; Adams, Peter D; Berger, Shelley L

    2016-08-01

    During autophagy, double-membrane autophagosomes are observed in the cytoplasm. Thus, extensive studies have focused on autophagic turnover of cytoplasmic material. Whether autophagy has a role in degrading nuclear constituents is poorly understood. We reveal that the autophagy protein LC3/Atg8 directly interacts with the nuclear lamina protein LMNB1 (lamin B1), and binds to LMN/lamin-associated chromatin domains (LADs). Through these interactions, autophagy specifically mediates destruction of nuclear lamina during tumorigenic stress, such as by activated oncogenes and DNA damage. This nuclear lamina degradation upon aberrant cellular stress impairs cell proliferation by inducing cellular senescence, a stable form of cell-cycle arrest and a tumor-suppressive mechanism. Our findings thus suggest that, in response to cancer-promoting stress, autophagy degrades nuclear material to drive cellular senescence, as a means to restrain tumorigenesis. Our work provokes a new direction in studying the role of autophagy in the nucleus and in tumor suppression. PMID:26654219

  2. The cellular response to curvature-induced stress

    NASA Astrophysics Data System (ADS)

    Biton, Y. Y.; Safran, S. A.

    2009-12-01

    We present a theoretical model to explain recent observations of the orientational response of cells to unidirectional curvature. Experiments show that some cell types when plated on a rigid cylindrical surface tend to reorient their shape and stress fibers along the axis of the cylinder, while others align their stress fibers perpendicular to that axis. Our model focuses on the competition of the shear stress—that results from cell adhesion and active contractility—and the anisotropic bending stiffness of the stress fibers. We predict the cell orientation angle that results from the balance of these two forces in a mechanical equilibrium. The conditions under which the different experimental observations can be obtained are discussed in terms of the theory.

  3. Job stress factors, stress response, and social support in association with insomnia of Japanese male workers.

    PubMed

    Nishitani, Naoko; Sakakibara, Hisataka

    2010-01-01

    The aim of the present study was to examine the relation of insomnia with job stress factors, stress response, and social support. A self-completed questionnaire survey was conducted in 212 male Japanese workers at a synthetic fiber plant. With regard to insomnia, subjects were asked the first 5 of the 8 questions on the Athens Insomnia Scale (AIS). Job stress factors, stress response and social support were assessed using the Job Stress Questionnaire. Multiple regression analyses showed that psychological job stress factors of poor appropriateness of work and high qualitative workload were associated with insomnia. The psychological stress response of depression and physical stress responses were also related with insomnia. Depression was also related to appropriateness of work. The present results showed that insomnia was closely related with the psychological job stress factor of appropriateness of work and the psychological response of depression. These mutual relationships between insomnia and poor mental health need be investigated further. PMID:20424348

  4. Long-term moderate exercise accelerates the recovery of stress-evoked cardiovascular responses.

    PubMed

    Hsu, Yuan-Chang; Tsai, Sheng-Feng; Yu, Lung; Chuang, Jih-Ing; Wu, Fong-Sen; Jen, Chauying J; Kuo, Yu-Min

    2016-01-01

    Psychological stress is an important global health problem. It is well documented that stress increases the incidences of various cardiovascular disorders. Regular exercise is known to reduce resting blood pressure (BP) and heart rate (HR). This study was designed to clarify the effects of long-term exercise on stress-evoked cardiovascular responses and to emphasize post-stress recovery effects. Male Wistar rats underwent 8 weeks of moderate treadmill training, with cardiovascular responses, autonomic nervous system activities and local Fos reactivity changes in the cardiovascular regulation center were monitored before, during and after immobilization stress. A spectral analysis of cardiovascular parameters was used to examine autonomic nervous activities. We found that long-term exercise (i) lowered resting BP, HR and sympathetic activity, but increased resting parasympathetic activity and baroreflex sensitivity (BRS); (ii) accelerated post-stress recovery of stress-evoked cardiovascular and sympathetic responses along with increased BRS and (iii) accelerated post-stress recovery of stress-evoked neuron activations in the paraventricular nucleus, but delayed it in the nucleus of the tractus solitarius. We conclude that, in rats, long-term exercise accelerated recovery of stress-evoked cardiovascular responses differentially altering hypothalamic and medullar neuron activities. PMID:26473638

  5. Activation of an AP1-Like Transcription Factor of the Maize Pathogen Cochliobolus heterostrophus in Response to Oxidative Stress and Plant Signals

    SciTech Connect

    Lev, Sophie; hadar, Ruthi; Amedeo, Paolo; Baker, Scott E.; Yoder, Olen; Horwitz, Benjamin A.

    2005-02-01

    Redox sensing is a ubiquitous mechanism regulating cellular activity. Fungal pathogens face reactive oxygen species produced by the host plant's oxidative burst in addition to endogenous reactive oxygen species produced during aerobic metabolism. An array of preformed and induced detoxifying enzymes, including superoxide dismutase, catalases, and peroxidases, could allow fungi to infect plants despite the oxidative burst. We isolated a gene (CHAP1) encoding a redox-regulated transcription factor in Cochliobolus heterostrophus, a fungal pathogen of maize. CHAP1 is a bZIP protein that possesses two cysteine-rich domains structurally and functionally related to Saccharomyces cerevisiae YAP1. Deletion of CHAP1 in C. heterostrophus resulted in decreased resistance to oxidative stress caused by hydrogen peroxide and menadione, but the virulence of chap1 mutants was unaffected. Upon activation by oxidizing agents or plant signals, a green fluorescent protein (GFP)-CHAP1 fusion protein became localized in the nucleus. Expression of genes encoding antioxidant proteins was induced in the wild type but not in chap1 mutants. Activation of CHAP1 occurred from the earliest stage of plant infection, in conidial germ tubes on the leaf surface, and persisted during infection. Late in the course of infection, after extensive necrotic lesions were formed, GFP-CHAP1 redistributed to the cytosol in hyphae growing on the leaf surface. Localization of CHAP1 to the nucleus may, through changes in the redox state of the cell, provide a mechanism linking extracellular cues to transcriptional regulation during the plant-pathogen interaction.

  6. Ubiquitin-proteasome pathway and cellular responses to oxidative stress

    PubMed Central

    Taylor, Allen

    2011-01-01

    The ubiquitin-proteasome pathway (UPP) is the primary cytosolic proteolytic machinery for the selective degradation of various forms of damaged proteins. Thus, the UPP is an important protein quality control mechanism. In the canonical UPP, both ubiquitin and the 26S proteasome are involved. Substrate proteins of the canonical UPP are first tagged by multiple ubiquitin molecules and then degraded by the 26S proteasome. However, in non-canonical UPP, proteins can be degraded by the 26S or the 20S proteasome without being ubiquitinated. It is clear that a proteasome is responsible for selective degradation of oxidized proteins, but the extent to which ubiquitination is involved in this process remains a subject of debate. While many publications suggest that the 20S proteasome degrades oxidized proteins independent of ubiquitin, there is also solid evidence indicating that ubiquitin and ubiquitination are involved in degradation of some forms of oxidized proteins. A fully functional UPP is required for cells to cope with oxidative stress and the activity of the UPP is also modulated by cellular redox status. Mild or transient oxidative stress up-regulates the ubiquitination system and proteasome activity in cells and tissues and transiently enhances intracellular proteolysis. Severe or sustained oxidative stress impairs the function of the UPP and decreases intracellular proteolysis. Both the ubiquitin conjugation enzymes and the proteasome can be inactivated by sustained oxidative stress, especially the 26S proteasome. Differential susceptibilities of the ubiquitin conjugation enzymes and the 26S proteasome to oxidative damage lead to an accumulation of ubiquitin conjugates in cells in response to mild oxidative stress. Thus, increased levels of ubiquitin conjugates in cells appear to be an indicator of mild oxidative stress. PMID:21530648

  7. A Network Biology Approach to Decipher Stress Response in Bacteria Using Escherichia coli As a Model.

    PubMed

    Nagar, Shashwat Deepali; Aggarwal, Bhavye; Joon, Shikha; Bhatnagar, Rakesh; Bhatnagar, Sonika

    2016-05-01

    The development of drug-resistant pathogenic bacteria poses challenges to global health for their treatment and control. In this context, stress response enables bacterial populations to survive extreme perturbations in the environment but remains poorly understood. Specific modules are activated for unique stressors with few recognized global regulators. The phenomenon of cross-stress protection strongly suggests the presence of central proteins that control the diverse stress responses. In this work, Escherichia coli was used to model the bacterial stress response. A Protein-Protein Interaction Network was generated by integrating differentially expressed genes in eight stress conditions of pH, temperature, and antibiotics with relevant gene ontology terms. Topological analysis identified 24 central proteins. The well-documented role of 16 central proteins in stress indicates central control of the response, while the remaining eight proteins may have a novel role in stress response. Cluster analysis of the generated network implicated RNA binding, flagellar assembly, ABC transporters, and DNA repair as important processes during response to stress. Pathway analysis showed crosstalk of Two Component Systems with metabolic processes, oxidative phosphorylation, and ABC transporters. The results were further validated by analysis of an independent cross-stress protection dataset. This study also reports on the ways in which bacterial stress response can progress to biofilm formation. In conclusion, we suggest that drug targets or pathways disrupting bacterial stress responses can potentially be exploited to combat antibiotic tolerance and multidrug resistance in the future. PMID:27195968

  8. Oxidative Stress and Response to Thymidylate Synthase-Targeted Antimetabolites.

    PubMed

    Ozer, Ufuk; Barbour, Karen W; Clinton, Sarah A; Berger, Franklin G

    2015-12-01

    Thymidylate synthase (TYMS; EC 2.1.1.15) catalyzes the reductive methylation of 2'-deoxyuridine-5'-monophosphate (dUMP) by N(5),N(10)-methyhlenetetrahydrofolate, forming dTMP for the maintenance of DNA replication and repair. Inhibitors of TYMS have been widely used in the treatment of neoplastic disease. A number of fluoropyrimidine and folate analogs have been developed that lead to inhibition of the enzyme, resulting in dTMP deficiency and cell death. In the current study, we have examined the role of oxidative stress in response to TYMS inhibitors. We observed that intracellular reactive oxygen species (ROS) concentrations are induced by these inhibitors and promote apoptosis. Activation of the enzyme NADPH oxidase (NOX), which catalyzes one-electron reduction of O2 to generate superoxide (O2 (●-)), is a significant source of increased ROS levels in drug-treated cells. However, gene expression profiling revealed a number of other redox-related genes that may contribute to ROS generation. TYMS inhibitors also induce a protective response, including activation of the transcription factor nuclear factor E2-related factor 2 (NRF2), a critical mediator of defense against oxidative and electrophilic stress. Our results show that exposure to TYMS inhibitors induces oxidative stress that leads to cell death, while simultaneously generating a protective response that may underlie resistance against such death. PMID:26443810

  9. Lower Electrodermal Activity to Acute Stress in Caregivers of People with Autism Spectrum Disorder: An Adaptive Habituation to Stress

    ERIC Educational Resources Information Center

    Ruiz-Robledillo, Nicolás; Moya-Albiol, Luis

    2015-01-01

    Caring for a relative with autism spectrum disorder (ASD) entails being under chronic stress that could alter body homeostasis. Electrodermal activity (EDA) is an index of the sympathetic activity of the autonomic nervous system related to emotionality and homeostasis. This study compares EDA in response to acute stress in the laboratory between…

  10. High-resolution chromatin dynamics during a yeast stress response.

    PubMed

    Weiner, Assaf; Hsieh, Tsung-Han S; Appleboim, Alon; Chen, Hsiuyi V; Rahat, Ayelet; Amit, Ido; Rando, Oliver J; Friedman, Nir

    2015-04-16

    Covalent histone modifications are highly conserved and play multiple roles in eukaryotic transcription regulation. Here, we mapped 26 histone modifications genome-wide in exponentially growing yeast and during a dramatic transcriptional reprogramming-the response to diamide stress. We extend prior studies showing that steady-state histone modification patterns reflect genomic processes, especially transcription, and display limited combinatorial complexity. Interestingly, during the stress response we document a modest increase in the combinatorial complexity of histone modification space, resulting from roughly 3% of all nucleosomes transiently populating rare histone modification states. Most of these rare histone states result from differences in the kinetics of histone modification that transiently uncouple highly correlated marks, with slow histone methylation changes often lagging behind the more rapid acetylation changes. Explicit analysis of modification dynamics uncovers ordered sequences of events in gene activation and repression. Together, our results provide a comprehensive view of chromatin dynamics during a massive transcriptional upheaval. PMID:25801168

  11. High-Resolution Chromatin Dynamics during a Yeast Stress Response

    PubMed Central

    Weiner, Assaf; Hsieh, Tsung-Han S.; Appleboim, Alon; Chen, Hsiuyi V.; Rahat, Ayelet; Amit, Ido; Rando, Oliver J.; Friedman, Nir

    2015-01-01

    Summary Covalent histone modifications are highly conserved and play multiple roles in eukaryotic transcription regulation. Here, we mapped 26 histone modifications genome-wide in exponentially growing yeast and during a dramatic transcriptional reprogramming—the response to diamide stress. We extend prior studies showing that steady-state histone modification patterns reflect genomic processes, especially transcription, and display limited combinatorial complexity. Interestingly, during the stress response we document a modest increase in the combinatorial complexity of histone modification space, resulting from roughly 3% of all nucleosomes transiently populating rare histone modification states. Most of these rare histone states result from differences in the kinetics of histone modification that transiently uncouple highly correlated marks, with slow histone methylation changes often lagging behind the more rapid acetylation changes. Explicit analysis of modification dynamics uncovers ordered sequences of events in gene activation and repression. Together, our results provide a comprehensive view of chromatin dynamics during a massive transcriptional upheaval. PMID:25801168

  12. Stress and Androgen Activity During Fetal Development

    PubMed Central

    Swan, Shanna H.

    2015-01-01

    Prenatal stress is known to alter hypothalamic-pituitary-adrenal axis activity, and more recent evidence suggests that it may also affect androgen activity. In animal models, prenatal stress disrupts the normal surge of testosterone in the developing male, whereas in females, associations differ by species. In humans, studies show that (1) associations between prenatal stress and child outcomes are often sex-dependent, (2) prenatal stress predicts several disorders with notable sex differences in prevalence, and (3) prenatal exposure to stressful life events may be associated with masculinized reproductive tract development and play behavior in girls. In this minireview, we examine the existing literature on prenatal stress and androgenic activity and present new, preliminary data indicating that prenatal stress may also modify associations between prenatal exposure to diethylhexyl phthalate, (a synthetic, antiandrogenic chemical) and reproductive development in infant boys. Taken together, these data support the hypothesis that prenatal exposure to both chemical and nonchemical stressors may alter sex steroid pathways in the maternal-placental-fetal unit and ultimately alter hormone-dependent developmental endpoints. PMID:26241065

  13. Stress and Androgen Activity During Fetal Development.

    PubMed

    Barrett, Emily S; Swan, Shanna H

    2015-10-01

    Prenatal stress is known to alter hypothalamic-pituitary-adrenal axis activity, and more recent evidence suggests that it may also affect androgen activity. In animal models, prenatal stress disrupts the normal surge of testosterone in the developing male, whereas in females, associations differ by species. In humans, studies show that (1) associations between prenatal stress and child outcomes are often sex-dependent, (2) prenatal stress predicts several disorders with notable sex differences in prevalence, and (3) prenatal exposure to stressful life events may be associated with masculinized reproductive tract development and play behavior in girls. In this minireview, we examine the existing literature on prenatal stress and androgenic activity and present new, preliminary data indicating that prenatal stress may also modify associations between prenatal exposure to diethylhexyl phthalate, (a synthetic, antiandrogenic chemical) and reproductive development in infant boys. Taken together, these data support the hypothesis that prenatal exposure to both chemical and nonchemical stressors may alter sex steroid pathways in the maternal-placental-fetal unit and ultimately alter hormone-dependent developmental endpoints. PMID:26241065

  14. Lipid signalling in plant responses to abiotic stress.

    PubMed

    Hou, Quancan; Ufer, Guido; Bartels, Dorothea

    2016-05-01

    Lipids are one of the major components of biological membranes including the plasma membrane, which is the interface between the cell and the environment. It has become clear that membrane lipids also serve as substrates for the generation of numerous signalling lipids such as phosphatidic acid, phosphoinositides, sphingolipids, lysophospholipids, oxylipins, N-acylethanolamines, free fatty acids and others. The enzymatic production and metabolism of these signalling molecules are tightly regulated and can rapidly be activated upon abiotic stress signals. Abiotic stress like water deficit and temperature stress triggers lipid-dependent signalling cascades, which control the expression of gene clusters and activate plant adaptation processes. Signalling lipids are able to recruit protein targets transiently to the membrane and thus affect conformation and activity of intracellular proteins and metabolites. In plants, knowledge is still scarce of lipid signalling targets and their physiological consequences. This review focuses on the generation of signalling lipids and their involvement in response to abiotic stress. We describe lipid-binding proteins in the context of changing environmental conditions and compare different approaches to determine lipid-protein interactions, crucial for deciphering the signalling cascades. PMID:26510494

  15. Severe Injury Is Associated With Insulin Resistance, Endoplasmic Reticulum Stress Response, and Unfolded Protein Response

    PubMed Central

    Jeschke, Marc G.; Finnerty, Celeste C.; Herndon, David N.; Song, Juquan; Boehning, Darren; Tompkins, Ronald G.; Baker, Henry V.; Gauglitz, Gerd G.

    2012-01-01

    Objective We determined whether postburn hyperglycemia and insulin resistance are associated with endoplasmic reticulum (ER) stress/unfolded protein response (UPR) activation leading to impaired insulin receptor signaling. Background Inflammation and cellular stress, hallmarks of severely burned and critically ill patients, have been causally linked to insulin resistance in type 2 diabetes via induction of ER stress and the UPR. Methods Twenty severely burned pediatric patients were compared with 36 nonburned children. Clinical markers, protein, and GeneChip analysis were used to identify transcriptional changes in ER stress and UPR and insulin resistance–related signaling cascades in peripheral blood leukocytes, fat, and muscle at admission and up to 466 days postburn. Results Burn-induced inflammatory and stress responses are accompanied by profound insulin resistance and hyperglycemia. Genomic and protein analysis revealed that burn injury was associated with alterations in the signaling pathways that affect insulin resistance, ER/sarcoplasmic reticulum stress, inflammation, and cell growth/apoptosis up to 466 days postburn. Conclusion Burn-induced insulin resistance is associated with persistent ER/sarcoplasmic reticulum stress/UPR and subsequent suppressed insulin receptor signaling over a prolonged period of time. PMID:22241293

  16. Ezrin Inhibition Up-regulates Stress Response Gene Expression.

    PubMed

    Çelik, Haydar; Bulut, Gülay; Han, Jenny; Graham, Garrett T; Minas, Tsion Z; Conn, Erin J; Hong, Sung-Hyeok; Pauly, Gary T; Hayran, Mutlu; Li, Xin; Özdemirli, Metin; Ayhan, Ayşe; Rudek, Michelle A; Toretsky, Jeffrey A; Üren, Aykut

    2016-06-17

    Ezrin is a member of the ERM (ezrin/radixin/moesin) family of proteins that links cortical cytoskeleton to the plasma membrane. High expression of ezrin correlates with poor prognosis and metastasis in osteosarcoma. In this study, to uncover specific cellular responses evoked by ezrin inhibition that can be used as a specific pharmacodynamic marker(s), we profiled global gene expression in osteosarcoma cells after treatment with small molecule ezrin inhibitors, NSC305787 and NSC668394. We identified and validated several up-regulated integrated stress response genes including PTGS2, ATF3, DDIT3, DDIT4, TRIB3, and ATF4 as novel ezrin-regulated transcripts. Analysis of transcriptional response in skin and peripheral blood mononuclear cells from NSC305787-treated mice compared with a control group revealed that, among those genes, the stress gene DDIT4/REDD1 may be used as a surrogate pharmacodynamic marker of ezrin inhibitor compound activity. In addition, we validated the anti-metastatic effects of NSC305787 in reducing the incidence of lung metastasis in a genetically engineered mouse model of osteosarcoma and evaluated the pharmacokinetics of NSC305787 and NSC668394 in mice. In conclusion, our findings suggest that cytoplasmic ezrin, previously considered a dormant and inactive protein, has important functions in regulating gene expression that may result in down-regulation of stress response genes. PMID:27137931

  17. Effects of chlorpyrifos on the transcription of CYP3A cDNA, activity of acetylcholinesterase, and oxidative stress response of goldfish (Carassius auratus).

    PubMed

    Ma, Junguo; Liu, Yang; Niu, Daichun; Li, Xiaoyu

    2015-04-01

    Chlorpyrifos (CPF) is the widely used organophosphate pesticide in agriculture throughout the world. It has been found that CPF is relatively safe to human but highly toxic to fish. In this study, acute toxicity of CPF on goldfish was determined and then the transcription of goldfish cytochrome P450 (CYP) 3A was evaluated after 96 h of CPF exposure at concentrations of 15.3 [1/10 50% lethal concentration (LC50 )] or 51 μg L(-1) (1/3 LC50 ) of CPF. Meanwhile, the enzymatic activities of acetylcholinesterase (AChE), superoxide dismutase (SOD), and catalase (CAT), total antioxidant activity (T-AOC), and the contents of malondialdehyde (MDA) in the liver or brain of goldfish were also determined. The results of acute toxicity testing showed that the 96-h LC50 of CPF to the goldfish was 153 μg L(-1) . Moreover, a length sequence of 1243 bp CYP3A cDNA encoding for 413 amino acids from goldfish liver was cloned. Polymerase chain reaction results reveal that CPF exposure downregulates CYP 3A transcription in goldfish liver, suggesting that goldfish CYP 3A may be not involved in CPF bioactivation. Finally, the results of biochemical assays indicate that 96 h of CPF exposure remarkably inhibits AChE activity in fish liver or brain, alters hepatic antioxidant enzyme activities, decreases brain T-AOC, and causes lipid peroxidation in fish liver. These results suggest that oxidative stress might be involved in CPF toxicity on goldfish. PMID:24190793

  18. Autophagy is activated for cell survival after endoplasmic reticulum stress.

    PubMed

    Ogata, Maiko; Hino, Shin-ichiro; Saito, Atsushi; Morikawa, Keisuke; Kondo, Shinichi; Kanemoto, Soshi; Murakami, Tomohiko; Taniguchi, Manabu; Tanii, Ichiro; Yoshinaga, Kazuya; Shiosaka, Sadao; Hammarback, James A; Urano, Fumihiko; Imaizumi, Kazunori

    2006-12-01

    Eukaryotic cells deal with accumulation of unfolded proteins in the endoplasmic reticulum (ER) by the unfolded protein response, involving the induction of molecular chaperones, translational attenuation, and ER-associated degradation, to prevent cell death. Here, we found that the autophagy system is activated as a novel signaling pathway in response to ER stress. Treatment of SK-N-SH neuroblastoma cells with ER stressors markedly induced the formation of autophagosomes, which were recognized at the ultrastructural level. The formation of green fluorescent protein (GFP)-LC3-labeled structures (GFP-LC3 "dots"), representing autophagosomes, was extensively induced in cells exposed to ER stress with conversion from LC3-I to LC3-II. In IRE1-deficient cells or cells treated with c-Jun N-terminal kinase (JNK) inhibitor, the autophagy induced by ER stress was inhibited, indicating that the IRE1-JNK pathway is required for autophagy activation after ER stress. In contrast, PERK-deficient cells and ATF6 knockdown cells showed that autophagy was induced after ER stress in a manner similar to the wild-type cells. Disturbance of autophagy rendered cells vulnerable to ER stress, suggesting that autophagy plays important roles in cell survival after ER stress. PMID:17030611

  19. Tolerant and Susceptible Sesame Genotypes Reveal Waterlogging Stress Response Patterns

    PubMed Central

    Wang, Linhai; Li, Donghua; Zhang, Yanxin; Gao, Yuan; Yu, Jingyin; Wei, Xin; Zhang, Xiurong

    2016-01-01

    Waterlogging is a common adverse environmental condition that limits plant growth. Sesame (Sesamum indicum) is considered a drought-tolerant oil crop but is typically susceptible to harmful effects from waterlogging. The present study used comparative analysis to explore the waterlogging stress response associated with two sesame genotypes. The RNA-seq dataset generated during a time course of 0, 3, 9 and 15 h of waterlogging as well as 20 h post-drainage indicated that stress gradually suppressed the expression of sesame genes, with 9 h as the critical time point for the response of sesame to waterlogging stress. Of the 19,316 genes expressed during waterlogging, 72.1% were affected significantly. Sesame of both tolerant and susceptible genotypes showed decreased numbers of upregulated differentially expressed genes (DEGs) but increased numbers of downregulated DEGs at the onset of waterlogging. However, the tolerant-genotype sesame exhibited 25.5% more upregulated DEGs and 29.7% fewer downregulated DEGs than those of the susceptible-genotype strain between 3 and 15 h. The results indicated that the tolerant sesame displayed a more positive gene response to waterlogging. A total of 1,379 genes were significantly induced and commonly expressed in sesame under waterlogging conditions from 3 to 15 h regardless of tolerance level; of these genes, 98 are known homologous stress responsive genes, while the remaining 1,281 are newly reported here. This gene set may represent the core genes that function in response to waterlogging, including those related mainly to energy metabolism and phenylpropanoid biosynthesis. Furthermore, a set of 3,016 genes functioning in energy supply and cell repair or formation was activated in sesame recovery from waterlogging stress. A comparative analysis between sesame of the tolerant and susceptible genotypes revealed 66 genes that may be candidates for improving sesame tolerance to waterlogging. This study provided a comprehensive

  20. Pythium infection activates conserved plant defense responses in mosses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The moss Physcomitrella patens (P. patens) is a useful model to study abiotic stress responses since it is highly tolerant to drought, salt and osmotic stress. However, little is known about the defense mechanisms activated in this moss after pathogen assault. Here the induction of defense responses...

  1. Stress responses in probiotic Lactobacillus casei.

    PubMed

    Hosseini Nezhad, Marzieh; Hussain, Malik Altaf; Britz, Margaret Lorraine

    2015-01-01

    Survival in harsh environments is critical to both the industrial performance of lactic acid bacteria (LAB) and their competitiveness in complex microbial ecologies. Among the LAB, members of the Lactobacillus casei group have industrial applications as acid-producing starter cultures for milk fermentations and as specialty cultures for the intensification and acceleration of flavor development in certain bacterial-ripened cheese varieties. They are amongst the most common organisms in the gastrointestinal (GI) tract of humans and other animals, and have the potential to function as probiotics. Whether used in industrial or probiotic applications, environmental stresses will affect the physiological status and properties of cells, including altering their functionality and biochemistry. Understanding the mechanisms of how LAB cope with different environments is of great biotechnological importance, from both a fundamental and applied perspective: hence, interaction between these strains and their environment has gained increased interest in recent years. This paper presents an overview of the important features of stress responses in Lb. casei, and related proteomic or gene expression patterns that may improve their use as starter cultures and probiotics. PMID:24915363

  2. Personality traits modulate emotional and physiological responses to stress

    PubMed Central

    Childs, Emma; White, Tara L.; de Wit, Harriet

    2014-01-01

    An individual’s susceptibility to psychological and physical disorders associated with chronic stress exposure e.g., cardiovascular and infectious disease, may also be predicted by their reactivity to acute stress. One factor associated with both stress resilience and health outcomes is personality. An understanding of how personality influences responses to acute stress may shed light upon individual differences in susceptibility to chronic stress-linked disease. This study examined relationships between personality and acute responses to stress in 125 healthy adults, using hierarchical linear regression. We assessed personality traits using the Multidimensional Personality Questionnaire (MPQ-BF), and responses to acute stress (cortisol, heart rate, blood pressure, mood) using a standardised laboratory psychosocial stress task, the Trier Social Stress Test (TSST). Individuals with high Negative Emotionality exhibited greater emotional distress and lower blood pressure responses to the TSST. Individuals with high Agentic Positive Emotionality exhibited prolonged heart rate responses to stress, whereas those with high Communal Positive Emotionality exhibited smaller cortisol and blood pressure responses. Separate personality traits differentially predicted emotional, cardiovascular, and cortisol responses to a psychosocial stressor in healthy volunteers. Future research investigating the association of personality with chronic stress-related disease may provide further clues to the relationship between acute stress reactivity and susceptibility to disease. PMID:25036730

  3. The mitochondrial unfolded protein response, a conserved stress response pathway with implications in health and disease

    PubMed Central

    Jovaisaite, Virginija; Mouchiroud, Laurent; Auwerx, Johan

    2014-01-01

    The ability to respond to various intracellular and/or extracellular stresses allows the organism to adapt to changing environmental conditions and drives evolution. It is now well accepted that a progressive decline of the efficiency of stress response pathways occurs with aging. In this context, a correct proteostasis is essential for the functionality of the cell, and its dysfunction has been associated with protein aggregation and age-related degenerative diseases. Complex response mechanisms have evolved to deal with unfolded protein stress in different subcellular compartments and their moderate activation translates into positive effects on health. In this review, we focus on the mitochondrial unfolded protein response (UPRmt), a response to proteotoxic stress specifically in mitochondria, an organelle with a wide array of fundamental functions, most notably the harvesting of energy from food and the control of cell death. We compare UPRmt with the extensively characterized cytosolic heat shock response (HSR) and the unfolded protein response in endoplasmic reticulum (UPRER), and discuss the current knowledge about UPRmt signaling pathways as well as their potential involvement in physiology. PMID:24353213

  4. RNA-seq analysis of stress response in rainbow trout

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fish under intensive rearing conditions experience various stress conditions, which have negative impacts on survival, growth and fillet quality. Understanding the molecular mechanisms underlying stress responses will facilitate improvement of animal welfare and production efficiency. Our objective ...

  5. The atypical hyperosmotic stress response of Campylobacter jejuni

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Atypical Hyperosmotic Stress Response of Campylobacter jejuni Background. Campylobacter species are unusually sensitive to hyperosmotic stress conditions imposed in the laboratory and encode no characterized osmoprotectant systems. Despite these limitations, the Gram-negative Campylobacter jeju...

  6. The Plant Heat Stress Transcription Factors (HSFs): Structure, Regulation, and Function in Response to Abiotic Stresses

    PubMed Central

    Guo, Meng; Liu, Jin-Hong; Ma, Xiao; Luo, De-Xu; Gong, Zhen-Hui; Lu, Ming-Hui

    2016-01-01

    Abiotic stresses such as high temperature, salinity, and drought adversely affect the survival, growth, and reproduction of plants. Plants respond to such unfavorable changes through developmental, physiological, and biochemical ways, and these responses require expression of stress-responsive genes, which are regulated by a network of transcription factors (TFs), including heat stress transcription factors (HSFs). HSFs play a crucial role in plants response to several abiotic stresses by regulating the expression of stress-responsive genes, such as heat shock proteins (Hsps). In this review, we describe the conserved structure of plant HSFs, the identification of HSF gene families from various plant species, their expression profiling under abiotic stress conditions, regulation at different levels and function in abiotic stresses. Despite plant HSFs share highly conserved structure, their remarkable diversification across plants reflects their numerous functions as well as their integration into the complex stress signaling and response networks, which can be employed in crop improvement strategies via biotechnological intervention. PMID:26904076

  7. Estrogen Receptor-β Agonist Diarylpropionitrile: Biological Activities of R- and S-Enantiomers on Behavior and Hormonal Response to Stress

    PubMed Central

    Weiser, Michael J.; Wu, T. John; Handa, Robert J.

    2009-01-01

    Estrogens have been shown to have positive and negative effects on anxiety and depressive-like behaviors, perhaps explained by the existence of two distinct estrogen receptor (ER) systems, ERα and ERβ. The ERβ agonist, diarylpropionitrile (DPN) has been shown to have anxiolytic properties in rats. DPN exists as a racemic mixture of two enantiomers, R-DPN and S-DPN. In this study, we compared R-DPN and S-DPN for their in vitro binding affinity, ability to activate transcription in vitro at an estrogen response element, and in vivo endocrine and behavioral responses. In vitro binding studies using recombinant rat ERβ revealed that S-DPN has a severalfold greater relative binding affinity for ERβ than does R-DPN. Furthermore, cotransfection of N-38 immortalized hypothalamic cells with an estrogen response element-luc reporter and ERβ revealed that S-DPN is a potent activator of transcription in vitro, whereas R-DPN is not. Subsequently, we examined anxiety-like behaviors using the open-field test and elevated plus maze or depressive-like behaviors, using the forced swim test. Ovariectomized young adult female Sprague Dawley rats treated with racemic DPN, S-DPN, and the ERβ agonist, WAY-200070, showed significantly decreased anxiety-like behaviors in both the open-field and elevated plus maze and significantly less depressive-like behaviors in the forced swim test compared with vehicle-, R-DPN-, or propylpyrazoletriol (ERα agonist)-treated animals. In concordance with the relative binding affinity and transcriptional potency, these results demonstrate that the S-enantiomer is the biologically active form of DPN. These studies also indicate that estrogen's positive effects on mood, including its anxiolytic and antidepressive actions, are due to its actions at ERβ. PMID:19074580

  8. A Fluorescent Reporter of AMPK activity and Cellular Energy Stress

    PubMed Central

    Tsou, Peiling; Zheng, Bin; Hsu, Chia-Hsien; Sasaki, Atsuo T; Cantley, Lewis C.

    2011-01-01

    SUMMARY AMP-activated protein kinase (AMPK) is activated when the AMP/ATP ratio in cells is elevated due to energy stress. Here we describe a biosensor, AMPKAR, which exhibits enhanced fluorescence resonance energy transfer (FRET) in response to phosphorylation by AMPK, allowing spatio-temporal monitoring of AMPK activity in single cells. We show that this reporter responds to a variety of stimuli that are known to induce energy stress and that the response is dependent on AMPK α1 & α2 and on the upstream kinase, LKB1. Interestingly we found that AMPK activation is confined to the cytosol in response to energy stress but can be observed in both the cytosol and nucleus in response to calcium elevation. Finally, using this probe with U2OS cells in a microfluidics device, we observed a very high cell-to-cell variability in the amplitude and time course of AMPK activation and recovery in response to pulses of glucose deprivation. PMID:21459332

  9. Stress-induced NF-κB activation differentiates promyelocytic leukemia cells to macrophages in response to all-trans-retinoic acid.

    PubMed

    Imran, Muhammad; Park, Joon Seong; Lim, In Kyoung

    2015-03-01

    All-trans-retinoic acid (ATRA) has been known as a choice of treatment for inducing differentiation of promyelocytic leukemia cells to granulocytes. NF-κB plays a crucial role in inflammation and immunity and its activation is an important event for macrophage differentiation both in vivo and in vitro. We report here that NF-κB activation is critical for determining ATRA-induced lineage specific differentiation of myeloid leukemia cells. Our data revealed that ATRA treatment to HL-60 cells enhanced IκBα degradation and NF-κB nuclear translocation and the activated NF-κB potentiated the ability of ATRA for differentiation and switched differentiation to macrophages instead of granulocytes. Serum withdrawal and LPS treatment dampened IκBα expression via MAPK activation and reactive oxygen species generation leading to NF-κB nuclear translocation and ATRA treatment further corroborated these effects in myeloid leukemia cells. Activated NF-κB enhanced the degree of ATRA-induced differentiation of HL-60 cells to macrophages, rather than granulocytes, as assessed by morphologic examination and expressions of differentiation markers such as CD11b, CD38, CD68, MMP9 and Btg2. Employing LLnL or dominant negative IκBα attenuated NF-κB associated enhanced cell maturation and differentiation switch thus suggesting NF-κB as one of the factors that determines ATRA induced lineage specificity of myeloid leukemia cells. Furthermore, MAPK activation was observed to be central both for the differentiation of promyelocytic cells to macrophages or granulocytes regulating NF-κB or C/EBPα expressions, respectively; however, MAPK-mediated signals are modulated under various conditions affecting lineage specificity. In summary, our present data demonstrate that activation of NF-κB directly affects differentiation program of promyelocytes to macrophages, rather than granulocyte, in response to ATRA treatment. PMID:25435432

  10. Oxidative stress responses in the human fungal pathogen, Candida albicans.

    PubMed

    Dantas, Alessandra da Silva; Day, Alison; Ikeh, Mélanie; Kos, Iaroslava; Achan, Beatrice; Quinn, Janet

    2015-01-01

    Candida albicans is a major fungal pathogen of humans, causing approximately 400,000 life-threatening systemic infections world-wide each year in severely immunocompromised patients. An important fungicidal mechanism employed by innate immune cells involves the generation of toxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. Consequently, there is much interest in the strategies employed by C. albicans to evade the oxidative killing by macrophages and neutrophils. Our understanding of how C. albicans senses and responds to ROS has significantly increased in recent years. Key findings include the observations that hydrogen peroxide triggers the filamentation of this polymorphic fungus and that a superoxide dismutase enzyme with a novel mode of action is expressed at the cell surface of C. albicans. Furthermore, recent studies have indicated that combinations of the chemical stresses generated by phagocytes can actively prevent C. albicans oxidative stress responses through a mechanism termed the stress pathway interference. In this review, we present an up-date of our current understanding of the role and regulation of oxidative stress responses in this important human fungal pathogen. PMID:25723552

  11. Effect of prenatal stress on subsequent response to mixing stress and a lipopolysaccharide challenge in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sows subjected to prenatal stress have been found to produce offspring that alter the manner in which they respond to stress. Our objective was to determine if exposing a sow to stress altered the response of the offspring to lipopolysaccharide (LPS) at 2 mo of age or their response to mixing stres...

  12. Effects of cold pressor stress on the human startle response.

    PubMed

    Deuter, Christian E; Kuehl, Linn K; Blumenthal, Terry D; Schulz, André; Oitzl, Melly S; Schachinger, Hartmut

    2012-01-01

    Both emotion and attention are known to influence the startle response. Stress influences emotion and attention, but the impact of stress on the human startle response remains unclear. We used an established physiological stressor, the Cold Pressor Test (CPT), to induce stress in a non-clinical human sample (24 student participants) in a within-subjects design. Autonomic (heart rate and skin conductance) and somatic (eye blink) responses to acoustic startle probes were measured during a pre-stress baseline, during a three minutes stress intervention, and during the subsequent recovery period. Startle skin conductance and heart rate responses were facilitated during stress. Compared to baseline, startle eye blink responses were not affected during the intervention but were diminished afterwards. These data describe a new and unique startle response pattern during stress: facilitation of autonomic stress responses but no such facilitation of somatic startle eye blink responses. The absence of an effect of stress on startle eye blink responsiveness may illustrate the importance of guaranteeing uninterrupted visual input during periods of stress. PMID:23166784

  13. Effects of Cold Pressor Stress on the Human Startle Response

    PubMed Central

    Deuter, Christian E.; Kuehl, Linn K.; Blumenthal, Terry D.; Schulz, André; Oitzl, Melly S.; Schachinger, Hartmut

    2012-01-01

    Both emotion and attention are known to influence the startle response. Stress influences emotion and attention, but the impact of stress on the human startle response remains unclear. We used an established physiological stressor, the Cold Pressor Test (CPT), to induce stress in a non-clinical human sample (24 student participants) in a within-subjects design. Autonomic (heart rate and skin conductance) and somatic (eye blink) responses to acoustic startle probes were measured during a pre-stress baseline, during a three minutes stress intervention, and during the subsequent recovery period. Startle skin conductance and heart rate responses were facilitated during stress. Compared to baseline, startle eye blink responses were not affected during the intervention but were diminished afterwards. These data describe a new and unique startle response pattern during stress: facilitation of autonomic stress responses but no such facilitation of somatic startle eye blink responses. The absence of an effect of stress on startle eye blink responsiveness may illustrate the importance of guaranteeing uninterrupted visual input during periods of stress. PMID:23166784

  14. Chronic variable stress activates hematopoietic stem cells

    PubMed Central

    Courties, Gabriel; Dutta, Partha; Iwamoto, Yoshiko; Zaltsman, Alex; von zur Muhlen, Constantin; Bode, Christoph; Fricchione, Gregory L.; Denninger, John; Lin, Charles P.; Vinegoni, Claudio; Libby, Peter; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias

    2014-01-01

    Exposure to psychosocial stress is a risk factor for many diseases, including atherosclerosis1,2. While incompletely understood, interaction between the psyche and the immune system provides one potential mechanism linking stress and disease inception and progression. Known crosstalk between the brain and immune system includes the hypothalamic–pituitary–adrenal axis, which centrally drives glucocorticoid production in the adrenal cortex, and the sympathetic–adrenal–medullary axis, which controls stress–induced catecholamine release in support of the fight–or–flight reflex3,4. It remains unknown however if chronic stress changes hematopoietic stem cell activity. Here we show that stress increases proliferation of these most primitive progenitors, giving rise to higher levels of disease–promoting inflammatory leukocytes. We found that chronic stress induced monocytosis and neutrophilia in humans. While investigating the source of leukocytosis in mice, we discovered that stress activates upstream hematopoietic stem cells. Sympathetic nerve fibers release surplus noradrenaline, which uses the β3 adrenergic receptor to signal bone marrow niche cells to decrease CXCL12 levels. Consequently, elevated hematopoietic stem cell proliferation increases output of neutrophils and inflammatory monocytes. When atherosclerosis–prone ApoE−/− mice encounter chronic stress, accelerated hematopoiesis promotes plaque features associated with vulnerable lesions that cause myocardial infarction and stroke in humans. PMID:24952646

  15. Enhanced lipoxygenase activity is involved in the stress response but not in the harmful lipid peroxidation and cell death of short-term cadmium-treated barley root tip.

    PubMed

    Liptáková, Ľubica; Huttová, Jana; Mistrík, Igor; Tamás, Ladislav

    2013-05-01

    Root growth inhibition and radial root swelling were the characteristic symptoms of barley root tips after the short-term exposure of roots to 15 and 30μM Cd. Higher Cd concentrations caused extensive cell death and root growth arrest. Enhanced lipid peroxidation was observed as early as 1h after the short-term treatment in a Cd concentration-dependent manner. In contrast to lipid peroxidation, the induction of lipoxygenase activity was detected only 3h after the exposure of roots to 15 or 30μM Cd. In addition, it was not observed in 60μM Cd-treated root tips. The highest lipoxygenase activity was detected 6h after 15μM Cd treatment in the meristematic and elongation zone of root tip and was probably associated with the radial expansion of cells. Our results indicate that the upregulation of lipoxygenase is an important component of stress response in barley roots to toxic Cd. It is probably involved in the morphological stress response of root tips or/and in the alleviation of Cd-induced toxic alterations in plant cell membranes, but it is not responsible for the Cd-induced harmful lipid peroxidation and cell death. PMID:23395539

  16. YoeB toxin is activated during thermal stress.

    PubMed

    Janssen, Brian D; Garza-Sánchez, Fernando; Hayes, Christopher S

    2015-08-01

    Type II toxin-antitoxin (TA) modules are thought to mediate stress-responses by temporarily suppressing protein synthesis while cells redirect transcription to adapt to environmental change. Here, we show that YoeB, a ribosome-dependent mRNase toxin, is activated in Escherichia coli cells grown at elevated temperatures. YoeB activation is dependent on Lon protease, suggesting that thermal stress promotes increased degradation of the YefM antitoxin. Though YefM is efficiently degraded in response to Lon overproduction, we find that Lon antigen levels do not increase during heat shock, indicating that another mechanism accounts for temperature-induced YefM proteolysis. These observations suggest that YefM/YoeB functions in adaptation to temperature stress. However, this response is distinct from previously described models of TA function. First, YoeB mRNase activity is maintained over several hours of culture at 42°C, indicating that thermal activation is not transient. Moreover, heat-activated YoeB does not induce growth arrest nor does it suppress global protein synthesis. In fact, E. coli cells proliferate more rapidly at elevated temperatures and instantaneously accelerate their growth rate in response to acute heat shock. We propose that heat-activated YoeB may serve a quality control function, facilitating the recycling of stalled translation complexes through ribosome rescue pathways. PMID:26147890

  17. YoeB toxin is activated during thermal stress

    PubMed Central

    Janssen, Brian D; Garza-Sánchez, Fernando; Hayes, Christopher S

    2015-01-01

    Type II toxin-antitoxin (TA) modules are thought to mediate stress-responses by temporarily suppressing protein synthesis while cells redirect transcription to adapt to environmental change. Here, we show that YoeB, a ribosome-dependent mRNase toxin, is activated in Escherichia coli cells grown at elevated temperatures. YoeB activation is dependent on Lon protease, suggesting that thermal stress promotes increased degradation of the YefM antitoxin. Though YefM is efficiently degraded in response to Lon overproduction, we find that Lon antigen levels do not increase during heat shock, indicating that another mechanism accounts for temperature-induced YefM proteolysis. These observations suggest that YefM/YoeB functions in adaptation to temperature stress. However, this response is distinct from previously described models of TA function. First, YoeB mRNase activity is maintained over several hours of culture at 42°C, indicating that thermal activation is not transient. Moreover, heat-activated YoeB does not induce growth arrest nor does it suppress global protein synthesis. In fact, E. coli cells proliferate more rapidly at elevated temperatures and instantaneously accelerate their growth rate in response to acute heat shock. We propose that heat-activated YoeB may serve a quality control function, facilitating the recycling of stalled translation complexes through ribosome rescue pathways. PMID:26147890

  18. Stressors, Resources, and Stress Responses in Pregnant African American Women

    PubMed Central

    Giurgescu, Carmen; Kavanaugh, Karen; Norr, Kathleen F.; Dancy, Barbara L.; Twigg, Naomi; McFarlin, Barbara L.; Engeland, Christopher G.; Hennessy, Mary Dawn; White-Traut, Rosemary C.

    2013-01-01

    This research aimed to develop an initial understanding of the stressors, stress responses, and personal resources that impact African American women during pregnancy, potentially leading to preterm birth. Guided by the ecological model, a prospective, mixed-methods, complementarity design was used with 11 pregnant women and 8 of their significant others. Our integrated analysis of quantitative and qualitative data revealed 2 types of stress responses: high stress responses (7 women) and low stress responses (4 women). Patterns of stress responses were seen in psychological stress and cervical remodeling (attenuation or cervical length). All women in the high stress responses group had high depression and/or low psychological well-being and abnormal cervical remodeling at one or both data collection times. All but 1 woman had at least 3 sources of stress (racial, neighborhood, financial, or network). In contrast, 3 of the 4 women in the low stress responses group had only 2 sources of stress (racial, neighborhood, financial, or network) and 1 had none; these women also reported higher perceived support. The findings demonstrate the importance of periodically assessing stress in African American women during pregnancy, particularly related to their support network as well as the positive supports they receive. PMID:23360946

  19. Stress affects salivary alpha-Amylase activity in bonobos.

    PubMed

    Behringer, Verena; Deschner, Tobias; Möstl, Erich; Selzer, Dieter; Hohmann, Gottfried

    2012-01-18

    Salivary alpha-Amylase (sAA) is a starch digesting enzyme. In addition to its function in the context of nutrition, sAA has also turned out to be useful for monitoring sympathetic nervous system activity. Recent studies on humans have found a relationship between intra-individual changes in sAA activity and physical and psychological stress. In studies on primates and other vertebrates, non-invasive monitoring of short-term stress responses is usually based on measurements of cortisol levels, which are indicative of hypothalamic-pituitary-adrenal activity. The few studies that have used both cortisol levels and sAA activity indicate that these two markers may respond differently and independently to different types of stress such that variation in the degree of the activation of different stress response systems might reflect alternative coping mechanisms or individual traits. Here, we present the first data on intra- and inter-individual variation of sAA activity in captive bonobos and compare the results with information from other ape species and humans. Our results indicate that sAA activity in the bonobo samples was significantly lower than in the human samples but within the range of other great ape species. In addition, sAA activity was significantly higher in samples collected at times when subjects had been exposed to stressors (judged by changes in behavioral patterns and cortisol levels) than in samples collected at other times. Our results indicate that bonobos possess functioning sAA and, as in other species, sAA activity is influenced by autonomic nervous system activity. Monitoring sAA activity could therefore be a useful tool for evaluating stress in bonobos. PMID:21945369

  20. Ketamine Strengthens CRF-Activated Amygdala Inputs to Basal Dendrites in mPFC Layer V Pyramidal Cells in the Prelimbic but not Infralimbic Subregion, A Key Suppressor of Stress Responses.

    PubMed

    Liu, Rong-Jian; Ota, Kristie T; Dutheil, Sophie; Duman, Ronald S; Aghajanian, George K

    2015-08-01

    A single sub-anesthetic dose of ketamine, a short-acting NMDA receptor blocker, induces a rapid and prolonged antidepressant effect in treatment-resistant major depression. In animal models, ketamine (24 h) reverses depression-like behaviors and associated deficits in excitatory postsynaptic currents (EPSCs) generated in apical dendritic spines of layer V pyramidal cells of medial prefrontal cortex (mPFC). However, little is known about the effects of ketamine on basal dendrites. The basal dendrites of layer V cells receive an excitatory input from pyramidal cells of the basolateral amygdala (BLA), neurons that are activated by the stress hormone CRF. Here we found that CRF induces EPSCs in PFC layer V cells and that ketamine enhanced this effect through the mammalian target of rapamycin complex 1 synaptogenic pathway; the CRF-induced EPSCs required an intact BLA input and were generated primarily in basal dendrites. In contrast to its detrimental effects on apical dendritic structure and function, chronic stress did not induce a loss of CRF-induced EPSCs in basal dendrites, thereby creating a relative imbalance in favor of amygdala inputs. The effects of ketamine were complex: ketamine enhanced apical EPSC responses in all mPFC subregions, anterior cingulate (AC), prelimbic (PL), and infralimbic (IL) but enhanced CRF-induced EPSCs only in AC and PL-responses were unchanged in IL, a critical area for suppression of stress responses. We propose that by restoring the strength of apical inputs relative to basal amygdala inputs, especially in IL, ketamine would ameliorate the hypothesized disproportional negative influence of the amygdala in chronic stress and major depression. PMID:25759300

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

    PubMed Central

    Spiers, Jereme G.; Chen, Hsiao-Jou Cortina; Sernia, Conrad; Lavidis, Nickolas A.

    2015-01-01

    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. PMID:25646076

  2. Silicon stress/strain activities at JPL

    NASA Technical Reports Server (NTRS)

    Chen, C. P.

    1986-01-01

    In-house Jet Propulsion Laboratory (JPL) work is described for silicon stress/strain, including the study of fracture mechanics, and on the high-temperature test program in which the low-strain response of silicon sheet materials above 1000 C is being measured and high temperature material property data are being determined.

  3. Scolopendin 2 leads to cellular stress response in Candida albicans.

    PubMed

    Lee, Heejeong; Hwang, Jae-Sam; Lee, Dong Gun

    2016-07-01

    Centipedes, a kind of arthropod, have been reported to produce antimicrobial peptides as part of an innate immune response. Scolopendin 2 (AGLQFPVGRIGRLLRK) is a novel antimicrobial peptide derived from the body of the centipede Scolopendra subspinipes mutilans by using RNA sequencing. To investigate the intracellular responses induced by scolopendin 2, reactive oxygen species (ROS) and glutathione accumulation and lipid peroxidation were monitored over sublethal and lethal doses. Intracellular ROS and antioxidant molecule levels were elevated and lipids were peroxidized at sublethal concentrations. Moreover, the Ca(2+) released from the endoplasmic reticulum accumulated in the cytosol and mitochondria. These stress responses were considered to be associated with yeast apoptosis. Candida albicans cells exposed to scolopendin 2 were identified using diagnostic markers of apoptotic response. Various responses such as phosphatidylserine externalization, chromatin condensation, and nuclear fragmentation were exhibited. Scolopendin 2 disrupted the mitochondrial membrane potential and activated metacaspase, which was mediated by cytochrome c release. In conclusion, treatment of C. albicans with scolopendin 2 induced the apoptotic response at sublethal doses, which in turn led to mitochondrial dysfunction, metacaspase activation, and cell death. The cationic antimicrobial peptide scolopendin 2 from the centipede is a potential antifungal peptide, triggering the apoptotic response. PMID:27207682

  4. WRKY Transcription Factors: Molecular Regulation and Stress Responses in Plants

    PubMed Central

    Phukan, Ujjal J.; Jeena, Gajendra S.; Shukla, Rakesh K.

    2016-01-01

    Plants in their natural habitat have to face multiple stresses simultaneously. Evolutionary adaptation of developmental, physiological, and biochemical parameters give advantage over a single window of stress but not multiple. On the other hand transcription factors like WRKY can regulate diverse responses through a complicated network of genes. So molecular orchestration of WRKYs in plant may provide the most anticipated outcome of simultaneous multiple responses. Activation or repression through W-box and W-box like sequences is regulated at transcriptional, translational, and domain level. Because of the tight regulation involved in specific recognition and binding of WRKYs to downstream promoters, they have become promising candidate for crop improvement. Epigenetic, retrograde and proteasome mediated regulation enable WRKYs to attain the dynamic cellular homeostatic reprograming. Overexpression of several WRKYs face the paradox of having several beneficial affects but with some unwanted traits. These overexpression-associated undesirable phenotypes need to be identified and removed for proper growth, development and yeild. Taken together, we have highlighted the diverse regulation and multiple stress response of WRKYs in plants along with the future prospects in this field of research. PMID:27375634

  5. The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A–ARF locus in response to oncogene- and stress-induced senescence

    PubMed Central

    Agger, Karl; Cloos, Paul A.C.; Rudkjær, Lise; Williams, Kristine; Andersen, Gitte; Christensen, Jesper; Helin, Kristian

    2009-01-01

    The tumor suppressor proteins p16INK4A and p14ARF, encoded by the INK4A–ARF locus, are key regulators of cellular senescence. The locus is epigenetically silenced by the repressive H3K27me3 mark in normally growing cells, but becomes activated in response to oncogenic stress. Here, we show that expression of the histone H3 Lys 27 (H3K27) demethylase JMJD3 is induced upon activation of the RAS–RAF signaling pathway. JMJD3 is recruited to the INK4A–ARF locus and contributes to the transcriptional activation of p16INK4A in human diploid fibroblasts. Additionally, inhibition of Jmjd3 expression in mouse embryonic fibroblasts results in suppression of p16Ink4a and p19Arf expression and in their immortalization. PMID:19451217

  6. Origins of asymmetric stress-strain response in phase transformations

    SciTech Connect

    Sehitoglu, H.; Gall, K.

    1997-12-31

    It has been determined that the transformation stress-strain behavior of CuZnAl and NiTi shape memory alloys is dependent on the applied stress state. The uniaxial compressive stress necessary to macroscopically trigger the transformation is approximately 34% (CuZnAl) and 26% (NiTi) larger than the required uniaxial tensile stress. For three dimensional stress states, the response of either alloy system is dependent on the directions of the dominant principal stresses along with the hydrostatic stress component of the stress state. The stress state effects are dominated by the favored growth and nucleation of more martensite plates in tension versus compression. The effect of different hydrostatic pressure levels between stress states on martensite plates volume change is considered small.

  7. The Response Regulator RRG-1 Functions Upstream of a Mitogen-activated Protein Kinase Pathway Impacting Asexual Development, Female Fertility, Osmotic Stress, and Fungicide Resistance in Neurospora crassa

    PubMed Central

    Jones, Carol A.; Greer-Phillips, Suzanne E.

    2007-01-01

    Two-component systems, consisting of proteins with histidine kinase and/or response regulator domains, regulate environmental responses in bacteria, Archaea, fungi, slime molds, and plants. Here, we characterize RRG-1, a response regulator protein from the filamentous fungus Neurospora crassa. The cell lysis phenotype of Δrrg-1 mutants is reminiscent of osmotic-sensitive (os) mutants, including nik-1/os-1 (a histidine kinase) and strains defective in components of a mitogen-activated protein kinase (MAPK) pathway: os-4 (MAPK kinase kinase), os-5 (MAPK kinase), and os-2 (MAPK). Similar to os mutants, Δrrg-1 strains are sensitive to hyperosmotic conditions, and they are resistant to the fungicides fludioxonil and iprodione. Like os-5, os-4, and os-2 mutants, but in contrast to nik-1/os-1 strains, Δrrg-1 mutants do not produce female reproductive structures (protoperithecia) when nitrogen starved. OS-2-phosphate levels are elevated in wild-type cells exposed to NaCl or fludioxonil, but they are nearly undetectable in Δrrg-1 strains. OS-2-phosphate levels are also low in Δrrg-1, os-2, and os-4 mutants under nitrogen starvation. Analysis of the rrg-1D921N allele, mutated in the predicted phosphorylation site, provides support for phosphorylation-dependent and -independent functions for RRG-1. The data indicate that RRG-1 controls vegetative cell integrity, hyperosmotic sensitivity, fungicide resistance, and protoperithecial development through regulation of the OS-4/OS-5/OS-2 MAPK pathway. PMID:17392518

  8. A High-Throughput Screen Identifies 2,9-Diazaspiro[5.5]Undecanes as Inducers of the Endoplasmic Reticulum Stress Response with Cytotoxic Activity in 3D Glioma Cell Models

    PubMed Central

    Yasgar, Adam; Lea, Wendy A.; Sun, Hongmao; Wang, Yuhong; Luci, Diane K.; Yang, Shyh-Ming; Nishihara, Kana; Takeda, Shunichi; Sagor, Mohiuddin; Earnshaw, Irina; Okada, Tetsuya; Mori, Kazutoshi; Wilson, Kelli; Riggins, Gregory J.; Xia, Menghang; Grimaldi, Maurizio; Jadhav, Ajit; Maloney, David J.; Simeonov, Anton

    2016-01-01

    The endoplasmic reticulum (ER) is involved in Ca2+ signaling and protein folding. ER Ca2+ depletion and accumulation of unfolded proteins activate the molecular chaperone GRP78 (glucose-regulated protein 78) which in turn triggers the ER stress response (ERSR) pathway aimed to restore ER homeostasis. Failure to adapt to stress, however, results in apoptosis. We and others have shown that malignant cells are more susceptible to ERSR-induced apoptosis than their normal counterparts, implicating the ERSR as a potential target for cancer therapeutics. Predicated on these findings, we developed an assay that uses a GRP78 biosensor to identify small molecule activators of ERSR in glioma cells. We performed a quantitative high-throughput screen (qHTS) against a collection of ~425,000 compounds and a comprehensive panel of orthogonal secondary assays was formulated for stringent compound validation. We identified novel activators of ERSR, including a compound with a 2,9-diazaspiro[5.5]undecane core, which depletes intracellular Ca2+ stores and induces apoptosis-mediated cell death in several cancer cell lines, including patient-derived and 3D cultures of glioma cells. This study demonstrates that our screening platform enables the identification and profiling of ERSR inducers with cytotoxic activity and advocates for characterization of these compound in in vivo models. PMID:27570969

  9. Maternal Influences on Youth Responses to Peer Stress

    ERIC Educational Resources Information Center

    Abaied, Jamie L.; Rudolph, Karen D.

    2011-01-01

    Understanding how youths develop particular styles of responding to stress is critical for promoting effective coping. This research examined the prospective, interactive contribution of maternal socialization of coping and peer stress to youth responses to peer stress. A sample of 144 early adolescents (mean age = 12.44 years, SD = 1.22) and…

  10. An overview of stress response proteomes in Listeria monocytogenes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Listeria monocytogenes adapts to diverse stress conditions including cold, osmotic, heat, acid, and alkali stresses encountered during food processing and preservation which is a serious food safety threat. In this review, we have presented the major findings on this bacterium’s stress response prot...

  11. The Stress Response Regulator AflSkn7 Influences Morphological Development, Stress Response, and Pathogenicity in the Fungus Aspergillus flavus.

    PubMed

    Zhang, Feng; Xu, Gaopo; Geng, Longpo; Lu, Xiaoyan; Yang, Kunlong; Yuan, Jun; Nie, Xinyi; Zhuang, Zhenhong; Wang, Shihua

    2016-01-01

    This study focused on AflSkn7, which is a stress response regulator in the aflatoxin-producing Aspergillus flavus. The ΔAflSkn7 mutants exhibited partially defective conidial formation and a complete inability to generate sclerotia, indicating AflSkn7 affects A. flavus asexual and sexual development. The mutants tolerated osmotic stress but were partially susceptible to the effects of cell wall stress. Additionally, the ΔAflSkn7 mutants were especially sensitive to oxidative stress. These observations confirmed that AflSkn7 influences oxidative stress responses rather than osmotic stress responses. Additionally, AflSkn7 was observed to increase aflatoxin biosynthesis and seed infection rates. These results indicate AflSkn7 affects A. flavus morphological development, stress response, aflatoxin production, and pathogenicity. The results of this study may facilitate the development of new methods to manage A. flavus infections. PMID:27399770

  12. The Stress Response Regulator AflSkn7 Influences Morphological Development, Stress Response, and Pathogenicity in the Fungus Aspergillus flavus

    PubMed Central

    Zhang, Feng; Xu, Gaopo; Geng, Longpo; Lu, Xiaoyan; Yang, Kunlong; Yuan, Jun; Nie, Xinyi; Zhuang, Zhenhong; Wang, Shihua

    2016-01-01

    This study focused on AflSkn7, which is a stress response regulator in the aflatoxin-producing Aspergillus flavus. The ΔAflSkn7 mutants exhibited partially defective conidial formation and a complete inability to generate sclerotia, indicating AflSkn7 affects A. flavus asexual and sexual development. The mutants tolerated osmotic stress but were partially susceptible to the effects of cell wall stress. Additionally, the ΔAflSkn7 mutants were especially sensitive to oxidative stress. These observations confirmed that AflSkn7 influences oxidative stress responses rather than osmotic stress responses. Additionally, AflSkn7 was observed to increase aflatoxin biosynthesis and seed infection rates. These results indicate AflSkn7 affects A. flavus morphological development, stress response, aflatoxin production, and pathogenicity. The results of this study may facilitate the development of new methods to manage A. flavus infections. PMID:27399770

  13. Nitrogen stress response and stringent response are coupled in Escherichia coli

    PubMed Central

    Brown, Daniel R.; Barton, Geraint; Pan, Zhensheng; Buck, Martin; Wigneshweraraj, Sivaramesh

    2014-01-01

    Assimilation of nitrogen is an essential process in bacteria. The nitrogen regulation stress response is an adaptive mechanism used by nitrogen-starved Escherichia coli to scavenge for alternative nitrogen sources and requires the global transcriptional regulator NtrC. In addition, nitrogen-starved E. coli cells synthesize a signal molecule, guanosine tetraphosphate (ppGpp), which serves as an effector molecule of many processes including transcription to initiate global physiological changes, collectively termed the stringent response. The regulatory mechanisms leading to elevated ppGpp levels during nutritional stresses remain elusive. Here, we show that transcription of relA, a key gene responsible for the synthesis of ppGpp, is activated by NtrC during nitrogen starvation. The results reveal that NtrC couples these two major bacterial stress responses to manage conditions of nitrogen limitation, and provide novel mechanistic insights into how a specific nutritional stress leads to elevating ppGpp levels in bacteria. PMID:24947454

  14. Modulation of Ethylene Responses Affects Plant Salt-Stress Responses1[OA

    PubMed Central

    Cao, Wan-Hong; Liu, Jun; He, Xin-Jian; Mu, Rui-Ling; Zhou, Hua-Lin; Chen, Shou-Yi; Zhang, Jin-Song

    2007-01-01

    Ethylene signaling plays important roles in multiple aspects of plant growth and development. Its functions in abiotic stress responses remain largely unknown. Here, we report that alteration of ethylene signaling affected plant salt-stress responses. A type II ethylene receptor homolog gene NTHK1 (Nicotiana tabacum histidine kinase 1) from tobacco (N. tabacum) conferred salt sensitivity in NTHK1-transgenic Arabidopsis (Arabidopsis thaliana) plants as judged from the phenotypic change, the relative electrolyte leakage, and the relative root growth under salt stress. Ethylene precursor 1-aminocyclopropane-1-carboxylic acid suppressed the salt-sensitive phenotype. Analysis of Arabidopsis ethylene receptor gain-of-function mutants further suggests that receptor function may lead to salt-sensitive responses. Mutation of EIN2, a central component in ethylene signaling, also results in salt sensitivity, suggesting that EIN2-mediated signaling is beneficial for plant salt tolerance. Overexpression of the NTHK1 gene or the receptor gain-of-function activated expression of salt-responsive genes AtERF4 and Cor6.6. In addition, the transgene NTHK1 mRNA was accumulated under salt stress, suggesting a posttranscriptional regulatory mechanism. These findings imply that ethylene signaling may be required for plant salt tolerance. PMID:17189334

  15. Sch9 regulates intracellular protein ubiquitination by controlling stress responses.

    PubMed

    Qie, Beibei; Lyu, Zhou; Lyu, Lei; Liu, Jun; Gao, Xuejie; Liu, Yanyan; Duan, Wei; Zhang, Nianhui; Du, Linfang; Liu, Ke

    2015-08-01

    Protein ubiquitination and the subsequent degradation are important means by which aberrant proteins are removed from cells, a key requirement for long-term survival. In this study, we found that the overall level of ubiquitinated proteins dramatically decreased as yeast cell grew from log to stationary phase. Deletion of SCH9, a gene encoding a key protein kinase for longevity control, decreased the level of ubiquitinated proteins in log phase and this effect could be reversed by restoring Sch9 function. We demonstrate here that the decrease of ubiquitinated proteins in sch9Δ cells in log phase is not caused by changes in ubiquitin expression, proteasome activity, or autophagy, but by enhanced expression of stress response factors and a decreased level of oxidative stress. Our results revealed for the first time how Sch9 regulates the level of ubiquitinated proteins and provides new insight into how Sch9 controls longevity. PMID:26087116

  16. Sch9 regulates intracellular protein ubiquitination by controlling stress responses

    PubMed Central

    Qie, Beibei; Lyu, Zhou; Lyu, Lei; Liu, Jun; Gao, Xuejie; Liu, Yanyan; Duan, Wei; Zhang, Nianhui; Du, Linfang; Liu, Ke

    2015-01-01

    Protein ubiquitination and the subsequent degradation are important means by which aberrant proteins are removed from cells, a key requirement for long-term survival. In this study, we found that the overall level of ubiquitinated proteins dramatically decreased as yeast cell grew from log to stationary phase. Deletion of SCH9, a gene encoding a key protein kinase for longevity control, decreased the level of ubiquitinated proteins in log phase and this effect could be reversed by restoring Sch9 function. We demonstrate here that the decrease of ubiquitinated proteins in sch9Δ cells in log phase is not caused by changes in ubiquitin expression, proteasome activity, or autophagy, but by enhanced expression of stress response factors and a decreased level of oxidative stress. Our results revealed for the first time how Sch9 regulates the level of ubiquitinated proteins and provides new insight into how Sch9 controls longevity. PMID:26087116

  17. Exogenous progesterone exacerbates running response of adolescent female mice to repeated food restriction stress by changing α4-GABAA receptor activity of hippocampal pyramidal cells.

    PubMed

    Wable, G S; Chen, Y-W; Rashid, S; Aoki, C

    2015-12-01

    Adolescent females are particularly vulnerable to mental illnesses with co-morbidity of anxiety, such as anorexia nervosa (AN). We used an animal model of AN, called activity-based anorexia (ABA), to investigate the neurobiological basis of vulnerability to repeated, food restriction (FR) stress-evoked anxiety. Twenty-one of 23 adolescent female mice responded to the 1st FR with increased wheel-running activity (WRA), even during the limited period of food access, thereby capturing AN's symptoms of voluntary FR and over-exercise. Baseline WRA was an excellent predictor of FR-elicited WRA (severity of ABA, SOA), with high baseline runners responding to FR with minimal SOA (i.e., negative correlation). Nine gained resistance to ABA following the 1st FR. Even though allopregnanolone (3α-OH-5α-pregnan-20-one, THP), the metabolite of progesterone (P4), is a well-recognized anxiolytic agent, subcutaneous P4 to these ABA-resistant animals during the 2nd FR was exacerbative, evoking greater WRA than the counterpart resistant group that received oil vehicle, only. Moreover, P4 had no WRA-reducing effect on animals that remained ABA-vulnerable. To explain the sensitizing effect of P4 upon the resistant mice, we examined the relationship between P4 treatment and levels of the α4 subunit of GABAARs at spines of pyramidal cells of the hippocampal CA1, a parameter previously shown to correlate with resistance to ABA. α4 levels at spine membrane correlated strongly and negatively with SOA during the 1st ABA (prior to P4 injection), confirming previous findings. α4 levels were greater among P4-treated animals that had gained resistance than of vehicle-treated resistant animals or of the vulnerable animals with or without P4. We propose that α4-GABAARs play a protective role by counterbalancing the ABA-induced increase in excitability of CA1 pyramidal neurons, and although exogenous P4's metabolite, THP, enhances α4 expression, especially among those that can gain resistance

  18. Regulation of Stress Responses and Translational Control by Coronavirus

    PubMed Central

    Fung, To Sing; Liao, Ying; Liu, Ding Xiang

    2016-01-01

    Similar to other viruses, coronavirus infection triggers cellular stress responses in infected host cells. The close association of coronavirus replication with the endoplasmic reticulum (ER) results in the ER stress responses, which impose a challenge to the viruses. Viruses, in turn, have come up with various mechanisms to block or subvert these responses. One of the ER stress responses is inhibition of the global protein synthesis to reduce the amount of unfolded proteins inside the ER lumen. Viruses have evolved the capacity to overcome the protein translation shutoff to ensure viral protein production. Here, we review the strategies exploited by coronavirus to modulate cellular stress response pathways. The involvement of coronavirus-induced stress responses and translational control in viral pathogenesis will also be briefly discussed. PMID:27384577

  19. Regulation of Stress Responses and Translational Control by Coronavirus.

    PubMed

    Fung, To Sing; Liao, Ying; Liu, Ding Xiang

    2016-01-01

    Similar to other viruses, coronavirus infection triggers cellular stress responses in infected host cells. The close association of coronavirus replication with the endoplasmic reticulum (ER) results in the ER stress responses, which impose a challenge to the viruses. Viruses, in turn, have come up with various mechanisms to block or subvert these responses. One of the ER stress responses is inhibition of the global protein synthesis to reduce the amount of unfolded proteins inside the ER lumen. Viruses have evolved the capacity to overcome the protein translation shutoff to ensure viral protein production. Here, we review the strategies exploited by coronavirus to modulate cellular stress response pathways. The involvement of coronavirus-induced stress responses and translational control in viral pathogenesis will also be briefly discussed. PMID:27384577

  20. Chronic stress alters the density and morphology of microglia in a subset of stress-responsive brain regions.

    PubMed

    Tynan, Ross J; Naicker, Sundresan; Hinwood, Madeleine; Nalivaiko, Eugene; Buller, Kathryn M; Pow, David V; Day, Trevor A; Walker, Frederick R

    2010-10-01

    The current study, in parallel experiments, evaluated the impact of chronic psychological stress on physiological and behavioural measures, and on the activation status of microglia in 15 stress-responsive brain regions. Rats were subjected, for 14 days, to two 30 min sessions of restraint per day, applied at random times each day. In one experiment the effects of stress on sucrose preference, weight gain, core body temperature, and struggling behaviour during restraint, were determined. In the second experiment we used immunohistochemistry to investigate stress-induced changes in ionized calcium-binding adaptor molecule-1 (Iba1), a marker constitutively expressed by microglia, and major histocompatibility complex-II (MHC-II), a marker often expressed on activated microglia, in a total of 15 stress-responsive nuclei. We also investigated cellular proliferation in these regions using Ki67 immunolabelling, to check for the possibility of microglial proliferation. Collectively, the results we obtained showed that chronic stress induced a significant increase in anhedonia, a decrease in weight gain across the entire observation period, a significant elevation in core body temperature during restraint, and a progressive decrease in struggling behaviour within and over sessions. With regard to microglial activation, chronic stress induced a significant increase in the density of Iba1 immunolabelling (nine of 15 regions) and the number of Iba1-positive cells (eight of 15 regions). Within the regions that exhibited an increased number of Iba1-positive cells after chronic stress, we found no evidence of a between group difference in the number of MHC-II or Ki67 positive cells. In summary, these results clearly demonstrate that chronic stress selectively increases the number of microglia in certain stress-sensitive brain regions, and also causes a marked transition of microglia from a ramified-resting state to a non-resting state. These findings are consistent with the view

  1. Role of c-Abl in the DNA damage stress response.

    PubMed

    Shaul, Yosef; Ben-Yehoyada, Merav

    2005-01-01

    c-Abl has been implicated in many cellular processes including differentiation, division, adhesion, death, and stress response. c-Abl is a latent tyrosine kinase that becomes activated in response to numerous extra- and intra-cellular stimuli. Here we briefly review the current knowledge about c-Abl involvement in the DNA-damage stress response and its implication on cell physiology. PMID:15686624

  2. Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation

    PubMed Central

    Muralidharan, Sujatha; Mandrekar, Pranoti

    2013-01-01

    Extensive research in the past decade has identified innate immune recognition receptors and intracellular signaling pathways that culminate in inflammatory responses. Besides its role in cytoprotection, the importance of cell stress in inflammation and host defense against pathogens is emerging. Recent studies have shown that proteins in cellular stress responses, including the heat shock response, ER stress response, and DNA damage response, interact with and regulate signaling intermediates involved in the activation of innate and adaptive immune responses. The effect of such regulation by cell stress proteins may dictate the inflammatory profile of the immune response during infection and disease. In this review, we describe the regulation of innate immune cell activation by cell stress pathways, present detailed descriptions of the types of stress response proteins and their crosstalk with immune signaling intermediates that are essential in host defense, and illustrate the relevance of these interactions in diseases characteristic of aberrant immune responses, such as chronic inflammatory diseases, autoimmune disorders, and cancer. Understanding the crosstalk between cellular stress proteins and immune signaling may have translational implications for designing more effective regimens to treat immune disorders. PMID:23990626

  3. The stress response system of proteins: Implications for bioreactor scaleup

    NASA Technical Reports Server (NTRS)

    Goochee, Charles F.

    1988-01-01

    Animal cells face a variety of environmental stresses in large scale bioreactors, including periodic variations in shear stress and dissolved oxygen concentration. Diagnostic techniques were developed for identifying the particular sources of environmental stresses for animal cells in a given bioreactor configuration. The mechanisms by which cells cope with such stresses was examined. The individual concentrations and synthesis rates of hundreds of intracellular proteins are affected by the extracellular environment (medium composition, dissolved oxygen concentration, ph, and level of surface shear stress). Techniques are currently being developed for quantifying the synthesis rates and concentrations of the intracellular proteins which are most sensitive to environmental stress. Previous research has demonstrated that a particular set of stress response proteins are synthesized by mammalian cells in response to temperature fluctuations, dissolved oxygen deprivation, and glucose deprivation. Recently, it was demonstrated that exposure of human kidney cells to high shear stress results in expression of a completely distinct set of intracellular proteins.

  4. Nicotine as a Factor in Stress Responsiveness Among Detoxified Alcoholics

    PubMed Central

    Gilbertson, Rebecca; Frye, Reginald F.; Nixon, Sara Jo

    2011-01-01

    Aims: The effect of transdermal nicotine on stress reactivity was investigated in currently smoking, detoxified, substance-dependent individuals (65% alcohol dependent, n = 51; 31 male) following a psychosocial stressor. Methods: Using a randomized, double-blind, placebo-controlled design, subjects were assigned to receive either active transdermal nicotine (low or high dose) or placebo. Six hours following nicotine administration, subjects performed a laboratory psychosocial stressor consisting of two 4-min public-speaking sessions. Results: Consistent with prior reports, substance-dependent individuals displayed a blunted stress response. However, a review of the cortisol distribution data encouraged additional analyses. Notably, a significant minority of the substance-dependent individuals (33%) demonstrated elevated poststress cortisol levels. This group of responders was more likely to be alcohol dependent and to have received the high dose of nicotine [χ2(2) = 32, P < 0.0001], [χ2(2) = 18.66, P < 0.0001]. Differences in salivary cortisol responses between responders and nonresponders could not be accounted for by the length of sobriety, nicotine withdrawal levels, anxiety or depressive symptomatology at the time of the psychosocial stressor. Conclusion: These results suggest that nicotine administration may support a normalization of the salivary cortisol response following psychosocial stress in subgroups of substance-dependent individuals, particularly those who are alcohol dependent. Given the association between blunted cortisol levels and relapse, and the complex actions of nicotine at central and peripheral sites, these findings support the systematic study of factors including nicotine, which may influence stress reactivity and the recovery process in alcohol-dependent individuals. PMID:21045074

  5. Relation between stress-precipitated seizures and the stress response in childhood epilepsy.

    PubMed

    van Campen, Jolien S; Jansen, Floor E; Pet, Milou A; Otte, Willem M; Hillegers, Manon H J; Joels, Marian; Braun, Kees P J

    2015-08-01

    The majority of patients with epilepsy report that seizures are sometimes triggered or provoked. Stress is the most frequently self-reported seizure-precipitant. The mechanisms underlying stress-sensitivity of seizures are currently unresolved. We hypothesized that stress-sensitivity of seizures relates to alteration of the stress response, which could affect neuronal excitability and hence trigger seizures. To study this, children with epilepsy between 6 and 17 years of age and healthy controls, with similar age, sex and intelligence, were exposed to a standardized acute psychosocial stressor (the Trier Social Stress Test for Children), during which salivary cortisol and sympathetic parameters were measured. Beforehand, the relation between stress and seizures in children with epilepsy was assessed by (i) a retrospective questionnaire; and (ii) a prospective 6-week diary on stress and seizure occurrence. Sixty-four children with epilepsy and 40 control subjects were included in the study. Of all children with epilepsy, 49% reported that seizures were precipitated by acute stress. Diary analysis showed a positive association between acute stress and seizures in 62% of children who experienced at least one seizure during the diary period. The acute social stress test was completed by 56 children with epilepsy and 37 control subjects. Children with sensitivity of seizures for acute stress, either determined by the questionnaire or by the prospective diary, showed a blunted cortisol response to stress compared with patients without acute stress-precipitated seizures and healthy controls (questionnaire-based F = 2.74, P = 0.018; diary-based F = 4.40, P = 0.007). No baseline differences in cortisol were observed, nor differences in sympathetic stress response. The relation between acute stress-sensitivity of seizures and the cortisol response to stress remained significant in multivariable analysis (β = -0.30, P = 0.03). Other variables associated with the acute stress

  6. Adaptation or Malignant Transformation: The Two Faces of Epigenetically Mediated Response to Stress

    PubMed Central

    Zoldoš, Vlatka

    2013-01-01

    Adaptive response to stress is a fundamental property of living systems. At the cellular level, many different types of stress elicit an essentially limited repertoire of adaptive responses. Epigenetic changes are the main mechanism for medium- to long-term adaptation to accumulated (intense, long-term, or repeated) stress. We propose the adaptive deregulation of the epigenome in response to stress (ADERS) hypothesis which assumes that the unspecific adaptive stress response grows stronger with the increasing stress level, epigenetically activating response gene clusters while progressively deregulating other cellular processes. The balance between the unspecific adaptive response and the general epigenetic deregulation is critical because a strong response can lead to pathology, particularly to malignant transformation. The main idea of our hypothesis is the continuum traversed by a cell subjected to accumulated stress, which lies between an unspecific adaptive response and pathological deregulation—the two extremes sharing the same underlying cause, which is a manifestation of a unified epigenetically mediated adaptive response to stress. The evolutionary potential of epigenetic regulation in multigenerational adaptation is speculatively discussed in the light of neo-Lamarckism. Finally, an approach to testing the proposed hypothesis is presented, relying on either the publicly available datasets or on conducting new experiments. PMID:24187667

  7. Adaptation or malignant transformation: the two faces of epigenetically mediated response to stress.

    PubMed

    Vojta, Aleksandar; Zoldoš, Vlatka

    2013-01-01

    Adaptive response to stress is a fundamental property of living systems. At the cellular level, many different types of stress elicit an essentially limited repertoire of adaptive responses. Epigenetic changes are the main mechanism for medium- to long-term adaptation to accumulated (intense, long-term, or repeated) stress. We propose the adaptive deregulation of the epigenome in response to stress (ADERS) hypothesis which assumes that the unspecific adaptive stress response grows stronger with the increasing stress level, epigenetically activating response gene clusters while progressively deregulating other cellular processes. The balance between the unspecific adaptive response and the general epigenetic deregulation is critical because a strong response can lead to pathology, particularly to malignant transformation. The main idea of our hypothesis is the continuum traversed by a cell subjected to accumulated stress, which lies between an unspecific adaptive response and pathological deregulation--the two extremes sharing the same underlying cause, which is a manifestation of a unified epigenetically mediated adaptive response to stress. The evolutionary potential of epigenetic regulation in multigenerational adaptation is speculatively discussed in the light of neo-Lamarckism. Finally, an approach to testing the proposed hypothesis is presented, relying on either the publicly available datasets or on conducting new experiments. PMID:24187667

  8. Resistance to Antimicrobial Peptides and Stress Response in Mycoplasma pulmonis

    PubMed Central

    Fehri, Lina Fassi; Sirand-Pugnet, Pascal; Gourgues, Géraldine; Jan, Gwenaël; Wróblewski, Henri; Blanchard, Alain

    2005-01-01

    Antimicrobial peptides are widely distributed in nature, and in vertebrates, they play a key function in the innate immune defense system. It is generally agreed that these molecules may provide new antibiotics with therapeutic value. However, there are still many unsolved questions regarding the mechanisms underlying their antimicrobial activity as well as the mechanisms of resistance evolved by microorganisms against these molecules. The second point was addressed in this study. After determining the activity of 10 antimicrobial peptides against Mycoplasma pulmonis, a murine respiratory pathogen, the development of resistance was investigated. Following in vitro selection using subinhibitory concentrations of peptides, clones of this bacterium showing increased resistance to melittin or gramicidin D were obtained. For some of the clones, a cross-resistance was observed between these two peptides, in spite of their deep structural differences, and also with tetracycline. A proteomic analysis suggested that the stress response in these clones was constitutively activated, and this was confirmed by finding mutations in the hrcA gene; in mycoplasmas, bacteria which lack alternative sigma factors, the HrcA protein is supposed to play a key role as a negative regulator of heat shock proteins. By complementation of the hrcA mutants with the wild-type gene, the initial MICs of melittin and gramicidin D decreased to values close to the initial ones. This indicates that the resistance of M. pulmonis to these two antimicrobial peptides could result from a stress response involving HrcA-regulated genes. PMID:16189093

  9. Parent Stress and the Active Child

    ERIC Educational Resources Information Center

    Erickson, Karen; Prom, Megan

    2006-01-01

    The purpose of the current study was to look at whether a child's activity level was correlated with the level of stress a mother experiences. Parents can describe their children as having distinct and recognizable patterns of behavior as young as in infancy (Paaren, Hewitt, Lemery, Bihun & Goldsmith, 2000). Even at birth, some children are much…

  10. Stress and Coping Activity: Reframing Negative Thoughts

    ERIC Educational Resources Information Center

    Hughes, Jamie S.; Gourley, Mary K.; Madson, Laura; Le Blanc, Katya

    2011-01-01

    Stress management and coping techniques are not only relevant in many psychology courses but also personally relevant for undergraduate students. In this article, the authors describe an activity designed to provide students with practice evaluating and challenging negative self-talk. Students responded to scenarios individually, were paired with…

  11. Fault activation due to glacially induced stresses

    NASA Astrophysics Data System (ADS)

    Steffen, R.; Lund, B.; Wu, P. P.

    2013-12-01

    Melting glaciers worldwide have an effect on sea level, but also on the stability of pre-existing faults. The load due to continental ice sheets or glaciers depresses the surface below, leading to changes in the lithospheric stresses. The accumulation of ice mass increases the vertical stress, and the horizontal stresses increase due to the accompanying flexure of the lithosphere. During deglaciation, ice-mass loss causes a simultaneous decrease in vertical stress; however, horizontal stresses decrease only slowly due to the slow readjusting of the Earth. After the end of deglaciation, only the induced horizontal stresses remain as the process of glacial isostatic adjustment (GIA) proceeds visco-elastically. The modelling of this process and the estimation of fault slip is enabled by a new GIA-fault model. However, this finite-element model is only available in two dimensions, and the extension to three dimensions is a necessary step further to allow the comparison of obtained fault slips to observations of glacially induced faults in Europe and North America. The model has several input parameters, which affect the activation time of faults and their resulting slip (e.g. ice history, rheology of the Earth, frictional properties, pore-fluid pressure). We will present the results of the new 3D model and show the sensitivity of faults with respect to modelling parameters. Furthermore, a comparison to observations will be presented.

  12. Fault activation due to glacially induced stresses

    NASA Astrophysics Data System (ADS)

    Steffen, Rebekka; Lund, Björn

    2014-05-01

    Melting glaciers worldwide have an effect on sea level, but also on the stability of pre-existing faults. The load due to continental ice sheets or glaciers depresses the surface below, leading to changes in the lithospheric stresses. The accumulation of ice mass increases the vertical stress, and the horizontal stresses increase due to the accompanying flexure of the lithosphere. During deglaciation, ice-mass loss causes a simultaneous decrease in vertical stress; however, horizontal stresses decrease only slowly due to the slow readjusting of the Earth. After the end of deglaciation, only the induced horizontal stresses remain as the process of glacial isostatic adjustment (GIA) proceeds visco-elastically. The modelling of this process and the estimation of fault slip is enabled by a new GIA-fault model. However, this finite-element model is only available in two dimensions, and the extension to three dimensions is a necessary step further to allow the comparison of obtained fault slips to observations of glacially induced faults in Europe and North America. The model has several input parameters, which affect the activation time of faults and their resulting slip (e.g. ice history, rheology of the Earth, frictional properties, pore-fluid pressure). We will present the results of the new 3D model and show the sensitivity of faults with respect to modelling parameters. Furthermore, a comparison to observations will be presented.

  13. Respiratory Syncytial Virus and Cellular Stress Responses: Impact on Replication and Physiopathology

    PubMed Central

    Cervantes-Ortiz, Sandra L.; Zamorano Cuervo, Natalia; Grandvaux, Nathalie

    2016-01-01

    Human respiratory syncytial virus (RSV), a member of the Paramyxoviridae family, is a major cause of severe acute lower respiratory tract infection in infants, elderly and immunocompromised adults. Despite decades of research, a complete integrated picture of RSV-host interaction is still missing. Several cellular responses to stress are involved in the host-response to many virus infections. The endoplasmic reticulum stress induced by altered endoplasmic reticulum (ER) function leads to activation of the unfolded-protein response (UPR) to restore homeostasis. Formation of cytoplasmic stress granules containing translationally stalled mRNAs is a means to control protein translation. Production of reactive oxygen species is balanced by an antioxidant response to prevent oxidative stress and the resulting damages. In recent years, ongoing research has started to unveil specific regulatory interactions of RSV with these host cellular stress responses. Here, we discuss the latest findings regarding the mechanisms evolved by RSV to induce, subvert or manipulate the ER stress, the stress granule and oxidative stress responses. We summarize the evidence linking these stress responses with the regulation of RSV replication and the associated pathogenesis. PMID:27187445

  14. Measuring Physiological Stress Responses in Children: Lessons from a Novice

    ERIC Educational Resources Information Center

    Quas, Jodi A.

    2011-01-01

    In this article the author describes challenges associated with integrating physiological measures of stress into developmental research, especially in the domains of memory and cognition. An initial critical challenge concerns how to define stress, which can refer to one or a series of events, a response, the consequence of that response, an…

  15. Swim pressure: stress generation in active matter.

    PubMed

    Takatori, S C; Yan, W; Brady, J F

    2014-07-11

    We discover a new contribution to the pressure (or stress) exerted by a suspension of self-propelled bodies. Through their self-motion, all active matter systems generate a unique swim pressure that is entirely athermal in origin. The origin of the swim pressure is based upon the notion that an active body would swim away in space unless confined by boundaries-this confinement pressure is precisely the swim pressure. Here we give the micromechanical basis for the swim stress and use this new perspective to study self-assembly and phase separation in active soft matter. The swim pressure gives rise to a nonequilibrium equation of state for active matter with pressure-volume phase diagrams that resemble a van der Waals loop from equilibrium gas-liquid coexistence. Theoretical predictions are corroborated by Brownian dynamics simulations. Our new swim stress perspective can help analyze and exploit a wide class of active soft matter, from swimming bacteria to catalytic nanobots to molecular motors that activate the cellular cytoskeleton. PMID:25062240

  16. Signaling pathways for stress responses and adaptation in Aspergillus species: stress biology in the post-genomic era.

    PubMed

    Hagiwara, Daisuke; Sakamoto, Kazutoshi; Abe, Keietsu; Gomi, Katsuya

    2016-09-01

    Aspergillus species are among the most important filamentous fungi in terms of industrial use and because of their pathogenic or toxin-producing features. The genomes of several Aspergillus species have become publicly available in this decade, and genomic analyses have contributed to an integrated understanding of fungal biology. Stress responses and adaptation mechanisms have been intensively investigated using the accessible genome infrastructure. Mitogen-activated protein kinase (MAPK) cascades have been highlighted as being fundamentally important in fungal adaptation to a wide range of stress conditions. Reverse genetics analyses have uncovered the roles of MAPK pathways in osmotic stress, cell wall stress, development, secondary metabolite production, and conidia stress resistance. This review summarizes the current knowledge on the stress biology of Aspergillus species, illuminating what we have learned from the genomic data in this "post-genomic era." PMID:27007956

  17. AMPK-independent inhibition of human macrophage ER stress response by AICAR.

    PubMed

    Boß, Marcel; Newbatt, Yvette; Gupta, Sahil; Collins, Ian; Brüne, Bernhard; Namgaladze, Dmitry

    2016-01-01

    Obesity-associated insulin resistance is driven by inflammatory processes in response to metabolic overload. Obesity-associated inflammation can be recapitulated in cell culture by exposing macrophages to saturated fatty acids (SFA), and endoplasmic reticulum (ER) stress responses essentially contribute to pro-inflammatory signalling. AMP-activated protein kinase (AMPK) is a central metabolic regulator with established anti-inflammatory actions. Whether pharmacological AMPK activation suppresses SFA-induced inflammation in a human system is unclear. In a setting of hypoxia-potentiated inflammation induced by SFA palmitate, we found that the AMP-mimetic AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) potently suppressed upregulation of ER stress marker mRNAs and pro-inflammatory cytokines. Furthermore, AICAR inhibited macrophage ER stress responses triggered by ER-stressors thapsigargin or tunicamycin. Surprisingly, AICAR acted independent of AMPK or AICAR conversion to 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl monophosphate (ZMP) while requiring intracellular uptake via the equilibrative nucleoside transporter (ENT) ENT1 or the concentrative nucleoside transporter (CNT) CNT3. AICAR did not affect the initiation of the ER stress response, but inhibited the expression of major ER stress transcriptional effectors. Furthermore, AICAR inhibited autophosphorylation of the ER stress sensor inositol-requiring enzyme 1α (IRE1α), while activating its endoribonuclease activity in vitro. Our results suggest that AMPK-independent inhibition of ER stress responses contributes to anti-inflammatory and anti-diabetic effects of AICAR. PMID:27562249

  18. AMPK-independent inhibition of human macrophage ER stress response by AICAR

    PubMed Central

    Boß, Marcel; Newbatt, Yvette; Gupta, Sahil; Collins, Ian; Brüne, Bernhard; Namgaladze, Dmitry

    2016-01-01

    Obesity-associated insulin resistance is driven by inflammatory processes in response to metabolic overload. Obesity-associated inflammation can be recapitulated in cell culture by exposing macrophages to saturated fatty acids (SFA), and endoplasmic reticulum (ER) stress responses essentially contribute to pro-inflammatory signalling. AMP-activated protein kinase (AMPK) is a central metabolic regulator with established anti-inflammatory actions. Whether pharmacological AMPK activation suppresses SFA-induced inflammation in a human system is unclear. In a setting of hypoxia-potentiated inflammation induced by SFA palmitate, we found that the AMP-mimetic AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) potently suppressed upregulation of ER stress marker mRNAs and pro-inflammatory cytokines. Furthermore, AICAR inhibited macrophage ER stress responses triggered by ER-stressors thapsigargin or tunicamycin. Surprisingly, AICAR acted independent of AMPK or AICAR conversion to 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl monophosphate (ZMP) while requiring intracellular uptake via the equilibrative nucleoside transporter (ENT) ENT1 or the concentrative nucleoside transporter (CNT) CNT3. AICAR did not affect the initiation of the ER stress response, but inhibited the expression of major ER stress transcriptional effectors. Furthermore, AICAR inhibited autophosphorylation of the ER stress sensor inositol-requiring enzyme 1α (IRE1α), while activating its endoribonuclease activity in vitro. Our results suggest that AMPK-independent inhibition of ER stress responses contributes to anti-inflammatory and anti-diabetic effects of AICAR. PMID:27562249

  19. Mechanical Stress Induces Biotic and Abiotic Stress Responses via a Novel cis-Element

    PubMed Central

    Walley, Justin W; Coughlan, Sean; Hudson, Matthew E; Covington, Michael F; Kaspi, Roy; Banu, Gopalan; Harmer, Stacey L; Dehesh, Katayoon

    2007-01-01

    Plants are continuously exposed to a myriad of abiotic and biotic stresses. However, the molecular mechanisms by which these stress signals are perceived and transduced are poorly understood. To begin to identify primary stress signal transduction components, we have focused on genes that respond rapidly (within 5 min) to stress signals. Because it has been hypothesized that detection of physical stress is a mechanism common to mounting a response against a broad range of environmental stresses, we have utilized mechanical wounding as the stress stimulus and performed whole genome microarray analysis of Arabidopsis thaliana leaf tissue. This led to the identification of a number of rapid wound responsive (RWR) genes. Comparison of RWR genes with published abiotic and biotic stress microarray datasets demonstrates a large overlap across a wide range of environmental stresses. Interestingly, RWR genes also exhibit a striking level and pattern of circadian regulation, with induced and repressed genes displaying antiphasic rhythms. Using bioinformatic analysis, we identified a novel motif overrepresented in the promoters of RWR genes, herein designated as the Rapid Stress Response Element (RSRE). We demonstrate in transgenic plants that multimerized RSREs are sufficient to confer a rapid response to both biotic and abiotic stresses in vivo, thereby establishing the functional involvement of this motif in primary transcriptional stress responses. Collectively, our data provide evidence for a novel cis-element that is distributed across the promoters of an array of diverse stress-responsive genes, poised to respond immediately and coordinately to stress signals. This structure suggests that plants may have a transcriptional network resembling the general stress signaling pathway in yeast and that the RSRE element may provide the key to this coordinate regulation. PMID:17953483

  20. RAD18, WRNIP1 and ATMIN promote ATM signalling in response to replication stress.

    PubMed

    Kanu, N; Zhang, T; Burrell, R A; Chakraborty, A; Cronshaw, J; DaCosta, C; Grönroos, E; Pemberton, H N; Anderton, E; Gonzalez, L; Sabbioneda, S; Ulrich, H D; Swanton, C; Behrens, A

    2016-07-28

    The DNA replication machinery invariably encounters obstacles that slow replication fork progression, and threaten to prevent complete replication and faithful segregation of sister chromatids. The resulting replication stress activates ATR, the major kinase involved in resolving impaired DNA replication. In addition, replication stress also activates the related kinase ATM, which is required to prevent mitotic segregation errors. However, the molecular mechanism of ATM activation by replication stress is not defined. Here, we show that monoubiquitinated Proliferating Cell Nuclear Antigen (PCNA), a marker of stalled replication forks, interacts with the ATM cofactor ATMIN via WRN-interacting protein 1 (WRNIP1). ATMIN, WRNIP1 and RAD18, the E3 ligase responsible for PCNA monoubiquitination, are specifically required for ATM signalling and 53BP1 focus formation induced by replication stress, not ionising radiation. Thus, WRNIP1 connects PCNA monoubiquitination with ATMIN/ATM to activate ATM signalling in response to replication stress and contribute to the maintenance of genomic stability. PMID:26549024

  1. Stress responses of spring rape plants to soil flooding

    NASA Astrophysics Data System (ADS)

    Balakhnina, T.; Bennicelli, R.; Stêpniewska, Z.; Stêpniewski, W.; Borkowska, A.; Fomina, I.

    2012-10-01

    Stress responses of spring rape to soil hypoxia were investigated during 8-days flooding. Soil air-filled porosity decreased from 25-30% to 0%, oxygen diffusion rate - from 2.6-3.5 to 0.34 μmol O2 m-2 s-1, and redox potential - from 460 to 150mVwithin few hours. Alcohol dehydrogenase activity in roots increased up to 7-fold after one day of flooding and then decreased to 170% of control. Superoxide dismutase activity in roots increased by 27% during first 3 days and then dropped to 60% of control; in the leaves superoxide dismutase activity increased in average by 44%. Ascorbate peroxidase activity in leaves increased by 37% during first 3 days and then decreased to control value. Glutathione reductase activity increased by 45% in roots of flooded plants but did not change in leaves. Proline concentration in leaves increased up to 4-fold on the 3d day of flooding and then decreased to control value. Thus soil flooding induces increase of alcohol dehydrogenase activity and subsequent increase of superoxide dismutase and glutathione reductase activities in roots while the leaves display a few days increase of free proline concentration and ascorbate peroxidase activity, and a long-term increase of superoxide dismutase activity.

  2. Child Anxiety Symptoms Related to Longitudinal Cortisol Trajectories and Acute Stress Responses: Evidence of Developmental Stress Sensitization

    PubMed Central

    Laurent, Heidemarie K.; Gilliam, Kathryn S.; Wright, Dorianne B.; Fisher, Philip A.

    2015-01-01

    Cross-sectional research suggests that individuals at risk for internalizing disorders show differential activation levels and/or dynamics of stress-sensitive physiological systems, possibly reflecting a process of stress sensitization. However, there is little longitudinal research to clarify how the development of these systems over time relates to activation during acute stress, and how aspects of such activation map onto internalizing symptoms. We investigated children’s (n=107) diurnal hypothalamic-pituitary-adrenal activity via salivary cortisol (morning and evening levels) across 29 assessments spanning 6+ years, and related longitudinal patterns to acute stress responses at the end of this period (age 9–10). Associations with child psychiatric symptoms at age 10 were also examined to determine internalizing risk profiles. Increasing morning cortisol levels across assessments predicted less of a cortisol decline following interpersonal stress at age 9, and higher cortisol levels during performance stress at age 10. These same profiles of high and/or sustained cortisol elevation during psychosocial stress were associated with child anxiety symptoms. Results suggest developmental sensitization to stress—reflected in rising morning cortisol and eventual hyperactivation during acute stress exposure—may distinguish children at risk for internalizing disorders. PMID:25688433

  3. Campylobacter: stress responses and biofilm formation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ability of Campylobacter jejuni to tolerate stresses, including heat and acid stress, in the presence and absence of a competitive microflora was investigated. D-values showed that C. jejuni 81-176 parent and luxS mutant strains were inactivated more rapidly when in the presence of a competitiv...

  4. [Modality of individual response to stress ].

    PubMed

    Cassitto, M G

    2009-01-01

    "Stress is a state which is accompanied by physical, psychological or social complaints or dysfunctions and which results from individuals feeling unable to bridge the gap with the requirements or expectations placed on them......stress is not a disease but prolonged exposure to it may reduce effectiveness at work and may cause ill health". This is the stress definition reported by the EU Framework Agreement on Work Related Stress signed 8 October '04 by four workers and employers signatory parties. In order to describe this state of distress, four observation levels can be used, namely data from literature, the subjective symptoms, the related or observed behaviour dysfunctions and the occupational, social performance dysfunctions. Analysis of and interrelations among these four areas can help a better identification of the stress effects and characterize the most frequently observed aspects. PMID:19827284

  5. Biochemical identification of a neutral sphingomyelinase 1 (NSM1)-like enzyme as the major NSM activity in the DT40 B-cell line: absence of a role in the apoptotic response to endoplasmic reticulum stress.

    PubMed Central

    Fensome, Amanda C; Josephs, Michelle; Katan, Matilda; Rodrigues-Lima, Fernando

    2002-01-01

    DT40 cells have approx. 10-fold higher Mg2+-dependent neutral sphingomyelinase (NSM) activity in comparison with other B-cell lines and contain very low acidic sphingomyelinase activity. Purification of this activity from DT40 cell membranes suggested the presence of one major NSM isoform. Although complete purification of this isoform could not be achieved, partially purified fractions were examined further with regard to the known characteristics of previously partially purified NSMs and the two cloned enzymes exhibiting in vitro NSM activity (NSM1 and NSM2). For a direct comparative study, highly purified brain preparations, purified NSM1 protein and Bacillus cereus enzyme were used. Analysis of the enzymic properties of the partially purified DT40 NSM, such as cation dependence, substrate specificity, redox regulation and stimulation by phosphatidylserine, together with the localization of this enzyme to the endoplasmic reticulum (ER), suggested that this NSM from DT40 cells corresponds to NSM1. Further studies aimed to correlate presence of the high levels of this NSM1-like activity in DT40 cells with the ability of these cells to accumulate ceramide and undergo apoptosis. When DT40 cells were stimulated to apoptose by a variety of agents, including the ER stress, an increase in endogenous ceramide levels was observed. However, these responses were not enhanced compared with another B-cell line (Nalm-6), characterized by low sphingomyelinase activity. In addition, DT40 cells were not more susceptible to ceramide accumulation and apoptosis when exposed to the ER stress compared with other apoptotic agents. Inhibition of de novo synthesis of ceramide partially inhibited its accumulation, indicating that the ceramide production in DT40 cells could be complex and, under some conditions, could involve both sphingomyelin hydrolysis and ceramide synthesis. PMID:12071841

  6. Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress

    PubMed Central

    Picard, Martin; McManus, Meagan J.; Gray, Jason D.; Nasca, Carla; Moffat, Cynthia; Kopinski, Piotr K.; Seifert, Erin L.; McEwen, Bruce S.; Wallace, Douglas C.

    2015-01-01

    The experience of psychological stress triggers neuroendocrine, inflammatory, metabolic, and transcriptional perturbations that ultimately predispose to disease. However, the subcellular determinants of this integrated, multisystemic stress response have not been defined. Central to stress adaptation is cellular energetics, involving mitochondrial energy production and oxidative stress. We therefore hypothesized that abnormal mitochondrial functions would differentially modulate the organism’s multisystemic response to psychological stress. By mutating or deleting mitochondrial genes encoded in the mtDNA [NADH dehydrogenase 6 (ND6) and cytochrome c oxidase subunit I (COI)] or nuclear DNA [adenine nucleotide translocator 1 (ANT1) and nicotinamide nucleotide transhydrogenase (NNT)], we selectively impaired mitochondrial respiratory chain function, energy exchange, and mitochondrial redox balance in mice. The resulting impact on physiological reactivity and recovery from restraint stress were then characterized. We show that mitochondrial dysfunctions altered the hypothalamic–pituitary–adrenal axis, sympathetic adrenal–medullary activation and catecholamine levels, the inflammatory cytokine IL-6, circulating metabolites, and hippocampal gene expression responses to stress. Each mitochondrial defect generated a distinct whole-body stress-response signature. These results demonstrate the role of mitochondrial energetics and redox balance as modulators of key pathophysiological perturbations previously linked to disease. This work establishes mitochondria as stress-response modulators, with implications for understanding the mechanisms of stress pathophysiology and mitochondrial diseases. PMID:26627253

  7. RpoHII Activates Oxidative-Stress Defense Systems and Is Controlled by RpoE in the Singlet Oxygen-Dependent Response in Rhodobacter sphaeroides▿ †

    PubMed Central

    Nuss, Aaron M.; Glaeser, Jens; Klug, Gabriele

    2009-01-01

    Photosynthetic organisms need defense systems against photooxidative stress caused by the generation of highly reactive singlet oxygen (1O2). Here we show that the alternative sigma factor RpoHII is required for the expression of important defense factors and that deletion of rpoHII leads to increased sensitivity against exposure to 1O2 and methylglyoxal in Rhodobacter sphaeroides. The gene encoding RpoHII is controlled by RpoE, and thereby a sigma factor cascade is constituted. We provide the first in vivo study that identifies genes controlled by an RpoHII-type sigma factor, which is widely distributed in the Alphaproteobacteria. RpoHII-dependent genes encode oxidative-stress defense systems, including proteins for the degradation of methylglyoxal, detoxification of peroxides, 1O2 scavenging, and redox and iron homeostasis. Our experiments indicate that glutathione (GSH)-dependent mechanisms are involved in the defense against photooxidative stress in photosynthetic bacteria. Therefore, we conclude that systems pivotal for the organism's defense against photooxidative stress are strongly dependent on GSH and are specifically recognized by RpoHII in R. sphaeroides. PMID:18978062

  8. Gender affects sympathetic and hemodynamic response to postural stress

    NASA Technical Reports Server (NTRS)

    Shoemaker, J. K.; Hogeman, C. S.; Khan, M.; Kimmerly, D. S.; Sinoway, L. I.

    2001-01-01

    We tested the hypothesis that differences in sympathetic reflex responses to head-up tilt (HUT) between males (n = 9) and females (n = 8) were associated with decrements in postural vasomotor responses in women. Muscle sympathetic nerve activity (MSNA; microneurography), heart rate, stroke volume (SV; Doppler), and blood pressure (Finapres) were measured during a progressive HUT protocol (5 min at each of supine, 20 degrees, 40 degrees, and 60 degrees ). MSNA and hemodynamic responses were also measured during the cold pressor test (CPT) to examine nonbaroreflex neurovascular control. SV was normalized to body surface area (SV(i)) to calculate the index of cardiac output (Q(i)), and total peripheral resistance (TPR). During HUT, heart rate increased more in females versus males (P < 0.001) and SV(i) and Q(i) decreased similarly in both groups. Mean arterial pressure (MAP) increased to a lesser extent in females versus males in the HUT (P < 0.01) but increases in TPR during HUT were similar. MSNA burst frequency was lower in females versus males in supine (P < 0.03) but increased similarly during HUT. Average amplitude/burst increased in 60 degrees HUT for males but not females. Both males and females demonstrated an increase in MAP as well as MSNA burst frequency, mean burst amplitude, and total MSNA during the CPT. However, compared with females, males demonstrated a greater neural response (DeltaTotal MSNA) due to a larger increase in mean burst amplitude (P < 0.05). Therefore, these data point to gender-specific autonomic responses to cardiovascular stress. The different MSNA response to postural stress between genders may contribute importantly to decrements in blood pressure control during HUT in females.

  9. Dimethylsulfoniopropionate, superoxide dismutase and glutathione as stress response indicators in three corals under short-term hyposalinity stress.

    PubMed

    Gardner, Stephanie G; Nielsen, Daniel A; Laczka, Olivier; Shimmon, Ronald; Beltran, Victor H; Ralph, Peter J; Petrou, Katherina

    2016-02-10

    Corals are among the most active producers of dimethylsulfoniopropionate (DMSP), a key molecule in marine sulfur cycling, yet the specific physiological role of DMSP in corals remains elusive. Here, we examine the oxidative stress response of three coral species (Acropora millepora, Stylophora pistillata and Pocillopora damicornis) and explore the antioxidant role of DMSP and its breakdown products under short-term hyposalinity stress. Symbiont photosynthetic activity declined with hyposalinity exposure in all three reef-building corals. This corresponded with the upregulation of superoxide dismutase and glutathione in the animal host of all three species. For the symbiont component, there were differences in antioxidant regulation, demonstrating differential responses to oxidative stress between the Symbiodinium subclades. Of the three coral species investigated, only A. millepora provided any evidence of the role of DMSP in the oxidative stress response. Our study reveals variability in antioxidant regulation in corals and highlights the influence life-history traits, and the subcladal differences can have on coral physiology. Our data expand on the emerging understanding of the role of DMSP in coral stress regulation and emphasizes the importance of exploring both the host and symbiont responses for defining the threshold of the coral holobiont to hyposalinity stress. PMID:26865302

  10. Transcriptional profiling in response to terminal drought stress reveals differential responses along the wheat genome

    PubMed Central

    Aprile, Alessio; Mastrangelo, Anna M; De Leonardis, Anna M; Galiba, Gabor; Roncaglia, Enrica; Ferrari, Francesco; De Bellis, Luigi; Turchi, Luana; Giuliano, Giovanni; Cattivelli, Luigi

    2009-01-01

    Background Water stress during grain filling has a marked effect on grain yield, leading to a reduced endosperm cell number and thus sink capacity to accumulate dry matter. The bread wheat cultivar Chinese Spring (CS), a Chinese Spring terminal deletion line (CS_5AL-10) and the durum wheat cultivar Creso were subjected to transcriptional profiling after exposure to mild and severe drought stress at the grain filling stage to find evidences of differential stress responses associated to different wheat genome regions. Results The transcriptome analysis of Creso, CS and its deletion line revealed 8,552 non redundant probe sets with different expression levels, mainly due to the comparisons between the two species. The drought treatments modified the expression of 3,056 probe sets. Besides a set of genes showing a similar drought response in Creso and CS, cluster analysis revealed several drought response features that can be associated to the different genomic structure of Creso, CS and CS_5AL-10. Some drought-related genes were expressed at lower level (or not expressed) in Creso (which lacks the D genome) or in the CS_5AL-10 deletion line compared to CS. The chromosome location of a set of these genes was confirmed by PCR-based mapping on the D genome (or the 5AL-10 region). Many clusters were characterized by different level of expression in Creso, CS and CS_AL-10, suggesting that the different genome organization of the three genotypes may affect plant adaptation to stress. Clusters with similar expression trend were grouped and functional classified to mine the biological mean of their activation or repression. Genes involved in ABA, proline, glycine-betaine and sorbitol pathways were found up-regulated by drought stress. Furthermore, the enhanced expression of a set of transposons and retrotransposons was detected in CS_5AL-10. Conclusion Bread and durum wheat genotypes were characterized by a different physiological reaction to water stress and by a

  11. Hemodynamic response patterns to mental stress: diagnostic and therapeutic implications.

    PubMed

    Rüddel, H; Langewitz, W; Schächinger, H; Schmieder, R; Schulte, W

    1988-08-01

    Stress has been identified as contributing to the development of cardiovascular disease. The pathophysiologic link between stress and disease still remains unclear. Because experimental stress testing in the laboratory permits the examination of the underlying mechanism for stress-induced blood pressure, analyses of cardiovascular reactivity during emotional stress could be of particular clinical importance. The analyses of pooled data during the past 6 years (n = 298, age from 20 to 60 years, normotensive subjects as well as patients with borderline and mild essential hypertension) reveal that stress-induced changes in stroke volume and especially in total peripheral resistance are crucial parameters to analyze the hemodynamic stress response. However, neither those simple nor complex response patterns such as "hot reactor" describe clinically distinct subgroups of persons. When physiologic testing was repeated in hypertensive patients after effective long-term antihypertensive therapy with clonidine, oxprenolol, nitrendipine, or enalapril, no attenuation of the stress-induced increase in blood pressure was found in any of these groups. However, heart rate reactivity and stress-induced changes in total peripheral resistance were altered significantly by oxprenolol and nitrendipine. The beta-adrenoceptor blocker decreased heart rate reactivity and increased reactivity of peripheral resistance; the calcium antagonist decreased stress-induced changes in peripheral resistance and increased the heart rate response. The centrally acting sympatholytic regimen and the angiotensin-converting enzyme inhibitor had no impact on the hemodynamic response pattern during emotional challenge. PMID:3394640

  12. Hypothalamic oxytocin mediates social buffering of the stress response

    PubMed Central

    Smith, Adam S.; Wang, Zuoxin

    2013-01-01

    Background While stressful life events can enhance the risk of mental disorders, positive social interactions can propagate good mental health and normal behavioral routines. Still, the neural systems that promote these benefits are undetermined. Oxytocin is a hormone involved in social behavior and stress; thus, we focus on the impact that social buffering has on the stress response and the governing effects of oxytocin. Methods Female prairie voles (Microtus ochrogaster) were exposed to 1 hr immobilization stress then recovered alone or with their male partner to characterize the effect of social contact on the behavioral, physiological, and neuroendocrine stress response. In addition, we treated immobilized females recovering alone with oxytocin, or vehicle, and females recovering with their male partner with a selective oxytocin receptor antagonist, or vehicle. Group sizes varied from 6 to 8 voles (n = 98 total). Results We found that 1 hr immobilization increased anxiety-like behaviors and circulating levels of corticosterone, a stress hormone, in females recovering alone, but not the females recovering with their male partner. This social buffering by the male partner on biobehavioral responses to stress was accompanied by increased oxytocin release in the paraventricular nucleus (PVN) of the hypothalamus. Intra-PVN oxytocin injections reduced behavioral and corticosterone responses to immobilization whereas injections of an oxytocin receptor antagonist blocked the effects of the social buffering. Conclusions Together, our data demonstrate that PVN oxytocin mediates the social buffering effects on the stress response, and thus may be a target for treatment of stress-related disorders. PMID:24183103

  13. Molecular mechanisms of the plant heat stress response

    SciTech Connect

    Qu, Ai-Li; Ding, Yan-Fei; Jiang, Qiong; Zhu, Cheng

    2013-03-08

    Highlights: ► This review elaborates the response networks of heat stress in plants. ► It elaborates proteins responding to heat stress in special physiological period. ► The proteins and pathways have formed a basic network of the heat stress response. ► Achievements of the various technologies are also combined. -- Abstract: High temperature has become a global concern, which seriously affects the growth and production of plants, particularly crops. Thus, the molecular mechanism of the heat stress response and breeding of heat-tolerant plants is necessary to protect food production and ensure crop safety. This review elaborates on the response networks of heat stress in plants, including the Hsf and Hsp response pathways, the response of ROS and the network of the hormones. In addition, the production of heat stress response elements during particular physiological periods of the plant is described. We also discuss the existing problems and future prospects concerning the molecular mechanisms of the heat stress response in plants.

  14. Chronic stress increases the opioid-mediated inhibition of the pituitary-adrenocortical response to acute stress in pigs.

    PubMed

    Janssens, C J; Helmond, F A; Loyens, L W; Schouten, W G; Wiegant, V M

    1995-04-01

    The role of endogenous opioid mechanisms in the pituitary-adrenocortical response to acute stress was investigated in a longitudinal study in cyclic female pigs before and after exposure to chronic stress (long term tethered housing). Challenge of loose-housed pigs with acute nose-sling stress for 15 min induced an activation of the hypothalamic-pituitary-adrenocortical axis, evidenced by a transient increase in plasma ACTH (peak height above basal, 98 +/- 12 pg/ml; mean +/- SEM) and cortisol (54 +/- 3 ng/ml) concentrations. Pretreatment with the opioid receptor antagonist naloxone (0.5 mg/kg BW, iv bolus) increased the challenge-induced ACTH and cortisol responses to 244 +/- 36 pg/ml and 65 +/- 5 ng/ml, respectively. This indicates that during acute nose-sling stress, endogenous opioid systems are activated that inhibit the pituitary-adrenocortical response. After exposure of the pigs to chronic stress (10-11 weeks of tethered housing), the challenge-induced ACTH response was attenuated, whereas the cortisol response remained unchanged, suggesting an increased adrenocortical sensitivity to circulating ACTH. In addition, pretreatment with naloxone induced a greater increment in the ACTH and cortisol responses in tethered pigs than in loose-housed pigs. As no such changes were found in control animals housed loose during the entire experimental period, this indicates that the impact of opioid systems had increased due to chronic stress. The increased impact of opioid systems during chronic stress may prevent excessive hypothalamic-pituitary-adrenocortical responses to acute stressors and, thus, may be of adaptive value. PMID:7895656

  15. Role of shame and body esteem in cortisol stress responses.

    PubMed

    Lupis, Sarah B; Sabik, Natalie J; Wolf, Jutta M

    2016-04-01

    Studies assessing the role of shame in HPA axis reactivity report mixed findings. Discrepancies may be due to methodological difficulties and inter-individual differences in the propensity to experience shame in a stressful situation. Hence, the current study combined self-report of shame and facial coding of shame expressions and assessed the role of body esteem as a moderator of the shame-stress link. For this, 44 healthy students (24F, age 20.5 ± 2.1 years) were exposed to an acute psychosocial stress paradigm (Trier Social Stress Test: TSST). Salivary cortisol levels were measured throughout the protocol. Trait shame was measured before the stress test, and state shame immediately afterwards. Video recordings of the TSST were coded to determine emotion expressions. State shame was neither associated with cortisol stress responses nor with body esteem (self-report: all ps ≥ .24; expression: all ps ≥ .31). In contrast, higher trait shame was associated with both negative body esteem (p = .049) and stronger cortisol stress responses (p = .013). Lastly, having lower body esteem predicted stronger cortisol stress responses (p = .022); however, it did not significantly moderate the association between shame indices and cortisol stress responses (all ps ≥ .94). These findings suggest that body esteem and trait shame independently contribute to strength of cortisol stress responses. Thus, in addition to trait shame, body esteem emerged as an important predictor of cortisol stress responses and as such, a potential contributor to stress-related negative health outcomes. PMID:26577952

  16. Genome-wide expression analysis upon constitutive activation of the HacA bZIP transcription factor in Aspergillus niger reveals a coordinated cellular response to counteract ER stress

    PubMed Central

    2012-01-01

    Background HacA/Xbp1 is a conserved bZIP transcription factor in eukaryotic cells which regulates gene expression in response to various forms of secretion stress and as part of secretory cell differentiation. In the present study, we replaced the endogenous hacA gene of an Aspergillus niger strain with a gene encoding a constitutively active form of the HacA transcription factor (HacACA). The impact of constitutive HacA activity during exponential growth was explored in bioreactor controlled cultures using transcriptomic analysis to identify affected genes and processes. Results Transcription profiles for the wild-type strain (HacAWT) and the HacACA strain were obtained using Affymetrix GeneChip analysis of three replicate batch cultures of each strain. In addition to the well known HacA targets such as the ER resident foldases and chaperones, GO enrichment analysis revealed up-regulation of genes involved in protein glycosylation, phospholipid biosynthesis, intracellular protein transport, exocytosis and protein complex assembly in the HacACA mutant. Biological processes over-represented in the down-regulated genes include those belonging to central metabolic pathways, translation and transcription. A remarkable transcriptional response in the HacACA strain was the down-regulation of the AmyR transcription factor and its target genes. Conclusions The results indicate that the constitutive activation of the HacA leads to a coordinated regulation of the folding and secretion capacity of the cell, but with consequences on growth and fungal physiology to reduce secretion stress. PMID:22846479

  17. StressMicrobesInfo: Database of Microorganisms Responsive to Stress Conditions.

    PubMed

    Prabha, Ratna; Singh, Dhananjaya P; Rai, Anil

    2016-09-01

    Microorganisms are continuously exposed to numerous stress conditions and had evolved with numerous evolutionary adaptations and physiological acclimation mechanisms against stress effects. Any information related to the microbes responsive to stress conditions will help scientists working in the area of stress biology. Currently, there is lack of information resource on this aspect and for getting information about microbes susceptible or tolerant to different environmental changes, literature searching is the only option. Here, we present a database StressMicrobesInfo that was developed with a mandate to provide information about microbes responding to various biotic and abiotic stress conditions. This database currently contains information about 183 microbes along with a brief detail for each. StressMicrobesInfo will facilitate researchers working on stress-related microbes as a starting point and will facilitate them with the microbes which are susceptible or resistant towards particular stress conditions. PMID:26264053

  18. Proteomic analysis of endoplasmic reticulum stress responses in rice seeds.

    PubMed

    Qian, Dandan; Tian, Lihong; Qu, Leqing

    2015-01-01

    The defects in storage proteins secretion in the endosperm of transgenic rice seeds often leads to endoplasmic reticulum (ER) stress, which produces floury and shrunken seeds, but the mechanism of this response remains unclear. We used an iTRAQ-based proteomics analysis of ER-stressed rice seeds due to the endosperm-specific suppression of OsSar1 to identify changes in the protein levels in response to ER stress. ER stress changed the expression of 405 proteins in rice seed by >2.0- fold compared with the wild-type control. Of these proteins, 140 were upregulated and 265 were downregulated. The upregulated proteins were mainly involved in protein modification, transport and degradation, and the downregulated proteins were mainly involved in metabolism and stress/defense responses. A KOBAS analysis revealed that protein-processing in the ER and degradation-related proteasome were the predominant upregulated pathways in the rice endosperm in response to ER stress. Trans-Golgi protein transport was also involved in the ER stress response. Combined with bioinformatic and molecular biology analyses, our proteomic data will facilitate our understanding of the systemic responses to ER stress in rice seeds. PMID:26395408

  19. Proteomic analysis of endoplasmic reticulum stress responses in rice seeds

    PubMed Central

    Qian, Dandan; Tian, Lihong; Qu, Leqing

    2015-01-01

    The defects in storage proteins secretion in the endosperm of transgenic rice seeds often leads to endoplasmic reticulum (ER) stress, which produces floury and shrunken seeds, but the mechanism of this response remains unclear. We used an iTRAQ-based proteomics analysis of ER-stressed rice seeds due to the endosperm-specific suppression of OsSar1 to identify changes in the protein levels in response to ER stress. ER stress changed the expression of 405 proteins in rice seed by >2.0- fold compared with the wild-type control. Of these proteins, 140 were upregulated and 265 were downregulated. The upregulated proteins were mainly involved in protein modification, transport and degradation, and the downregulated proteins were mainly involved in metabolism and stress/defense responses. A KOBAS analysis revealed that protein-processing in the ER and degradation-related proteasome were the predominant upregulated pathways in the rice endosperm in response to ER stress. Trans-Golgi protein transport was also involved in the ER stress response. Combined with bioinformatic and molecular biology analyses, our proteomic data will facilitate our understanding of the systemic responses to ER stress in rice seeds. PMID:26395408

  20. Cellular Stress Responses Elicited by Engineered Nanomaterials

    EPA Science Inventory

    Engineered nanomaterials are being incorporated continuously into consumer products, resulting in increased human exposures. The study of engineered nanomaterials has focused largely on oxidative stress and inflammation endpoints without further investigation of underlying pathwa...

  1. Seismic stress responses of soybean to different photosynthetic photon flux

    NASA Technical Reports Server (NTRS)

    Jones, R. S.; Coe, L. L.; Montgomery, L.; Mitchell, C. A.

    1990-01-01

    Physical agitation applied as periodic seismic stress (shaking) reduced stem elongation, leaf expansion, and biomass accumulation by vegetative soybeans. Level of photon flux (PPF) influenced the type and extent of plant response to mechanical stress. Plant parts responded differently as PPF varied between 135 and 592 micromoles m-2 s-1. Stem length was significantly reduced by seismic stress at 135 micromoles m-2 s-1 but this effect was insignificant at higher PPFs. Reduced stem length resulted from an inhibition of internode elongation. Stem diameter was unaffected by stress at the PPFs tested. In contrast to effects on stem elongation, leaf area was insensitive to stress treatments at 135 micromoles m-2 s-1 but was progressively inhibited by stress as PPF increased. Statistically significant reductions in shoot f. wt and d. wt by seismic stress occurred only at 295 micromoles m-2 s-1. Root biomass accumulation was not affected by seismic stress at any PPF used in this study.

  2. Endoplasmic reticulum stress activates transglutaminase 2 leading to protein aggregation

    PubMed Central

    LEE, JIN-HAENG; JEONG, JAEHO; JEONG, EUI MAN; CHO, SUNG-YUP; KANG, JEONG WOOK; LIM, JISUN; HEO, JINBEOM; KANG, HYUNSOOK; KIM, IN-GYU; SHIN, DONG-MYUNG

    2014-01-01

    Aberrant activation of transglutaminase 2 (TGase2) contributes to a variety of protein conformational disorders such as neurodegenerative diseases and age-related cataracts. The accumulation of improperly folded proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), which promotes either repair or degradation of the damaged proteins. Inadequate UPR results in protein aggregation that may contribute to the development of age-related degenerative diseases. TGase2 is a calcium-dependent enzyme that irreversibly modifies proteins by forming cross-linked protein aggregates. Intracellular TGase2 is activated by oxidative stress which generates large quantities of unfolded proteins. However, the relationship between TGase2 activity and UPR has not yet been established. In the present study, we demonstrated that ER stress activated TGase2 in various cell types. TGase2 activation was dependent on the ER stress-induced increase in the intracellular calcium ion concentration but not on the TGase2 protein expression level. Enzyme substrate analysis revealed that TGase2-mediated protein modification promoted protein aggregation concurrently with decreasing water solubility. Moreover, treatment with KCC009, a TGase2 inhibitor, abrogated ER stress-induced TGase2 activation and subsequent protein aggregation. However, TGase2 activation had no effect on ER stress-induced cell death. These results demonstrate that the accumulation of misfolded proteins activates TGase2, which further accelerates the formation of protein aggregates. Therefore, we suggest that inhibition of TGase2 may be a novel strategy by which to prevent the protein aggregation in age-related degenerative diseases. PMID:24481335

  3. Transcriptional regulation of gene expression during osmotic stress responses by the mammalian target of rapamycin.

    PubMed

    Ortells, M Carmen; Morancho, Beatriz; Drews-Elger, Katherine; Viollet, Benoit; Laderoute, Keith R; López-Rodríguez, Cristina; Aramburu, Jose

    2012-05-01

    Although stress can suppress growth and proliferation, cells can induce adaptive responses that allow them to maintain these functions under stress. While numerous studies have focused on the inhibitory effects of stress on cell growth, less is known on how growth-promoting pathways influence stress responses. We have approached this question by analyzing the effect of mammalian target of rapamycin (mTOR), a central growth controller, on the osmotic stress response. Our results showed that mammalian cells exposed to moderate hypertonicity maintained active mTOR, which was required to sustain their cell size and proliferative capacity. Moreover, mTOR regulated the induction of diverse osmostress response genes, including targets of the tonicity-responsive transcription factor NFAT5 as well as NFAT5-independent genes. Genes sensitive to mTOR-included regulators of stress responses, growth and proliferation. Among them, we identified REDD1 and REDD2, which had been previously characterized as mTOR inhibitors in other stress contexts. We observed that mTOR facilitated transcription-permissive conditions for several osmoresponsive genes by enhancing histone H4 acetylation and the recruitment of RNA polymerase II. Altogether, these results reveal a previously unappreciated role of mTOR in regulating transcriptional mechanisms that control gene expression during cellular stress responses. PMID:22287635

  4. Antagonistic interplay between hypocretin and leptin in the lateral hypothalamus regulates stress responses.

    PubMed

    Bonnavion, Patricia; Jackson, Alexander C; Carter, Matthew E; de Lecea, Luis

    2015-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis functions to coordinate behavioural and physiological responses to stress in a manner that depends on the behavioural state of the organism. However, the mechanisms through which arousal and metabolic states influence the HPA axis are poorly understood. Here using optogenetic approaches in mice, we show that neurons that produce hypocretin (Hcrt)/orexin in the lateral hypothalamic area (LHA) regulate corticosterone release and a variety of behaviours and physiological hallmarks of the stress response. Interestingly, we found that Hcrt neuronal activity and Hcrt-mediated stress responses were inhibited by the satiety hormone leptin, which acts, in part, through a network of leptin-sensitive neurons in the LHA. These data demonstrate how peripheral metabolic signals interact with hypothalamic neurons to coordinate stress and arousal and suggest one mechanism through which hyperarousal or altered metabolic states may be linked with abnormal stress responses. PMID:25695914

  5. Maternal Sensitivity and Infant Autonomic and Endocrine Stress Responses

    PubMed Central

    Enlow, Michelle Bosquet; King, Lucy; Schreier, Hannah; Howard, Jamie M.; Rosenfield, David; Ritz, Thomas; Wright, Rosalind J.

    2014-01-01

    Background Early environmental exposures may help shape the development of the autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis, influencing vulnerability for health problems across the lifespan. Little is known about the role of maternal sensitivity in influencing the development of the ANS in early life. Aims To examine associations among maternal sensitivity and infant behavioral distress and ANS and HPA axis reactivity to the Repeated Still-Face Paradigm (SFP-R), a dyadic stress task. Study Design Observational repeated measures study. Subjects Thirty-five urban, sociodemographically diverse mothers and their 6-month-old infants. Outcome Measures Changes in infant affective distress, heart rate, respiratory sinus arrhythmia (RSA), and T-wave amplitude (TWA) across episodes of the SFP-R were assessed. A measure of cortisol output (area under the curve) in the hour following cessation of the SFP-R was also obtained. Results Greater maternal insensitivity was associated with greater infant sympathetic activation (TWA) during periods of stress and tended to be associated with greater cortisol output following the SFP-R. There was also evidence for greater affective distress and less parasympathetic activation (RSA) during the SFP-R among infants of predominantly insensitive mothers. Conclusions Caregiving quality in early life may influence the responsiveness of the sympathetic and parasympathetic branches of the ANS as well as the HPA axis. Consideration of the ANS and HPA axis systems together provides a fuller representation of adaptive versus maladaptive stress responses. The findings highlight the importance of supporting high quality caregiving in the early years of life, which is likely to promote later health. PMID:24794304

  6. Extracytoplasmic Stress Responses Induced by Antimicrobial Cationic Polyethylenimines

    PubMed Central

    Lander, Blaine A.; Checchi, Kyle D.; Koplin, Stephen A.; Smith, Virginia F.; Domanski, Tammy L.; Isaac, Daniel D.; Lin, Shirley

    2014-01-01

    The ability of an antimicrobial, cationic polyethylenimine (PEI+) to induce the three known extracytoplasmic stress responses of Escherichia coli was quantified. Exposure of E. coli to PEI+ in solution revealed specific, concentration-dependent induction of the Cpx extracytoplasmic cellular stress response, ~2.0-2.5 fold at 320 μg/mL after 1.5 hours without significant induction of the σE or Bae stress responses. In comparison, exposure of E. coli to a non-antimicrobial polymer, polyethylene oxide (PEO), resulted in no induction of the three stress responses. The antimicrobial small molecule vanillin, a known membrane pore-forming compound, was observed to cause specific, concentration-dependent induction of the σE stress response, ~6-fold at 640 μg/mL after 1.5 hours, without significant induction of the Cpx or Bae stress responses. The different stress response induction profiles of PEI+ and vanillin suggest that although both are antimicrobial compounds, they interact with the bacterial membrane and extracytoplasmic area by unique mechanisms. EPR studies of liposomes containing spin-labeled lipids exposed to PEI+, vanillin, and PEO reveal that PEI+ and PEO increased membrane stability whereas vanillin was found to have no effect. PMID:22797865

  7. Stress Response Pathways in Ameloblasts: Implications for Amelogenesis and Dental Fluorosis

    PubMed Central

    Sierant, Megan L.; Bartlett, John D.

    2012-01-01

    Human enamel development of the permanent teeth takes place during childhood and stresses encountered during this period can have lasting effects on the appearance and structural integrity of the enamel. One of the most common examples of this is the development of dental fluorosis after childhood exposure to excess fluoride, an elemental agent used to increase enamel hardness and prevent dental caries. Currently the molecular mechanism responsible for dental fluorosis remains unknown; however, recent work suggests dental fluorosis may be the result of activated stress response pathways in ameloblasts during the development of permanent teeth. Using fluorosis as an example, the role of stress response pathways during enamel maturation is discussed. PMID:23745169

  8. Overexpression of a Cytosolic Abiotic Stress Responsive Universal Stress Protein (SbUSP) Mitigates Salt and Osmotic Stress in Transgenic Tobacco Plants

    PubMed Central

    Udawat, Pushpika; Jha, Rajesh K.; Sinha, Dinkar; Mishra, Avinash; Jha, Bhavanath

    2016-01-01

    The universal stress protein (USP) is a ubiquitous protein and plays an indispensable role in plant abiotic stress tolerance. The genome of Salicornia brachiata contains two homologs of intron less SbUSP gene which encodes for salt and osmotic responsive USP. In vivo localization reveals that SbUSP is a membrane bound cytosolic protein. The role of the gene was functionally validated by developing transgenic tobacco and compared with control [wild-type (WT) and vector control (VC)] plants under different abiotic stress condition. Transgenic lines (T1) exhibited higher chlorophyll, relative water, proline, total sugar, reducing sugar, free amino acids, polyphenol contents, osmotic potential, membrane stability, and lower electrolyte leakage and lipid peroxidation (malondialdehyde content) under stress treatments than control (WT and VC) plants. Lower accumulation of H2O2 and O2− radicals was also detected in transgenic lines compared to control plants under stress conditions. Present study confers that overexpression of the SbUSP gene enhances plant growth, alleviates ROS buildup, maintains ion homeostasis and improves the physiological status of the plant under salt and osmotic stresses. Principal component analysis exhibited a statistical distinction of plant response to salinity stress, and a significant response was observed for transgenic lines under stress, which provides stress endurance to the plant. A possible signaling role is proposed that some downstream genes may get activated by abiotic stress responsive cytosolic SbUSP, which leads to the protection of cell from oxidative damages. The study unveils that ectopic expression of the gene mitigates salt or osmotic stress by scavenging ROS and modulating the physiological process of the plant. PMID:27148338

  9. Overexpression of a Cytosolic Abiotic Stress Responsive Universal Stress Protein (SbUSP) Mitigates Salt and Osmotic Stress in Transgenic Tobacco Plants.

    PubMed

    Udawat, Pushpika; Jha, Rajesh K; Sinha, Dinkar; Mishra, Avinash; Jha, Bhavanath

    2016-01-01

    The universal stress protein (USP) is a ubiquitous protein and plays an indispensable role in plant abiotic stress tolerance. The genome of Salicornia brachiata contains two homologs of intron less SbUSP gene which encodes for salt and osmotic responsive USP. In vivo localization reveals that SbUSP is a membrane bound cytosolic protein. The role of the gene was functionally validated by developing transgenic tobacco and compared with control [wild-type (WT) and vector control (VC)] plants under different abiotic stress condition. Transgenic lines (T1) exhibited higher chlorophyll, relative water, proline, total sugar, reducing sugar, free amino acids, polyphenol contents, osmotic potential, membrane stability, and lower electrolyte leakage and lipid peroxidation (malondialdehyde content) under stress treatments than control (WT and VC) plants. Lower accumulation of H2O2 and [Formula: see text] radicals was also detected in transgenic lines compared to control plants under stress conditions. Present study confers that overexpression of the SbUSP gene enhances plant growth, alleviates ROS buildup, maintains ion homeostasis and improves the physiological status of the plant under salt and osmotic stresses. Principal component analysis exhibited a statistical distinction of plant response to salinity stress, and a significant response was observed for transgenic lines under stress, which provides stress endurance to the plant. A possible signaling role is proposed that some downstream genes may get activated by abiotic stress responsive cytosolic SbUSP, which leads to the protection of cell from oxidative damages. The study unveils that ectopic expression of the gene mitigates salt or osmotic stress by scavenging ROS and modulating the physiological process of the plant. PMID:27148338

  10. How plants handle multiple stresses: hormonal interactions underlying responses to abiotic stress and insect herbivory.

    PubMed

    Nguyen, Duy; Rieu, Ivo; Mariani, Celestina; van Dam, Nicole M

    2016-08-01

    Adaptive plant responses to specific abiotic stresses or biotic agents are fine-tuned by a network of hormonal signaling cascades, including abscisic acid (ABA), ethylene, jasmonic acid (JA) and salicylic acid. Moreover, hormonal cross-talk modulates plant responses to abiotic stresses and defenses against insect herbivores when they occur simultaneously. How such interactions affect plant responses under multiple stresses, however, is less understood, even though this may frequently occur in natural environments. Here, we review our current knowledge on how hormonal signaling regulates abiotic stress responses and defenses against insects, and discuss the few recent studies that attempted to dissect hormonal interactions occurring under simultaneous abiotic stress and herbivory. Based on this we hypothesize that drought stress enhances insect resistance due to synergistic interactions between JA and ABA signaling. Responses to flooding or waterlogging involve ethylene signaling, which likely reduces plant resistance to chewing herbivores due to its negative cross-talk with JA. However, the outcome of interactions between biotic and abiotic stress signaling is often plant and/or insect species-dependent and cannot simply be predicted based on general knowledge on the involvement of signaling pathways in single stress responses. More experimental data on non-model plant and insect species are needed to reveal general patterns and better understand the molecular mechanisms allowing plants to optimize their responses in complex environments. PMID:27095445

  11. Mesolimbic neuropeptide W coordinates stress responses under novel environments.

    PubMed

    Motoike, Toshiyuki; Long, Jeffrey M; Tanaka, Hirokazu; Sinton, Christopher M; Skach, Amber; Williams, S Clay; Hammer, Robert E; Sakurai, Takeshi; Yanagisawa, Masashi

    2016-05-24

    Neuropeptide B (NPB) and neuropeptide W (NPW) are endogenous neuropeptide ligands for the G protein-coupled receptors NPBWR1 and NPBWR2. Here we report that the majority of NPW neurons in the mesolimbic region possess tyrosine hydroxylase immunoreactivity, indicating that a small subset of dopaminergic neurons coexpress NPW. These NPW-containing neurons densely and exclusively innervate two limbic system nuclei in adult mouse brain: the lateral bed nucleus of the stria terminalis and the lateral part of the central amygdala nucleus (CeAL). In the CeAL of wild-type mice, restraint stress resulted in an inhibition of cellular activity, but this stress-induced inhibition was attenuated in the CeAL neurons of NPW(-/-) mice. Moreover, the response of NPW(-/-) mice to either formalin-induced pain stimuli or a live rat (i.e., a potential predator) was abnormal only when they were placed in a novel environment: The mice failed to show the normal species-specific self-protective and aversive reactions. In contrast, the behavior of NPW(-/-) mice in a habituated environment was indistinguishable from that of wild-type mice. These results indicate that the NPW/NPBWR1 system could play a critical role in the gating of stressful stimuli during exposure to novel environments. PMID:27140610

  12. Response of human cells to desiccation: comparison with hyperosmotic stress response

    PubMed Central

    Huang, Zebo; Tunnacliffe, Alan

    2004-01-01

    Increasing interest in anhydrobiosis (‘life without water’) has prompted the use of mammalian cells as a model in which candidate adaptations suspected of conferring desiccation tolerance can be tested. Despite this, there is no information on whether mammalian cells are able to sense and respond to desiccation. We have therefore examined the effect of desiccation on stress signalling pathways and on genes which are proposed to be expressed in response to water loss through osmotic stress. Depending on the severity of the drying regime, human cells survived for at least 24 h. Both SAPK/JNK and p38 mitogen-activated protein kinases (MAPKs) were activated within 30 min by desiccation as well as by all osmotica tested, and therefore MAPK pathways probably play an important role in both responses. Gene induction profiles differed under the two stress conditions, however: quantitative polymerase chain reaction (PCR) experiments showed that AR, BGT-1 and SMIT, which encode proteins governing organic osmolyte accumulation, were induced by hypersalinity but not by desiccation. This was surprising, since these genes have been proposed to be regulated by ionic strength and cell volume, both of which should be significantly affected in drying cells. Further investigation demonstrated that AR, BGT-1 and SMIT expression was dependent on the nature of the osmolyte. This suggests that their regulation involves factors other than intracellular ionic strength and cell volume changes, consistent with the lack of induction by desiccation. Our results show for the first time that human cells react rapidly to desiccation by MAPK activation, and that the response partially overlaps with that to hyperosmotic stress. PMID:15146043

  13. Association between neuroticism and amygdala responsivity emerges under stressful conditions.

    PubMed

    Everaerd, Daphne; Klumpers, Floris; van Wingen, Guido; Tendolkar, Indira; Fernández, Guillén

    2015-05-15

    Increased amygdala reactivity in response to salient stimuli is seen in patients with affective disorders, in healthy subjects at risk for these disorders, and in stressed individuals, making it a prime target for mechanistic studies into the pathophysiology of affective disorders. However, whereas individual differences in neuroticism are thought to modulate the effect of stress on mental health, the mechanistic link between stress, neuroticism and amygdala responsivity is unknown. Thus, we studied the relationship between experimentally induced stress, individual differences in neuroticism, and amygdala responsivity. To this end, fearful and happy faces were presented to a large cohort of young, healthy males (n=120) in two separate functional MRI sessions (stress versus control) in a randomized, controlled cross-over design. We revealed that amygdala reactivity was modulated by an interaction between the factors of stress, neuroticism, and the emotional valence of the facial stimuli. Follow-up analysis showed that neuroticism selectively enhanced amygdala responses to fearful faces in the stress condition. Thus, we show that stress unmasks an association between neuroticism and amygdala responsivity to potentially threatening stimuli. This effect constitutes a possible mechanistic link within the complex pathophysiology of affective disorders, and our novel approach appears suitable for further studies targeting the underlying mechanisms. PMID:25776217

  14. Psychosocial versus physiological stress - Meta-analyses on deactivations and activations of the neural correlates of stress reactions.

    PubMed

    Kogler, Lydia; Müller, Veronika I; Chang, Amy; Eickhoff, Simon B; Fox, Peter T; Gur, Ruben C; Derntl, Birgit

    2015-10-01

    Stress is present in everyday life in various forms and situations. Two stressors frequently investigated are physiological and psychosocial stress. Besides similar subjective and hormonal responses, it has been suggested that they also share common neural substrates. The current study used activation-likelihood-estimation meta-analysis to test this assumption by integrating results of previous neuroimaging studies on stress processing. Reported results are cluster-level FWE corrected. The inferior frontal gyrus (IFG) and the anterior insula (AI) were the only regions that demonstrated overlapping activation for both stressors. Analysis of physiological stress showed consistent activation of cognitive and affective components of pain processing such as the insula, striatum, or the middle cingulate cortex. Contrarily, analysis across psychosocial stress revealed consistent activation of the right superior temporal gyrus and deactivation of the striatum. Notably, parts of the striatum appeared to be functionally specified: the dorsal striatum was activated in physiological stress, whereas the ventral striatum was deactivated in psychosocial stress. Additional functional connectivity and decoding analyses further characterized this functional heterogeneity and revealed higher associations of the dorsal striatum with motor regions and of the ventral striatum with reward processing. Based on our meta-analytic approach, activation of the IFG and the AI seems to indicate a global neural stress reaction. While physiological stress activates a motoric fight-or-flight reaction, during psychosocial stress attention is shifted towards emotion regulation and goal-directed behavior, and reward processing is reduced. Our results show the significance of differentiating physiological and psychosocial stress in neural engagement. Furthermore, the assessment of deactivations in addition to activations in stress research is highly recommended. PMID:26123376

  15. Detection of early plant stress responses in hyperspectral images

    NASA Astrophysics Data System (ADS)

    Behmann, Jan; Steinrücken, Jörg; Plümer, Lutz

    2014-07-01

    Early stress detection in crop plants is highly relevant, but hard to achieve. We hypothesize that close range hyperspectral imaging is able to uncover stress related processes non-destructively in the early stages which are invisible to the human eye. We propose an approach which combines unsupervised and supervised methods in order to identify several stages of progressive stress development from series of hyperspectral images. Stress of an entire plant is detected by stress response levels at pixel scale. The focus is on drought stress in barley (Hordeum vulgare). Unsupervised learning is used to separate hyperspectral signatures into clusters related to different stages of stress response and progressive senescence. Whereas all such signatures may be found in both, well watered and drought stressed plants, their respective distributions differ. Ordinal classification with Support Vector Machines (SVM) is used to quantify and visualize the distribution of progressive stages of senescence and to separate well watered from drought stressed plants. For each senescence stage a distinctive set of most relevant Vegetation Indices (VIs) is identified. The method has been applied on two experiments involving potted barley plants under well watered and drought stress conditions in a greenhouse. Drought stress is detected up to ten days earlier than using NDVI. Furthermore, it is shown that some VIs have overall relevance, while others are specific to particular senescence stages. The transferability of the method to the field is illustrated by an experiment on maize (Zea mays).

  16. Natural variation reveals relationships between pre-stress carbohydrate nutritional status and subsequent responses to xenobiotic and oxidative stress in Arabidopsis thaliana

    PubMed Central

    Ramel, Fanny; Sulmon, Cécile; Gouesbet, Gwenola; Couée, Ivan

    2009-01-01

    Background Soluble sugars are involved in responses to stress, and act as signalling molecules that activate specific or hormone cross-talk transduction pathways. Thus, exogenous sucrose treatment efficiently induces tolerance to the herbicide atrazine in Arabidopsis thaliana plantlets, at least partially through large-scale modifications of expression of stress-related genes. Methods Availability of sugars in planta for stress responses is likely to depend on complex dynamics of soluble sugar accumulation, sucrose–starch partition and organ allocation. The question of potential relationships between endogenous sugar levels and stress responses to atrazine treatment was investigated through analysis of natural genetic accessions of A. thaliana. Parallel quantitative and statistical analysis of biochemical parameters and of stress-sensitive physiological traits was carried out on a set of 11 accessions. Key Results Important natural variation was found between accessions of A. thaliana in pre-stress shoot endogenous sugar levels and responses of plantlets to subsequent atrazine stress. Moreover, consistent trends and statistically significant correlations were detected between specific endogenous sugar parameters, such as the pre-stress end of day sucrose level in shoots, and physiological markers of atrazine tolerance. Conclusions These significant relationships between endogenous carbohydrate metabolism and stress response therefore point to an important integration of carbon nutritional status and induction of stress tolerance in plants. The specific correlation between pre-stress sucrose level and greater atrazine tolerance may reflect adaptive mechanisms that link sucrose accumulation, photosynthesis-related stress and sucrose induction of stress defences. PMID:19789177

  17. A NAP-Family Histone Chaperone Functions in Abiotic Stress Response and Adaptation.

    PubMed

    Tripathi, Amit K; Pareek, Ashwani; Singla-Pareek, Sneh Lata

    2016-08-01

    Modulation of gene expression is one of the most significant molecular mechanisms of abiotic stress response in plants. Via altering DNA accessibility, histone chaperones affect the transcriptional competence of genomic loci. However, in contrast to other factors affecting chromatin dynamics, the role of plant histone chaperones in abiotic stress response and adaptation remains elusive. Here, we studied the physiological function of a stress-responsive putative rice (Oryza sativa) histone chaperone of the NAP superfamily: OsNAPL6. We show that OsNAPL6 is a nuclear-localized H3/H4 histone chaperone capable of assembling a nucleosome-like structure. Utilizing overexpression and knockdown approaches, we found a positive correlation between OsNAPL6 expression levels and adaptation to multiple abiotic stresses. Results of comparative transcriptome profiling and promoter-recruitment studies indicate that OsNAPL6 functions during stress response via modulation of expression of various genes involved in diverse functions. For instance, we show that OsNAPL6 is recruited to OsRad51 promoter, activating its expression and leading to more efficient DNA repair and abrogation of programmed cell death under salinity and genotoxic stress conditions. These results suggest that the histone chaperone OsNAPL6 may serve a regulatory role in abiotic stress physiology possibly via modulating nucleosome dynamics at various stress-associated genomic loci. Taken together, our findings establish a hitherto unknown link between histone chaperones and abiotic stress response in plants. PMID:27342307

  18. A NAP-Family Histone Chaperone Functions in Abiotic Stress Response and Adaptation1[OPEN

    PubMed Central

    Pareek, Ashwani; Singla-Pareek, Sneh Lata

    2016-01-01

    Modulation of gene expression is one of the most significant molecular mechanisms of abiotic stress response in plants. Via altering DNA accessibility, histone chaperones affect the transcriptional competence of genomic loci. However, in contrast to other factors affecting chromatin dynamics, the role of plant histone chaperones in abiotic stress response and adaptation remains elusive. Here, we studied the physiological function of a stress-responsive putative rice (Oryza sativa) histone chaperone of the NAP superfamily: OsNAPL6. We show that OsNAPL6 is a nuclear-localized H3/H4 histone chaperone capable of assembling a nucleosome-like structure. Utilizing overexpression and knockdown approaches, we found a positive correlation between OsNAPL6 expression levels and adaptation to multiple abiotic stresses. Results of comparative transcriptome profiling and promoter-recruitment studies indicate that OsNAPL6 functions during stress response via modulation of expression of various genes involved in diverse functions. For instance, we show that OsNAPL6 is recruited to OsRad51 promoter, activating its expression and leading to more efficient DNA repair and abrogation of programmed cell death under salinity and genotoxic stress conditions. These results suggest that the histone chaperone OsNAPL6 may serve a regulatory role in abiotic stress physiology possibly via modulating nucleosome dynamics at various stress-associated genomic loci. Taken together, our findings establish a hitherto unknown link between histone chaperones and abiotic stress response in plants. PMID:27342307

  19. Activation response of martensitic steels

    SciTech Connect

    Forty, C.B.A.

    1997-09-01

    A hypothetical martensitic steel has been compositionally designed in order to optimize both metallurgical and reduced activation properties. When compared with two other martensitic steels, its activation characteristics are shown to be superior for all activation indices examined. However, these excellent properties are found to be due to the assumed absence of deleterious tramp impurities. When limiting impurity concentrations are determined for the hypothetical steel, they are found to be extremely stringent, and wholly unachievable using industrial scale production methods. It is concluded that only slight improvements can be made to currently available low activation martensitic steels to reduce residual activity responses further. 26 refs., 1 fig., 2 tabs.

  20. Activation Response of Martensitic Steels

    NASA Astrophysics Data System (ADS)

    Forty, C. B. A.

    1997-09-01

    A hypothetical martensitic steel has been compositionally designed in order to optimize both metallurgical and reduced activation properties. When compared with two other martensitic steels, its activation characteristics are shown to be superior for all activation indices examined. However, these excellent properties are found to be due to the assumed absence of deleterious tramp impurities. When limiting impurity concentrations are determined for the hypothetical steel, they are found to be extremely stringent, and wholly unachievable using industrial scale production methods. It is concluded that only slight improvements can be made to currently available low activation martensitic steels to reduce residual activity responses further.

  1. Stress Generation and Adolescent Depression: Contribution of Interpersonal Stress Responses

    ERIC Educational Resources Information Center

    Flynn, Megan; Rudolph, Karen D.

    2011-01-01

    This research examined the proposal that ineffective responses to common interpersonal problems disrupt youths' relationships, which, in turn, contributes to depression during adolescence. Youth (86 girls, 81 boys; M age = 12.41, SD = 1.19) and their primary female caregivers participated in a three-wave longitudinal study. Youth completed a…

  2. Stress Response and Translation Control in Rotavirus Infection.

    PubMed

    López, Susana; Oceguera, Alfonso; Sandoval-Jaime, Carlos

    2016-01-01

    The general stress and innate immune responses are closely linked and overlap at many levels. The outcomes of these responses serve to reprogram host expression patterns to prevent viral invasions. In turn, viruses counter attack these cell responses to ensure their replication. The mechanisms by which viruses attempt to control host cell responses are as varied as the number of different virus families. One of the most recurrent strategies used by viruses to control the antiviral response of the cell is to hijack the translation machinery of the host, such that viral proteins are preferentially synthesized, while the expression of the stress and antiviral responses of the cell are blocked at the translation level. Here, we will review how rotaviruses, an important agent of acute severe gastroenteritis in children, overcome the stress responses of the cell to establish a productive infectious cycle. PMID:27338442

  3. Stress Response and Translation Control in Rotavirus Infection

    PubMed Central

    López, Susana; Oceguera, Alfonso; Sandoval-Jaime, Carlos

    2016-01-01

    The general stress and innate immune responses are closely linked and overlap at many levels. The outcomes of these responses serve to reprogram host expression patterns to prevent viral invasions. In turn, viruses counter attack these cell responses to ensure their replication. The mechanisms by which viruses attempt to control host cell responses are as varied as the number of different virus families. One of the most recurrent strategies used by viruses to control the antiviral response of the cell is to hijack the translation machinery of the host, such that viral proteins are preferentially synthesized, while the expression of the stress and antiviral responses of the cell are blocked at the translation level. Here, we will review how rotaviruses, an important agent of acute severe gastroenteritis in children, overcome the stress responses of the cell to establish a productive infectious cycle. PMID:27338442

  4. The dopaminergic response to acute stress in health and psychopathology: A systematic review.

    PubMed

    Vaessen, Thomas; Hernaus, Dennis; Myin-Germeys, Inez; van Amelsvoort, Thérèse

    2015-09-01

    Previous work in animals has shown that dopamine (DA) in cortex and striatum plays an essential role in stress processing. For the first time, we systematically reviewed the in vivo evidence for DAergic stress processing in health and psychopathology in humans. All studies included (n studies=25, n observations=324) utilized DA D2/3 positron emission tomography and measured DAergic activity during an acute stress challenge. The evidence in healthy volunteers (HV) suggests that physiological, but not psychological, stress consistently increases striatal DA release. Instead, increased medial prefrontal cortex (mPFC) DAergic activity in HV was observed during psychological stress. Across brain regions, stress-related DAergic activity was correlated with the physiological and psychological intensity of the stressor. The magnitude of stress-induced DA release was dependent on rearing conditions, personality traits and genetic variations in several SNPs. In psychopathology, preliminary evidence was found for stress-related dorsal striatal DAergic hyperactivity in psychosis spectrum and a blunted response in chronic cannabis use and pain-related disorders, but results were inconsistent. Physiological stress-induced DAergic activity in striatum in HV may reflect somatosensory properties of the stressor and readiness for active fight-or-flight behavior. DAergic activity in HV in the ventral striatum and mPFC may be more related to expectations about the stressor and threat evaluation, respectively. Future studies with increased sample size in HV and psychopathology assessing the functional relevance of stress-induced DAergic activity, the association between cortical and subcortical DAergic activity and the direct comparison of different stressors are necessary to conclusively elucidate the role of the DA system in the stress response. PMID:26196459

  5. Antioxidant responses of wheat plants under stress

    PubMed Central

    Caverzan, Andréia; Casassola, Alice; Brammer, Sandra Patussi

    2016-01-01

    Abstract Currently, food security depends on the increased production of cereals such as wheat (Triticum aestivum L.), which is an important source of calories and protein for humans. However, cells of the crop have suffered from the accumulation of reactive oxygen species (ROS), which can cause severe oxidative damage to the plants, due to environmental stresses. ROS are toxic molecules found in various subcellular compartments. The equilibrium between the production and detoxification of ROS is sustained by enzymatic and nonenzymatic antioxidants. In the present review, we offer a brief summary of antioxidant defense and hydrogen peroxide (H2O2) signaling in wheat plants. Wheat plants increase antioxidant defense mechanisms under abiotic stresses, such as drought, cold, heat, salinity and UV-B radiation, to alleviate oxidative damage. Moreover, H2O2 signaling is an important factor contributing to stress tolerance in cereals. PMID:27007891

  6. Antioxidant responses of wheat plants under stress.

    PubMed

    Caverzan, Andréia; Casassola, Alice; Brammer, Sandra Patussi

    2016-03-01

    Currently, food security depends on the increased production of cereals such as wheat (Triticum aestivum L.), which is an important source of calories and protein for humans. However, cells of the crop have suffered from the accumulation of reactive oxygen species (ROS), which can cause severe oxidative damage to the plants, due to environmental stresses. ROS are toxic molecules found in various subcellular compartments. The equilibrium between the production and detoxification of ROS is sustained by enzymatic and nonenzymatic antioxidants. In the present review, we offer a brief summary of antioxidant defense and hydrogen peroxide (H2O2) signaling in wheat plants. Wheat plants increase antioxidant defense mechanisms under abiotic stresses, such as drought, cold, heat, salinity and UV-B radiation, to alleviate oxidative damage. Moreover, H2O2 signaling is an important factor contributing to stress tolerance in cereals. PMID:27007891

  7. Cumulative Adversity Sensitizes Neural Response to Acute Stress: Association with Health Symptoms

    PubMed Central

    Seo, Dongju; Tsou, Kristen A; Ansell, Emily B; Potenza, Marc N; Sinha, Rajita

    2014-01-01

    Cumulative adversity (CA) increases stress sensitivity and risk of adverse health outcomes. However, neural mechanisms underlying these associations in humans remain unclear. To understand neural responses underlying the link between CA and adverse health symptoms, the current study assessed brain activity during stress and neutral-relaxing states in 75 demographically matched, healthy individuals with high, mid, and low CA (25 in each group), and their health symptoms using the Cornell Medical Index. CA was significantly associated with greater adverse health symptoms (P=0.01) in all participants. Functional magnetic resonance imaging results indicated significant associations between CA scores and increased stress-induced activity in the lateral prefrontal cortex, insula, striatum, right amygdala, hippocampus, and temporal regions in all 75 participants (p<0.05, whole-brain corrected). In addition to these regions, the high vs low CA group comparison revealed decreased stress-induced activity in the medial orbitofrontal cortex (OFC) in the high CA group (p<0.01, whole-brain corrected). Specifically, hypoactive medial OFC and hyperactive right hippocampus responses to stress were each significantly associated with greater adverse health symptoms (p<0.01). Furthermore, an inverse correlation was found between activity in the medial OFC and right hippocampus (p=0.01). These results indicate that high CA sensitizes limbic–striatal responses to acute stress and also identifies an important role for stress-related medial OFC and hippocampus responses in the effects of CA on increasing vulnerability to adverse health consequences. PMID:24051900

  8. Neural activation during response competition

    NASA Technical Reports Server (NTRS)

    Hazeltine, E.; Poldrack, R.; Gabrieli, J. D.

    2000-01-01

    The flanker task, introduced by Eriksen and Eriksen [Eriksen, B. A., & Eriksen, C. W. (1974). Effects of noise letters upon the identification of a target letter in a nonsearch task. Perception & Psychophysics, 16, 143--149], provides a means to selectively manipulate the presence or absence of response competition while keeping other task demands constant. We measured brain activity using functional magnetic resonance imaging (fMRI) during performance of the flanker task. In accordance with previous behavioral studies, trials in which the flanking stimuli indicated a different response than the central stimulus were performed significantly more slowly than trials in which all the stimuli indicated the same response. This reaction time effect was accompanied by increases in activity in four regions: the right ventrolateral prefrontal cortex, the supplementary motor area, the left superior parietal lobe, and the left anterior parietal cortex. The increases were not due to changes in stimulus complexity or the need to overcome previously learned associations between stimuli and responses. Correspondences between this study and other experiments manipulating response interference suggest that the frontal foci may be related to response inhibition processes whereas the posterior foci may be related to the activation of representations of the inappropriate responses.

  9. Sexual Dimorphism in the Response of Mercurialis annua to Stress.

    PubMed

    Orlofsky, Ezra M; Kozhoridze, Giorgi; Lyubenova, Lyudmila; Ostrozhenkova, Elena; Winkler, J Barbro; Schröder, Peter; Bacher, Adelbert; Eisenreich, Wolfgang; Guy, Micha; Golan-Goldhirsh, Avi

    2016-01-01

    The research presented stemmed from the observations that female plants of the annual dioecious Mercurialis annua outlive male plants. This led to the hypothesis that female plants of M. annua would be more tolerant to stress than male plants. This hypothesis was addressed in a comprehensive way, by comparing morphological, biochemical and metabolomics changes in female and male plants during their development and under salinity. There were practically no differences between the genders in vegetative development and physiological parameters. However, under salinity conditions, female plants produced significantly more new reproductive nodes. Gender-linked differences in peroxidase (POD) and glutathione transferases (GSTs) were involved in anti-oxidation, detoxification and developmental processes in M. annua. ¹H NMR metabolite profiling of female and male M. annua plants showed that under salinity the activity of the TCA cycle increased. There was also an increase in betaine in both genders, which may be explainable by its osmo-compatible function under salinity. The concentration of ten metabolites changed in both genders, while 'Female-only-response' to salinity was detected for five metabolites. In conclusion, dimorphic responses of M. annua plant genders to stress may be attributed to female plants' capacity to survive and complete the reproductive life cycle. PMID:27128954

  10. Habitual Response to Stress in Recovering Adolescent Anorexic Patients

    ERIC Educational Resources Information Center

    Miller, Samantha P.; Erickson, Sarah J.; Branom, Christina; Steiner, Hans

    2009-01-01

    Objective: Although previous research has investigated the stress response in acutely anorexic patients, there is currently little research addressing this response in recovering adolescent anorexic girls. Therefore, this study investigated partially and fully weight-restored anorexic adolescent girls' psychological and physiological response to a…

  11. The Early Endocrine Stress Response in Experimental Subarachnoid Hemorrhage

    PubMed Central

    Nyberg, Christoffer; Karlsson, Torbjörn; Hillered, Lars; Stridsberg, Mats; Ronne Engström, Elisabeth

    2016-01-01

    Introduction In patients with severe illness, such as aneurysmal subarachnoid hemorrhage (SAH), a physiologic stress response is triggered. This includes activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. The aim of this study was to investigate the very early responses of these systems. Methods A porcine animal model of aneurysmal SAH was used. In this model, blood is injected slowly to the basal cisterns above the anterior skull base until the cerebral perfusion pressure is 0 mm Hg. Sampling was done from blood and urine at -10, +15, +75 and +135 minutes from time of induction of SAH. Analyses of adrenocorticotropic hormone (ACTH), cortisol, aldosterone, catecholamines and chromogranin-A were performed. Results Plasma ACTH, serum cortisol and plasma aldosterone increased in the samples following induction of SAH, and started to decline after 75 minutes. Urine cortisol also increased after SAH. Urine catecholamines and their metabolites were found to increase after SAH. Many samples were however below detection level, not allowing for statistical analysis. Plasma chromogranin-A peaked at 15 minutes after SAH, and thereafter decreased. Conclusions The endocrine stress response after aneurysmal SAH was found to start within 15 minutes in the HPA axis with early peak values of ACTH, cortisol and aldosterone. The fact that the concentrations of the HPA axis hormones decreased 135 minutes after SAH may suggest that a similar pattern exists in SAH patients, thus making it difficult to catch these early peak values. There were also indications of early activation of the sympathetic nervous system, but the small number of valid samples made interpretation difficult. PMID:27007694

  12. Stress and thermoregulation: different sympathetic responses and different effects on experimental pain.

    PubMed

    Fechir, M; Schlereth, T; Kritzmann, S; Balon, S; Pfeifer, N; Geber, C; Breimhorst, M; Eberle, T; Gamer, M; Birklein, F

    2009-10-01

    Stress and thermoregulation both activate the sympathetic nervous system (SNS) but might differently affect pain. Studies investigating possible interactions in patients are problematic because of the high prevalence of SNS disturbances in patients. We therefore analyzed the influence of these different sympathetic challenges on experimentally-induced pain in healthy subjects. SNS was activated in two different ways: by mental stress (Stroop task, mental arithmetic task), and by thermoregulatory stimulation using a water-perfused thermal suit (7 degrees C, 32 degrees C, or 50 degrees C). Attentional effects of the mental stress tasks were controlled by using easy control tasks. Both, stress and thermoregulatory stimuli, robustly activated SNS parameters. However, the patterns of activation were different. While stress co-activated heart rate, blood pressure, peripheral vasoconstriction and sweating, thermal stimulation either increased blood pressure (cold) or heart rate and sweating (warm). Only stress was able to induce a significant reduction of pain. The control tasks neither activated the SNS nor altered pain perception. Our results suggest that (1) different patterns of sympathetic activation can be recorded after stress and thermoregulatory challenges and (2) that only stress is able to interfere with sensation of experimental pain. Whether SNS activation is causally responsible for analgesia needs to be further investigated. PMID:19136286

  13. Refining the multisystem view of the stress response: Coordination among cortisol, alpha-amylase, and subjective stress in response to relationship conflict

    PubMed Central

    Powers, Sally I.; Granger, Douglas A.

    2013-01-01

    This study investigated associations among young adults' hypothalamic-pituitary-adrenal axis activity, autonomic nervous system activity, and subjective stress in response to interpersonal conflict to better characterize coordination across stress systems. Seven saliva samples were collected from 199 young adult opposite-sex couples before, during, and after they discussed an unresolved relationship conflict. Samples were later assayed for cortisol and alpha-amylase (sAA). Couples rated anticipatory stress prior to the conflict and perceived stress immediately following the task. Growth curve modeling was used to examine two possible levels of within-person coordination across physiological systems: alignment between cortisol and sAA responses throughout the sampling period (“matched phase coordination”), and association between overall levels of cortisol and sAA in response to conflict (“average level coordination”). Whereas both partners showed the former type of coordination, only women showed the latter type. Positive anticipation of the stressor predicted stronger cortisol-sAA matched phase coordination for women. Pre-task ratings related to women's sAA, and post-task ratings related to both partners' cortisol responses. Implications for a multisystem interpretation of normal and pathological responses to daily stress are discussed. PMID:23684904

  14. The stress-response-dampening effects of placebo.

    PubMed

    Balodis, Iris M; Wynne-Edwards, Katherine E; Olmstead, Mary C

    2011-04-01

    This experiment used both biological and self-report measures to examine how alcohol modifies stress responses, and to test whether the interaction between these two factors alters risk-taking in healthy young adults. Participants were divided into stress or no-stress conditions and then further divided into one of three beverage groups. The alcohol group consumed a binge-drinking level of alcohol; the placebo group consumed soda, but believed they were consuming alcohol; the sober group was aware that they were not consuming alcohol. Following beverage consumption, the stress group was subjected to the Trier Social Stress Test (TSST) while the no-stress group completed crossword puzzles; all participants subsequently completed a computerized risk-taking task. Exposure to the TSST significantly increased salivary levels of the hormone cortisol and the enzyme alpha-amylase, as well as subjective self-ratings of anxiety and tension. In the stress condition, both placebo and intoxicated groups reported less tension and anxiety, and exhibited a smaller increase in cortisol, following the TSST than did the sober group. Thus, the expectation of receiving alcohol altered subjective and physiological responses to the stressor. Neither alcohol nor stress increased risk taking, however the sober group demonstrated lower risk-taking on the computer task on the second session. These findings clearly demonstrate that the expectation of alcohol (placebo) alters subsequent physiological responses to stress. PMID:21272586

  15. Cell Wall Metabolism in Response to Abiotic Stress

    PubMed Central

    Gall, Hyacinthe Le; Philippe, Florian; Domon, Jean-Marc; Gillet, Françoise; Pelloux, Jérôme; Rayon, Catherine

    2015-01-01

    This review focuses on the responses of the plant cell wall to several abiotic stresses including drought, flooding, heat, cold, salt, heavy metals, light, and air pollutants. The effects of stress on cell wall metabolism are discussed at the physiological (morphogenic), transcriptomic, proteomic and biochemical levels. The analysis of a large set of data shows that the plant response is highly complex. The overall effects of most abiotic stress are often dependent on the plant species, the genotype, the age of the plant, the timing of the stress application, and the intensity of this stress. This shows the difficulty of identifying a common pattern of stress response in cell wall architecture that could enable adaptation and/or resistance to abiotic stress. However, in most cases, two main mechanisms can be highlighted: (i) an increased level in xyloglucan endotransglucosylase/hydrolase (XTH) and expansin proteins, associated with an increase in the degree of rhamnogalacturonan I branching that maintains cell wall plasticity and (ii) an increased cell wall thickening by reinforcement of the secondary wall with hemicellulose and lignin deposition. Taken together, these results show the need to undertake large-scale analyses, using multidisciplinary approaches, to unravel the consequences of stress on the cell wall. This will help identify the key components that could be targeted to improve biomass production under stress conditions. PMID:27135320

  16. Cell Wall Metabolism in Response to Abiotic Stress.

    PubMed

    Le Gall, Hyacinthe; Philippe, Florian; Domon, Jean-Marc; Gillet, Françoise; Pelloux, Jérôme; Rayon, Catherine

    2015-01-01

    This review focuses on the responses of the plant cell wall to several abiotic stresses including drought, flooding, heat, cold, salt, heavy metals, light, and air pollutants. The effects of stress on cell wall metabolism are discussed at the physiological (morphogenic), transcriptomic, proteomic and biochemical levels. The analysis of a large set of data shows that the plant response is highly complex. The overall effects of most abiotic stress are often dependent on the plant species, the genotype, the age of the plant, the timing of the stress application, and the intensity of this stress. This shows the difficulty of identifying a common pattern of stress response in cell wall architecture that could enable adaptation and/or resistance to abiotic stress. However, in most cases, two main mechanisms can be highlighted: (i) an increased level in xyloglucan endotransglucosylase/hydrolase (XTH) and expansin proteins, associated with an increase in the degree of rhamnogalacturonan I branching that maintains cell wall plasticity and (ii) an increased cell wall thickening by reinforcement of the secondary wall with hemicellulose and lignin deposition. Taken together, these results show the need to undertake large-scale analyses, using multidisciplinary approaches, to unravel the consequences of stress on the cell wall. This will help identify the key components that could be targeted to improve biomass production under stress conditions. PMID:27135320

  17. Stressed to Death: Targeting Endoplasmic Reticulum Stress Response Induced Apoptosis in Gliomas

    PubMed Central

    Johnson, Guyla G.; White, Misti C.; Grimaldi, Maurizio

    2012-01-01

    Glial tumors are the main primary adult brain tumor. Even with the most advanced treatments, which include stereotactic microscope aided surgical resection, internal and external radiation therapy and local and systemic chemotherapy, median survival time for patients diagnosed with these malignancies is about 12 months. We explore here the possibility that the endoplasmic reticulum stress response (ERSR) could be a possible target to develop chemotherapeutic agents to induce toxicity in glioma cells. ERSR has the dual capacity of activating repair and/or cytotoxic mechanisms. ERSR is triggered by the accumulation of unfolded proteins in the ER. The presence of unfolded proteins in the ER regulates, via a complex biochemical cascade, the upregulation of molecular chaperones, inhibition of protein synthesis, and an increase of proteasome mediated unfolded protein degradation. ERSR in particular conditions can also contribute to cell death via activation of programmed cell death. Apoptosis activation during ERSR is usually caused by the activation of one or a combination of three biochemical cascades. Induction of these pathways ultimately leads to caspase 3 activation culminating in apoptosis. Glioma cells are in a condition of constant low grade ERSR, which possibly contributes to their resistance to treatment protocols. It is conceivable that small molecules that interact with this phenomenon ultimately could be used to modulate the system to activate apoptosis and cause gliotoxicity. We will discuss here ERSR biochemically relevant features to death mechanisms and already identified small molecules that by modulating ERSR are able to activate glioma cell death. PMID:21348829

  18. Are karrikins involved in plant abiotic stress responses?

    PubMed

    Li, Weiqiang; Tran, Lam-Son Phan

    2015-09-01

    Recent reports have shown that strigolactones play a positive role in plant responses to drought and salt stress through MAX2 (More Axillary Growth 2). Increasing evidence suggests that MAX2 is also involved in karrikin signaling, raising the question whether karrikins play any role in plant adaptation to abiotic stresses. PMID:26255855

  19. Personality, Stressful Life Events, and Treatment Response in Major Depression

    ERIC Educational Resources Information Center

    Bulmash, Eric; Harkness, Kate L.; Stewart, Jeremy G.; Bagby, R. Michael

    2009-01-01

    The current study examined whether the personality traits of self-criticism or dependency moderated the effect of stressful life events on treatment response. Depressed outpatients (N = 113) were randomized to 16 weeks of cognitive-behavioral therapy, interpersonal psychotherapy, or antidepressant medication (ADM). Stressful life events were…

  20. STRESS INTERACTIONS AND MYCRORRHIZAL PLANT RESPONSE: UNDERSTANDING CARBON ALLOCATION PRIORITIES

    EPA Science Inventory

    This paper presents a framework for studying responses of mycorrhizal roots to external stresses, including possible feedback effects, which are likely to occur. A conceptual model is presented to discuss how carbon may be involved in singular and multiple stress interactions of ...

  1. Traumatic Experience in Infancy: How Responses to Stress Affect Development

    ERIC Educational Resources Information Center

    Witten, Molly Romer

    2010-01-01

    Responses to traumatic stress during the earliest years of life can change quickly and can be difficult to identify because of the young child's rapid rate of development. The symptoms of traumatic stress will depend on the child's developmental level and individual coping styles, as well as the quality and nature of the child's most important…

  2. Stress memory induced transcriptional and metabolic changes of perennial ryegrass (Lolium perenne) in response to salt stress.

    PubMed

    Hu, Tao; Jin, Yupei; Li, Huiying; Amombo, Erick; Fu, Jinmin

    2016-01-01

    Preexposure to a stress could induce stable signals and reactions on plant physiology and gene expression during future encounters as a 'stress memory'. In this study, we found that two trainable genes, BPSP encoding putative brown plant hopper susceptibility protein and sucs encoding sucrose synthase displayed transcriptional memory for their considerably higher transcript levels during two or more subsequent stresses (S3, S4) relative to the initial stress (S0), and their expression returning to basal transcript levels (non-stressed) during the recovery states (R1, R2 and R3). Removing the repetitive