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Sample records for liver stress response

  1. Host homeostatic responses to alcohol-induced cellular stress in animal models of alcoholic liver disease.

    Science.gov (United States)

    Wang, He Joe; Murray, Gary J; Jung, Mary Katherine

    2015-01-01

    Humans develop various clinical phenotypes of severe alcoholic liver disease, including alcoholic hepatitis and cirrhosis, generally after decades of heavy drinking. In such individuals, following each episode of drinking, their livers experience heightened intracellular and extracellular stresses that are closely associated with alcohol consumption and alcohol metabolism. This article focuses on the latest advances made in animal models on evolutionarily conserved homeostatic mechanisms for coping with and resolving these stress conditions. The mechanisms discussed include the stress-activated protein kinase JNK, energy regulator AMPK, autophagy and the inflammatory response. Over time, the host may respond variably to stress with protective mechanisms that are critical in determining an individual's vulnerability to developing severe alcoholic liver disease. A systematic review of these mechanisms and their temporal changes in animal models provides the basis for general conclusions, and raises questions for future studies. The relevance of these data to human conditions is also discussed.

  2. Oxidative stress and inflammation: liver responses and adaptations to acute and regular exercise.

    Science.gov (United States)

    Pillon Barcelos, Rômulo; Freire Royes, Luiz Fernando; Gonzalez-Gallego, Javier; Bresciani, Guilherme

    2017-02-01

    The liver is remarkably important during exercise outcomes due to its contribution to detoxification, synthesis, and release of biomolecules, and energy supply to the exercising muscles. Recently, liver has been also shown to play an important role in redox status and inflammatory modulation during exercise. However, while several studies have described the adaptations of skeletal muscles to acute and chronic exercise, hepatic changes are still scarcely investigated. Indeed, acute intense exercise challenges the liver with increased reactive oxygen species (ROS) and inflammation onset, whereas regular training induces hepatic antioxidant and anti-inflammatory improvements. Acute and regular exercise protocols in combination with antioxidant and anti-inflammatory supplementation have been also tested to verify hepatic adaptations to exercise. Although positive results have been reported in some acute models, several studies have shown an increased exercise-related stress upon liver. A similar trend has been observed during training: while synergistic effects of training and antioxidant/anti-inflammatory supplementations have been occasionally found, others reported a blunting of relevant adaptations to exercise, following the patterns described in skeletal muscles. This review discusses current data regarding liver responses and adaptation to acute and regular exercise protocols alone or combined with antioxidant and anti-inflammatory supplementation. The understanding of the mechanisms behind these modulations is of interest for both exercise-related health and performance outcomes.

  3. Seasonal variations in fine particle composition from Beijing prompt oxidative stress response in mouse lung and liver.

    Science.gov (United States)

    Pardo, Michal; Xu, Fanfan; Qiu, Xinghua; Zhu, Tong; Rudich, Yinon

    2018-06-01

    Exposure to air pollution can induce oxidative stress, inflammation and adverse health effects. To understand how seasonal and chemical variations drive health impacts, we investigated indications for oxidative stress and inflammation in mice exposed to water and organic extracts from urban fine particles/PM 2.5 (particles with aerodynamic diameter ≤ 2.5 μm) collected in Beijing, China. Higher levels of pollution components were detected in heating season (HS, winter and part of spring) PM 2.5 than in the non-heating season (NHS, summer and part of spring and autumn) PM 2.5 . HS samples were high in metals for the water extraction and high in polycyclic aromatic hydrocarbons (PAHs) for the organic extraction compared to their controls. An increased inflammatory response was detected in the lung and liver following exposure to the organic extracts compared to the water extracts, and mostly in the HS PM 2.5 . While reduced antioxidant response was observed in the lung, it was activated in the liver, again, more in the HS extracts. Nrf2 transcription factor, a master regulator of stress response that controls the basal oxidative capacity and induces the expression of antioxidant response, and its related genes were induced. In the liver, elevated levels of lipid peroxidation adducts were measured, correlated with histologic analysis that revealed morphologic features of cell damage and proliferation, indicating oxidative and toxic damage. In addition, expression of genes related to detoxification of PAHs was observed. Altogether, the study suggests that the acute effects of PM 2.5 can vary seasonally with stronger health effects in the HS than in the NHS in Beijing, China and that some secondary organs may be susceptible for the exposure damage. Specifically, the liver is a potential organ influenced by exposure to organic components such as PAHs from coal or biomass burning and heating. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Changes in Liver Proteome Expression of Senegalese Sole (Solea senegalensis) in Response to Repeated Handling Stress

    DEFF Research Database (Denmark)

    Cordeiro, O. D.; Silva, Tomé Santos; Alves, R. N.

    2012-01-01

    The Senegalese sole, a high-value flatfish, is a good candidate for aquaculture production. Nevertheless, there are still issues regarding this species’ sensitivity to stress in captivity. We aimed to characterize the hepatic proteome expression for this species in response to repeated handling...... and identify potential molecular markers that indicate a physiological response to chronic stress. Two groups of fish were reared in duplicate for 28 days, one of them weekly exposed to handling stress (including hypoxia) for 3 min, and the other left undisturbed. Two-dimensional electrophoresis enabled...... the detection of 287 spots significantly affected by repeated handling stress (Wilcoxon–Mann–Whitney U test, p stress seems to have affected protein synthesis, folding and turnover (40S ribosomal protein S12...

  5. The Adaptive Endoplasmic Reticulum Stress Response to Lipotoxicity in Progressive Human Nonalcoholic Fatty Liver Disease

    Czech Academy of Sciences Publication Activity Database

    Lake, A.D.; Novák, Petr; Hardwick, R.N.; Flores-Keown, B.; Zhao, F.; Klimecki, W. T.; Cherrington, N.J.

    2014-01-01

    Roč. 137, č. 1 (2014), s. 26-35 ISSN 1096-6080 Institutional support: RVO:60077344 Keywords : nonalcoholic fatty liver disease * lipotoxicity * nonalcoholic steatohepatitis Subject RIV: CE - Biochemistry Impact factor: 3.854, year: 2014

  6. Nickel oxide nanoparticles exert cytotoxicity via oxidative stress and induce apoptotic response in human liver cells (HepG2).

    Science.gov (United States)

    Ahamed, Maqusood; Ali, Daoud; Alhadlaq, Hisham A; Akhtar, Mohd Javed

    2013-11-01

    Increasing use of nickel oxide nanoparticles (NiO NPs) necessitates an improved understanding of their potential impact on human health. Previously, toxic effects of NiO NPs have been investigated, mainly on airway cells. However, information on effect of NiO NPs on human liver cells is largely lacking. In this study, we investigated the reactive oxygen species (ROS) mediated cytotoxicity and induction of apoptotic response in human liver cells (HepG2) due to NiO NPs exposure. Prepared NiO NPs were crystalline and spherical shaped with an average diameter of 44 nm. NiO NPs induced cytotoxicity (cell death) and ROS generation in HepG2 cells in dose-dependent manner. Further, ROS scavenger vitamin C reduced cell death drastically caused by NiO NPs exposure indicating that oxidative stress plays an important role in NiO NPs toxicity. Micronuclei induction, chromatin condensation and DNA damage in HepG2 cells treated with NiO NPs suggest that NiO NPs induced cell death via apoptotic pathway. Quantitative real-time PCR analysis showed that following the exposure of HepG2 cells to NiO NPs, the expression level of mRNA of apoptotic genes (bax and caspase-3) were up-regulated whereas the expression level of anti-apoptotic gene bcl-2 was down-regulated. Moreover, activity of caspase-3 enzyme was also higher in NiO NPs treated cells. To the best of our knowledge this is the first report demonstrating that NiO NPs caused cytotoxicity via ROS and induced apoptosis in HepG2 cells, which is likely to be mediated through bax/bcl-2 pathway. This work warrants careful assessment of Ni NPs before their commercial and industrial applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Nrf2-inducing anti-oxidation stress response in the rat liver--new beneficial effect of lansoprazole.

    Science.gov (United States)

    Yamashita, Yasunobu; Ueyama, Takashi; Nishi, Toshio; Yamamoto, Yuta; Kawakoshi, Akatsuki; Sunami, Shogo; Iguchi, Mikitaka; Tamai, Hideyuki; Ueda, Kazuki; Ito, Takao; Tsuruo, Yoshihiro; Ichinose, Masao

    2014-01-01

    Lansoprazole is a potent anti-gastric ulcer drug that inhibits gastric proton pump activity. We identified a novel function for lansoprazole, as an inducer of anti-oxidative stress responses in the liver. Gastric administration of lansoprazole (10-100 mg/kg) to male Wistar rats produced a dose-dependent increase in hepatic mRNA levels of nuclear factor, erythroid-derived 2, -like 2 (Nrf2), a redox-sensitive transcription factor, at 3 h and Nrf2 immunoreactivity (IR) in whole hepatic lysates at 6 h. Conversely, the levels of Kelch-like ECH-associated protein (Keap1), which sequesters Nrf2 in the cytoplasm under un-stimulated conditions, were unchanged. Translocation of Nrf2 into the nuclei of hepatocytes was observed using western blotting and immunohistochemistry. Expression of mRNAs for Nrf2-dependent antioxidant and phase II enzymes, such as heme oxygenase 1 (HO-1), NAD (P) H dehydrogenase, quinone 1 (Nqo1), glutathione S-transferase A2 (Gsta2), UDP glucuronosyltransferase 1 family polypeptide A6 (Ugt1a6), were dose-dependently up-regulated at 3 h. Furthermore, the levels of HO-1 IR were dose-dependently increased in hepatocytes at 6 h. Subcutaneous administration of lansoprazole (30 mg/kg/day) for 7 successive days resulted in up-regulation and nuclear translocation of Nrf2 IR in hepatocytes and up-regulation of HO-1 IR in the liver. Pretreatment with lansoprazole attenuated thioacetamide (500 mg/kg)-induced acute hepatic damage via both HO-1-dependent and -independent pathways. Up-stream networks related to Nrf2 expression were investigated using microarray analysis, followed by data mining with Ingenuity Pathway Analysis. Up-regulation of the aryl hydrocarbon receptor (AhR)-cytochrome P450, family 1, subfamily a, polypeptide 1 (Cyp1a1) pathway was associated with up-regulation of Nrf2 mRNA. In conclusion, lansoprazole might have an alternative indication in the prevention and treatment of oxidative hepatic damage through the induction of both phase I and phase

  8. Nrf2-Inducing Anti-Oxidation Stress Response in the Rat Liver - New Beneficial Effect of Lansoprazole

    Science.gov (United States)

    Yamashita, Yasunobu; Ueyama, Takashi; Nishi, Toshio; Yamamoto, Yuta; Kawakoshi, Akatsuki; Sunami, Shogo; Iguchi, Mikitaka; Tamai, Hideyuki; Ueda, Kazuki; Ito, Takao; Tsuruo, Yoshihiro; Ichinose, Masao

    2014-01-01

    Lansoprazole is a potent anti-gastric ulcer drug that inhibits gastric proton pump activity. We identified a novel function for lansoprazole, as an inducer of anti-oxidative stress responses in the liver. Gastric administration of lansoprazole (10–100 mg/kg) to male Wistar rats produced a dose-dependent increase in hepatic mRNA levels of nuclear factor, erythroid-derived 2, -like 2 (Nrf2), a redox-sensitive transcription factor, at 3 h and Nrf2 immunoreactivity (IR) in whole hepatic lysates at 6 h. Conversely, the levels of Kelch-like ECH-associated protein (Keap1), which sequesters Nrf2 in the cytoplasm under un-stimulated conditions, were unchanged. Translocation of Nrf2 into the nuclei of hepatocytes was observed using western blotting and immunohistochemistry. Expression of mRNAs for Nrf2-dependent antioxidant and phase II enzymes, such as heme oxygenase 1 (HO-1), NAD (P) H dehydrogenase, quinone 1 (Nqo1), glutathione S-transferase A2 (Gsta2), UDP glucuronosyltransferase 1 family polypeptide A6 (Ugt1a6), were dose-dependently up-regulated at 3 h. Furthermore, the levels of HO-1 IR were dose-dependently increased in hepatocytes at 6 h. Subcutaneous administration of lansoprazole (30 mg/kg/day) for 7 successive days resulted in up-regulation and nuclear translocation of Nrf2 IR in hepatocytes and up-regulation of HO-1 IR in the liver. Pretreatment with lansoprazole attenuated thioacetamide (500 mg/kg)-induced acute hepatic damage via both HO-1-dependent and -independent pathways. Up-stream networks related to Nrf2 expression were investigated using microarray analysis, followed by data mining with Ingenuity Pathway Analysis. Up-regulation of the aryl hydrocarbon receptor (AhR)-cytochrome P450, family 1, subfamily a, polypeptide 1 (Cyp1a1) pathway was associated with up-regulation of Nrf2 mRNA. In conclusion, lansoprazole might have an alternative indication in the prevention and treatment of oxidative hepatic damage through the induction of both phase I and

  9. Metabolic Response to Heat Stress in Late-Pregnant and Early Lactation Dairy Cows: Implications to Liver-Muscle Crosstalk.

    Science.gov (United States)

    Koch, Franziska; Lamp, Ole; Eslamizad, Mehdi; Weitzel, Joachim; Kuhla, Björn

    2016-01-01

    Climate changes lead to rising temperatures during summer periods and dramatic economic losses in dairy production. Modern high-yielding dairy cows experience severe metabolic stress during the transition period between late gestation and early lactation to meet the high energy and nutrient requirements of the fetus or the mammary gland, and additional thermal stress during this time has adverse implications on metabolism and welfare. The mechanisms enabling metabolic adaptation to heat apart from the decline in feed intake and milk yield are not fully elucidated yet. To distinguish between feed intake and heat stress related effects, German Holstein dairy cows were first kept at thermoneutral conditions at 15°C followed by exposure to heat-stressed (HS) at 28°C or pair-feeding (PF) at 15°C for 6 days; in late-pregnancy and again in early lactation. Liver and muscle biopsies and plasma samples were taken to assess major metabolic pathway regulation using real-time PCR and Western Blot. The results indicate that during heat stress, late pregnant cows activate Cahill but reduce Cori cycling, prevent increase in skeletal muscle fatty acid oxidation, and utilize increased amounts of pyruvate for gluconeogenesis, without altering ureagenesis despite reduced plane of nutrition. These homeorhetic adaptations are employed to reduce endogenous heat production while diverting amino acids to the growing fetus. Metabolic adaptation to heat stress in early lactation involves increased long-chain fatty acid degradation in muscle peroxisomes, allowance for muscle glucose utilization but diminished hepatic use of amino acid-derived pyruvate for gluconeogenesis and reduced peroxisomal fatty acid oxidation and ATP production in liver of HS compared to PF cows in early lactation. Consequently, metabolic adaptation to heat stress and reduced feed intake differ between late pregnancy and early lactation of dairy cows to maintain energy supply for fetus development or milk production

  10. Metabolic Response to Heat Stress in Late-Pregnant and Early Lactation Dairy Cows: Implications to Liver-Muscle Crosstalk

    Science.gov (United States)

    Eslamizad, Mehdi; Weitzel, Joachim; Kuhla, Björn

    2016-01-01

    Climate changes lead to rising temperatures during summer periods and dramatic economic losses in dairy production. Modern high-yielding dairy cows experience severe metabolic stress during the transition period between late gestation and early lactation to meet the high energy and nutrient requirements of the fetus or the mammary gland, and additional thermal stress during this time has adverse implications on metabolism and welfare. The mechanisms enabling metabolic adaptation to heat apart from the decline in feed intake and milk yield are not fully elucidated yet. To distinguish between feed intake and heat stress related effects, German Holstein dairy cows were first kept at thermoneutral conditions at 15°C followed by exposure to heat-stressed (HS) at 28°C or pair-feeding (PF) at 15°C for 6 days; in late-pregnancy and again in early lactation. Liver and muscle biopsies and plasma samples were taken to assess major metabolic pathway regulation using real-time PCR and Western Blot. The results indicate that during heat stress, late pregnant cows activate Cahill but reduce Cori cycling, prevent increase in skeletal muscle fatty acid oxidation, and utilize increased amounts of pyruvate for gluconeogenesis, without altering ureagenesis despite reduced plane of nutrition. These homeorhetic adaptations are employed to reduce endogenous heat production while diverting amino acids to the growing fetus. Metabolic adaptation to heat stress in early lactation involves increased long-chain fatty acid degradation in muscle peroxisomes, allowance for muscle glucose utilization but diminished hepatic use of amino acid-derived pyruvate for gluconeogenesis and reduced peroxisomal fatty acid oxidation and ATP production in liver of HS compared to PF cows in early lactation. Consequently, metabolic adaptation to heat stress and reduced feed intake differ between late pregnancy and early lactation of dairy cows to maintain energy supply for fetus development or milk production

  11. Chronic waterborne zinc and cadmium exposures induced different responses towards oxidative stress in the liver of zebrafish

    International Nuclear Information System (INIS)

    Zheng, Jia-Lang; Yuan, Shuang-Shuang; Wu, Chang-Wen; Li, Wei-Ye

    2016-01-01

    Highlights: • Zn and Cd induced some differences in oxidative damage in the liver of zebrafish. • Zn and Cd enhanced expression of Cu/Zn-SOD and CAT through Nrf2 pathway. • Zn and Cd did not affected protein levels of CAT. • Cd inhibited biological activities of Cu/Zn-SOD and CAT proteins. • Zn stimulated activity and protein levels of Cu/Zn-SOD. - Abstract: Based on the same toxic level of 0.6% LC_5_0 for 96-h and the severe situation of water pollution, we compared effects of chronic Zn (180 μg L"−"1) and Cd exposures (30 μg L"−"1) on growth, survival, histology, ultrastructure, and oxidative stress in the liver of zebrafish for 5 weeks. Growth performance and survival rate remained relatively constant under Zn stress, but was reduced under Cd exposure. Cd exposure also induced severe pyknotic nuclei, evident ultrastructure damage, and considerable lipid inclusions in the hepatocytes. However, these phenomena were not pronounced under Zn exposure. The negative effects caused by Cd may be explained by an increase in hepatic oxidative damage, as reflected by the enhanced levels of lipid peroxidation (LPO) and protein carbonylation (PC). The reduced activity of Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and catalase (CAT) may result in the enhanced hepatic oxidative damage, though the mRNA and protein levels of both genes increased and remained unchanged respectively. On the contrary, Zn up-regulated the levels of mRNA, protein and activity of Cu/Zn-SOD, which may contribute to the decreased LPO levels. Nonetheless, the sharply up-regulated mRNA levels of CAT did not induce an increase in the protein and activity levels of CAT under Zn stress. Furthermore, transcription factor NF-E2-related factor 2 (Nrf2) expression parelleled with its target genes, suggesting that Nrf2 is required for the protracted induction of antioxidant genes. In conclusion, our data demonstrated that essential and non-essential metals induced some differences in oxidative damage

  12. Chronic waterborne zinc and cadmium exposures induced different responses towards oxidative stress in the liver of zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jia-Lang, E-mail: zhengjialang@aliyun.com [National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan 316022 (China); Yuan, Shuang-Shuang; Wu, Chang-Wen [National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan 316022 (China); Li, Wei-Ye [Zhoushan fisheries research institute, Zhoushan 316022 (China)

    2016-08-15

    Highlights: • Zn and Cd induced some differences in oxidative damage in the liver of zebrafish. • Zn and Cd enhanced expression of Cu/Zn-SOD and CAT through Nrf2 pathway. • Zn and Cd did not affected protein levels of CAT. • Cd inhibited biological activities of Cu/Zn-SOD and CAT proteins. • Zn stimulated activity and protein levels of Cu/Zn-SOD. - Abstract: Based on the same toxic level of 0.6% LC{sub 50} for 96-h and the severe situation of water pollution, we compared effects of chronic Zn (180 μg L{sup −1}) and Cd exposures (30 μg L{sup −1}) on growth, survival, histology, ultrastructure, and oxidative stress in the liver of zebrafish for 5 weeks. Growth performance and survival rate remained relatively constant under Zn stress, but was reduced under Cd exposure. Cd exposure also induced severe pyknotic nuclei, evident ultrastructure damage, and considerable lipid inclusions in the hepatocytes. However, these phenomena were not pronounced under Zn exposure. The negative effects caused by Cd may be explained by an increase in hepatic oxidative damage, as reflected by the enhanced levels of lipid peroxidation (LPO) and protein carbonylation (PC). The reduced activity of Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and catalase (CAT) may result in the enhanced hepatic oxidative damage, though the mRNA and protein levels of both genes increased and remained unchanged respectively. On the contrary, Zn up-regulated the levels of mRNA, protein and activity of Cu/Zn-SOD, which may contribute to the decreased LPO levels. Nonetheless, the sharply up-regulated mRNA levels of CAT did not induce an increase in the protein and activity levels of CAT under Zn stress. Furthermore, transcription factor NF-E2-related factor 2 (Nrf2) expression parelleled with its target genes, suggesting that Nrf2 is required for the protracted induction of antioxidant genes. In conclusion, our data demonstrated that essential and non-essential metals induced some differences in

  13. Oxidative stress response of Forster's terns (Sterna forsteri) and Caspian terns (Hydroprogne caspia) to mercury and selenium bioaccumulation in liver, kidney, and brain

    Science.gov (United States)

    Hoffman, David J.; Eagles-Smith, Collin A.; Ackerman, Joshua T.; Adelsbach, Terrence L.; Stebbins, Katherine R.

    2011-01-01

    Bioindicators of oxidative stress were examined in prebreeding and breeding adult and chick Forster's terns (Sterna forsteri) and in prebreeding adult Caspian terns (Hydroprogne caspia) in San Francisco Bay, California. Highest total mercury (THg) concentrations (mean±standard error;μg/g dry wt) in liver (17.7±1.7), kidney (20.5±1.9), and brain (3.0±0.3) occurred in breeding adult Forster's terns. The THg concentrations in liver were significantly correlated with hepatic depletion of reduced glutathione (GSH), increased oxidized glutathione (GSSG):GSH ratio, and decreased hepatic gamma-glutamyl transferase (GGT) activity in adults of both tern species. Prefledging Forster's tern chicks with one-fourth the hepatic THg concentration of breeding adults exhibited effects similar to adults. Total mercury-related renal GSSG increased in adults and chicks. In brains of prebreeding adults, THg was correlated with a small increase in glucose-6-phosphate dehydrogenase (G-6-PDH) activity, suggestive of a compensatory response. Brain THg concentrations were highest in breeding adult Forster's terns and brain tissue exhibited increased lipid peroxidation as thiobarbituric acid-reactive substances, loss of protein bound thiols (PBSH), and decreased activity of antioxidant enzymes, GSSG reductase (GSSGrd), and G-6-PDH. In brains of Forster's tern chicks there was a decrease in total reduced thiols and PBSH. Multiple indicator responses also pointed to greater oxidative stress in breeding Forster's terns relative to prebreeding terns, attributable to the physiological stress of reproduction. Some biondicators also were related to age and species, including thiol concentrations. Enzymes GGT, G-6-PDH, and GSSGred activities were related to species. Our results indicate that THg concentrations induced oxidative stress in terns, and suggest that histopathological, immunological, and behavioral effects may occur in terns as reported in other species.

  14. Protective action of the immunomodulator ginsan against carbon tetrachloride-induced liver injury via control of oxidative stress and the inflammatory response

    International Nuclear Information System (INIS)

    Shim, Ji-Young; Kim, Mi-Hyoung; Kim, Hyung-Doo; Ahn, Ji-Yeon; Yun, Yeon-Sook; Song, Jie-Young

    2010-01-01

    The aim of the present study was to evaluate immunomodulator ginsan, a polysaccharide extracted from Panax ginseng, on carbon tetrachloride (CCl 4 )-induced liver injury. BALB/c mice were injected i.p. with ginsan 24 h prior to CCl 4 administration. Serum liver enzyme levels, histology, expression of antioxidant enzymes, and several cytokines/chemokines were subsequently evaluated. Ginsan treatment markedly suppressed the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and hepatic histological necrosis increased by CCl 4 treatment. Ginsan inhibited CCl 4 induced lipid peroxidation through the cytochrome P450 2E1 (CYP2E1) downregulation. The hepatoprotective effect of ginsan was attributed to induction of anti-oxidant protein contents, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) as well as restoration of the hepatic glutathione (GSH) concentration. The marked increase of proinflammatory cytokines (IL-1β, IFN-γ) and chemokines (MCP-1, MIP-2β, KC) in CCl 4 treated mice was additionally attenuated by ginsan, thereby preventing leukocyte infiltration and local inflammation. Our results suggest that ginsan effectively prevent liver injury, mainly through downregulation of oxidative stress and inflammatory response.

  15. Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells.

    Directory of Open Access Journals (Sweden)

    Raimundo Fernandes de Araújo Júnior

    type III (PCIII, and NF-κB were decreased in the alcohol-CARV 5 mg/kg group relative to the alcohol-only group.CARV can reduce the stress oxidative, inflammatory response and fibrosis in ethanol-induced liver injury in a rat model by downregulating signalling of Kuppfer cells and hepatic stellate cells (HSCs through suppression of inflammatory cytokines.

  16. Oxidative stress and inflammation in liver carcinogenesis

    Directory of Open Access Journals (Sweden)

    Natalia Olaya

    2007-02-01

    Full Text Available

    Inflammation is a common response in the human liver. It is involved in chronic hepatitis, cirrhosis, steatosis, ischemiareperfusion damage, hepatocarcinomas and in the development of metastasis. Reactive oxygen species (ROS production is part of the inflammatory processes. It is implicated in many physiological and pathological situations and can induce mutations in key cancer genes. Normally, this process is prevented by DNA repair enzymatic systems that maintain sequence fidelity during DNA replication. However, overproduction of free radicals in chronic inflammatory diseases is thought to saturate the ability of the cell to repair DNA damage prior to replications. Inflammation-induced genetic damage is not unique to the liver, and it might contribute to the development of mutations in several organs. An example is the chronic inflammatory response in ulcerative colitis that ultimately could lead to neoplasia.

    There is compelling evidence to suggest that most known environmental risk factors for HCC development lead to generation of reactive oxygen species (ROS. Indeed, hepatitis C virus (HCV, alcohol and hepatitis B virus (HBV have all been associated with oxidative stress. Direct production of oxidative stress by HCV core protein has been shown. A link between oxidative stress and liver pathogenesis is also supported by the successful use of antioxidant therapy to treat liver injury caused by chronic HCV infection, although it is not currently used for effective therapy. Ethanol metabolism via the alcohol dehydrogenase pathway and microsomal ethanol oxidizing system contribute substantially to the production of acetaldehyde and generation of ROS. HBx via its association with mitochondria has been shown to induce oxidative stress which in turn leads to activation of a

  17. Nrf2-mediated antioxidant response by ethanolic extract of Sida cordifolia provides protection against alcohol-induced oxidative stress in liver by upregulation of glutathione metabolism.

    Science.gov (United States)

    Rejitha, S; Prathibha, P; Indira, M

    2015-03-01

    Objective The study aimed to evaluate the antioxidant property of ethanolic extract of Sida cordifolia (SAE) on alcohol-induced oxidative stress and to elucidate its mechanism of action. Methods Male albino rats of the Sprague-Dawley strain were grouped into four: (1) control, (2) alcohol (4 g/kg body weight), (3) SAE (50 mg/100 g body weight), and (4) alcohol (4 g/kg body weight) + SAE (50 mg/100 g body weight). Alcohol and SAE were given orally each day by gastric intubation. The duration of treatment was 90 days. Results The activities of toxicity markers in liver and serum increased significantly in alcohol-treated rats and to a lesser extent in the group administered SAE + alcohol. The activity of alcohol dehydrogenase and the reactive oxygen species level were increased significantly in alcohol-treated rats but attenuated in the SAE co-administered group. Oxidative stress was increased in alcohol-treated rats as evidenced by the lowered activities of antioxidant enzymes, decreased level of reduced glutathione (GSH), increased lipid peroxidation products, and decreased expression of γ-glutamyl cysteine synthase in liver. The co-administration of SAE with alcohol almost reversed these changes. The activity of glutathione-S-transferase and translocation of Nrf2 from cytosol to nucleus in the liver was increased in both the alcohol and alcohol + SAE groups, but the maximum changes were observed in the latter group. Discussion The SAE most likely elicits its antioxidant potential by reducing oxidative stress, enhancing the translocation of Nrf2 to nucleus and thereby regulating glutathione metabolism, leading to enhanced GSH content.

  18. The Role of Oxidative Stress and Antioxidants in Liver Diseases

    Directory of Open Access Journals (Sweden)

    Sha Li

    2015-11-01

    Full Text Available A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed.

  19. ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis

    Directory of Open Access Journals (Sweden)

    Diane DeZwaan-McCabe

    2017-05-01

    Full Text Available The unfolded protein response (UPR, induced by endoplasmic reticulum (ER stress, regulates the expression of factors that restore protein folding homeostasis. However, in the liver and kidney, ER stress also leads to lipid accumulation, accompanied at least in the liver by transcriptional suppression of metabolic genes. The mechanisms of this accumulation, including which pathways contribute to the phenotype in each organ, are unclear. We combined gene expression profiling, biochemical assays, and untargeted lipidomics to understand the basis of stress-dependent lipid accumulation, taking advantage of enhanced hepatic and renal steatosis in mice lacking the ER stress sensor ATF6α. We found that impaired fatty acid oxidation contributed to the early development of steatosis in the liver but not the kidney, while anorexia-induced lipolysis promoted late triglyceride and free fatty acid accumulation in both organs. These findings provide evidence for both direct and indirect regulation of peripheral metabolism by ER stress.

  20. Chronic stress does not impair liver regeneration in rats

    DEFF Research Database (Denmark)

    Andersen, Kasper J; Knudsen, Anders Riegels; Wiborg, Ove

    2015-01-01

    a 70 % partial hepatectomy (PHx). The animals were evaluated on postoperative day 2 or 4. Blood samples were collected to examine circulating markers of inflammation and liver cell damage. Additionally, liver tissues were sampled to evaluate liver weight and regeneration rate. RESULTS: None......BACKGROUND: Although wound healing is a simple regenerative process that is critical after surgery, it has been shown to be impaired under psychological stress. The liver has a unique capacity to regenerate through highly complex mechanisms. The aim of this study was to investigate the effects...... of chronic stress, which may induce a depression-like state, on the complex process of liver regeneration in rats. METHODS: Twenty rats were included in this study. The animals received either a standard housing protocol or were subjected to a Chronic Mild Stress (CMS) stress paradigm. All rats underwent...

  1. SIRT7 Represses Myc Activity to Suppress ER Stress and Prevent Fatty Liver Disease

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    Jiyung Shin

    2013-11-01

    Full Text Available Nonalcoholic fatty liver disease is the most common chronic liver disorder in developed countries. Its pathogenesis is poorly understood, and therapeutic options are limited. Here, we show that SIRT7, an NAD+-dependent H3K18Ac deacetylase, functions at chromatin to suppress ER stress and prevent the development of fatty liver disease. SIRT7 is induced upon ER stress and is stabilized at the promoters of ribosomal proteins through its interaction with the transcription factor Myc to silence gene expression and to relieve ER stress. SIRT7-deficient mice develop chronic hepatosteatosis resembling human fatty liver disease. Myc inactivation or pharmacological suppression of ER stress alleviates fatty liver caused by SIRT7 deficiency. Importantly, SIRT7 suppresses ER stress and reverts the fatty liver disease in diet-induced obese mice. Our study identifies SIRT7 as a cofactor of Myc for transcriptional repression and delineates a druggable regulatory branch of the ER stress response that prevents and reverts fatty liver disease.

  2. Various levels and forms of dietary α-lipoic acid in broiler chickens: Impact on blood biochemistry, stress response, liver enzymes, and antibody titers.

    Science.gov (United States)

    Kim, D W; Mushtaq, M M H; Parvin, R; Kang, H K; Kim, J H; Na, J C; Hwangbo, J; Kim, J D; Yang, C B; Park, B J; Choi, H C

    2015-02-01

    The present experiment was conducted to evaluate the impact of various levels and forms of α-lipoic acid (ALA) on blood biochemistry, immune and stress response, and antibody titers in broiler chickens. The four levels (7.5, 15, 75, and 150 ppm) and 2 sources (powder, P-ALA and encapsulated, E-ALA) of ALA along with negative (C-) and positive control (C+; contains antibiotics) diets consisted of 10 dietary treatments, and these treatments were allocated to 1,200 1-d-old chicks and were replicated 12 times with 10 birds per replicate. Among the blood biochemistry parameters, creatinine levels were almost 3 times lower in E-ALA-supplemented diets compared to the C- diet (0.09 vs. 0.25 mg/dL; PBirds did not respond to infectious bronchitis virus (IBV) vaccination at any observed stage (P>0.05). The concentration of cortisol was reduced in chickens fed ALA-supplemented diets as compared to the C- diet (Pbiochemistry profiles and immune responses and reduced stress in broiler chickens. The encapsulated form of ALA was more effective than the powder form. © 2015 Poultry Science Association Inc.

  3. Bruxism affects stress responses in stressed rats.

    Science.gov (United States)

    Sato, Chikatoshi; Sato, Sadao; Takashina, Hirofumi; Ishii, Hidenori; Onozuka, Minoru; Sasaguri, Kenichi

    2010-04-01

    It has been proposed that suppression of stress-related emotional responses leads to the simultaneous activation of both sympathetic and parasympathetic divisions of the autonomic nervous system (ANS) and that the expression of these emotional states has a protective effect against ulcerogenesis. In the present study, we investigated whether stress-induced bruxism activity (SBA) has a physiological effect of on the stress-induced changes of the stomach, thymus, and spleen as well as blood leukocytes, cortisol, and adrenaline. This study demonstrated that SBA attenuated the stress-induced ulcer genesis as well as degenerative changes of thymus and spleen. SBA also attenuated increases of adrenaline, cortisol, and neutrophils in the blood. In conclusion, expression of aggression through SBA during stress exposure attenuates both stress-induced ANS response, including gastric ulcer formation.

  4. Stress Responses in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Frees, Dorte; Ingmer, Hanne

    2016-01-01

    stress responses allowing it to sense and adapt to its very different niches. The stress responses often involve dramatic cellular reprogramming, and the technological advances provided by the access to whole genome sequences have let to an unprecedented insight into the global reorganization of gene...... and protein expression following stress-exposure. Characterization of global gene responses has been very helpful both in identifying regulators sensing specific environmental stress signals and overlaps between different stress responses. In this chapter we review the recent progress in our understanding...... of the specific and general S. aureusstress responses, with a special emphasis on how stress responses contribute to virulence and antibiotic resistance in this important human pathogen....

  5. Staphylococcal response to oxidative stress

    Directory of Open Access Journals (Sweden)

    Rosmarie eGaupp

    2012-03-01

    Full Text Available 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.

  6. Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Oliveira C.P.M.S.

    2006-01-01

    Full Text Available Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7 or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7 for 4 weeks. The control group (N = 7 was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4 and a decrease in respiratory control rate (RCR in the CD group (S4: 32.70 ± 3.35; RCR: 2.55 ± 0.15 ng atoms of O2 min-1 mg protein-1 when compared to the H and control groups (S4: 23.09 ± 1.53, 17.04 ± 2.03, RCR: 3.15 ± 0.15, 3.68 ± 0.15 ng atoms of O2 min-1 mg protein-1, respectively, P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

  7. ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis.

    Science.gov (United States)

    DeZwaan-McCabe, Diane; Sheldon, Ryan D; Gorecki, Michelle C; Guo, Deng-Fu; Gansemer, Erica R; Kaufman, Randal J; Rahmouni, Kamal; Gillum, Matthew P; Taylor, Eric B; Teesch, Lynn M; Rutkowski, D Thomas

    2017-05-30

    The unfolded protein response (UPR), induced by endoplasmic reticulum (ER) stress, regulates the expression of factors that restore protein folding homeostasis. However, in the liver and kidney, ER stress also leads to lipid accumulation, accompanied at least in the liver by transcriptional suppression of metabolic genes. The mechanisms of this accumulation, including which pathways contribute to the phenotype in each organ, are unclear. We combined gene expression profiling, biochemical assays, and untargeted lipidomics to understand the basis of stress-dependent lipid accumulation, taking advantage of enhanced hepatic and renal steatosis in mice lacking the ER stress sensor ATF6α. We found that impaired fatty acid oxidation contributed to the early development of steatosis in the liver but not the kidney, while anorexia-induced lipolysis promoted late triglyceride and free fatty acid accumulation in both organs. These findings provide evidence for both direct and indirect regulation of peripheral metabolism by ER stress. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-10-27

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

  9. Resveratrol Ameliorates Experimental Alcoholic Liver Disease by Modulating Oxidative Stress

    Directory of Open Access Journals (Sweden)

    He Peiyuan

    2017-01-01

    Full Text Available The aim of this study was to investigate the hepatoprotective effects of resveratrol in alcoholic liver disease (ALD. Alcohol was administered to healthy female rats starting from 6% (v/v and gradually increased to 20% (v/v by the fifth week. After 16 weeks of intervention, liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] were analyzed using a chemistry analyzer, while hepatic antioxidant enzymes, oxidative stress markers, and caspase 3 activity were assessed using ELISA kits. Furthermore, hepatic CYP2E1 protein levels and mRNA levels of antioxidant and inflammation-related genes were determined using western blotting and RT-PCR, respectively. The results showed that resveratrol significantly attenuated alcohol-induced elevation of liver enzymes and improved hepatic antioxidant enzymes. Resveratrol also attenuated alcohol-induced CYP2E1 increase, oxidative stress, and apoptosis (caspase 3 activity. Moreover, genes associated with oxidative stress and inflammation were regulated by resveratrol supplementation. Taken together, the results suggested that resveratrol alleviated ALD through regulation of oxidative stress, apoptosis, and inflammation, which was mediated at the transcriptional level. The data suggests that resveratrol is a promising natural therapeutic agent against chronic ALD.

  10. Neuronal responses to physiological stress

    DEFF Research Database (Denmark)

    Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger David John

    2012-01-01

    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......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...

  11. Plant responses to water stress

    Science.gov (United States)

    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

  12. Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Gentric, Géraldine; Maillet, Vanessa; Paradis, Valérie; Couton, Dominique; L'Hermitte, Antoine; Panasyuk, Ganna; Fromenty, Bernard; Celton-Morizur, Séverine; Desdouets, Chantal

    2015-03-02

    Polyploidization is one of the most dramatic changes that can occur in the genome. In the liver, physiological polyploidization events occur during both liver development and throughout adult life. Here, we determined that a pathological polyploidization takes place in nonalcoholic fatty liver disease (NAFLD), a widespread hepatic metabolic disorder that is believed to be a risk factor for hepatocellular carcinoma (HCC). In murine models of NAFLD, the parenchyma of fatty livers displayed alterations of the polyploidization process, including the presence of a large proportion of highly polyploid mononuclear cells, which are rarely observed in normal hepatic parenchyma. Biopsies from patients with nonalcoholic steatohepatitis (NASH) revealed the presence of alterations in hepatocyte ploidy compared with tissue from control individuals. Hepatocytes from NAFLD mice revealed that progression through the S/G2 phases of the cell cycle was inefficient. This alteration was associated with activation of a G2/M DNA damage checkpoint, which prevented activation of the cyclin B1/CDK1 complex. Furthermore, we determined that oxidative stress promotes the appearance of highly polyploid cells, and antioxidant-treated NAFLD hepatocytes resumed normal cell division and returned to a physiological state of polyploidy. Collectively, these findings indicate that oxidative stress promotes pathological polyploidization and suggest that this is an early event in NAFLD that may contribute to HCC development.

  13. Individual heat stress response

    NARCIS (Netherlands)

    Havenith, G.

    1997-01-01

    In 5 experiments, heterogeneous subject groups (large variations in _VO2 max, regular daily activity level, mass, body surface area (AD), % body fat, and AD/mass ratio) were tested for their physiological response while exercising on a cycle ergometer at a relative (45% _VO2 max; REL) or an absolute

  14. Seasonal variations in PM composition from Beijing, China drive liver oxidative stress

    Science.gov (United States)

    Pardo, M.; Rudich, Y.

    2017-12-01

    Air pollution can cause oxidative stress, inflammation and adverse health effects, but the underlying biological mechanisms are not completely understood. In order to understand how seasonal and chemical variations drive health impacts, we investigated the oxidative stress and inflammation in mice exposed to extracts (water and DCM) from urban PM collected in Beijing (China). Higher levels of pollution components were detected in the heating season (HS, winter) than in the non-heating season (NHS, summer). Higher concentrations of PM were measured in the heating season, mostly from coal and wood burning used for domestic heating. This was accompanied by increased levels of polyaromatic hydrocarbons (PAHs) in the DCM extracts. An increased inflammatory response was detected in the lung and liver with DCM extracts compared to the water extracts, and mostly in the winter aerosol. Reduced antioxidant response was observed in the lung, whereas it was activated in the liver. Gene expression of the Nrf2 transcription factor (A master regulator of stress response that controls the basal oxidative capacity and induces the expression of antioxidant response) and its related genes were induced. In the liver, higher levels of lipid peroxidation adducts were measured, correlated with histologic analysis that revealed morphologic features of damage/proliferation in the liver, indicating oxidative and toxic damage. Altogether, our study suggests that the acute effects of PM can vary by the season with the largest effect observed in winter than summer in Beijing, and that some secondary organs may be susceptible for exposure damage. This suggests that the liver is a potential organ to be influenced from PM especially by PAHs

  15. Abiotic stressors and stress responses

    DEFF Research Database (Denmark)

    Sulmon, Cecile; Van Baaren, Joan; Cabello-Hurtado, Francisco

    2015-01-01

    Abstract Organisms are regularly subjected to abiotic stressors related to increasing anthropogenic activities, including chemicals and climatic changes that induce major stresses. Based on various key taxa involved in ecosystem functioning (photosynthetic microorganisms, plants, invertebrates), we...... review how organisms respond and adapt to chemical- and temperature-induced stresses from molecular to population level. Using field-realistic studies, our integrative analysis aims to compare i) how molecular and physiological mechanisms related to protection, repair and energy allocation can impact...... life history traits of stressed organisms, and ii) to what extent trait responses influence individual and population responses. Common response mechanisms are evident at molecular and cellular scales but become rather difficult to define at higher levels due to evolutionary distance and environmental...

  16. Deciphering hepatocellular responses to metabolic and oncogenic stress

    Directory of Open Access Journals (Sweden)

    Kathrina L. Marcelo

    2015-08-01

    Full Text Available Each cell type responds uniquely to stress and fractionally contributes to global and tissue-specific stress responses. Hepatocytes, liver macrophages (MΦ, and sinusoidal endothelial cells (SEC play functionally important and interdependent roles in adaptive processes such as obesity and tumor growth. Although these cell types demonstrate significant phenotypic and functional heterogeneity, their distinctions enabling disease-specific responses remain understudied. We developed a strategy for the simultaneous isolation and quantification of these liver cell types based on antigenic cell surface marker expression. To demonstrate the utility and applicability of this technique, we quantified liver cell-specific responses to high-fat diet (HFD or diethylnitrosamine (DEN, a liver-specific carcinogen, and found that while there was only a marginal increase in hepatocyte number, MΦ and SEC populations were quantitatively increased. Global gene expression profiling of hepatocytes, MΦ and SEC identified characteristic gene signatures that define each cell type in their distinct physiological or pathological states. Integration of hepatic gene signatures with available human obesity and liver cancer microarray data provides further insight into the cell-specific responses to metabolic or oncogenic stress. Our data reveal unique gene expression patterns that serve as molecular “fingerprints” for the cell-centric responses to pathologic stimuli in the distinct microenvironment of the liver. The technical advance highlighted in this study provides an essential resource for assessing hepatic cell-specific contributions to metabolic and oncogenic stress, information that could unveil previously unappreciated molecular mechanisms for the cellular crosstalk that underlies the continuum from metabolic disruption to obesity and ultimately hepatic cancer.

  17. Oxidative Stress and Liver Cancer: Etiology and Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Zhanpeng Wang

    2016-01-01

    Full Text Available Accumulating evidence has indicated that oxidative stress (OS is associated with the development of hepatocellular carcinoma (HCC. However, the mechanisms remain largely unknown. Normally, OS occurs when the body receives any danger signal—from either an internal or external source—and further induces DNA oxidative damage and abnormal protein expression, placing the body into a state of vulnerability to the development of various diseases such as cancer. There are many factors involved in liver carcinogenesis, including hepatitis B virus (HBV and hepatitis C virus (HCV infection, alcohol abuse, and nonalcoholic fatty liver disease (NAFLD. The relationship between OS and HCC has recently been attracting increasing attention. Therefore, elucidation of the impact of OS on the development of liver carcinogenesis is very important for the prevention and treatment of liver cancer. This review focuses mainly on the relationship between OS and the development of HCC from the perspective of cellular and molecular mechanisms and the etiology and therapeutic targets of HCC.

  18. Distinct cellular responses differentiating alcohol- and hepatitis C virus-induced liver cirrhosis

    Directory of Open Access Journals (Sweden)

    Boix Loreto

    2006-11-01

    Full Text Available Abstract Background Little is known at the molecular level concerning the differences and/or similarities between alcohol and hepatitis C virus induced liver disease. Global transcriptional profiling using oligonucleotide microarrays was therefore performed on liver biopsies from patients with cirrhosis caused by either chronic alcohol consumption or chronic hepatitis C virus (HCV. Results Global gene expression patterns varied significantly depending upon etiology of liver disease, with a greater number of differentially regulated genes seen in HCV-infected patients. Many of the gene expression changes specifically observed in HCV-infected cirrhotic livers were expectedly associated with activation of the innate antiviral immune response. We also compared severity (CTP class of cirrhosis for each etiology and identified gene expression patterns that differentiated ethanol-induced cirrhosis by class. CTP class A ethanol-cirrhotic livers showed unique expression patterns for genes implicated in the inflammatory response, including those related to macrophage activation and migration, as well as lipid metabolism and oxidative stress genes. Conclusion Stages of liver cirrhosis could be differentiated based on gene expression patterns in ethanol-induced, but not HCV-induced, disease. In addition to genes specifically regulating the innate antiviral immune response, mechanisms responsible for differentiating chronic liver damage due to HCV or ethanol may be closely related to regulation of lipid metabolism and to effects of macrophage activation on deposition of extracellular matrix components.

  19. A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution

    DEFF Research Database (Denmark)

    Maida, Adriano; Zota, Annika; Sjøberg, Kim Anker

    2016-01-01

    of impaired glucose homeostasis independently of obesity and food intake. DPD-mediated metabolic inefficiency and improvement of glucose homeostasis were independent of uncoupling protein 1 (UCP1), but required expression of liver-derived fibroblast growth factor 21 (FGF21) in both lean and obese mice. FGF21...... expression and secretion as well as the associated metabolic remodeling induced by DPD also required induction of liver-integrated stress response-driven nuclear protein 1 (NUPR1). Insufficiency of select nonessential amino acids (NEAAs) was necessary and adequate for NUPR1 and subsequent FGF21 induction...... and secretion in hepatocytes in vitro and in vivo. Taken together, these data indicate that DPD promotes improved glucose homeostasis through an NEAA insufficiency-induced liver NUPR1/FGF21 axis....

  20. Plant Responses to Nanoparticle Stress

    Directory of Open Access Journals (Sweden)

    Zahed Hossain

    2015-11-01

    Full Text Available 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.

  1. Characterizing the Role of Hep27 in Liver and Colorectal Cancer Stress Tolerance

    Science.gov (United States)

    2018-01-01

    AWARD NUMBER: W81XWH-16-1-0402 TITLE: Characterizing the Role of Hep27 in Liver and Colorectal Cancer Stress Tolerance PRINCIPAL INVESTIGATOR...Sep 2016 – 14 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Characterizing the Role of Hep27 in Liver and Colorectal Cancer Stress Tolerance...project has not demonstrated that Hep27 plays a role in ROS tolerance in liver cancer cells. 15. SUBJECT TERMS Hep27, ROS, stress , cancer 16. SECURITY

  2. STRESS RESPONSE STUDIES USING ANIMAL MODELS

    Science.gov (United States)

    This presentation will provide the evidence that ozone exposure in animal models induce neuroendocrine stress response and this stress response modulates lung injury and inflammation through adrenergic and glucocorticoid receptors.

  3. Effects of cortisol and lipopolysaccharide on expression of select growth-, stress- and immune-related genes in rainbow trout liver

    Science.gov (United States)

    Many studies have shown that stress-induced cortisol levels negatively influence growth and immunity in finfish. Despite this knowledge, few studies have assessed the direct effects of cortisol on liver immune function in finfish. Using real-time PCR, the expression of three cortisol-responsive ge...

  4. Exogenous FABP4 induces endoplasmic reticulum stress in HepG2 liver cells.

    Science.gov (United States)

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

    2016-06-01

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

  5. Chicken hepatic response to chronic heat stress using integrated transcriptome and metabolome analysis.

    Directory of Open Access Journals (Sweden)

    Sara F Jastrebski

    Full Text Available The liver plays a central role in metabolism and is important in maintaining homeostasis throughout the body. This study integrated transcriptomic and metabolomic data to understand how the liver responds under chronic heat stress. Chickens from a rapidly growing broiler line were heat stressed for 8 hours per day for one week and liver samples were collected at 28 days post hatch. Transcriptome analysis reveals changes in genes responsible for cell cycle regulation, DNA replication, and DNA repair along with immune function. Integrating the metabolome and transcriptome data highlighted multiple pathways affected by heat stress including glucose, amino acid, and lipid metabolism along with glutathione production and beta-oxidation.

  6. Interactive effects of chronic stress and a high-sucrose diet on nonalcoholic fatty liver in young adult male rats.

    Science.gov (United States)

    Corona-Pérez, Adriana; Díaz-Muñoz, Mauricio; Cuevas-Romero, Estela; Luna-Moreno, Dalia; Valente-Godínez, Héctor; Vázquez-Martínez, Olivia; Martínez-Gómez, Margarita; Rodríguez-Antolín, Jorge; Nicolás-Toledo, Leticia

    2017-11-01

    Glucocorticoids have been implicated in nonalcoholic fatty liver diseases (NAFLD). The influence of a palatable diet on the response to stress is controversial. This study explored whether a high-sucrose diet could protect from hepatic steatosis induced by chronic restraint stress in young adult rats. Male Wistar rats aged 21 days were allocated into four groups (n = 6-8 per group): control, chronic restraint stress, 30% sucrose diet, and 30% sucrose diet plus chronic restraint stress. After being exposed to either tap water or sucrose solution during eight weeks, half of the rats belonging to each group were subject or not to repeated restraint stress (1 h per day, 5 days per week) during four weeks. Triacylglycerol (TAG), oxidative stress, activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1), infiltration of immune cells, and glycogen amount in the liver were quantified. Serum concentrations of corticosterone and testosterone were also measured. The stressed group showed normal serum concentrations of corticosterone and did not have hepatic steatosis. However, this group showed increased glycogen, inflammation, mild fibrosis, oxidative stress, and a high activity of 11β-HSD-1 in the liver. The group exposed to the high-sucrose diet had lower concentrations of corticosterone, hepatic steatosis and moderate fibrosis. The group subject to high-sucrose diet plus chronic restraint stress showed low concentrations of corticosterone, hepatic steatosis, oxidative stress, and high concentrations of testosterone. Thus, restraint stress and a high-sucrose diet each generate different components of nonalcoholic fatty liver in young adult rats. The combination of both the factors could promote a faster development of NAFLD.

  7. Longevity and the stress response in Drosophila

    DEFF Research Database (Denmark)

    Vermeulen, Corneel J.; Loeschcke, Volker

    2007-01-01

    briefly review the state of the art of research on ageing and longevity in the model organism Drosophila, with focus on the role of the general stress response. We will conclude by contemplating some of the implications of the findings in this research and will suggest several directions for future...... research. Keywords: Ageing; Stress response; Hsp; Drosophila; Stress......The concept that lifespan is a function of the capacity to withstand extrinsic stress is very old. In concordance with this, long-lived individuals often have increased resistance against a variety of stresses throughout life. Genes underlying the stress response may therefore have the ability...

  8. Spontaneous nonalcoholic fatty liver disease and ER stress in Sidt2 deficiency mice

    International Nuclear Information System (INIS)

    Gao, Jialin; Zhang, Yao; Yu, Cui; Tan, Fengbiao; Wang, Lizhuo

    2016-01-01

    Sidt2 is a newly discovered lysosomal membrane protein that is closely related to glucose metabolism. In the present study, we found that Sidt2 is also closely related to lipid metabolism. Gradual increases in serum triglyceride (TG) and free fatty acid, as well as elevated aspartate transaminase and alanine transaminase levels were observed in Sidt2"−"/"− mice fed a normal diet from the age of 3 months, suggesting the presence of lipid metabolism disorders and impaired liver function in these mice. In the liver slices of 6-month-old Sidt2"−"/"− mice, there were obvious fat degeneration and inflammatory changes. Almost all of the liver cells demonstrated different levels of lipid droplet accumulation and cell swelling, and some of the cells demonstrated balloon-like changes. Infiltration of inflammatory cells was observed in the portal area and hepatic lobule. Electron microscopy showed that macrophages tended to be attached to the endothelial cells, and a large number of lipid droplets were present in the liver cells. Oil red O staining showed that there were significantly increased number of deep straining particles in the liver cells of Sidt2"−"/"− mice, and the TG content in liver tissue was also significantly increased. Detection of key genes and proteins related to fat synthesis showed that mRNA and protein levels of the SREBP1c in the liver of Sidt2"−"/"− mice were significantly elevated, and the downstream genes acetyl-CoA carboxylase, fatty acid synthase, and mitochondrial glycerol 3-phosphate acyltransferase were significantly upregulated. In addition, there was severe endoplasmic reticulum stress (ERS) in the liver of Sidt2"−"/"− mice, which had significantly increased levels of markers specific for unfolded protein response activation, Grp78 and CHOP, as well as significant elevation of downstream p-PERK, p-eIF2a, p-IRE1a, along with ER damage. These results suggest that Sidt2"−"/"− mice had spontaneous nonalcoholic fatty liver

  9. Spontaneous nonalcoholic fatty liver disease and ER stress in Sidt2 deficiency mice

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Jialin [Department of Endocrinology and Genetic Metabolism, Yijishan Hospital of Wannan Medical College, Wuhu, 241002 (China); Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Zhang, Yao [Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Department of Biochemistry and Molecular Biology, Wannan Medical Collage, Wuhu, 241002 (China); Yu, Cui [Department of Endocrinology and Genetic Metabolism, Yijishan Hospital of Wannan Medical College, Wuhu, 241002 (China); Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Tan, Fengbiao [Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Department of Biochemistry and Molecular Biology, Wannan Medical Collage, Wuhu, 241002 (China); Wang, Lizhuo, E-mail: 19277924@qq.com [Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Department of Biochemistry and Molecular Biology, Wannan Medical Collage, Wuhu, 241002 (China)

    2016-08-05

    Sidt2 is a newly discovered lysosomal membrane protein that is closely related to glucose metabolism. In the present study, we found that Sidt2 is also closely related to lipid metabolism. Gradual increases in serum triglyceride (TG) and free fatty acid, as well as elevated aspartate transaminase and alanine transaminase levels were observed in Sidt2{sup −/−} mice fed a normal diet from the age of 3 months, suggesting the presence of lipid metabolism disorders and impaired liver function in these mice. In the liver slices of 6-month-old Sidt2{sup −/−} mice, there were obvious fat degeneration and inflammatory changes. Almost all of the liver cells demonstrated different levels of lipid droplet accumulation and cell swelling, and some of the cells demonstrated balloon-like changes. Infiltration of inflammatory cells was observed in the portal area and hepatic lobule. Electron microscopy showed that macrophages tended to be attached to the endothelial cells, and a large number of lipid droplets were present in the liver cells. Oil red O staining showed that there were significantly increased number of deep straining particles in the liver cells of Sidt2{sup −/−} mice, and the TG content in liver tissue was also significantly increased. Detection of key genes and proteins related to fat synthesis showed that mRNA and protein levels of the SREBP1c in the liver of Sidt2{sup −/−} mice were significantly elevated, and the downstream genes acetyl-CoA carboxylase, fatty acid synthase, and mitochondrial glycerol 3-phosphate acyltransferase were significantly upregulated. In addition, there was severe endoplasmic reticulum stress (ERS) in the liver of Sidt2{sup −/−} mice, which had significantly increased levels of markers specific for unfolded protein response activation, Grp78 and CHOP, as well as significant elevation of downstream p-PERK, p-eIF2a, p-IRE1a, along with ER damage. These results suggest that Sidt2{sup −/−} mice had spontaneous

  10. Shear stress upregulates regeneration-related immediate early genes in liver progenitors in 3D ECM-like microenvironments.

    Science.gov (United States)

    Nishii, Kenichiro; Brodin, Erik; Renshaw, Taylor; Weesner, Rachael; Moran, Emma; Soker, Shay; Sparks, Jessica L

    2018-05-01

    The role of fluid stresses in activating the hepatic stem/progenitor cell regenerative response is not well understood. This study hypothesized that immediate early genes (IEGs) with known links to liver regeneration will be upregulated in liver progenitor cells (LPCs) exposed to in vitro shear stresses on the order of those produced from elevated interstitial flow after partial hepatectomy. The objectives were: (1) to develop a shear flow chamber for application of fluid stress to LPCs in 3D culture; and (2) to determine the effects of fluid stress on IEG expression in LPCs. Two hours of shear stress exposure at ∼4 dyn/cm 2 was applied to LPCs embedded individually or as 3D spheroids within a hyaluronic acid/collagen I hydrogel. Results were compared against static controls. Quantitative reverse transcriptase polymerase chain reaction was used to evaluate the effect of experimental treatments on gene expression. Twenty-nine genes were analyzed, including IEGs and other genes linked to liver regeneration. Four IEGs (CFOS, IP10, MKP1, ALB) and three other regeneration-related genes (WNT, VEGF, EpCAM) were significantly upregulated in LPCs in response to fluid mechanical stress. LPCs maintained an early to intermediate stage of differentiation in spheroid culture in the absence of the hydrogel, and addition of the gel initiated cholangiocyte differentiation programs which were abrogated by the onset of flow. Collectively the flow-upregulated genes fit the pattern of an LPC-mediated proliferative/regenerative response. These results suggest that fluid stresses are potentially important regulators of the LPC-mediated regeneration response in liver. © 2017 Wiley Periodicals, Inc.

  11. Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver.

    Science.gov (United States)

    Petrović, Anja; Bogojević, Desanka; Korać, Aleksandra; Golić, Igor; Jovanović-Stojanov, Sofija; Martinović, Vesna; Ivanović-Matić, Svetlana; Stevanović, Jelena; Poznanović, Goran; Grigorov, Ilijana

    2017-11-01

    The progression of oxidative stress, resulting cell damage, and cell death underlies the etiology of liver damage/dysfunction as a complication of diabetes. High-mobility group box 1 (HMGB1) protein, a chromatin-binding nuclear protein and damage-associated molecular pattern molecule, is integral to oxidative stress and signaling pathways regulating cell death and cell survival. We previously found that in streptozotocin (STZ)-induced diabetic rats, reduction of oxidative stress after melatonin administration lowered necrotic cell death and increased expression of HMGB1 and hepatocellular damage. In the present study, we examined whether alleviation of diabetes-attendant oxidative stress and ensuing change in HMGB1 expression influence the dynamic equilibrium between apoptosis/autophagy and liver damage. We observed that elevated HMGB1 protein levels in diabetic rat liver accompanied increased interactions of HMGB1 with TLR4 and RAGE, and activation of the intrinsic apoptotic pathway and Beclin 1-dependent autophagy. The absence of p62 degradation in diabetic rat liver pointed to defective autophagy which was responsible for lower autophagosome/autophagolysosome formation and an increased apoptosis/autophagy ratio. Compared to diabetic rats, in melatonin-treated diabetic rats, the structure of liver cells was preserved, HMGB1/TLR4 interaction and downstream apoptotic signaling were significantly reduced, HMGB1/Beclin 1 colocalization and interactions were augmented and Beclin 1-mediated autophagy, mithophagy in particular, were increased. We concluded that in mild oxidative stress, HMGB1 is cytoprotective, whereas in intense oxidative stress, HMGB1 actions promote cell death and liver damage. Since reduced HMGB1 binds to RAGE but not to TLR4, redox modification of HMGB1 as a mechanism regulating the cross-talk between apoptosis and autophagy in diabetes is discussed.

  12. 3-Tesla MRI Response to TACE in HCC (Liver Cancer)

    Science.gov (United States)

    2016-08-22

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Stage A Adult Primary Liver Cancer (BCLC); Stage B Adult Primary Liver Cancer (BCLC)

  13. Agreeableness, Extraversion, Stressor and Physiological Stress Response

    OpenAIRE

    Xiaoyuan Chu; Zhentao Ma; Yuan Li; Jing Han

    2015-01-01

    Based on the theoretical analysis, with first-hand data collection and using multiple regression models, this study explored the relationship between agreeableness, extraversion, stressor and stress response and figured out interactive effect of agreeableness, extraversion, and stressor on stress response. We draw on the following conclusions: (1) the interaction term of stressor (work) and agreeableness can negatively predict physiological stress response; (2) the interaction term of stresso...

  14. Liver enzymes and psychological well-being response to aerobic ...

    African Journals Online (AJOL)

    2014-06-02

    Jun 2, 2014 ... Background: Chronic hepatitis C (CHC) is a medical condition that has broad implications for a person's physical and ... Objective: The aim of this study was to detect changes in liver enzymes and psychological well-being in response to aerobic .... of mood that can be used to calculate a Total Mood.

  15. Drug-induced oxidative stress in rat liver from a toxicogenomics perspective

    International Nuclear Information System (INIS)

    McMillian, Michael; Nie, Alex; Parker, J. Brandon; Leone, Angelique; Kemmerer, Michael; Bryant, Stewart; Herlich, Judy; Yieh, Lynn; Bittner, Anton; Liu, Xuejun; Wan, Jackson; Johnson, Mark D.; Lord, Peter

    2005-01-01

    Macrophage activators (MA), peroxisome proliferators (PP), and oxidative stressors/reactive metabolites (OS/RM) all produce oxidative stress and hepatotoxicity in rats. However, these three classes of hepatotoxicants give three distinct gene transcriptional profiles on cDNA microarrays, an indication that rat hepatocytes respond/adapt quite differently to these three classes of oxidative stressors. The differential gene responses largely reflect differential activation of transcription factors: MA activate Stat-3 and NFkB, PP activate PPARa, and OS/RM activate Nrf2. We have used gene signature profiles for each of these three classes of hepatotoxicants to categorize over 100 paradigm (and 50+ in-house proprietary) compounds as to their oxidative stress potential in rat liver. In addition to a role for microarrays in predictive toxicology, analyses of small subsets of these signature profiles, genes within a specific pathway, or even single genes often provide important insights into possible mechanisms involved in the toxicities of these compounds

  16. Tonic immobility differentiates stress responses in PTSD

    NARCIS (Netherlands)

    Fragkaki, I; Stins, J.F.; Roelofs, K.; Jongedijk, R.A.; Hagenaars, M.A.

    2016-01-01

    Background: Tonic immobility (TI) is a state of physical immobility associated with extreme stress and the development of posttraumatic stress disorder (PTSD). However, it is unknown whether TI is associated with a distinct actual stress response, i.e., objective immobility measured by a

  17. Swimming training induces liver mitochondrial adaptations to oxidative stress in rats submitted to repeated exhaustive swimming bouts.

    Directory of Open Access Journals (Sweden)

    Frederico D Lima

    Full Text Available BACKGROUND AND AIMS: Although acute exhaustive exercise is known to increase liver reactive oxygen species (ROS production and aerobic training has shown to improve the antioxidant status in the liver, little is known about mitochondria adaptations to aerobic training. The main objective of this study was to investigate the effects of the aerobic training on oxidative stress markers and antioxidant defense in liver mitochondria both after training and in response to three repeated exhaustive swimming bouts. METHODS: Wistar rats were divided into training (n = 14 and control (n = 14 groups. Training group performed a 6-week swimming training protocol. Subsets of training (n = 7 and control (n = 7 rats performed 3 repeated exhaustive swimming bouts with 72 h rest in between. Oxidative stress biomarkers, antioxidant activity, and mitochondria functionality were assessed. RESULTS: Trained group showed increased reduced glutathione (GSH content and reduced/oxidized (GSH/GSSG ratio, higher superoxide dismutase (MnSOD activity, and decreased lipid peroxidation in liver mitochondria. Aerobic training protected against exhaustive swimming ROS production herein characterized by decreased oxidative stress markers, higher antioxidant defenses, and increases in methyl-tetrazolium reduction and membrane potential. Trained group also presented higher time to exhaustion compared to control group. CONCLUSIONS: Swimming training induced positive adaptations in liver mitochondria of rats. Increased antioxidant defense after training coped well with exercise-produced ROS and liver mitochondria were less affected by exhaustive exercise. Therefore, liver mitochondria also adapt to exercise-induced ROS and may play an important role in exercise performance.

  18. Loss of c-Met signaling sensitizes hepatocytes to lipotoxicity and induces cholestatic liver damage by aggravating oxidative stress

    International Nuclear Information System (INIS)

    Gomez-Quiroz, Luis E.; Seo, Daekwan; Lee, Yun-Han; Kitade, Mitsuteru; Gaiser, Timo; Gillen, Matthew; Lee, Seung-Bum; Gutierrez-Ruiz, Ma Concepcion; Conner, Elizabeth A.; Factor, Valentina M; Thorgeirsson, Snorri S.; Marquardt, Jens U.

    2016-01-01

    Recent studies confirmed a critical importance of c-Met signaling for liver regeneration by modulating redox balance. Here we used liver-specific conditional knockout mice (MetKO) and a nutritional model of hepatic steatosis to address the role of c-Met in cholesterol-mediated liver toxicity. Liver injury was assessed by histopathology and plasma enzymes levels. Global transcriptomic changes were examined by gene expression microarray, and key molecules involved in liver damage and lipid homeostasis were evaluated by Western blotting. Loss of c-Met signaling amplified the extent of liver injury in MetKO mice fed with high-cholesterol diet for 30 days as evidenced by upregulation of liver enzymes and increased synthesis of total bile acids, aggravated inflammatory response and enhanced intrahepatic lipid deposition. Global transcriptomic changes confirmed the enrichment of networks involved in steatosis and cholestasis. In addition, signaling pathways related to glutathione and lipid metabolism, oxidative stress and mitochondria dysfunction were significantly affected by the loss of c-Met function. Mechanistically, exacerbation of oxidative stress in MetKO livers was corroborated by increased lipid and protein oxidation. Western blot analysis further revealed suppression of Erk, NF-kB and Nrf2 survival pathways and downstream target genes (e.g. cyclin D1, SOD1, gamma-GCS), as well as up-regulation of proapoptotic signaling (e.g. p53, caspase 3). Consistent with the observed steatotic and cholestatic phenotype, nuclear receptors RAR, RXR showed increased activation while expression levels of CAR, FXR and PPAR-alpha were decreased in MetKO. Collectively, our data provide evidence for the critical involvement of c-Met signaling in cholesterol and bile acids toxicity.

  19. Effects of Bauhinia forficata Tea on Oxidative Stress and Liver Damage in Diabetic Mice.

    Science.gov (United States)

    Salgueiro, Andréia Caroline Fernandes; Folmer, Vanderlei; da Silva, Marianne Pires; Mendez, Andreas Sebastian Loureiro; Zemolin, Ana Paula Pegoraro; Posser, Thaís; Franco, Jeferson Luis; Puntel, Robson Luiz; Puntel, Gustavo Orione

    2016-01-01

    This study was designed to evaluate the effects of Bauhinia forficata Link subsp. pruinosa (BF) tea on oxidative stress and liver damage in streptozotocin (STZ)-induced diabetic mice. Diabetic male mice have remained 30 days without any treatment. BF treatment started on day 31 and continued for 21 days as a drinking-water substitute. We evaluated (1) BF chemical composition; (2) glucose levels; (3) liver/body weight ratio and liver transaminases; (4) reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation in liver; (5) superoxide dismutase (SOD) and catalase (CAT) activities in liver; (6) δ-aminolevulinate dehydratase (δ-ALA-D) and nonprotein thiols (NPSH) in liver; (7) Nrf2, NQO-1, and HSP70 levels in liver and pancreas. Phytochemical analyses identified four phenols compounds. Diabetic mice present high levels of NQO-1 in pancreas, increased levels of ROS and lipid peroxidation in liver, and decrease in CAT activity. BF treatment normalized all these parameters. BF did not normalize hyperglycemia, liver/body weight ratio, aspartate aminotransferase, protein carbonyl, NPSH levels, and δ-ALA-D activity. The raised oxidative stress seems to be a potential mechanism involved in liver damage in hyperglycemic conditions. Our results indicated that BF protective effect could be attributed to its antioxidant capacity, more than a hypoglycemic potential.

  20. Effects of Bauhinia forficata Tea on Oxidative Stress and Liver Damage in Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Andréia Caroline Fernandes Salgueiro

    2016-01-01

    Full Text Available This study was designed to evaluate the effects of Bauhinia forficata Link subsp. pruinosa (BF tea on oxidative stress and liver damage in streptozotocin (STZ-induced diabetic mice. Diabetic male mice have remained 30 days without any treatment. BF treatment started on day 31 and continued for 21 days as a drinking-water substitute. We evaluated (1 BF chemical composition; (2 glucose levels; (3 liver/body weight ratio and liver transaminases; (4 reactive oxygen species (ROS, lipid peroxidation, and protein carbonylation in liver; (5 superoxide dismutase (SOD and catalase (CAT activities in liver; (6 δ-aminolevulinate dehydratase (δ-ALA-D and nonprotein thiols (NPSH in liver; (7 Nrf2, NQO-1, and HSP70 levels in liver and pancreas. Phytochemical analyses identified four phenols compounds. Diabetic mice present high levels of NQO-1 in pancreas, increased levels of ROS and lipid peroxidation in liver, and decrease in CAT activity. BF treatment normalized all these parameters. BF did not normalize hyperglycemia, liver/body weight ratio, aspartate aminotransferase, protein carbonyl, NPSH levels, and δ-ALA-D activity. The raised oxidative stress seems to be a potential mechanism involved in liver damage in hyperglycemic conditions. Our results indicated that BF protective effect could be attributed to its antioxidant capacity, more than a hypoglycemic potential.

  1. Proteomic analysis of physiological function response to hot summer in liver from lactating dairy cows.

    Science.gov (United States)

    Wang, Qiangjun; Zhao, Xiaowei; Zhang, Zijun; Zhao, Huiling; Huang, Dongwei; Cheng, Guanglong; Yang, Yongxin

    2017-04-01

    Lactation performance of dairy cattle is susceptible to heat stress. The liver is one of the most crucial organs affected by high temperature in dairy cows. However, the physiological adaption by the liver to hot summer conditions has not been well elucidated in lactating dairy cows. In the present study, proteomic analysis of the liver in dairy cows in spring and hot summer was performed using a label-free method. In total, 127 differentially expressed proteins were identified; most of the upregulated proteins were involved in protein metabolic processes and responses to stimuli, whereas most of the downregulated proteins were related to oxidation-reduction. Pathway analysis indicated that 3 upregulated heat stress proteins (HSP90α, HSP90β, and endoplasmin) were enriched in the NOD-like receptor signaling pathway, whereas several downregulated NADH dehydrogenase proteins were involved in the oxidative phosphorylation pathway. The protein-protein interaction network indicated that several upregulated HSPs (HSP90α, HSP90β, and GRP78) were involved in more interactions than other proteins and were thus considered as central hub nodes. Our findings provide novel insights into the physiological adaption of liver function in lactating dairy cows to natural high temperature. Copyright © 2017. Published by Elsevier Ltd.

  2. General Stress Responses in the Honey Bee

    Directory of Open Access Journals (Sweden)

    Naïla Even

    2012-12-01

    Full Text Available 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.

  3. Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-15

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

  4. Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish

    International Nuclear Information System (INIS)

    Christen, Verena; Capelle, Martinus; Fent, Karl

    2013-01-01

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

  5. Alternative Splicing Control of Abiotic Stress Responses.

    Science.gov (United States)

    Laloum, Tom; Martín, Guiomar; Duque, Paula

    2018-02-01

    Alternative splicing, which generates multiple transcripts from the same gene, is an important modulator of gene expression that can increase proteome diversity and regulate mRNA levels. In plants, this post-transcriptional mechanism is markedly induced in response to environmental stress, and recent studies have identified alternative splicing events that allow rapid adjustment of the abundance and function of key stress-response components. In agreement, plant mutants defective in splicing factors are severely impaired in their response to abiotic stress. Notably, mounting evidence indicates that alternative splicing regulates stress responses largely by targeting the abscisic acid (ABA) pathway. We review here current understanding of post-transcriptional control of plant stress tolerance via alternative splicing and discuss research challenges for the near future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. High hydrostatic pressure influences the in vitro response to xenobiotics in Dicentrarchus labrax liver

    Energy Technology Data Exchange (ETDEWEB)

    Lemaire, Benjamin; Mignolet, Eric; Debier, Cathy [Institut des Sciences de la Vie, Université Catholique de Louvain, Croix du Sud 2, B-1348 Louvain-la-Neuve (Belgium); Calderon, Pedro Buc [Louvain Drug Research Institute, Université Catholique de Louvain, Avenue Mounier 73, B-1200 Woluwé-Saint-Lambert (Belgium); Thomé, Jean Pierre [Laboratoire d’Ecologie Animale et Ecotoxicologie, Université de Liège, Allée du 6 août 15, B-4000 Liège (Belgium); Rees, Jean François, E-mail: jf.rees@uclouvain.be [Institut des Sciences de la Vie, Université Catholique de Louvain, Croix du Sud 2, B-1348 Louvain-la-Neuve (Belgium)

    2016-04-15

    Highlights: • The methodology of precision-cut liver slices was applied to the European seabass. • Liver slices remained viable and functional in short-term co-exposure studies. • CYP1A induction was blocked in slices exposed to an AhR agonist at high pressure. • HSP70 induction was lower in slices exposed to an AhR agonist at high pressure. • Oxidative stress responses to tBHP were less pronounced at high pressure. - Abstract: Hydrostatic pressure (HP) increases by about 1 atmosphere (0.1 MPa) for each ten-meter depth increase in the water column. This thermodynamical parameter could well influence the response to and effects of xenobiotics in the deep-sea biota, but this possibility remains largely overlooked. To grasp the extent of HP adaptation in deep-sea fish, comparative studies with living cells of surface species exposed to chemicals at high HP are required. We initially conducted experiments with precision-cut liver slices of a deep-sea fish (Coryphaenoides rupestris), co-exposed for 15 h to the aryl hydrocarbon receptor (AhR) agonist 3-methylcholanthrene at HP levels representative of the surface (0.1 MPa) and deep-sea (5–15 MPa; i.e., 500–1500 m depth) environments. The transcript levels of a suite of stress-responsive genes, such as the AhR battery CYP1A, were subsequently measured (Lemaire et al., 2012; Environ. Sci. Technol. 46, 10310–10316). Strikingly, the AhR agonist-mediated increase of CYP1A mRNA content was pressure-dependently reduced in C. rupestris. Here, the same co-exposure scenario was applied for 6 or 15 h to liver slices of a surface fish, Dicentrarchus labrax, a coastal species presumably not adapted to high HP. Precision-cut liver slices of D. labrax were also used in 1 h co-exposure studies with the pro-oxidant tert-butylhydroperoxide (tBHP) as to investigate the pressure-dependence of the oxidative stress response (i.e., reactive oxygen production, glutathione and lipid peroxidation status). Liver cells remained

  7. High hydrostatic pressure influences the in vitro response to xenobiotics in Dicentrarchus labrax liver

    International Nuclear Information System (INIS)

    Lemaire, Benjamin; Mignolet, Eric; Debier, Cathy; Calderon, Pedro Buc; Thomé, Jean Pierre; Rees, Jean François

    2016-01-01

    Highlights: • The methodology of precision-cut liver slices was applied to the European seabass. • Liver slices remained viable and functional in short-term co-exposure studies. • CYP1A induction was blocked in slices exposed to an AhR agonist at high pressure. • HSP70 induction was lower in slices exposed to an AhR agonist at high pressure. • Oxidative stress responses to tBHP were less pronounced at high pressure. - Abstract: Hydrostatic pressure (HP) increases by about 1 atmosphere (0.1 MPa) for each ten-meter depth increase in the water column. This thermodynamical parameter could well influence the response to and effects of xenobiotics in the deep-sea biota, but this possibility remains largely overlooked. To grasp the extent of HP adaptation in deep-sea fish, comparative studies with living cells of surface species exposed to chemicals at high HP are required. We initially conducted experiments with precision-cut liver slices of a deep-sea fish (Coryphaenoides rupestris), co-exposed for 15 h to the aryl hydrocarbon receptor (AhR) agonist 3-methylcholanthrene at HP levels representative of the surface (0.1 MPa) and deep-sea (5–15 MPa; i.e., 500–1500 m depth) environments. The transcript levels of a suite of stress-responsive genes, such as the AhR battery CYP1A, were subsequently measured (Lemaire et al., 2012; Environ. Sci. Technol. 46, 10310–10316). Strikingly, the AhR agonist-mediated increase of CYP1A mRNA content was pressure-dependently reduced in C. rupestris. Here, the same co-exposure scenario was applied for 6 or 15 h to liver slices of a surface fish, Dicentrarchus labrax, a coastal species presumably not adapted to high HP. Precision-cut liver slices of D. labrax were also used in 1 h co-exposure studies with the pro-oxidant tert-butylhydroperoxide (tBHP) as to investigate the pressure-dependence of the oxidative stress response (i.e., reactive oxygen production, glutathione and lipid peroxidation status). Liver cells remained

  8. Global transcriptional response to Hfe deficiency and dietary iron overload in mouse liver and duodenum.

    Directory of Open Access Journals (Sweden)

    Alejandra Rodriguez

    2009-09-01

    Full Text Available Iron is an essential trace element whose absorption is usually tightly regulated in the duodenum. HFE-related hereditary hemochromatosis (HH is characterized by abnormally low expression of the iron-regulatory hormone, hepcidin, which results in increased iron absorption. The liver is crucial for iron homeostasis as it is the main production site of hepcidin. The aim of this study was to explore and compare the genome-wide transcriptome response to Hfe deficiency and dietary iron overload in murine liver and duodenum. Illumina arrays containing over 47,000 probes were used to study global transcriptional changes. Quantitative RT-PCR (Q-RT-PCR was used to validate the microarray results. In the liver, the expression of 151 genes was altered in Hfe(-/- mice while dietary iron overload changed the expression of 218 genes. There were 173 and 108 differentially expressed genes in the duodenum of Hfe(-/- mice and mice with dietary iron overload, respectively. There was 93.5% concordance between the results obtained by microarray analysis and Q-RT-PCR. Overexpression of genes for acute phase reactants in the liver and a strong induction of digestive enzyme genes in the duodenum were characteristic of the Hfe-deficient genotype. In contrast, dietary iron overload caused a more pronounced change of gene expression responsive to oxidative stress. In conclusion, Hfe deficiency caused a previously unrecognized increase in gene expression of hepatic acute phase proteins and duodenal digestive enzymes.

  9. Diet-induced obesity associated with steatosis, oxidative stress, and inflammation in liver.

    Science.gov (United States)

    Peng, Yanhua; Rideout, Drew; Rakita, Steven; Lee, James; Murr, Michel

    2012-01-01

    Obesity induces steatosis and increases oxidative stress, as well as chronic inflammation in the liver. The balance between lipogenesis and lipolysis is disrupted in obese animals. At a cellular level, the changes in metabolic sensors and energy regulators are poorly understood. We hypothesized that diet-induced steatosis increases oxidative stress, inflammation, and changes the metabolic regulators to promote energy storage in mice. The setting was a university-affiliated basic science research laboratory. Four-week-old C57BL mice were fed a high-fat diet (n = 8) or regular chow (n = 8) for 7 weeks. The liver sections were stained for fat content and immunofluorescence. Liver homogenates were used for protein analysis by immunoblotting and mRNA analysis by reverse transcriptase-polymerase chain reaction. The gels were quantified using densitometry P ≤ .05 was considered significant. The high-fat diet upregulated protein kinase-C atypical isoforms ζ and λ and decreased glucose tolerance and the interaction of insulin receptor substrate 2 with phosphoinositide kinase-3. The high-fat diet increased the transcriptional factors liver X receptor (4321 ± 98 versus 2981 ± 80) and carbohydrate response element-binding protein (5132 ± 135 versus 3076 ± 91), the lipogenesis genes fatty acid binding protein 5, stearoyl-co-enzyme A desaturase-1, and acetyl-co-enzyme A carboxylase protein, and fatty acid synthesis. The high-fat diet decreased 5'-adenosine monophosphate-activated protein kinase (2561 ± 78 versus 1765 ± 65), glucokinase-3β (2.214 ± 34 versus 3356 ± 86), and SIRT1 (2015 ± 76 versus 3567 ± 104) and increased tumor necrosis factor-α (3415 ± 112 versus 2042 ± 65), nuclear factor kappa B (5123 ± 201 versus 2562 ± 103), cyclooxygenase-2 (4230 ± 113 versus 2473 ± 98), nicotinamide-adenine dinucleotide phosphate oxidase (3501 ± 106 versus 1600 ± 69) and reactive oxygen species production (all P high-fat diet impairs glucose tolerance and hepatic

  10. ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis

    DEFF Research Database (Denmark)

    DeZwaan-McCabe, Diane; Sheldon, Ryan D; Gorecki, Michelle C

    2017-01-01

    advantage of enhanced hepatic and renal steatosis in mice lacking the ER stress sensor ATF6α. We found that impaired fatty acid oxidation contributed to the early development of steatosis in the liver but not the kidney, while anorexia-induced lipolysis promoted late triglyceride and free fatty acid...

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Xiaoqing Ma

    2018-01-01

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

  13. Cadmium Chloride Induces DNA Damage and Apoptosis of Human Liver Carcinoma Cells via Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Anthony Skipper

    2016-01-01

    Full Text Available Cadmium is a heavy metal that has been shown to cause its toxicity in humans and animals. Many documented studies have shown that cadmium produces various genotoxic effects such as DNA damage and chromosomal aberrations. Ailments such as bone disease, renal damage, and several forms of cancer are attributed to overexposure to cadmium.  Although there have been numerous studies examining the effects of cadmium in animal models and a few case studies involving communities where cadmium contamination has occurred, its molecular mechanisms of action are not fully elucidated. In this research, we hypothesized that oxidative stress plays a key role in cadmium chloride-induced toxicity, DNA damage, and apoptosis of human liver carcinoma (HepG2 cells. To test our hypothesis, cell viability was determined by MTT assay. Lipid hydroperoxide content stress was estimated by lipid peroxidation assay. Genotoxic damage was tested by the means of alkaline single cell gel electrophoresis (Comet assay. Cell apoptosis was measured by flow cytometry assessment (Annexin-V/PI assay. The result of MTT assay indicated that cadmium chloride induces toxicity to HepG2 cells in a concentration-dependent manner, showing a 48 hr-LD50 of 3.6 µg/mL. Data generated from lipid peroxidation assay resulted in a significant (p < 0.05 increase of hydroperoxide production, specifically at the highest concentration tested. Data obtained from the Comet assay indicated that cadmium chloride causes DNA damage in HepG2 cells in a concentration-dependent manner. A strong concentration-response relationship (p < 0.05 was recorded between annexin V positive cells and cadmium chloride exposure. In summary, these in vitro studies provide clear evidence that cadmium chloride induces oxidative stress, DNA damage, and programmed cell death in human liver carcinoma (HepG2 cells.

  14. The endoplasmic reticulum stress response in disease ...

    African Journals Online (AJOL)

    Rafael Vincent M. Manalo

    2017-07-12

    Jul 12, 2017 ... Review. The endoplasmic reticulum stress response in disease pathogenesis and pathophysiology .... This is an open access article under the CC BY-NC-ND license ... chain binding protein (BIP); however, ER stress permits the release, .... drugs designed to alleviate it often cause more harm long-term.

  15. Molecular insights into the mechanisms of liver-associated diseases in early-lactating dairy cows: hypothetical role of endoplasmic reticulum stress.

    Science.gov (United States)

    Ringseis, R; Gessner, D K; Eder, K

    2015-08-01

    The transition period represents the most critical period in the productive life of high-yielding dairy cows due to both metabolic and inflammatory stimuli, which challenge the liver and predispose dairy cows to develop liver-associated diseases such as fatty liver and ketosis. Despite the fact that all high-yielding dairy cows are affected by marked metabolic stress due to a severe negative energy balance (NEB) during early lactation, not all cows develop liver-associated diseases. Although the reason for this is largely unknown, this indicates that the capacity of the liver to cope with metabolic and inflammatory challenges varies between individual high-yielding dairy cows. Convincing evidence exists that endoplasmic reticulum (ER) stress plays a key role in the development of fatty liver, and it has been recently shown that ER stress occurs in the liver of high-yielding dairy cows. This indicates that ER stress may be involved in the development of liver-associated diseases in dairy cows. The present review shows that the liver of dairy cows during early lactation is exposed to several metabolic and inflammatory challenges, such as non-esterified fatty acids, tumour necrosis factor α, interleukin-1β, reactive oxygen species and lipopolysaccharides, which are known inducers of ER stress. Thus, ER stress may represent a molecular basis for fatty liver development and account for the frequent occurrence of fatty liver and ketosis in high-yielding dairy cows. Interindividual differences between dairy cows in the activation of hepatic stress response pathways, such as nuclear factor E2-related factor 2, which is activated during ER stress and reduces the sensitivity of tissues to oxidative and inflammatory damage, might provide an explanation at the molecular level for differences in the capacity to cope with pathological inflammatory challenges during early lactation and the susceptibility to develop liver-associated diseases between early-lactating dairy cows

  16. Adaptogenic potential of royal jelly in liver of rats exposed to chronic stress.

    Directory of Open Access Journals (Sweden)

    Douglas Carvalho Caixeta

    Full Text Available Restraint and cold stress increase both corticosterone and glycemia, which lead to oxidative damages in hepatic tissue. This study assessed the effect of royal jelly (RJ supplementation on the corticosterone level, glycemia, plasma enzymes and hepatic antioxidant system in restraint and cold stressed rats. Wistar rats were allocated into no-stress, stress, no-stress supplemented with RJ and stress supplemented with RJ groups. Initially, RJ (200mg/Kg was administered for fourteen days and stressed groups were submitted to chronic stress from the seventh day. The results showed that RJ supplementation decreases corticosterone levels and improves glycemia control after stress induction. RJ supplementation also decreased the body weight, AST, ALP and GGT. Moreover, RJ improved total antioxidant capacity, SOD activity and reduced GSH, GR and lipoperoxidation in the liver. Thus, RJ supplementation reestablished the corticosterone levels and the hepatic antioxidant system in stressed rats, indicating an adaptogenic and hepatoprotective potential of RJ.

  17. Salinity Effects on Strategies of Glycogen Utilization in Livers of Euryhaline Milkfish (Chanos chanos under Hypothermal Stress

    Directory of Open Access Journals (Sweden)

    Chia-Hao Chang

    2018-02-01

    Full Text Available The fluctuation of temperature affects many physiological responses in ectothermic organisms, including feed intake, growth, reproduction, and behavior. Changes in environmental temperatures affect the acquisition of energy, whereas hepatic glycogen plays a central role in energy supply for the homeostasis of the entire body. Glycogen phosphorylase (GP, which catalyzes the rate-limiting step in glycogenolysis, is also an indicator of environmental stress. Here, we examined the effects of salinity on glycogen metabolism in milkfish livers under cold stress. A reduction of feed intake was observed in both freshwater (FW and seawater (SW milkfish under cold adaptation. At normal temperature (28°C, compared to the FW milkfish, the SW milkfish exhibited greater mRNA abundance of the liver isoform of GP (Ccpygl, higher GP activity, and less glycogen content in the livers. Upon hypothermal (18°C stress, hepatic Ccpygl mRNA expression of FW milkfish surged at 3 h, declined at 6 and 12 h, increased again at 24 h, and increased significantly after 96 h. Increases in GP protein, GP activity, and the phosphorylation state and the breakdown of glycogen were also found in FW milkfish livers after 12 h of exposure at 18°C. Conversely, the Ccpygl transcript levels in SW milkfish were downregulated after 1 h of exposure at 18°C, whereas the protein abundance of GP, GP activity, and glycogen content were not significantly altered. Taken together, under 18°C cold stress, FW milkfish exhibited an acute response with the breakdown of hepatic glycogen for maintaining energy homeostasis of the entire body, whereas no change was observed in the hepatic glycogen content and GP activity of SW milkfish because of their greater tolerance to cold conditions.

  18. Effect of blood glucose level on acute stress response of grass carp Ctenopharyngodon idella.

    Science.gov (United States)

    Jiang, Danli; Wu, Yubo; Huang, Di; Ren, Xing; Wang, Yan

    2017-10-01

    Stress has a considerable impact on welfare and productivity of fish, and blood glucose level of fish may be a factor modulating stress response. This study evaluated the effect of blood glucose level and handling on acute stress response of grass carp Ctenopharyngodon idella. Fish were intraperitoneally injected with glucose at 0, 0.2, 0.5, and 1.0 mg g -1 body mass (BM) and then were exposed to handling for 5 min. Glucose injection resulted in increase of plasma glucose level and liver glycogen content and decrease of plasma lactate level. Handling resulted in increase of plasma levels of cortisol, glucose, and lactate and plasma lactic dehydrogenase (LDH) activity and decrease of liver glycogen content. At 1 h post-stress, the plasma cortisol level was lower in the stressed fish injected with glucose at 0.5 mg g -1 BM than the stressed fish injected with glucose at 0, 0.2, and 1.0 mg g -1 BM. No significant differences were found in the activities of phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate kinase (PK) in the liver between the stressed and unstressed fish, regardless of the dose of glucose injection. At 1 h post-stress, the liver glucose-6-phosphatase (G6Pase) activity was higher in the fish without glucose injection than in the fish injected with glucose. This study reveals that blood glucose level can affect stress response of grass carp by modulating cortisol release and glucose homeostasis through glycogen metabolism and gluconeogenesis in the liver.

  19. Stress proteins and the immune response.

    Science.gov (United States)

    Moseley, P

    2000-07-25

    The heat shock or stress response is one of the most highly conserved adaptive responses in nature. In single cell organisms, the stress response confers tolerance to a variety of stresses including hyperthermia, hyperoxia, hypoxia, and other perturbations, which alter protein synthesis. This tolerance phenomenon is also extremely important in the multicellular organism, resulting in not only thermal tolerance, but also resistance to stresses of the whole organism such as ischemia-reperfusion injury. Moreover, recent data indicates that these stress proteins have the ability to modulate the cellular immune response. Although the terms heat shock proteins (HSPs) and stress proteins are often used interchangeably, the term stress proteins includes the HSPs, the glucose-regulated proteins (GRPs) and ubiquitin. The stress proteins may be grouped by molecular weight ranging from the large 110 kDa HSP110 to ubiquitin at 8 kDa. These proteins serve as cellular chaperones, participating in protein synthesis and transport through the various cellular compartments. Because these proteins have unique cellular localizations, the chaperone function of the stress proteins often involves a transfer of peptides between stress proteins as the peptide is moved between cellular compartments. For example, HSP70 is a cytosolic and nuclear chaperone, which is critical for the transfer of cellular peptides in the mitochondrion through a hand-off that involves mitochondrial HSP60 at the inner mitochondrial membrane. Similarly, cytosolic proteins are transferred from HSP70 to gp96 as they move into the endoplasmic reticulum. The central role of the stress proteins in the transfer of peptides through the cell may be responsible for the recently recognized importance of the stress proteins in the modulation of the immune system [Feder, M.E., Hofmann, G.E., 1999. Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology. Annu. Rev. Physiol. 61

  20. Swimming training induces liver adaptations to oxidative stress and insulin sensitivity in rats submitted to high-fat diet.

    Science.gov (United States)

    Zacarias, Aline Cruz; Barbosa, Maria Andrea; Guerra-Sá, Renata; De Castro, Uberdan Guilherme Mendes; Bezerra, Frank Silva; de Lima, Wanderson Geraldo; Cardoso, Leonardo M; Santos, Robson Augusto Souza Dos; Campagnole-Santos, Maria José; Alzamora, Andréia Carvalho

    2017-11-01

    Oxidative stress, physical inactivity and high-fat (FAT) diets are associated with hepatic disorders such as metabolic syndrome (MS). The therapeutic effects of physical training (PT) were evaluated in rats with MS induced by FAT diet for 13 weeks, on oxidative stress and insulin signaling in the liver, during the last 6 weeks. FAT-sedentary (SED) rats increased body mass, retroperitoneal fat, mean arterial pressure (MAP) and heart rate (HR), and total cholesterol, serum alanine aminotransferase, glucose and insulin. Livers of FAT-SED rats increased superoxide dismutase activity, thiobarbituric acid-reactive substances, protein carbonyl and oxidized glutathione (GSSG); and decreased catalase activity, reduced glutathione/GSSG ratio, and the mRNA expression of insulin receptor substrate 1 (IRS-1) and serine/threonine kinase 2. FAT-PT rats improved in fitness and reduced their body mass, retroperitoneal fat, and glucose, insulin, total cholesterol, MAP and HR; and their livers increased superoxide dismutase and catalase activities, the reduced glutathione/GSSG ratio and the expression of peroxisome proliferator-activated receptor gamma and insulin receptor compared to FAT-SED rats. These findings indicated adaptive responses to PT by restoring the oxidative balance and insulin signaling in the liver and certain biometric and biochemical parameters as well as MAP in MS rats.

  1. Oxidative Stress and Pulmonary Changes in Experimental Liver Cirrhosis

    Directory of Open Access Journals (Sweden)

    Renata Salatti Ferrari

    2012-01-01

    Full Text Available The use of carbon tetrachloride (CCl4 in rats is an experimental model of hepatic tissue damage; which leads to fibrosis, and at the long term, cirrhosis. Cirrhosis is the consequence of progressive continued liver damage, it may be reversible when the damaging noxae have been withdrawn. The aim of this study is to evaluate the changes caused by cirrhosis in lung and liver, through the experimental model of intraperitoneal CCI4 administration. We used 18 male Wistar rats divided into three groups: control (CO and two groups divided by the time of cirrhosis induction by CCI4: G1 (11 weeks, G2 (16 weeks. We found significant increase of transaminase levels and lipid peroxidation (TBARS in liver and lung tissue and also increased antioxidant enzymes SOD and CAT, as well as the expression of TNF-α and IL-1β in the lung of cirrhotic animals. We observed changes in gas exchange in both cirrhotic groups. We can conclude that our model reproduces a model of liver cirrhosis, which causes alterations in the pulmonary system that leads to changes in gas exchange and size of pulmonary vessels.

  2. Response of Desulfovibrio vulgaris to Alkaline Stress

    Energy Technology Data Exchange (ETDEWEB)

    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).

  3. Adaptive Responses to Thermal Stress in Mammals

    Directory of Open Access Journals (Sweden)

    Yasser Lenis Sanin

    2015-12-01

    Full Text Available The environment animals have to cope with is a combination of natural factors such as temperature. Extreme changes in these factors can alter homeostasis, which can lead to thermal stress. This stress can be due to either high temperatures or low temperatures. Energy transference for thermoregulation in homoeothermic animals occurs through several mechanisms: conduction, convection, radiation and evaporation. When animals are subjected to thermal stress, physiological mechanisms are activated which may include endocrine, neuroendocrine and behavioral responses. Activation of the neuroendocrine system affects the secretion of hormones and neurotransmitters which act collectively as response mechanisms that allow them to adapt to stress. Mechanisms which have developed through evolution to allow animals to adapt to high environmental temperatures and to achieve thermo tolerance include physiological and physical changes in order to reduce food intake and metabolic heat production, to increase surface area of skin to dissipate heat, to increase blood flow to take heat from the body core to the skin and extremities to dissipate the heat, to increase numbers and activity of sweat glands, panting, water intake and color adaptation of integument system to reflect heat. Chronic exposure to thermal stress can cause disease, reduce growth, decrease productive and reproductive performance and, in extreme cases, lead to death. This paper aims to briefly explain the physical and physiological responses of mammals to thermal stress, like a tool for biological environment adaptation, emphasizing knowledge gaps and offering some recommendations to stress control for the animal production system.

  4. Functional proteomic analysis of corticosteroid pharmacodynamics in rat liver: Relationship to hepatic stress, signaling, energy regulation, and drug metabolism.

    Science.gov (United States)

    Ayyar, Vivaswath S; Almon, Richard R; DuBois, Debra C; Sukumaran, Siddharth; Qu, Jun; Jusko, William J

    2017-05-08

    Corticosteroids (CS) are anti-inflammatory agents that cause extensive pharmacogenomic and proteomic changes in multiple tissues. An understanding of the proteome-wide effects of CS in liver and its relationships to altered hepatic and systemic physiology remains incomplete. Here, we report the application of a functional pharmacoproteomic approach to gain integrated insight into the complex nature of CS responses in liver in vivo. An in-depth functional analysis was performed using rich pharmacodynamic (temporal-based) proteomic data measured over 66h in rat liver following a single dose of methylprednisolone (MPL). Data mining identified 451 differentially regulated proteins. These proteins were analyzed on the basis of temporal regulation, cellular localization, and literature-mined functional information. Of the 451 proteins, 378 were clustered into six functional groups based on major clinically-relevant effects of CS in liver. MPL-responsive proteins were highly localized in the mitochondria (20%) and cytosol (24%). Interestingly, several proteins were related to hepatic stress and signaling processes, which appear to be involved in secondary signaling cascades and in protecting the liver from CS-induced oxidative damage. Consistent with known adverse metabolic effects of CS, several rate-controlling enzymes involved in amino acid metabolism, gluconeogenesis, and fatty-acid metabolism were altered by MPL. In addition, proteins involved in the metabolism of endogenous compounds, xenobiotics, and therapeutic drugs including cytochrome P450 and Phase-II enzymes were differentially regulated. Proteins related to the inflammatory acute-phase response were up-regulated in response to MPL. Functionally-similar proteins showed large diversity in their temporal profiles, indicating complex mechanisms of regulation by CS. Clinical use of corticosteroid (CS) therapy is frequent and chronic. However, current knowledge on the proteome-level effects of CS in liver and

  5. Posttraumatic Stress Disorder, Quality of Life, and the Subjective Experience in Liver Transplant Recipients.

    Science.gov (United States)

    Paslakis, Georgios; Beckmann, Mingo; Beckebaum, Susanne; Klein, Christian; Gräf, Jan; Erim, Yesim

    2018-03-01

    A high prevalence of posttraumatic stress disorder (PTSD) symptoms among transplant recipients has been associated with a low adherence to treatment and poor survival. It is crucial to detect and prevent the development of posttraumatic stress in transplant settings. We examined the prevalence of posttraumatic stress symptoms in 3 liver transplant recipients by means of the Essen Trauma Inventory (ETI), a self-report questionnaire. The Short Form-36 was used to assess the perceived health-related quality of life. Patients were asked to indicate the most traumatic events within the context of the liver transplantation procedure. Five patients (4.9%) fulfilled the criteria for PTSD related to liver disease or transplantation (ETI score greater than 27). In these patients, diagnosis was confirmed by a structured clinical interview. Fourteen (13.6%) patients had a partial PTSD with the ETI score less than 27 and greater than 16. Posttraumatic stress symptoms were significantly associated with perceived poor physical and mental health-related quality of life. Patients reported that the physicians' disclosure of diagnosis was experienced as traumatic, followed by treatment in an intensive care unit and the liver transplantation itself. The ETI resulted in prevalence rates for PTSD comparable to previous studies in liver transplantation settings. Medical professionals requested additional training in how to deliver severe diagnoses to patients.

  6. Blood cell oxidative stress precedes hemolysis in whole blood-liver slice co-cultures of rat, dog, and human tissues

    International Nuclear Information System (INIS)

    Vickers, Alison E.M.; Sinclair, John R.; Fisher, Robyn L.; Morris, Stephen R.; Way, William

    2010-01-01

    A novel in vitro model to investigate time-dependent and concentration-dependent responses in blood cells and hemolytic events is studied for rat, dog, and human tissues. Whole blood is co-cultured with a precision-cut liver slice. Methimazole (MMI) was selected as a reference compound, since metabolism of its imidazole thione moiety is linked with hematologic disorders and hepatotoxicity. An oxidative stress response occurred in all three species, marked by a decline in blood GSH levels by 24 h that progressed, and preceded hemolysis, which occurred at high MMI concentrations in the presence of a liver slice with rat (≥ 1000 μM at 48 h) and human tissues (≥ 1000 μM at 48 h, ≥ 750 μM at 72 h) but not dog. Human blood-only cultures exhibited a decline of GSH levels but minimal to no hemolysis. The up-regulation of liver genes for heme degradation (Hmox1 and Prdx1), iron cellular transport (Slc40a1), and GSH synthesis and utilization (mGST1 and Gclc) were early markers of the oxidative stress response. The up-regulation of the Kupffer cell lectin Lgals3 gene expression indicated a response to damaged red blood cells, and Hp (haptoglobin) up-regulation is indicative of increased hemoglobin uptake. Up-regulation of liver IL-6 and IL-8 gene expression suggested an activation of an inflammatory response by liver endothelial cells. In summary, MMI exposure led to an oxidative stress response in blood cells, and an up-regulation of liver genes involved with oxidative stress and heme homeostasis, which was clearly separate and preceded frank hemolysis.

  7. Tonic immobility differentiates stress responses in PTSD.

    Science.gov (United States)

    Fragkaki, Iro; Stins, John; Roelofs, Karin; Jongedijk, Ruud A; Hagenaars, Muriel A

    2016-11-01

    Tonic immobility (TI) is a state of physical immobility associated with extreme stress and the development of posttraumatic stress disorder (PTSD). However, it is unknown whether TI is associated with a distinct actual stress response, i.e., objective immobility measured by a stabilometric platform. This study made a first step in exploring this as well as differences in body sway responses between PTSD patients and healthy controls. We hypothesized that PTSD would be related to increased body sway under stress, whereas TI would be related to decreased body sway under stress. Eye closure was selected as a PTSD-relevant stress induction procedure. Body sway and heart rate (HR) were measured in 12 PTSD patients and 12 healthy controls in four conditions: (1) maintaining a stable stance with eyes open, (2) with eyes closed, (3) during a mental arithmetic task with eyes open, and (4) with eyes closed. As predicted, PTSD patients showed increased body sway from eyes open to eyes closed compared to controls and this effect was eliminated by executing the arithmetic task. Most importantly, retrospective self-reported TI was associated with lower body sway increases in PTSD and higher body sway decreases in controls from eyes-open to eyes-closed conditions. These preliminary findings suggest that eye closure has a different effect on PTSD patients than controls and that high self-reported TI might indicate a distinct stress response pattern, i.e., a proneness for immobility. It may be relevant to take such individual differences in stress-response into account in PTSD treatment.

  8. The War Fighter's Stress Response: Telemetric and Noninvasive Assessment

    National Research Council Canada - National Science Library

    O'Donnell, Amanda

    2003-01-01

    ... and biological responses to stress. Specifically, stress-hardy individuals retain mental focus and clarity of memory under stress, commit fewer errors during stress, experience less burnout, demonstrate better navigational skills...

  9. Liver cirrhosis associated wiht a non-responsive ascites in a 10 ...

    African Journals Online (AJOL)

    Liver cirrhosis associated wiht a non-responsive ascites in a 10 month old alsatian dog. ... Exploratory laparotomy findings were that of a slightly enlarged liver with diffuse miliary nodules on .both the parietal and visceral surfaces. Few larger nodules 'were also present. 'The liver was firmer in consistency and two separate ...

  10. Accumulation of polystyrene microplastics in juvenile Eriocheir sinensis and oxidative stress effects in the liver.

    Science.gov (United States)

    Yu, Ping; Liu, Zhiquan; Wu, Donglei; Chen, Minghai; Lv, Weiwei; Zhao, Yunlong

    2018-04-24

    As a widespread and ubiquitous pollutant of marine ecosystems, microplastic has the potential to become an emerging global threat for aquatic organisms. The present study aims to elucidate the effects of microplastics on the growth, accumulation and oxidative stress response in the liver of Eriocheir sinensis. Fluorescent microplastic particles (diameter = 0.5 μm) accumulated in the gill, liver and gut tissues of E. sinensis were investigated when crabs were exposed to a concentration of 40000 μg/L for 7 days. A 21 day toxicity test suggested that the rate of weight gain, specific growth rate, and hepatosomatic index of E. sinensis decreased with increasing microplastic concentration (0 μg/L, 40 μg/L, 400 μg/L, 4000 μg/L and 40000 μg/L). The activities of AChE and GPT in crabs exposed to microplastics were lower than those in control group. GOT activity increased significantly after exposure to a low concentration of microplastics and then decreased continuously with increasing microplastic concentrations. The activities of superoxide dismutase (SOD), aspartate transaminase (GOT), glutathione (GSH), and glutathione peroxidase (GPx) increased in specimens exposed to low concentrations of microplastics (40 and 400 μg/L) compared to the control and decreased in organisms exposed to high concentrations (4000 and 40000 μg/L). In contrast, the activities of acetylcholinesterase, catalase (CAT), and alanine aminotransferase were significantly lower in the organisms exposed to microplastics compared to control animals. Upon exposure to increasing microplastic concentrations, the expression of genes encoding the antioxidants SOD, CAT, GPx and glutathione S-transferase in the liver decreased after first increasing. Exposure to microplastics increased the expression of the gene encoding p38 in the MAPK signaling pathway and significantly decreased the expressions of genes encoding ERK, AKT, and MEK. The results of this study demonstrate that

  11. High hydrostatic pressure influences the in vitro response to xenobiotics in Dicentrarchus labrax liver.

    Science.gov (United States)

    Lemaire, Benjamin; Mignolet, Eric; Debier, Cathy; Calderon, Pedro Buc; Thomé, Jean Pierre; Rees, Jean François

    2016-04-01

    Hydrostatic pressure (HP) increases by about 1 atmosphere (0.1MPa) for each ten-meter depth increase in the water column. This thermodynamical parameter could well influence the response to and effects of xenobiotics in the deep-sea biota, but this possibility remains largely overlooked. To grasp the extent of HP adaptation in deep-sea fish, comparative studies with living cells of surface species exposed to chemicals at high HP are required. We initially conducted experiments with precision-cut liver slices of a deep-sea fish (Coryphaenoides rupestris), co-exposed for 15h to the aryl hydrocarbon receptor (AhR) agonist 3-methylcholanthrene at HP levels representative of the surface (0.1MPa) and deep-sea (5-15MPa; i.e., 500-1500m depth) environments. The transcript levels of a suite of stress-responsive genes, such as the AhR battery CYP1A, were subsequently measured (Lemaire et al., 2012; Environ. Sci. Technol. 46, 10310-10316). Strikingly, the AhR agonist-mediated increase of CYP1A mRNA content was pressure-dependently reduced in C. rupestris. Here, the same co-exposure scenario was applied for 6 or 15h to liver slices of a surface fish, Dicentrarchus labrax, a coastal species presumably not adapted to high HP. Precision-cut liver slices of D. labrax were also used in 1h co-exposure studies with the pro-oxidant tert-butylhydroperoxide (tBHP) as to investigate the pressure-dependence of the oxidative stress response (i.e., reactive oxygen production, glutathione and lipid peroxidation status). Liver cells remained viable in all experiments (adenosine triphosphate content). High HP precluded the AhR agonist-mediated increase of CYP1A mRNA expression in D. labrax, as well as that of glutathione peroxidase, and significantly reduced that of heat shock protein 70. High HP (1h) also tended per se to increase the level of oxidative stress in liver cells of the surface fish. Trends to an increased resistance to tBHP were also noted. Whether the latter observation truly

  12. Dysfunctional stress responses in chronic pain.

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Stress response in medically important Mucorales.

    Science.gov (United States)

    Singh, Pankaj; Paul, Saikat; Shivaprakash, M Rudramurthy; Chakrabarti, Arunaloke; Ghosh, Anup K

    2016-10-01

    Mucorales are saprobes, ubiquitously distributed and able to infect a heterogeneous population of human hosts. The fungi require robust stress responses to survive in human host. We tested the growth of Mucorales in the presence of different abiotic stress. Eight pathogenic species of Mucorales, including Rhizopus arrhizus, Rhizopus microsporus, Rhizomucor pusillus, Apophysomyces elegans, Licthemia corymbifera, Cunninghamella bertholletiae, Syncephalastrum racemosum and Mucor racemosus, were exposed to different stress inducers: osmotic (sodium chloride and d-sorbitol), oxidative (hydrogen peroxide and menadione), pH, cell wall and metal ions (Cu, Zn, Fe and Mg). Wide variation in stress responses was noted: R. arrhizus showed maximum resistance to both osmotic and oxidative stresses, whereas R. pusillus and M. indicus were relatively sensitive. Rhizopus arrhizus and R. microsporus showed maximum resistance to alkaline pH, whereas C. bertholletiae, L. corymbifera, M. racemosus and A. elegans were resistant to acidic pH. Maximum tolerance was noted in R. microsporus to Cu, R. microsporus and R. arrhizus to Fe and C. bertholletiae to Zn. In contrast, L. corymbifera, A. elegans and M. indicus were sensitive to Cu, Zn and Fe respectively. In conclusion, R. arrhizus showed high stress tolerance in comparison to other species of Mucorales, and this could be the possible reason for high pathogenic potential of this fungi. © 2016 Blackwell Verlag GmbH.

  14. Troxerutin protects against 2,2',4,4'-tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD⁺-depletion.

    Science.gov (United States)

    Zhang, Zi-Feng; Zhang, Yan-Qiu; Fan, Shao-Hua; Zhuang, Juan; Zheng, Yuan-Lin; Lu, Jun; Wu, Dong-Mei; Shan, Qun; Hu, Bin

    2015-01-01

    Emerging evidence indicates that 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) induces liver injury through enhanced ROS production and lymphocytic infiltration, which may promote a liver inflammatory response. Antioxidants have been reported to attenuate the cellular toxicity associated with polybrominated diphenyl ethers (PBDEs). In this study, we investigated the effect of troxerutin, a trihydroxyethylated derivative of the natural bioflavonoid rutin, on BDE-47-induced liver inflammation and explored the potential mechanisms underlying this effect. Our results showed that NAD(+)-depletion was involved in the oxidative stress-mediated liver injury in a BDE-47 treated mouse model, which was confirmed by Vitamin E treatment. Furthermore, our data revealed that troxerutin effectively alleviated liver inflammation by mitigating oxidative stress-mediated NAD(+)-depletion in BDE-47 treated mice. Consequently, troxerutin remarkably restored SirT1 protein expression and activity in the livers of BDE-47-treated mice. Mechanistically, troxerutin dramatically repressed the nuclear translocation of NF-κB p65 and the acetylation of NF-κB p65 (Lys 310) and Histone H3 (Lys9) to abate the transcription of inflammatory genes in BDE-47-treated mouse livers. These inhibitory effects of troxerutin were markedly blunted by EX527 (SirT1 inhibitor) treatment. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that troxerutin might be used in the prevention and therapy of BDE-47-induced hepatotoxicity. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Troxerutin protects against 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD+-depletion

    International Nuclear Information System (INIS)

    Zhang, Zi-Feng; Zhang, Yan-qiu; Fan, Shao-Hua; Zhuang, Juan; Zheng, Yuan-Lin; Lu, Jun; Wu, Dong-Mei; Shan, Qun; Hu, Bin

    2015-01-01

    Highlights: • BDE-47 promotes liver inflammation by triggering oxidative stress-induced NAD + depletion. • Troxerutin inhibits BDE-47-induced liver inflammation via its antioxidant properties. • Troxerutin restores NAD + level and consequently abates SirT1 loss. • Troxerutin represses acetylation of NF-κB p65 (K310) and H3K9. • Troxerutin is a candidate for prevention and therapy of BDE-47-induced hepatotoxicity. - Abstract: Emerging evidence indicates that 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) induces liver injury through enhanced ROS production and lymphocytic infiltration, which may promote a liver inflammatory response. Antioxidants have been reported to attenuate the cellular toxicity associated with polybrominated diphenyl ethers (PBDEs). In this study, we investigated the effect of troxerutin, a trihydroxyethylated derivative of the natural bioflavonoid rutin, on BDE-47-induced liver inflammation and explored the potential mechanisms underlying this effect. Our results showed that NAD + -depletion was involved in the oxidative stress-mediated liver injury in a BDE-47 treated mouse model, which was confirmed by Vitamin E treatment. Furthermore, our data revealed that troxerutin effectively alleviated liver inflammation by mitigating oxidative stress-mediated NAD + -depletion in BDE-47 treated mice. Consequently, troxerutin remarkably restored SirT1 protein expression and activity in the livers of BDE-47-treated mice. Mechanistically, troxerutin dramatically repressed the nuclear translocation of NF-κB p65 and the acetylation of NF-κB p65 (Lys 310) and Histone H3 (Lys9) to abate the transcription of inflammatory genes in BDE-47-treated mouse livers. These inhibitory effects of troxerutin were markedly blunted by EX527 (SirT1 inhibitor) treatment. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that troxerutin might be used in the prevention and therapy of BDE-47-induced hepatotoxicity

  16. Sympathoneural and Adrenomedullary Responses to Mental Stress

    Science.gov (United States)

    Carter, Jason R.; Goldstein, David S.

    2017-01-01

    This concept-based review provides historical perspectives and updates about sympathetic noradrenergic and sympathetic adrenergic responses to mental stress. The topic of this review has incited perennial debate, because of disagreements over definitions, controversial inferences, and limited availability of relevant measurement tools. The discussion begins appropriately with Cannon's "homeostasis" and his pioneering work in the area. This is followed by mental stress as a scientific idea and the relatively new notions of allostasis and allostatic load. Experimental models of mental stress in rodents and humans are discussed, with particular attention to ethical constraints in humans. Sections follow on sympathoneural to mental stress, reactivity of catecholamine systems, clinical pathophysiologic states, and the cardiovascular reactivity hypothesis. Future advancement of the field will require integrative approaches and coordinated efforts between physiologists and psychologists on this interdisciplinary topic. PMID:25589266

  17. Anion channels: master switches of stress responses.

    Science.gov (United States)

    Roelfsema, M Rob G; Hedrich, Rainer; Geiger, Dietmar

    2012-04-01

    During stress, plant cells activate anion channels and trigger the release of anions across the plasma membrane. Recently, two new gene families have been identified that encode major groups of anion channels. The SLAC/SLAH channels are characterized by slow voltage-dependent activation (S-type), whereas ALMT genes encode rapid-activating channels (R-type). Both S- and R-type channels are stimulated in guard cells by the stress hormone ABA, which leads to stomatal closure. Besides their role in ABA-dependent stomatal movement, anion channels are also activated by biotic stress factors such as microbe-associated molecular patterns (MAMPs). Given that anion channels occur throughout the plant kingdom, they are likely to serve a general function as master switches of stress responses. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Plant Nucleolar Stress Response, a New Face in the NAC-Dependent Cellular Stress Responses.

    Science.gov (United States)

    Ohbayashi, Iwai; Sugiyama, Munetaka

    2017-01-01

    The nucleolus is the most prominent nuclear domain, where the core processes of ribosome biogenesis occur vigorously. All these processes are finely orchestrated by many nucleolar factors to build precisely ribosome particles. In animal cells, perturbations of ribosome biogenesis, mostly accompanied by structural disorders of the nucleolus, cause a kind of cellular stress to induce cell cycle arrest, senescence, or apoptosis, which is called nucleolar stress response. The best-characterized pathway of this stress response involves p53 and MDM2 as key players. p53 is a crucial transcription factor that functions in response to not only nucleolar stress but also other cellular stresses such as DNA damage stress. These cellular stresses release p53 from the inhibition by MDM2, an E3 ubiquitin ligase targeting p53, in various ways, which leads to p53-dependent activation of a set of genes. In plants, genetic impairments of ribosome biogenesis factors or ribosome components have been shown to cause characteristic phenotypes, including a narrow and pointed leaf shape, implying a common signaling pathway connecting ribosomal perturbations and certain aspects of growth and development. Unlike animals, however, plants have neither p53 nor MDM2 family proteins. Then the question arises whether plant cells have a nucleolar stress response pathway. In recent years, it has been reported that several members of the plant-specific transcription factor family NAC play critical roles in the pathways responsive to various cellular stresses. In this mini review, we outline the plant cellular stress response pathways involving NAC transcription factors with reference to the p53-MDM2-dependent pathways of animal cells, and discuss the possible involvement of a plant-unique, NAC-mediated pathway in the nucleolar stress response in plants.

  19. Plant Nucleolar Stress Response, a New Face in the NAC-Dependent Cellular Stress Responses

    Directory of Open Access Journals (Sweden)

    Iwai Ohbayashi

    2018-01-01

    Full Text Available The nucleolus is the most prominent nuclear domain, where the core processes of ribosome biogenesis occur vigorously. All these processes are finely orchestrated by many nucleolar factors to build precisely ribosome particles. In animal cells, perturbations of ribosome biogenesis, mostly accompanied by structural disorders of the nucleolus, cause a kind of cellular stress to induce cell cycle arrest, senescence, or apoptosis, which is called nucleolar stress response. The best-characterized pathway of this stress response involves p53 and MDM2 as key players. p53 is a crucial transcription factor that functions in response to not only nucleolar stress but also other cellular stresses such as DNA damage stress. These cellular stresses release p53 from the inhibition by MDM2, an E3 ubiquitin ligase targeting p53, in various ways, which leads to p53-dependent activation of a set of genes. In plants, genetic impairments of ribosome biogenesis factors or ribosome components have been shown to cause characteristic phenotypes, including a narrow and pointed leaf shape, implying a common signaling pathway connecting ribosomal perturbations and certain aspects of growth and development. Unlike animals, however, plants have neither p53 nor MDM2 family proteins. Then the question arises whether plant cells have a nucleolar stress response pathway. In recent years, it has been reported that several members of the plant-specific transcription factor family NAC play critical roles in the pathways responsive to various cellular stresses. In this mini review, we outline the plant cellular stress response pathways involving NAC transcription factors with reference to the p53-MDM2-dependent pathways of animal cells, and discuss the possible involvement of a plant-unique, NAC-mediated pathway in the nucleolar stress response in plants.

  20. The role of oxidative stress in the development of alcoholic liver disease

    Directory of Open Access Journals (Sweden)

    M. Galicia-Moreno

    2014-04-01

    Conclusions: Oxidative stress plays an important role in the development of liver damage resulting from alcohol consumption. The molecules that have currently displayed a hepatoprotective effect in preclinical and clinical trials must be studied further so that their effectiveness can be confirmed and they can possibly be used as adjuvant treatments for this disease.

  1. Protective effect of Momordica charantia water extract against liver injury in restraint-stressed mice and the underlying mechanism.

    Science.gov (United States)

    Deng, Yuanyuan; Tang, Qin; Zhang, Yan; Zhang, Ruifen; Wei, Zhencheng; Tang, Xiaojun; Zhang, Mingwei

    2017-01-01

    Background : Momordica charantia is used in China for its jianghuo (heat-clearing and detoxifying) effects. The concept of shanghuo (the antonym of jianghuo , excessive internal heat) in traditional Chinese medicine is considered a type of stress response of the body. The stress process involves internal organs, especially the liver. Objective : We hypothesized that Momordica charantia water extract (MWE) has a hepatoprotective effect and can protect the body from stress. The aim of this study was to investigate the possible effects of MWE against liver injury in restraint-stressed mice. Design : The mice were intragastrically administered with MWE (250, 500 and 750 mg/kg bw) daily for 7 days. The Normal Control (NC) and Model groups were administered distilled water. A positive control group was intragastrically administered vitamin C 250 mg/kg bw. After the last administration, mice were restrained for 20 h. Results : MWE reduced the serum AST and ALT, reduced the NO content and the protein expression level of iNOSin the liver; significantly reduced the mitochondrial ROS content, increased the mitochondrial membrane potential and the activities of mitochondrial respiratory chain complexes I and II in restraint-stressed mice. Conclusions : The results indicate that MWE has a protective effect against liver injury in restraint-stressed mice. Abbreviations : MWE: Momordica charantia water extract; M. charantia: Momordica charantia L.; ROS: reactive oxygen species; NO: nitric oxide; iNOS: inducible nitric oxide synthase; IL-1β: interleukin-1 beta; TNF-α: tumor necrosis factor alpha; IL-6: interleukin 6; IFN-γ: interferon gamma; VC: vitamin C; ALT: alanine transaminase; AST: aspartate aminotransferase; GSH: glutathione; GSH-PX: glutathione peroxidase; MDA: malondialdehyde; BCA: bicinchoninic acid; TBARS: thiobarbituric acid reactive substances; Trolox: 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; JC-B: Janus Green B; DW: dry weight; FC: Folin

  2. Increased Oxidative Stress and Mitochondrial Dysfunction in Zucker Diabetic Rat Liver and Brain

    Directory of Open Access Journals (Sweden)

    Haider Raza

    2015-02-01

    Full Text Available Background/Aims: The Zucker diabetic fatty (ZDF, FA/FA rat is a genetic model of type 2 diabetes, characterized by insulin resistance with progressive metabolic syndrome. We have previously demonstrated mitochondrial dysfunction and oxidative stress in the heart, kidneys and pancreas of ZDF rats. However, the precise molecular mechanism of disease progression is not clear. Our aim in the present study was to investigate oxidative stress and mitochondrial dysfunction in the liver and brain of ZDF rats. Methods: In this study, we have measured mitochondrial oxidative stress, bioenergetics and redox homeostasis in the liver and brain of ZDF rats. Results: Our results showed increased reactive oxygen species (ROS production in the ZDF rat brain compared to the liver, while nitric oxide (NO production was markedly increased both in the brain and liver. High levels of lipid and protein peroxidation were also observed in these tissues. Glutathione metabolism and mitochondrial respiratory functions were adversely affected in ZDF rats when compared to Zucker lean (ZL, +/FA control rats. Reduced ATP synthesis was also observed in the liver and brain of ZDF rats. Western blot analysis confirmed altered expression of cytochrome P450 2E1, iNOS, p-JNK, and IκB-a confirming an increase in oxidative and metabolic stress in ZDF rat tissues. Conclusions: Our data shows that, like other tissues, ZDF rat liver and brain develop complications associated with redox homeostasis and mitochondrial dysfunction. These results, thus, might have implications in understanding the etiology and pathophysiology of diabesity which in turn, would help in managing the disease associated complications.

  3. The endoplasmic reticulum stress response in disease ...

    African Journals Online (AJOL)

    These proteins are essential for cell survival, and intuitively the ER must activate stress responses to evade immediate cell dysfunction as the cell processes lag behind. This review will discuss mainly the ER and its role in the pathogenesis and pathophysiology of epidemiologically-relevant diseases, as well as updates on ...

  4. Effects of nutritional history on stress response in gibel carp (Carassius auratus gibelio) and largemouth bass (Micropterus salmoides).

    Science.gov (United States)

    Jiang, Danli; Wu, Yubo; Huang, Di; Ren, Xing; Wang, Yan

    2017-08-01

    The stress response of omnivorous gibel carp (Carassius auratus gibelio) and carnivorous largemouth bass (Micropterus salmoides) with different nutritional history were evaluated. A 2×2 layout, including two fish species (gibel carp or largemouth bass) and two nutritional history (fasted or fed to satiation for four weeks), was used. After feeding or fasting, the fishes were subjected to an acute handling. Fasting resulted in decrease of plasma glucose level and liver glycogen content of gibel carp and largemouth bass. After handling stress, plasma levels of cortisol, glucose and lactate of gibel carp and largemouth bass increased, regardless the fasted fish or fed fish. During the period from 0h to 24h post-stress, the fasted gibel carp exhibited lower plasma cortisol and glucose levels, brain and liver glycogen contents, and liver phosphoenolpyruvate carboxykinase (PEPCK) activity compared with the fed counterpart. The plasma glucose level, brain glucose level, brain and liver glycogen contents were lower, while the liver PEPCK and hexokinase (HK) activities were higher, in the faster largemouth bass than the fed counterpart. This study indicates that nutritional history can influence stress response of gibel carp and largemouth bass, and the stress response is less severe in the fasted fish relative to the fed counterpart. This study also reveals that gibel carp and largemouth bass may have different strategies in response to fasting and acute handling stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. N-Hydroxylation of 4-Aminobiphenyl by CYP2E1 Produces Oxidative Stress in a Mouse Model of Chemically Induced Liver Cancer

    Science.gov (United States)

    Wang, Shuang; Sugamori, Kim S.; Tung, Aveline; McPherson, J. Peter; Grant, Denis M.

    2015-01-01

    4-Aminobiphenyl (ABP) is a trace component of cigarette smoke and hair dyes, a suspected human carcinogen and a potent rodent liver carcinogen. Postnatal exposure of mice to ABP results in a higher incidence of liver tumors in males than in females, paralleling the sex difference in human liver cancer incidence. A traditional model of ABP tumorigenesis involves initial CYP1A2-mediated N-hydroxylation, which eventually leads to production of mutagenic ABP-DNA adducts that initiate tumor growth. However, several studies have found no correlation between sex or CYP1A2 function and the DNA-damaging, mutagenic, or tumorigenic effects of ABP. Oxidative stress may be an important etiological factor for liver cancer, and it has also been linked to ABP exposure. The goals of this study were to identify novel enzyme(s) that contribute to ABP N-oxidation, and to investigate a potential role for oxidative stress in ABP liver tumorigenicity. Isozyme-selective inhibition experiments using liver microsomes from wild-type and genetically modified mice identified CYP2E1 as a major ABP N-hydroxylating enzyme. The N-hydroxylation of ABP by transiently expressed CYP2E1 produced oxidative stress in cultured mouse hepatoma cells. In vivo postnatal exposure of mice to a tumorigenic dose of ABP also produced oxidative stress in male wild-type mice, but not in male Cyp2e1(−/−) mice or in female mice. However, a stronger NRF2-associated antioxidant response was observed in females. Our results identify CYP2E1 as a novel ABP-N-oxidizing enzyme, and suggest that sex differences in CYP2E1-dependent oxidative stress and antioxidant responses to ABP may contribute to the observed sex difference in tumor incidence. PMID:25601990

  6. Work stress and innate immune response.

    Science.gov (United States)

    Boscolo, P; Di Gioacchino, M; Reale, M; Muraro, R; Di Giampaolo, L

    2011-01-01

    Several reports highlight the relationship between blood NK cytotoxic activity and life style. Easy life style, including physical activity, healthy dietary habits as well as good mental health are characterized by an efficient immune response. Life style is related to the type of occupational activity since work has a central part in life either as source of income or contributing to represent the social identity. Not only occupational stress, but also job loss or insecurity are thus considered serious stressful situations, inducing emotional disorders which may affect both neuroendocrine and immune systems; reduced reactivity to mitogens and/or decreased blood NK cytotoxic activity was reported in unemployed workers or in those with a high perception of job insecurity and/or job stress. Although genetic factors have a key role in the pathogenesis of autoimmune disorders, occupational stress (as in night shifts) was reported associated to an increased incidence of autoimmune disorders. Monitoring blood NK response may thus be included in the health programs as an indirect index of stressful job and/or poor lifestyle.

  7. Replicative stress and alterations in cell cycle checkpoint controls following acetaminophen hepatotoxicity restrict liver regeneration.

    Science.gov (United States)

    Viswanathan, Preeti; Sharma, Yogeshwar; Gupta, Priya; Gupta, Sanjeev

    2018-03-05

    Acetaminophen hepatotoxicity is a leading cause of hepatic failure with impairments in liver regeneration producing significant mortality. Multiple intracellular events, including oxidative stress, mitochondrial damage, inflammation, etc., signify acetaminophen toxicity, although how these may alter cell cycle controls has been unknown and was studied for its significance in liver regeneration. Assays were performed in HuH-7 human hepatocellular carcinoma cells, primary human hepatocytes and tissue samples from people with acetaminophen-induced acute liver failure. Cellular oxidative stress, DNA damage and cell proliferation events were investigated by mitochondrial membrane potential assays, flow cytometry, fluorescence staining, comet assays and spotted arrays for protein expression after acetaminophen exposures. In experimental groups with acetaminophen toxicity, impaired mitochondrial viability and substantial DNA damage were observed with rapid loss of cells in S and G2/M and cell cycle restrictions or even exit in the remainder. This resulted from altered expression of the DNA damage regulator, ATM and downstream transducers, which imposed G1/S checkpoint arrest, delayed entry into S and restricted G2 transit. Tissues from people with acute liver failure confirmed hepatic DNA damage and cell cycle-related lesions, including restrictions of hepatocytes in aneuploid states. Remarkably, treatment of cells with a cytoprotective cytokine reversed acetaminophen-induced restrictions to restore cycling. Cell cycle lesions following mitochondrial and DNA damage led to failure of hepatic regeneration in acetaminophen toxicity but their reversibility offers molecular targets for treating acute liver failure. © 2018 John Wiley & Sons Ltd.

  8. Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice

    Directory of Open Access Journals (Sweden)

    Natalia Nuño-Lámbarri

    2016-01-01

    Full Text Available Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress.

  9. Perfluorooctanoic acid exposure induces endoplasmic reticulum stress in the liver and its effects are ameliorated by 4-phenylbutyrate.

    Science.gov (United States)

    Yan, Shengmin; Zhang, Hongxia; Wang, Jianshe; Zheng, Fei; Dai, Jiayin

    2015-10-01

    Perfluoroalkyl acids (PFAAs) are a group of widely used anthropogenic compounds. As one of the most dominant PFAAs, perfluorooctanoic acid (PFOA) has been suggested to induce hepatotoxicity and several other toxicological effects. However, details on the mechanisms for PFOA-induced hepatotoxicity still need to be elucidated. In this study, we observed the occurrence of endoplasmic reticulum (ER) stress in mouse livers and HepG2 cells after PFOA exposure using several familiar markers for the unfolded protein response (UPR). ER stress in HepG2 cells after PFOA exposure was not significantly influenced by autophagy inhibition or stimulation. The antioxidant defense system was significantly disturbed in mouse livers after PFOA exposure, and reactive oxygen species (ROS) were increased in cells exposed to PFOA for 24 h. However, N-acetyl-L-cysteine (NAC) pretreatment did not satisfactorily alleviate the UPR in cells exposed to PFOA even though the increase of ROS was less evident. Furthermore, exposure of HepG2 cells to PFOA in the presence of sodium 4-phenylbutyrate (4-PBA), a chemical chaperone and ER stress inhibitor, suggested that 4-PBA alleviated the UPR and autophagosome accumulation induced by PFOA in cells. In addition, several toxicological effects attributed to PFOA exposure, including cell cycle arrest, proteolytic activity impairment, and neutral lipid accumulation, were also improved by 4-PBA cotreatment in cells. In vivo study demonstrated that PFOA-induced lipid metabolism perturbation and liver injury were partially ameliorated by 4-PBA in mice after 28 days of exposure. These findings demonstrated that PFOA-induced ER stress leading to UPR might play an important role in PFOA-induced hepatotoxic effects, and chemical chaperone 4-PBA could ameliorate the effects. Copyright © 2015. Published by Elsevier Inc.

  10. Coeliac disease and the liver: spectrum of liver histology, serology and treatment response at a tertiary referral centre.

    Science.gov (United States)

    Majumdar, Kaushik; Sakhuja, Puja; Puri, Amarender Singh; Gaur, Kavita; Haider, Aiman; Gondal, Ranjana

    2018-05-01

    Coeliac disease (CD) is a gluten-sensitive enteropathy diagnosed on the basis of ESPGHAN criteria and clinical response to gluten-free diet (GFD). Histological abnormalities on liver biopsy have been noted in CD but have seldom been described. To assess the histological spectrum of 'coeliac hepatitis' and possibility of reversal of such features after a GFD. Twenty-five patients with concomitant CD and hepatic derangement were analysed for clinical profile, laboratory investigations and duodenal and liver biopsy. A histological comparison of pre- and post-GFD duodenal and liver biopsies was carried out, wherever possible. Fifteen patients presenting with CD subsequently developed abnormal liver function tests; 10 patients presenting with liver disease were found to have tissue positive transglutaminase in 70% and antigliadin antibodies in 60%. Serological markers for autoimmune liver disease (AILD) were positive in eight patients. Liver histology ranged from mild reactive hepatitis, chronic hepatitis, steatosis to cirrhosis. Liver biopsies after a GFD were available in six cases, of which five showed a decrease in steatosis, portal and lobular inflammation and fibrosis score. Coeliac hepatitis could be a distinct entity and the patients may present with either CD or secondary hepatic derangement. Evaluation for the presence of CD is recommended for patients presenting with AILD, unexplained transaminasaemia or anaemia. This is one of the very few studies demonstrating the continuum of liver histological changes in 'coeliac hepatitis'. Trial of a GFD may result in clinicopathological improvement of 'coeliac hepatitis'. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Acute exposure to waterborne cadmium induced oxidative stress and immunotoxicity in the brain, ovary and liver of zebrafish (Danio rerio)

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jia-Lang, E-mail: zhengjialang@aliyun.com; Yuan, Shuang-Shuang; Wu, Chang-Wen; Lv, Zhen-Ming

    2016-11-15

    Highlights: • Cd induced oxidative stress and immunotoxicity by the generation of ROS. • The toxic effects depended on exposure time and different tissues. • Nrf2 and NF-κB mediated antioxidant and inflammatory responses. • Gene changed at transcriptional, translational, post-translational levels. - Abstract: Cadmium (Cd) is an environmental contaminant that poses serious risks to aquatic organisms and their associated ecosystem. The mechanisms underlying Cd-induced oxidative stress and immunotoxicity in fish remain largely unknown. In this study, adult female zebrafish were exposed to 0 (control), 1 mg L{sup −1} Cd for 24 h and 96 h, and the oxidative stress and inflammatory responses induced by Cd were evaluated in the brain, liver and ovary. Reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) increased in a time-dependent manner after treatment with Cd in the brain and liver. The increase may result from the disturbance of genes including copper and zinc superoxide dismutase (Cu/Zn-SOD), catalase (CAT), inducible nitric oxide synthase (iNOS), and ciclooxigenase-2 (COX-2) at mRNA, protein and activity levels. Although ROS, NO and MDA were not significantly affected by Cd in the ovary, the up-regulation of Cu/Zn-SOD, CAT, iNOS, and COX-2 was observed. Exposure to Cd induced a sharp increase in the protein levels of tumor necrosis factor alpha (TNF-α) in the brain, liver and ovary, possibly contributing to activate inflammatory responses. Furthermore, we also found a dramatic increase in mRNA levels of NF-E2-related factor 2 (Nrf2) and nuclear transcription factor κB (NF-κB) at 24 h in the liver and ovary. The corresponding changes in the mRNA levels of Kelch-like-ECH-associated protein 1 (Keap1a and Keap1b) and the inhibitor of κBα (IκBαa and IκBαb) may contribute to regulate the transcriptional activity of Nrf2 and NF-κB, respectively. Contrarily, mRNA levels of Nrf2, NF-κB, Keap1, Keap1b, IκBαa and IκBαb remained

  12. Acute exposure to waterborne cadmium induced oxidative stress and immunotoxicity in the brain, ovary and liver of zebrafish (Danio rerio)

    International Nuclear Information System (INIS)

    Zheng, Jia-Lang; Yuan, Shuang-Shuang; Wu, Chang-Wen; Lv, Zhen-Ming

    2016-01-01

    Highlights: • Cd induced oxidative stress and immunotoxicity by the generation of ROS. • The toxic effects depended on exposure time and different tissues. • Nrf2 and NF-κB mediated antioxidant and inflammatory responses. • Gene changed at transcriptional, translational, post-translational levels. - Abstract: Cadmium (Cd) is an environmental contaminant that poses serious risks to aquatic organisms and their associated ecosystem. The mechanisms underlying Cd-induced oxidative stress and immunotoxicity in fish remain largely unknown. In this study, adult female zebrafish were exposed to 0 (control), 1 mg L"−"1 Cd for 24 h and 96 h, and the oxidative stress and inflammatory responses induced by Cd were evaluated in the brain, liver and ovary. Reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) increased in a time-dependent manner after treatment with Cd in the brain and liver. The increase may result from the disturbance of genes including copper and zinc superoxide dismutase (Cu/Zn-SOD), catalase (CAT), inducible nitric oxide synthase (iNOS), and ciclooxigenase-2 (COX-2) at mRNA, protein and activity levels. Although ROS, NO and MDA were not significantly affected by Cd in the ovary, the up-regulation of Cu/Zn-SOD, CAT, iNOS, and COX-2 was observed. Exposure to Cd induced a sharp increase in the protein levels of tumor necrosis factor alpha (TNF-α) in the brain, liver and ovary, possibly contributing to activate inflammatory responses. Furthermore, we also found a dramatic increase in mRNA levels of NF-E2-related factor 2 (Nrf2) and nuclear transcription factor κB (NF-κB) at 24 h in the liver and ovary. The corresponding changes in the mRNA levels of Kelch-like-ECH-associated protein 1 (Keap1a and Keap1b) and the inhibitor of κBα (IκBαa and IκBαb) may contribute to regulate the transcriptional activity of Nrf2 and NF-κB, respectively. Contrarily, mRNA levels of Nrf2, NF-κB, Keap1, Keap1b, IκBαa and IκBαb remained

  13. The role of oxidative stress in the development of alcoholic liver disease.

    Science.gov (United States)

    Galicia-Moreno, M; Gutiérrez-Reyes, G

    2014-01-01

    Alcohol is the most accepted addictive substance worldwide and its consumption is related to multiple health, economic, and social problems. The liver is the organ in charge of ethanol metabolism and it is susceptible to alcohol's toxic effects. To provide a detailed review of the role of oxidative stress in alcoholic liver disease and the mechanisms of damage involved, along with current information on the hepatoprotective effectiveness of the molecules that have been studied. A search of the PubMed database was conducted using the following keywords oxidative stress, alcoholic liver damage, alcoholic cirrhosis, and antioxidants. There was no time limit for gathering all available information on the subject at hand. According to the literature reviewed, oxidative stress plays an important role in the pathogenesis of alcoholic liver damage. Molecules such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), formed during ethanol metabolism, structurally and functionally modify organic molecules. Consequently, biologic processes are altered and hepatocytes are sensitized to the action of cytokines like tumor necrosis factor-α, as well as to the action of endotoxins, activating signaling pathways such as those controlled by nuclear factor kappa B, extracellular signal regulated kinases, and mitogen activated protein kinase. Oxidative stress plays an important role in the development of liver damage resulting from alcohol consumption. The molecules that have currently displayed a hepatoprotective effect in preclinical and clinical trials must be studied further so that their effectiveness can be confirmed and they can possibly be used as adjuvant treatments for this disease. Copyright © 2014 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

  14. Nilotinib counteracts thioacetamide-induced hepatic oxidative stress and attenuates liver fibrosis progression.

    Science.gov (United States)

    Shaker, Mohamed E; Salem, Hatem A; Shiha, Gamal E; Ibrahim, Tarek M

    2011-04-01

    The aim of this study was to evaluate and compare the effects of imatinib and nilotinib to that of silymarin on established liver fibrosis and oxidative stress in a thioacetamide (TAA) rat model. Male Wistar rats received intraperitoneal (i.p.) injections of TAA (150mg/kg, twice weekly) for 12weeks. Daily treatments with imatinib (10mg/kg), nilotinib (10mg/kg), and silymarin (100mg/kg) were administered orally during the last 4weeks of TAA-administration. At the end of the study, hepatic damage was evaluated by analysis of liver function tests in serum. Hepatic histopathology and collagen content were employed to quantify liver fibrosis. Hepatic oxidative stress was assessed by measuring malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), total nitrate/nitrite (NOx), and reduced glutathione (GSH) contents, as well as myeloperoxidase (MPO) and superoxide dismutase (SOD) activities. Nilotinib, silymarin and, to a lesser extent, imatinib treatments ameliorated TAA-induced hepatic oxidative stress and damage as indicated by hepatic MDA, 4-HNE, NOx, GSH, MPO and SOD levels, as well as liver function tests. Hepatic histopathology results revealed that nilotinib, imatinib, and silymarin treatments decreased the mean score of fibrosis in TAA-treated rats by 24, 14, and 3%, respectively. However, nilotinib and silymarin, but not imatinib, treatments decreased hepatic collagen content in TAA-treated rats by 17 and 36%, respectively. In conclusion, we demonstrated for the first time that nilotinib not only protected against hepatic oxidative stress, but also slowed down liver fibrosis progression. Thus, we provide the first evidence that nilotinib might be a promising anti-fibrotic drug. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

  15. An in vitro liver model--assessing oxidative stress and genotoxicity following exposure of hepatocytes to a panel of engineered nanomaterials

    DEFF Research Database (Denmark)

    Kermanizadeh, Ali; Gaiser, Birgit K; Hutchison, Gary R

    2012-01-01

    Following exposure via inhalation, intratracheal instillation or ingestion some nanomaterials (NM) have been shown to translocate to the liver. Since oxidative stress has been implicated as a possible mechanism for NM toxicity this study aimed to investigate the effects of various materials (five...... titanium dioxide (TiO2), two zinc oxide (ZnO), two multi-walled carbon nanotubes (MWCNT) and one silver (Ag) NM) on oxidative responses of C3A cell line as a model for potential detrimental properties of nanomaterials on the liver.......Following exposure via inhalation, intratracheal instillation or ingestion some nanomaterials (NM) have been shown to translocate to the liver. Since oxidative stress has been implicated as a possible mechanism for NM toxicity this study aimed to investigate the effects of various materials (five...

  16. Concomitant apoptosis and regeneration of liver cells as a mechanism of liver-tumor promotion by β-naphthoflavone involving TNFα-signaling due to oxidative cellular stress in rats

    International Nuclear Information System (INIS)

    Kuwata, Kazunori; Shibutani, Makoto; Hayashi, Hitomi; Shimamoto, Keisuke; Hayashi, Shim-Mo; Suzuki, Kazuhiko; Mitsumori, Kunitoshi

    2011-01-01

    β-Naphthoflavone (BNF) is a strong inducer of cytochrome P450 1A enzymes, and exerts liver tumor-promoting activity through enhancement of oxidative stress responses in rats. This study investigated the role of the tissue environment surrounding hepatocellular preneoplastic lesions in the early tumor-promotion stage by BNF, using enzymatically modified isoquercitrin (EMIQ) as an anti-oxidative chemopreventive agent. Male F344 rats were fed a diet containing BNF (0.5%) for 6 weeks, with or without EMIQ (0.2%) in the drinking water, 2 weeks after initiation with N-diethylnitrosamine, and were subjected to two-thirds partial hepatectomy 1 week after starting BNF-promotion. BNF-treatment increased concentrations of liver thiobarbituric acid-reactive substances, single liver cells expressing glutathione S-transferase placental form or heme oxygenase (HO)-1, and concomitant apoptosis and proliferation of liver cells. Transcript upregulation of anti-oxidative enzymes (Aldh1a1 and Nqo1), cell cycle-related molecules (Cdc20 and Cdkn2b) and inflammation-related molecules including proinflammatory cytokines (Ccl2, Col1a1, Il6, Nos2 and Serpine1) was also evident. Furthermore, BNF increased HO-1-expressing Kupffer cells and liver cells expressing tumor necrosis factor receptor 1 (TNFR1) and the TNFR1-associated death domain. Most of these BNF-induced fluctuations disappeared or were suppressed by EMIQ in conjunction with suppression of tumor-promotion. Tnf transcript levels with BNF were also suppressed by EMIQ. These results suggest that BNF-induced oxidative stress causes single liver cell toxicity, allowing subsequent concomitant apoptosis and regeneration involving inflammatory responses including TNFα-signaling, contributing to tumor promotion. Kupffer cells may act to protect against inflammatory stimuli induced as a result of oxidative cellular stress by BNF, causing proinflammatory cytokine level fluctuations.

  17. Gene expression of drug metabolizing enzymes in adult and aged mouse liver: A modulation by immobilization stress

    International Nuclear Information System (INIS)

    Mikhailova, O.N.; Gulyaeva, L.F.; Filipenko, M.L.

    2005-01-01

    The role of stress in the regulation of enzymatic systems involved in the biotransformation of xenobiotics, as well as endogenous substrates in the liver was investigated using single immobilization stress as a model. Adult (3 months of age) and aged (26 months) C3H/a male mice were used. Cytochrome P450 1A1 and 1A2 (CYP1A1 and CYP1A2), glutathione S-transferase M1 (GSTM1), aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT) and catechol-O-methyltransferase (COMT) mRNA levels in the mouse liver were measured by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. Excluding CYP1A1, experiments revealed significant differences in the expression of these genes between adult- and aged-control animals. The influence of stress on the expression of genes studied was shown to be higher in adult mice than in aged ones. Our results clearly demonstrate the lack of response or even the attenuation of gene expression in aged animals that may play an important role in age-related pathologies and diseases

  18. Physiological Responses to Thermal Stress and Exercise

    Science.gov (United States)

    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.

  19. Everyday stress response targets in the science of behavior change.

    Science.gov (United States)

    Smyth, Joshua M; Sliwinski, Martin J; Zawadzki, Matthew J; Scott, Stacey B; Conroy, David E; Lanza, Stephanie T; Marcusson-Clavertz, David; Kim, Jinhyuk; Stawski, Robert S; Stoney, Catherine M; Buxton, Orfeu M; Sciamanna, Christopher N; Green, Paige M; Almeida, David M

    2018-02-01

    Stress is an established risk factor for negative health outcomes, and responses to everyday stress can interfere with health behaviors such as exercise and sleep. In accordance with the Science of Behavior Change (SOBC) program, we apply an experimental medicine approach to identifying stress response targets, developing stress response assays, intervening upon these targets, and testing intervention effectiveness. We evaluate an ecologically valid, within-person approach to measuring the deleterious effects of everyday stress on physical activity and sleep patterns, examining multiple stress response components (i.e., stress reactivity, stress recovery, and stress pile-up) as indexed by two key response indicators (negative affect and perseverative cognition). Our everyday stress response assay thus measures multiple malleable stress response targets that putatively shape daily health behaviors (physical activity and sleep). We hypothesize that larger reactivity, incomplete recovery, and more frequent stress responses (pile-up) will negatively impact health behavior enactment in daily life. We will identify stress-related reactivity, recovery, and response in the indicators using coordinated analyses across multiple naturalistic studies. These results are the basis for developing a new stress assay and replicating the initial findings in a new sample. This approach will advance our understanding of how specific aspects of everyday stress responses influence health behaviors, and can be used to develop and test an innovative ambulatory intervention for stress reduction in daily life to enhance health behaviors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Liver

    International Nuclear Information System (INIS)

    Bernardino, M.E.; Sones, P.J. Jr.; Barton Price, R.; Berkman, W.A.

    1984-01-01

    Evaluation of the liver for focal lesions is extremely important because the liver is one of the most common sites for metastatic disease. Most patients with metastatic deposits to the liver have a survival rate of about 6 months. Thus, metastatic disease to the liver has an extremely grave prognosis. In the past patients with hepatic lesions had no therapeutic recourse. However, with recent aggressive surgical advances (such as partial hepatectomies) and hepatic artery embolization, survival of patients with hepatic metastases has increased. Thus it is important for noninvasive imaging not only to detect lesions early in their course, but also to give their true hepatic involvement and the extent of the neoplastic process elsewhere in the body. Recent advances in imaging have been rapidly changing over the past 5 years. These changes have been more rapid in computed tomography (CT) and ultrasound than in radionuclide imaging. Thus, the question addressed in this chapter is: What is the relationship of hepatic ultrasound to the other current diagnostic modalities in detecting metastatic liver disease and other focal liver lesions? Also, what is its possible future relationship to nuclear magnetic resonance?

  1. A small population of liver endothelial cells undergoes endothelial-to-mesenchymal transition in response to chronic liver injury.

    Science.gov (United States)

    Ribera, Jordi; Pauta, Montse; Melgar-Lesmes, Pedro; Córdoba, Bernat; Bosch, Anna; Calvo, Maria; Rodrigo-Torres, Daniel; Sancho-Bru, Pau; Mira, Aurea; Jiménez, Wladimiro; Morales-Ruiz, Manuel

    2017-11-01

    Rising evidence points to endothelial-to-mesenchymal transition (EndMT) as a significant source of the mesenchymal cell population in fibrotic diseases. In this context, we hypothesized that liver endothelial cells undergo EndMT during fibrosis progression. Cirrhosis in mice was induced by CCl 4 A transgenic mouse expressing a red fluorescent protein reporter under the control of Tie2 promoter (Tie2-tdTomato) was used to trace the acquisition of EndMT. Sinusoidal vascular connectivity was evaluated by intravital microscopy and high-resolution three-dimensional confocal microscopy. A modest but significant fraction of liver endothelial cells from both cirrhotic patients and CCl 4 -treated Tie2-tdTomato mice acquired an EndMT phenotype characterized by the coexpression of CD31 and α-smooth muscle actin, compared with noncirrhotic livers. Bone morphogenetic protein-7 (BMP-7) inhibited the acquisition of EndMT induced by transforming growth factor-β1 (TGF-β1) treatment in cultured primary mouse liver endothelial cells from control mice. EndMT was also reduced significantly in vivo in cirrhotic Tie2-tdTomato mice treated intraperitoneally with BMP-7 compared with untreated mice (1.9 ± 0.2 vs. 3.8 ± 0.3%, respectively; P livers correlated with a significant decrease in liver fibrosis ( P livers in both animal models and patients. BMP-7 treatment decreases the occurrence of the EndMT phenotype and has a positive impact on the severity of disease by reducing fibrosis and sinusoidal vascular disorganization. NEW & NOTEWORTHY A subpopulation of liver endothelial cells from cirrhotic patients and mice with liver fibrosis undergoes endothelial-to-mesenchymal transition. Liver endothelial cells from healthy mice could transition into a mesenchymal phenotype in culture in response to TGF-β1 treatment. Fibrotic livers treated chronically with BMP-7 showed lower EndMT acquisition, reduced fibrosis, and improved vascular organization. Copyright © 2017 the American

  2. Transcriptome analysis provides insights into hepatic responses to moderate heat stress in the rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Li, Yongjuan; Huang, Jinqiang; Liu, Zhe; Zhou, Yanjing; Xia, Binpeng; Wang, Yongjie; Kang, Yujun; Wang, Jianfu

    2017-07-01

    The rainbow trout is an economically important fish in the world. The limited stress tolerance of this species to high summer-like temperatures usually leads to mass mortality and great economic loss. However, there is limited information on the mechanisms underlying moderate heat responses in the liver of the rainbow trout. Here, we performed transcriptome profiling of rainbow trout liver under moderate heat stress by using the Hiseq™ 4000 sequencing platform. More than 277 million clean reads were obtained from 6 libraries and aligned against the rainbow trout genome. A total of 128 unique transcripts were differentially expressed in the liver under heat-stress and control conditions, many heat shock protein genes for thermoregulation and some novel genes involved in heat stress were identified. Nine of the differently expressed genes were further validated by qRT-PCR. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that several pathways, including those for protein metabolism, energy metabolism, and immune system, were influenced by heat stress. Moreover, an important protein-processing pathway in the endoplasmic reticulum (ER) was identified, and the key role of ER-associated degradation and function of calpain as an upstream regulator of apoptosis were confirmed under heat stress. The results of this study provide a comprehensive overview of heat stress-induced transcriptional patterns in rainbow trout liver and would be particularly useful for further studies on the molecular mechanisms underlying responses to heat stress in this species. Copyright © 2017. Published by Elsevier B.V.

  3. Effects of Various Drugs on Alcohol-induced Oxidative Stress in the Liver

    Directory of Open Access Journals (Sweden)

    Svetlana Trivic

    2008-09-01

    Full Text Available The major aim of this work was to investigate how alcohol-induced oxidative stress in combined chemotherapy changes the metabolic function of the liver in experimental animals. This research was conducted to establish how bromocriptine, haloperidol and azithromycin, applied to the experimental model, affected the antioxidative status of the liver. The following parameters were determined: reduced glutathione, activities of glutathione peroxidase, glutathione reductase, peroxidase, catalase, xanthine oxidase and lipid peroxidation intensity. Alanine transaminase was measured in serum. Alcohol stress (AO group reduced glutathione and the activity of xanthine oxidase and glutathione peroxidase, but increased catalase and alanine transaminase activity. The best protective effect was achieved with the bromocriptine (AB1 group, while other groups had similar effects on the studied parameters.

  4. The feasibility of a group stress management Liver SMART intervention for patients with end-stage liver disease: A pilot study.

    Science.gov (United States)

    Jutagir, Devika R; Saracino, Rebecca M; Cunningham, Amy; Foran-Tuller, Kelly A; Driscoll, Mary A; Sledge, William H; Emre, Sukru H; Fehon, Dwain C

    2018-06-04

    Structured, empirically supported psychological interventions are lacking for patients who require organ transplantation. This stage IA psychotherapy development project developed and tested the feasibility, acceptability, tolerability, and preliminary efficacy of an 8-week group cognitive behavioral stress management intervention adapted for patients with end-stage liver disease awaiting liver transplantation. Twenty-nine English-speaking United Network for Organ Sharing-registered patients with end-stage liver disease from a single transplantation center enrolled in 8-week, group cognitive-behavioral liver stress management and relaxation training intervention adapted for patients with end-stage liver disease. Patients completed pre- and postintervention surveys that included the Beck Depression Inventory II and the Beck Anxiety Inventory. Feasibility, acceptability, tolerability, and preliminary efficacy were assessed.ResultAttendance rate was 69.40%. The intervention was rated as "good" to "excellent" by 100% of participants who completed the postintervention survey in teaching them new skills to relax and to cope with stress, and by 94.12% of participants in helping them feel supported while waiting for a liver transplant. No adverse events were recorded over the course of treatment. Attrition was 13.79%. Anxious and depressive symptoms were not statistically different after the intervention.Significance of resultsThe liver stress management and relaxation training intervention is feasible, acceptable, and tolerable to end-stage liver disease patients within a transplant clinic setting. Anxious and depressive symptoms remained stable postintervention. Randomized controlled trials are needed to study the intervention's effectiveness in this population.

  5. Sodium 4-phenylbutyrate protects against liver ischemia reperfusion injury by inhibition of endoplasmic reticulum-stress mediated apoptosis.

    Science.gov (United States)

    Vilatoba, Mario; Eckstein, Christopher; Bilbao, Guadalupe; Smyth, Cheryl A; Jenkins, Stacie; Thompson, J Anthony; Eckhoff, Devin E; Contreras, Juan L

    2005-08-01

    Evidence is emerging that the endoplasmic reticulum (ER) participates in initiation of apoptosis induced by the unfolded protein response and by aberrant Ca(++) signaling during cellular stress such as ischemia/reperfusion injury (I/R injury). ER-induced apoptosis involves the activation of caspase-12 and C/EBP homologous protein (CHOP), and the shutdown of translation initiated by phosphorylation of eIF2alpha. Sodium 4-phenylbutyrate (PBA) is a low molecular weight fatty acid that acts as a chemical chaperone reducing the load of mutant or unfolded proteins retained in the ER during cellular stress and also exerting anti-inflammatory activity. It has been used successfully for treatment of urea cycle disorders and sickle cell disease. Thus, we hypothesized that PBA may reduce ER-induced apoptosis triggered by I/R injury to the liver. Groups of male C57BL/6 mice were subjected to warm ischemia (70% of the liver mass, 45 minutes). Serum aspartate aminotransferase was assessed 6 hours after reperfusion; apoptosis was evaluated by enzyme-linked immunosorbent assays of caspase-12 and plasma tumor necrosis factor alpha, Western blot analyses of eIF2alpha, and reverse transcriptase-polymerase chain reaction of CHOP expression. A dose-dependent decrease in aspartate aminotransferase was demonstrated in mice given intraperitoneal PBA (1 hour before and 12 hours after reperfusion), compared with vehicle-treated controls; this effect was associated with reduced pyknosis, parenchymal hemorrhages, and neutrophil infiltrates in PBA-treated mice, compared with controls. In a lethal model of total liver I/R injury, all vehicle-treated controls died within 3 days after reperfusion. In contrast, 50% survival (>30 days) was observed in animals given PBA. The beneficial effects of PBA were associated with a greater than 45% reduction in apoptosis, decreased ER-mediated apoptosis characterized by significant reduction in caspase-12 activation, and reduced levels of both phosphorylated

  6. Identifying salt stress-responsive transcripts from Roselle ( Hibiscus ...

    African Journals Online (AJOL)

    Hibiscus sabdariffa L.). Identifying the potentially novel transcripts responsible for salt stress tolerance in roselle will increase knowledge of the molecular mechanism underlying salt stress responses. In this study, differential display reverse ...

  7. Growth and physiological responses to water and nutrient stress in ...

    African Journals Online (AJOL)

    Growth and physiological responses to water and nutrient stress in oil palm. ... changes in growth, physiology and nutrient concentration in response to two watering regimes (well-watered and water-stress conditions) and ... from 32 Countries:.

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

    OpenAIRE

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

    2018-01-01

    Purpose. We investigated whether a DDP-4 inhibitor, vildagliptin, alleviated ER stress induced by a high fat diet and improved hepatic lipid deposition. Methods. C57BL/6 mice received standard chow diet (CD), high fat diet (HFD), and HFD administered with vildagliptin (50 mg/Kg) (V-HFD). After administration for 12 weeks, serum alanine aminotransferase, glucose, cholesterol, triglyceride, and insulin levels were analyzed. Samples of liver underwent histological examination and transmission el...

  9. The effect of aqueous extract of Avicennia marina (Forsk. Vierh. leaves on liver enzymes' activity, oxidative stress parameters and liver histopathology in male diabetic rats

    Directory of Open Access Journals (Sweden)

    Akram Hamzevi

    2017-12-01

    Full Text Available Background: Avicennia marina has antioxidant and anti-diabetic properties. This study was conducted to examine the effect of aqueous extract of A. marina on liver enzymes' activity, oxidative stress parameters and liver histopathology in diabetic rats. Materials and Methods: In this experimental study, 28 male rats were allocated into the equal groups of control, diabetic control and experimental diabetic 1 and 2. The diabetes in diabetic control and experimental diabetic groups was induced using an intraperitoneal injection of 120 mg/kg alloxan. The experimental diabetic groups received the aqueous extract of A. marina (100 and 200 mg/kg, i.p. in alternate days for one month. Sterile distilled water was injected to the animals of control and diabetic control groups. At the end of the treatment period, serum levels of ALT, AST, GGT and ALP were measured. Then, levels of SOD, GST, CAT and MDA were measured in the liver tissue. The liver sections were prepared and examined by an optical microscope. Results: Results showed that administration of the A. marina extract (100 and 300 mg/kg, ip to the diabetic rats significantly decreased the serum levels of liver enzymes and tissue level of MDA. Also, the activity of the liver tissue's antioxidant enzymes was increased (P<0.05. The A. marina extract dose-dependently decreased liver damages in diabetic rats. Conclusion: Administration of the A. marina extract improves liver tissue oxidative stress indices and decreases the serum level of liver enzymes. Also, A. marina extract improves liver tissue injuries induced by diabetes.

  10. Integrated transcriptomic and proteomic analysis of the bile stress response in probiotic Lactobacillus salivarius LI01.

    Science.gov (United States)

    Lv, Long-Xian; Yan, Ren; Shi, Hai-Yan; Shi, Ding; Fang, Dai-Qiong; Jiang, Hui-Yong; Wu, Wen-Rui; Guo, Fei-Fei; Jiang, Xia-Wei; Gu, Si-Lan; Chen, Yun-Bo; Yao, Jian; Li, Lan-Juan

    2017-01-06

    Lactobacillus salivarius LI01, isolated from healthy humans, has demonstrated probiotic properties in the prevention and treatment of liver failure. Tolerance to bile stress is crucial to allow lactobacilli to survive in the gastrointestinal tract and exert their benefits. In this work, we used a Digital Gene Expression transcriptomic and iTRAQ LC-MS/MS proteomic approach to examine the characteristics of LI01 in response to bile stress. Using culture medium with or without 0.15% ox bile, 591 differentially transcribed genes and 347 differentially expressed proteins were detected in LI01. Overall, we found the bile resistance of LI01 to be based on a highly remodeled cell envelope and a reinforced bile efflux system rather than on the activity of bile salt hydrolases. Additionally, some differentially expressed genes related to regulatory systems, the general stress response and central metabolism processes, also play roles in stress sensing, bile-induced damage prevention and energy efficiency. Moreover, bile salts appear to enhance proteolysis and amino acid uptake (especially aromatic amino acids) by LI01, which may support the liver protection properties of this strain. Altogether, this study establishes a model of global response mechanism to bile stress in L. salivarius LI01. L. salivarius strain LI01 exhibits not only antibacterial and antifungal properties but also exerts a good health-promoting effect in acute liver failure. As a potential probiotic strain, the bile-tolerance trait of strain LI01 is important, though this has not yet been explored. In this study, an analysis based on DGE and iTRAQ was performed to investigate the gene expression in strain LI01 under bile stress at the mRNA and protein levels, respectively. To our knowledge, this work also represents the first combined transcriptomic and proteomic analysis of the bile stress response mechanism in L. salivarius. Copyright © 2016. Published by Elsevier B.V.

  11. Thymoquinone restores liver fibrosis and improves oxidative stress status in a lipopolysaccharide-induced inflammation model in rats.

    Science.gov (United States)

    Asgharzadeh, Fereshteh; Bargi, Rahimeh; Beheshti, Farimah; Hosseini, Mahmoud; Farzadnia, Mehdi; Khazaei, Majid

    2017-01-01

    Liver fibrosis is the primary sign of chronic liver injury induced by various causes. Thymoquinone (TQ) is the major ingredient of Nigella sativa with several beneficial effects on the body. In the present study, we aimed to investigate the effect of TQ on liver fibrosis in a lipopolysaccharide (LPS)-induced inflammation in male rats. Fifty male Wistar rats were randomly divided into five groups (n=10 in each group) as follow: (1) control; (2) LPS (1 mg/kg/day; i.p); (3) LPS+TQ 2 mg/kg/day (i.p) (LPs+TQ2); (4) LPS+TQ 5 mg/kg/day (LPS+TQ5); (5) LPS+ TQ 10 mg/kg/day (LPS+ TQ10). After three weeks, blood samples were taken for evaluation of liver function tests. Then, the livers were harvested for histological evaluation of fibrosis and collagen content and measurement of oxidative stress markers including malondialdehyde (MDA), total thiol groups, superoxide dismutase (SOD) and catalase activity in tissue homogenates. LPS group showed higher levels of fibrosis and collagen content stained by Masson's trichrome in liver tissue with impaired liver function test and increased oxidative stress markers (pliver fibrosis, improved liver function tests and increased the levels of anti-oxidative enzymes (SOD and catalase), while reduced MDA concentration (pliver fibrosis possibly through affecting oxidative stress status. It seems that administration of TQ can be considered as a part of liver fibrosis management.

  12. Liver-Enriched Gene 1, a Glycosylated Secretory Protein, Binds to FGFR and Mediates an Anti-stress Pathway to Protect Liver Development in Zebrafish.

    Directory of Open Access Journals (Sweden)

    Minjie Hu

    2016-02-01

    Full Text Available Unlike mammals and birds, teleost fish undergo external embryogenesis, and therefore their embryos are constantly challenged by stresses from their living environment. These stresses, when becoming too harsh, will cause arrest of cell proliferation, abnormal cell death or senescence. Such organisms have to evolve a sophisticated anti-stress mechanism to protect the process of embryogenesis/organogenesis. However, very few signaling molecule(s mediating such activity have been identified. liver-enriched gene 1 (leg1 is an uncharacterized gene that encodes a novel secretory protein containing a single domain DUF781 (domain of unknown function 781 that is well conserved in vertebrates. In the zebrafish genome, there are two copies of leg1, namely leg1a and leg1b. leg1a and leg1b are closely linked on chromosome 20 and share high homology, but are differentially expressed. In this report, we generated two leg1a mutant alleles using the TALEN technique, then characterized liver development in the mutants. We show that a leg1a mutant exhibits a stress-dependent small liver phenotype that can be prevented by chemicals blocking the production of reactive oxygen species. Further studies reveal that Leg1a binds to FGFR3 and mediates a novel anti-stress pathway to protect liver development through enhancing Erk activity. More importantly, we show that the binding of Leg1a to FGFR relies on the glycosylation at the 70th asparagine (Asn(70 or N(70, and mutating the Asn(70 to Ala(70 compromised Leg1's function in liver development. Therefore, Leg1 plays a unique role in protecting liver development under different stress conditions by serving as a secreted signaling molecule/modulator.

  13. Ginseng essence, a medicinal and edible herbal formulation, ameliorates carbon tetrachloride-induced oxidative stress and liver injury in rats

    Directory of Open Access Journals (Sweden)

    Kuan-Hung Lu

    2017-07-01

    Conclusion: These findings demonstrate that GE improves CCl4-induced liver inflammation and fibrosis by attenuating oxidative stress. Therefore, GE could be a promising hepatoprotective herbal formulation for future development of phytotherapy.

  14. Plant Nucleolar Stress Response, a New Face in the NAC-Dependent Cellular Stress Responses

    OpenAIRE

    Iwai Ohbayashi; Munetaka Sugiyama

    2018-01-01

    The nucleolus is the most prominent nuclear domain, where the core processes of ribosome biogenesis occur vigorously. All these processes are finely orchestrated by many nucleolar factors to build precisely ribosome particles. In animal cells, perturbations of ribosome biogenesis, mostly accompanied by structural disorders of the nucleolus, cause a kind of cellular stress to induce cell cycle arrest, senescence, or apoptosis, which is called nucleolar stress response. The best-characterized p...

  15. Acute exposure to waterborne cadmium induced oxidative stress and immunotoxicity in the brain, ovary and liver of zebrafish (Danio rerio).

    Science.gov (United States)

    Zheng, Jia-Lang; Yuan, Shuang-Shuang; Wu, Chang-Wen; Lv, Zhen-Ming

    2016-11-01

    Cadmium (Cd) is an environmental contaminant that poses serious risks to aquatic organisms and their associated ecosystem. The mechanisms underlying Cd-induced oxidative stress and immunotoxicity in fish remain largely unknown. In this study, adult female zebrafish were exposed to 0 (control), 1mgL -1 Cd for 24h and 96h, and the oxidative stress and inflammatory responses induced by Cd were evaluated in the brain, liver and ovary. Reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) increased in a time-dependent manner after treatment with Cd in the brain and liver. The increase may result from the disturbance of genes including copper and zinc superoxide dismutase (Cu/Zn-SOD), catalase (CAT), inducible nitric oxide synthase (iNOS), and ciclooxigenase-2 (COX-2) at mRNA, protein and activity levels. Although ROS, NO and MDA were not significantly affected by Cd in the ovary, the up-regulation of Cu/Zn-SOD, CAT, iNOS, and COX-2 was observed. Exposure to Cd induced a sharp increase in the protein levels of tumor necrosis factor alpha (TNF-α) in the brain, liver and ovary, possibly contributing to activate inflammatory responses. Furthermore, we also found a dramatic increase in mRNA levels of NF-E2-related factor 2 (Nrf2) and nuclear transcription factor κB (NF-κB) at 24h in the liver and ovary. The corresponding changes in the mRNA levels of Kelch-like-ECH-associated protein 1 (Keap1a and Keap1b) and the inhibitor of κBα (IκBαa and IκBαb) may contribute to regulate the transcriptional activity of Nrf2 and NF-κB, respectively. Contrarily, mRNA levels of Nrf2, NF-κB, Keap1, Keap1b, IκBαa and IκBαb remained stable at 24 and 96h in the brain. Taken together, we demonstrated Cd-induced oxidative stress and immunotoxicity in fish, possibly through transcriptional regulation of Nrf2 and NF-κB and gene modifications at transcriptional, translational, post-translational levels, which would greatly extend our understanding on the Cd

  16. Effect of baicalin on toll-like receptor 4-mediated ischemia/reperfusion inflammatory responses in alcoholic fatty liver condition

    International Nuclear Information System (INIS)

    Kim, Seok-Joo; Lee, Sun-Mee

    2012-01-01

    Alcoholic fatty liver is susceptible to secondary stresses such as ischemia/reperfusion (I/R). Baicalin is an active component extracted from Scutellaria baicalensis, which is widely used in herbal preparations for treatment of hepatic diseases and inflammatory disorders. This study evaluated the potential beneficial effect of baicalin on I/R injury in alcoholic fatty liver. Rats were fed an alcohol liquid diet or a control isocaloric diet for 5 weeks, and then subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Baicalin (200 mg/kg) was intraperitoneally administered 24 and 1 h before ischemia. After reperfusion, baicalin attenuated the increases in serum alanine aminotransferase activity, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels in alcoholic fatty liver. The increased levels of TNF-α and IL-6 mRNA expression and inducible nitric oxide synthase and cyclooxygenase-2 protein and mRNA expressions increased after reperfusion, which were higher in ethanol-fed animals, were attenuated by baicalin. In ethanol-fed animals, baicalin attenuated the increases in toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 protein expressions and the nuclear translocation of NF-κB after reperfusion. In conclusion, our findings suggest that baicalin ameliorates I/R-induced hepatocellular damage by suppressing TLR4-mediated inflammatory responses in alcoholic fatty liver. -- Highlights: ► Baicalin attenuates hepatic I/R-induced inflammation in alcoholic fatty liver. ► Baicalin downregulates TLR4, MyD88 expression during I/R in alcoholic fatty liver. ► Baicalin attenuates NF-κB nuclear translocation during I/R in alcoholic fatty liver.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  19. Citric acid effects on brain and liver oxidative stress in lipopolysaccharide-treated mice.

    Science.gov (United States)

    Abdel-Salam, Omar M E; Youness, Eman R; Mohammed, Nadia A; Morsy, Safaa M Youssef; Omara, Enayat A; Sleem, Amany A

    2014-05-01

    Citric acid is a weak organic acid found in the greatest amounts in citrus fruits. This study examined the effect of citric acid on endotoxin-induced oxidative stress of the brain and liver. Mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 μg/kg). Citric acid was given orally at 1, 2, or 4 g/kg at time of endotoxin injection and mice were euthanized 4 h later. LPS induced oxidative stress in the brain and liver tissue, resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and nitrite, while significantly decreasing reduced glutathione, glutathione peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha (TNF-α) showed a pronounced increase in brain tissue after endotoxin injection. The administration of citric acid (1-2 g/kg) attenuated LPS-induced elevations in brain MDA, nitrite, TNF-α, GPx, and PON1 activity. In the liver, nitrite was decreased by 1 g/kg citric acid. GPx activity was increased, while PON1 activity was decreased by citric acid. The LPS-induced liver injury, DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric oxide synthase expression were attenuated by 1-2 g/kg citric acid. DNA fragmentation, however, increased after 4 g/kg citric acid. Thus in this model of systemic inflammation, citric acid (1-2 g/kg) decreased brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation.

  20. Royal Jelly Modulates Oxidative Stress and Apoptosis in Liver and Kidneys of Rats Treated with Cisplatin

    Directory of Open Access Journals (Sweden)

    Ali Karadeniz

    2011-01-01

    Full Text Available Cisplatin (CDDP is one of the most active cytotoxic agents in the treatment of cancer and has adverse side effects such as nephrotoxicity and hepatotoxicity. The present study was designed to determine the effects of royal jelly (RJ against oxidative stress caused by CDDP injury of the kidneys and liver, by measuring tissue biochemical and antioxidant parameters and investigating apoptosis immunohistochemically. Twenty-four Sprague Dawley rats were divided into four groups, group C: control group received 0.9% saline; group CDDP: injected i.p. with cisplatin (CDDP, 7 mg kg-1 body weight i.p., single dose; group RJ: treated for 15 consecutive days by gavage with RJ (300 mg/kg/day; group RJ + CDDP: treated by gavage with RJ 15 days following a single injection of CDDP. Malondialdehyde (MDA and glutathione (GSH levels, glutathione S-transferase (GST, glutathione peroxidase (GSH-Px, and superoxide dismutase (SOD activities were determined in liver and kidney homogenates, and the liver and kidney were also histologically examined. RJ elicited a significant protective effect towards liver and kidney by decreasing the level of lipid peroxidation (MDA, elevating the level of GSH, and increasing the activities of GST, GSH-Px, and SOD. In the immunohistochemical examinations were observed significantly enhanced apoptotic cell numbers and degenerative changes by cisplatin, but these histological changes were lower in the liver and kidney tissues of RJ + CDDP group. Besides, treatment with RJ lead to an increase in antiapoptotic activity hepatocytes and tubular epithelium. In conclusion, RJ may be used in combination with cisplatin in chemotherapy to improve cisplatin-induced oxidative stress parameters and apoptotic activity.

  1. LKB1 promotes metabolic flexibility in response to energy stress.

    Science.gov (United States)

    Parker, Seth J; Svensson, Robert U; Divakaruni, Ajit S; Lefebvre, Austin E; Murphy, Anne N; Shaw, Reuben J; Metallo, Christian M

    2017-09-01

    The Liver Kinase B1 (LKB1) tumor suppressor acts as a metabolic energy sensor to regulate AMP-activated protein kinase (AMPK) signaling and is commonly mutated in various cancers, including non-small cell lung cancer (NSCLC). Tumor cells deficient in LKB1 may be uniquely sensitized to metabolic stresses, which may offer a therapeutic window in oncology. To address this question we have explored how functional LKB1 impacts the metabolism of NSCLC cells using 13 C metabolic flux analysis. Isogenic NSCLC cells expressing functional LKB1 exhibited higher flux through oxidative mitochondrial pathways compared to those deficient in LKB1. Re-expression of LKB1 also increased the capacity of cells to oxidize major mitochondrial substrates, including pyruvate, fatty acids, and glutamine. Furthermore, LKB1 expression promoted an adaptive response to energy stress induced by anchorage-independent growth. Finally, this diminished adaptability sensitized LKB1-deficient cells to combinatorial inhibition of mitochondrial complex I and glutaminase. Together, our data implicate LKB1 as a major regulator of adaptive metabolic reprogramming and suggest synergistic pharmacological strategies for mitigating LKB1-deficient NSCLC tumor growth. Copyright © 2016. Published by Elsevier Inc.

  2. Opposite Effects of Stress on Pain Modulation Depend on the Magnitude of Individual Stress Response.

    Science.gov (United States)

    Geva, Nirit; Defrin, Ruth

    2018-04-01

    The effect of acute stress on pain threshold and intolerance threshold are reported as producing either hypoalgesia or hyperalgesia. Yet, the contribution of individual stress reactivity in this respect has not been established. The aim was to test 2 pain modulation paradigms under acute stress manipulation, to our knowledge, for the first time, to study whether stress differentially affects pain modulation, and whether the effect is related to individual stress response. Participants were 31 healthy subjects. Conditioned pain modulation (CPM) and pain adaptation were measured before and after inducing an acute stress response using the Montreal Imaging Stress Task. Subjects' stress response was evaluated according to salivary cortisol, autonomic function, and perceived stress and anxiety. The Montreal Imaging Stress Task induced a validated stress response. On a group level, stress induced reduction in CPM magnitude and increase in pain adaptation compared with baseline. These responses correlated with stress reactivity. When the group was subdivided according to stress reactivity, only high stress responders exhibited reduced CPM whereas only low stress responders exhibited increased pain adaptation. The results suggest that acute stress may induce opposite effects on pain modulation, depending on individual stress reactivity magnitude, with an advantage to low stress responders. This study evaluated the effect of acute stress on pain modulation. Pain modulation under stress is affected by individual stress responsiveness; decreased CPM occurs in high stress responders whereas increased pain adaptation occurs in low stress responders. Identification of high stress responders may promote better pain management. Copyright © 2017 The American Pain Society. Published by Elsevier Inc. All rights reserved.

  3. Preexposure to Olive Oil Polyphenols Extract Increases Oxidative Load and Improves Liver Mass Restoration after Hepatectomy in Mice via Stress-Sensitive Genes

    Directory of Open Access Journals (Sweden)

    Jelena Marinić

    2016-01-01

    Full Text Available Polyphenols can act as oxidants in some conditions, inducing redox-sensitive genes. We investigated the effect of preexposure to the olive oil polyphenols extract (PFE on time-dependent changes in the hepatic oxidative state in a model of liver regeneration—a process in which oxidative stress associated with the metabolic overload accounts for the early events that contribute to the onset of liver self-repair. Liver regeneration was induced by one-third hepatectomy in mice. Prior to hepatectomy, mice were intraperitoneally given either PFE (50 mg/kg body weight or saline for seven consecutive days, while respective controls received vehicle alone. Redox state-regulating enzymes and thiol proteins along with the mRNA levels of Nrf2 gene and its targets γ-glutamylcysteine synthetase and heme oxygenase-1 were determined at different time intervals after hepatectomy. The liver mass restoration was calculated to assess hepatic regeneration. The resulting data demonstrate the effectiveness of preexposure to PFE in stimulating liver regeneration in a model of a small tissue loss which may be ascribed to the transient increase in oxidant load during the first hours after hepatectomy and associated induction of stress response gene-profiles under the control of Nrf2.

  4. Oxaliplatin-induced Oxidative Stress Provokes Toxicity in Isolated Rat Liver Mitochondria.

    Science.gov (United States)

    Tabassum, Heena; Waseem, Mohammad; Parvez, Suhel; Qureshi, M Irfan

    2015-11-01

    Oxaliplatin is a widely employed platinum-derived chemotherapeutic agent commonly used for the treatment of colorectal cancer. Unfortunately, the benefit of this important drug is compromised by severe side effects such as neuropathy, ototoxicity, gastrointestinal toxicity, and hematological toxicity. Recently, few studies have also suggested the occurrence of hepatotoxicity in oxaliplatin-treated patients. Mitochondria have emerged as targets for anticancer drugs in various kinds of toxicity including hepatotoxicity that can lead to neoplastic disease. Oxidative stress is a well-established biomarker of mitochondrial toxicity. The purpose of this study was to investigate the dose-dependent damage caused by oxaliplatin on isolated liver mitochondria under in vitro conditions. The study was conducted in mitochondria isolated from liver of Wistar rats. Oxaliplatin was incubated with mitochondria in a dose-dependent manner under in vitro conditions. Oxidative stress indexes, non-enzymatic and enzymatic antioxidants were evaluated, looking at the overall armamentarium against the toxicity induced by oxaliplatin. Oxaliplatin caused a significant rise in the mitochondrial oxidative stress indexes lipid peroxidation and protein carbonyl. Alterations in the levels of non-enzymatic antioxidants and activities of enzymatic antioxidants were also observed. Oxidative stress plays an important role in the mitochondrial toxicity of oxaliplatin. The integrity of the hepatic tissue is compromised by the reactive oxygen species-mediated lipid peroxidation and protein carbonyl formation. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

  5. Increased Nitroxidative Stress Promotes Mitochondrial Dysfunction in Alcoholic and Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Byoung-Joon Song

    2013-01-01

    Full Text Available Increased nitroxidative stress causes mitochondrial dysfunctions through oxidative modifications of mitochondrial DNA, lipids, and proteins. Persistent mitochondrial dysfunction sensitizes the target cells/organs to other pathological risk factors and thus ultimately contributes to the development of more severe disease states in alcoholic and nonalcoholic fatty liver disease. The incidences of nonalcoholic fatty liver disease continuously increase due to high prevalence of metabolic syndrome including hyperlipidemia, hypercholesterolemia, obesity, insulin resistance, and diabetes. Many mitochondrial proteins including the enzymes involved in fat oxidation and energy supply could be oxidatively modified (including S-nitrosylation/nitration under increased nitroxidative stress and thus inactivated, leading to increased fat accumulation and ATP depletion. To demonstrate the underlying mechanism(s of mitochondrial dysfunction, we employed a redox proteomics approach using biotin-N-maleimide (biotin-NM as a sensitive biotin-switch probe to identify oxidized Cys residues of mitochondrial proteins in the experimental models of alcoholic and acute liver disease. The aims of this paper are to briefly describe the mechanisms, functional consequences, and detection methods of mitochondrial dysfunction. We also describe advantages and limitations of the Cys-targeted redox proteomics method with alternative approaches. Finally, we discuss various applications of this method in studying oxidatively modified mitochondrial proteins in extrahepatic tissues or different subcellular organelles and translational research.

  6. Melatonin attenuates oxidative stress, liver damage and hepatocyte apoptosis after bile-duct ligation in rats.

    Science.gov (United States)

    Aktas, Cevat; Kanter, Mehmet; Erboga, Mustafa; Mete, Rafet; Oran, Mustafa

    2014-10-01

    The goal of this study was to evaluate the possible protective effects of melatonin against cholestatic oxidative stress, liver damage and hepatocyte apoptosis in the common rats with bile duct ligation (BDL). A total of 24 male Wistar albino rats were divided into three groups: control, BDL and BDL + received melatonin; each group contains eight animals. Melatonin-treated BDL rats received daily melatonin 100 mg/kg/day via intraperitoneal injection. The application of BDL clearly increased the malondialdehyde (MDA) levels and decreased the superoxide dismutase (SOD) and glutathione (GSH) activities. Melatonin treatment significantly decreased the elevated tissue MDA levels and increased the reduced SOD and GSH enzyme levels in the tissues. The changes demonstrate that the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells and neutrophil infiltration into the widened portal areas as observed in the BDL group. The data indicate that melatonin attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis. The α-smooth muscle actin (α-SMA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the BDL were observed to be reduced with the melatonin treatment. These results suggest that administration of melatonin is a potentially beneficial agent to reduce liver damage in BDL by decreasing oxidative stress. © The Author(s) 2012.

  7. High fat diet aggravates arsenic induced oxidative stress in rat heart and liver.

    Science.gov (United States)

    Dutta, Mousumi; Ghosh, Debosree; Ghosh, Arnab Kumar; Bose, Gargi; Chattopadhyay, Aindrila; Rudra, Smita; Dey, Monalisa; Bandyopadhyay, Arkita; Pattari, Sanjib K; Mallick, Sanjaya; Bandyopadhyay, Debasish

    2014-04-01

    Arsenic is a well known global groundwater contaminant. Exposure of human body to arsenic causes various hazardous effects via oxidative stress. Nutrition is an important susceptible factor which can affect arsenic toxicity by several plausible mechanisms. Development of modern civilization led to alteration in the lifestyle as well as food habits of the people both in urban and rural areas which led to increased use of junk food containing high level of fat. The present study was aimed at investigating the effect of high fat diet on heart and liver tissues of rats when they were co-treated with arsenic. This study was established by elucidating heart weight to body weight ratio as well as analysis of the various functional markers, oxidative stress biomarkers and also the activity of the antioxidant enzymes. Histological analysis confirmed the biochemical investigations. From this study it can be concluded that high fat diet increased arsenic induced oxidative stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Personality traits modulate emotional and physiological responses to stress.

    Science.gov (United States)

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

    2014-09-01

    An individual's susceptibility to psychological and physical disorders associated with chronic stress exposure, for example, 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 the 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 standardized laboratory psychosocial stress task, the Trier Social Stress Test. Individuals with high Negative Emotionality exhibited greater emotional distress and lower blood pressure responses to the Trier Social Stress Test. 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.

  9. Effect of moderate hypoxia at three acclimation temperatures on stress responses in Atlantic cod with different haemoglobin types

    DEFF Research Database (Denmark)

    Methling, Caroline; Aluru, Neelakanteswar; Vijayan, Mathilakath M

    2010-01-01

    in a difference in stress response to hypoxia exposure. Two hsp70-isoforms (labelled a and b) were detected and they differed in expression in the gills but not in the liver of Atlantic cod. Acclimation temperature significantly affected the expression of hsp70 in the liver, and in an isoform-specific manner...... in the gills. Hypoxia exposure increased the expression of hsp70 in the liver, but not the gills, of cod and this response was not influenced by the acclimation temperature. The expression of hsp70 in both tissues did not differ between fish with different haemoglobin types. Acclimation temperature...... hypoxic exposure influence the organismal and cellular stress responses in Atlantic cod. We hypothesise that HbI-2 fish are more tolerant to short-term hypoxic episodes than HbI-1 fish, and this adaptation may be independent of tissue hsp70 expression....

  10. Co-ordinate but disproportionate activation of apoptotic, regenerative and inflammatory pathways characterizes the liver response to acute amebic infection.

    Science.gov (United States)

    Pelosof, Lorraine C; Davis, Paul H; Zhang, Zhi; Zhang, Xiaochun; Stanley, Samuel L

    2006-03-01

    The liver has the remarkable ability to respond to injury with repair and regeneration. The protozoan parasite Entamoeba histolytica is the major cause of liver abscess worldwide. We report a transcriptional analysis of the response of mouse liver to E. histolytica infection, the first study looking at acute liver infection by a non-viral pathogen. Focusing on early time points, we identified 764 genes with altered transcriptional levels in amebic liver abscess. The response to infection is rapid and complex, with concurrent increased expression of genes linked to host defence through IL-1, TLR2, or interferon-induced pathways, liver regeneration via activation of IL-6 pathways, and genes associated with programmed cell death possibly through TNFalpha or Fas pathways. A comparison of amebic liver infection with the liver response to partial hepatectomy or toxins reveals striking similarities between amebic liver abscess and non-infectious injury in key components of the liver regeneration pathways. However, the response in amebic liver abscess is biased towards apoptosis when compared with acute liver injury from hepatectomy, toxins, or other forms of liver infection. E. histolytica infection of the liver simultaneously activates inflammatory, regenerative and apoptotic pathways, but the sum of these early responses is biased towards programmed cell death.

  11. Hepatitis C Virus Infection Induces Autophagy as a Prosurvival Mechanism to Alleviate Hepatic ER-Stress Response

    Science.gov (United States)

    Dash, Srikanta; Chava, Srinivas; Aydin, Yucel; Chandra, Partha K.; Ferraris, Pauline; Chen, Weina; Balart, Luis A.; Wu, Tong; Garry, Robert F.

    2016-01-01

    Hepatitis C virus (HCV) infection frequently leads to chronic liver disease, liver cirrhosis and hepatocellular carcinoma (HCC). The molecular mechanisms by which HCV infection leads to chronic liver disease and HCC are not well understood. The infection cycle of HCV is initiated by the attachment and entry of virus particles into a hepatocyte. Replication of the HCV genome inside hepatocytes leads to accumulation of large amounts of viral proteins and RNA replication intermediates in the endoplasmic reticulum (ER), resulting in production of thousands of new virus particles. HCV-infected hepatocytes mount a substantial stress response. How the infected hepatocyte integrates the viral-induced stress response with chronic infection is unknown. The unfolded protein response (UPR), an ER-associated cellular transcriptional response, is activated in HCV infected hepatocytes. Over the past several years, research performed by a number of laboratories, including ours, has shown that HCV induced UPR robustly activates autophagy to sustain viral replication in the infected hepatocyte. Induction of the cellular autophagy response is required to improve survival of infected cells by inhibition of cellular apoptosis. The autophagy response also inhibits the cellular innate antiviral program that usually inhibits HCV replication. In this review, we discuss the physiological implications of the HCV-induced chronic ER-stress response in the liver disease progression. PMID:27223299

  12. Cutting Edge: Eosinophils Undergo Caspase-1-Mediated Pyroptosis in Response to Necrotic Liver Cells.

    Science.gov (United States)

    Palacios-Macapagal, Daphne; Connor, Jane; Mustelin, Tomas; Ramalingam, Thirumalai R; Wynn, Thomas A; Davidson, Todd S

    2017-08-01

    Many chronic liver disorders are characterized by dysregulated immune responses and hepatocyte death. We used an in vivo model to study the immune response to necrotic liver injury and found that necrotic liver cells induced eosinophil recruitment. Necrotic liver induced eosinophil IL-1β and IL-18 secretion, degranulation, and cell death. Caspase-1 inhibitors blocked all of these responses. Caspase-1-mediated cell death with accompanying cytokine release is the hallmark of a novel form of cell death termed pyroptosis. To confirm this response in a disease model, we isolated eosinophils from the livers of Schistosoma mansoni -infected mice. S. mansoni eggs lodge in the hepatic sinusoids of infected mice, resulting in hepatocyte death, inflammation, and progressive liver fibrosis. This response is typified by massive eosinophilia, and we were able to confirm pyroptosis in the infiltrating eosinophils. This demonstrated that pyroptosis is a cellular pathway used by eosinophils in response to large-scale hepatic cell death. Copyright © 2017 by The American Association of Immunologists, Inc.

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

    OpenAIRE

    Dues, Dylan J.; Andrews, Emily K.; Schaar, Claire E.; 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 oxi...

  14. Stress responses in probiotic Lactobacillus casei.

    Science.gov (United States)

    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.

  15. Effect of the combination of metformin hydrochloride and melatonin on oxidative stress before and during pregnancy, and biochemical and histopathological analysis of the livers of rats after treatment for polycystic ovary syndrome

    International Nuclear Information System (INIS)

    Lemos, Ana Janaina Jeanine M.; Peixoto, Christina A.; Teixeira, Álvaro Aguiar C.; Luna, Rayana Leal A.; Rocha, Sura Wanessa S.; Santos, Hilda Michelly P.; Silva, Amanda Karolina S.; Nunes, Ana Karolina S.; Wanderley-Teixeira, Valéria

    2014-01-01

    The aim of the present study was to analyze the effect of a combination of metformin hydrochloride and melatonin on oxidative stress together with a biochemical and histopathological analysis of the livers of Wistar rats induced with PCOS. The results indicated that a combination of the drugs was more effective in the reduction of plasmatic levels of liver enzyme alanine aminotransferase, nitric oxide and total glutathione, and decreased the inflammatory response and histopathological damage, producing results that were significantly similar to animals from the control group. A mixture of the drugs produced more effective results against liver toxicity caused by PCOS, encouraging the normalization of biochemical parameters. During pregnancy, there was reduced oxidative stress compared to monotherapeutic use of these drugs. Interestingly, the combination of the drugs caused a physiological reaction similar to responses identified in healthy rats without induction of the PCOS control group. However, the clinical and physiological effectiveness of the combination should be further explored, especially with respect to the possible side effects on offspring. - Highlights: • Studies have documented increased oxidative stress in patients with PCOS. • It has been noted that women with PCOS have a high prevalence of liver alterations. • Liver disease in pregnancy may be pre-existing increasing the newborn mortality. • Metformin/melatonin associated reduced oxidative stress in liver in pregnant rats. • Association of metformin/melatonin normalizes hepatic biochemical parameters

  16. Effect of the combination of metformin hydrochloride and melatonin on oxidative stress before and during pregnancy, and biochemical and histopathological analysis of the livers of rats after treatment for polycystic ovary syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lemos, Ana Janaina Jeanine M. [Department of Animal Morphology and Physiology, Universidade Federal Rural de Pernambuco, Recife (Brazil); Unit of Medical and Health Sciences, Universidade Federal de Campina Grande (Brazil); Peixoto, Christina A. [Centro de Pesquisa Aggeu Magalhães-Fiocruz Recife (Brazil); Teixeira, Álvaro Aguiar C. [Department of Animal Morphology and Physiology, Universidade Federal Rural de Pernambuco, Recife (Brazil); Luna, Rayana Leal A.; Rocha, Sura Wanessa S. [Centro de Pesquisa Aggeu Magalhães-Fiocruz Recife (Brazil); Santos, Hilda Michelly P. [Department of Animal Morphology and Physiology, Universidade Federal Rural de Pernambuco, Recife (Brazil); Silva, Amanda Karolina S.; Nunes, Ana Karolina S. [Centro de Pesquisa Aggeu Magalhães-Fiocruz Recife (Brazil); Wanderley-Teixeira, Valéria, E-mail: valeria@dmfa.ufrpe.br [Department of Animal Morphology and Physiology, Universidade Federal Rural de Pernambuco, Recife (Brazil)

    2014-10-01

    The aim of the present study was to analyze the effect of a combination of metformin hydrochloride and melatonin on oxidative stress together with a biochemical and histopathological analysis of the livers of Wistar rats induced with PCOS. The results indicated that a combination of the drugs was more effective in the reduction of plasmatic levels of liver enzyme alanine aminotransferase, nitric oxide and total glutathione, and decreased the inflammatory response and histopathological damage, producing results that were significantly similar to animals from the control group. A mixture of the drugs produced more effective results against liver toxicity caused by PCOS, encouraging the normalization of biochemical parameters. During pregnancy, there was reduced oxidative stress compared to monotherapeutic use of these drugs. Interestingly, the combination of the drugs caused a physiological reaction similar to responses identified in healthy rats without induction of the PCOS control group. However, the clinical and physiological effectiveness of the combination should be further explored, especially with respect to the possible side effects on offspring. - Highlights: • Studies have documented increased oxidative stress in patients with PCOS. • It has been noted that women with PCOS have a high prevalence of liver alterations. • Liver disease in pregnancy may be pre-existing increasing the newborn mortality. • Metformin/melatonin associated reduced oxidative stress in liver in pregnant rats. • Association of metformin/melatonin normalizes hepatic biochemical parameters.

  17. Bicyclol attenuates tetracycline-induced fatty liver associated with inhibition of hepatic ER stress and apoptosis in mice.

    Science.gov (United States)

    Yao, Xiao-Min; Li, Yue; Li, Hong-Wei; Cheng, Xiao-Yan; Lin, Ai-Bin; Qu, Jun-Ge

    2016-01-01

    Endoplasmic reticulum (ER) stress is known to be involved in the development of several metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). Tetracycline can cause hepatic steatosis, and ER stress may be involved in tetracycline-induced fatty liver. Our previous study showed that bicyclol has been proven to protect against tetracycline-induced fatty liver in mice, and ER stress may also be involved in bicyclol's hepatoprotective effect. Therefore, this study was performed to investigate the underlying mechanisms associated with ER stress and apoptosis, by which bicyclol attenuated tetracycline-induced fatty liver in mice. Bicyclol (300 mg/kg) was given to mice by gavage 3 times. Tetracycline (200 mg/kg, intraperitoneally) was injected at 1 h after the last dose of bicyclol. At 6 h and 24 h after single dose of tetracycline injection, serum ALT, AST, TG, CHO and hepatic histopathological examinations were performed to evaluate liver injuries. Hepatic steatosis was assessed by the accumulation of hepatic TG and CHO. Moreover, hepatic apoptosis and ER stress related markers were determined by TUNEL, real-time PCR, and western blot. As a result, bicyclol significantly protected against tetracycline-induced fatty liver as evidenced by the decrease of elevated serum transaminases and hepatic triglyceride, and the attenuation of histopathological changes in mice. In addition, bicyclol remarkably alleviated hepatic apoptosis and the gene expression of caspase-3, and increased the gene expression of XIAP. The gene expressions of ER stress-related markers, including CHOP, GRP78, IRE-1α, and ATF6, which were downregulated by bicyclol pretreatment in tetracycline-injected mice. These results suggested that bicyclol protected tetracycline-induced fatty liver partly due to its ability of anti-apoptosis associated with ER stress.

  18. The Role of the Transcriptional Response to DNA Replication Stress.

    Science.gov (United States)

    Herlihy, Anna E; de Bruin, Robertus A M

    2017-03-02

    During DNA replication many factors can result in DNA replication stress. The DNA replication stress checkpoint prevents the accumulation of replication stress-induced DNA damage and the potential ensuing genome instability. A critical role for post-translational modifications, such as phosphorylation, in the replication stress checkpoint response has been well established. However, recent work has revealed an important role for transcription in the cellular response to DNA replication stress. In this review, we will provide an overview of current knowledge of the cellular response to DNA replication stress with a specific focus on the DNA replication stress checkpoint transcriptional response and its role in the prevention of replication stress-induced DNA damage.

  19. The Role of the Transcriptional Response to DNA Replication Stress

    Science.gov (United States)

    Herlihy, Anna E.; de Bruin, Robertus A.M.

    2017-01-01

    During DNA replication many factors can result in DNA replication stress. The DNA replication stress checkpoint prevents the accumulation of replication stress-induced DNA damage and the potential ensuing genome instability. A critical role for post-translational modifications, such as phosphorylation, in the replication stress checkpoint response has been well established. However, recent work has revealed an important role for transcription in the cellular response to DNA replication stress. In this review, we will provide an overview of current knowledge of the cellular response to DNA replication stress with a specific focus on the DNA replication stress checkpoint transcriptional response and its role in the prevention of replication stress-induced DNA damage. PMID:28257104

  20. Interferon-Mediated Innate Immune Responses against Malaria Parasite Liver Stages

    Directory of Open Access Journals (Sweden)

    Jessica L. Miller

    2014-04-01

    Full Text Available Mosquito-transmitted malaria parasites infect hepatocytes and asymptomatically replicate as liver stages. Using RNA sequencing, we show that a rodent malaria liver-stage infection stimulates a robust innate immune response including type I interferon (IFN and IFNγ pathways. Liver-stage infection is suppressed by these infection-engendered innate responses. This suppression was abrogated in mice deficient in IFNγ, the type I IFN α/β receptor (IFNAR, and interferon regulatory factor 3. Natural killer and CD49b+CD3+ natural killer T (NKT cells increased in the liver after a primary infection, and CD1d-restricted NKT cells, which secrete IFNγ, were critical in reducing liver-stage burden of a secondary infection. Lack of IFNAR signaling abrogated the increase in NKT cell numbers in the liver, showing a link between type I IFN signaling, cell recruitment, and subsequent parasite elimination. Our findings demonstrate innate immune sensing of malaria parasite liver-stage infection and that the ensuing innate responses can eliminate the parasite.

  1. Predictors of response to radio-embolization (TheraSphere®) treatment of neuroendocrine liver metastasis.

    Science.gov (United States)

    Shaheen, Mohammed; Hassanain, Mazen; Aljiffry, Murad; Cabrera, Tatiana; Chaudhury, Prosanto; Simoneau, Eve; Kongkaewpaisarn, Nuttawut; Salman, Ayat; Rivera, Juan; Jamal, Mohammad; Lisbona, Robert; Khankan, Azzam; Valenti, David; Metrakos, Peter

    2012-01-01

    Neuroendocrine tumours (NET) frequently metastasize to the liver. NET liver metastasis has been shown to respond to Yttrium-90 microspheres therapy. The aims of the present study were to define factors that predict the response to radio-embolization in patients with NET liver metastases. From January 2006 until March 2009, all patients with NET liver metastasis that received radio-embolization using TheraSphere® (glass microspheres) were reviewed. The response was determined by a change in the percentage of necrosis (ΔN%) after the first radio-embolization based on the modified RECIST criteria (mRECIST) criteria. The following confounding variables were measured: age, gender, size of the lesions, liver involvement, World Health Organization (WHO) classification, the presence of extra-hepatic metastasis, octereotide treatment and previous operative [surgery and (RFA)] and non-operative treatments (chemo-embolization and bland-embolization). In all, 25 patients were identified, with a median follow-up of 21.7 months. The median age was 64.6 years, 28% had extra-hepatic metastasis and 56% were WHO stage 2. Post-treatment, the mean ΔN% was 48.4%. Previous surgical therapy was a significant predictor of the response with a response rate of 66.7 ΔN% vs. 31.5 ΔN% (P= 0.02). Bilateral liver disease, a high percentage of liver involvement and large metastatic lesions were inversely related to the degree of tumour response although did not reach statistical significance. Radio-embolization increased the necrosis of NET liver metastasis mainly in patients with less bulky disease. This may imply that surgical therapy before radio-embolization would increase the response rates. © 2011 International Hepato-Pancreato-Biliary Association.

  2. How age, sex and genotype shape the stress response.

    Science.gov (United States)

    Novais, Ashley; Monteiro, Susana; Roque, Susana; Correia-Neves, Margarida; Sousa, Nuno

    2017-02-01

    Exposure to chronic stress is a leading pre-disposing factor for several neuropsychiatric disorders as it often leads to maladaptive responses. The response to stressful events is heterogeneous, underpinning a wide spectrum of distinct changes amongst stress-exposed individuals'. Several factors can underlie a different perception to stressors and the setting of distinct coping strategies that will lead to individual differences on the susceptibility/resistance to stress. Beyond the factors related to the stressor itself, such as intensity, duration or predictability, there are factors intrinsic to the individuals that are relevant to shape the stress response, such as age, sex and genetics. In this review, we examine the contribution of such intrinsic factors to the modulation of the stress response based on experimental rodent models of response to stress and discuss to what extent that knowledge can be potentially translated to humans.

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

    International Nuclear Information System (INIS)

    Calabrese, Edward J.; 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.; Keller, John G.; Klaunig, James E.; Knudsen, Thomas B.; Kozumbo, Walter J.; Lettieri, Teresa; Liu, Shu-Zheng; Maisseu, Andre; Maynard, Kenneth I.; Masoro, Edward J.; McClellan, Roger O.; Mehendale, Harihara M.; Mothersill, Carmel; Newlin, David B.; Nigg, Herbert N.; Oehme, Frederick W.; Phalen, Robert F.; Philbert, Martin A.; Rattan, Suresh I.S.; Riviere, Jim E.; Rodricks, Joseph; Sapolsky, Robert M.; Scott, Bobby R.; Seymour, Colin; Sinclair, David A.; Smith-Sonneborn, Joan; Snow, Elizabeth T.; Spear, Linda; Stevenson, Donald E.; Thomas, Yolene; Tubiana, Maurice; Williams, Gary M.; Mattson, Mark P.

    2007-01-01

    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

  4. Psychophysiological responses to stress after stress management training in patients with rheumatoid arthritis.

    NARCIS (Netherlands)

    Brouwer, S.J.M. de; Kraaimaat, F.W.; Sweep, F.C.; Donders, A.R.T.; Eijsbouts, A.; Koulil, S. van; Riel, P.L.C.M. van; Evers, A.W.M.

    2011-01-01

    BACKGROUND: Stress management interventions may prove useful in preventing the detrimental effects of stress on health. This study assessed the effects of a stress management intervention on the psychophysiological response to stress in patients with rheumatoid arthritis (RA). METHODS: Seventy-four

  5. Waterborne cadmium and nickel impact oxidative stress responses and retinoid metabolism in yellow perch

    International Nuclear Information System (INIS)

    Defo, Michel A.; Bernatchez, Louis; Campbell, Peter G.C.; Couture, Patrice

    2014-01-01

    Highlights: • Cd and Ni affected indicators of retinoid metabolism and oxidative stress in fish. • Liver rdh-2 transcription levels increase in fish exposed to waterborne Cd. • Liver REH and LdRAT activities increase with increasing kidney Cd concentration. • Changes at molecular levels do not always mean changes at the functional levels. • Multi-level biological approaches are needed when assessing fish metal toxicology. - Abstract: In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to

  6. Waterborne cadmium and nickel impact oxidative stress responses and retinoid metabolism in yellow perch

    Energy Technology Data Exchange (ETDEWEB)

    Defo, Michel A. [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada); Bernatchez, Louis [Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval, Québec, Québec G1V 0A6 (Canada); Campbell, Peter G.C. [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada); Couture, Patrice, E-mail: patrice.couture@ete.inrs.ca [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada)

    2014-09-15

    Highlights: • Cd and Ni affected indicators of retinoid metabolism and oxidative stress in fish. • Liver rdh-2 transcription levels increase in fish exposed to waterborne Cd. • Liver REH and LdRAT activities increase with increasing kidney Cd concentration. • Changes at molecular levels do not always mean changes at the functional levels. • Multi-level biological approaches are needed when assessing fish metal toxicology. - Abstract: In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to

  7. Extraversion and cardiovascular responses to recurrent social stress: Effect of stress intensity.

    Science.gov (United States)

    Lü, Wei; Xing, Wanying; Hughes, Brian M; Wang, Zhenhong

    2017-10-28

    The present study sought to establish whether the effects of extraversion on cardiovascular responses to recurrent social stress are contingent on stress intensity. A 2×5×1 mixed-factorial experiment was conducted, with social stress intensity as a between-subject variable, study phase as a within-subject variable, extraversion as a continuous independent variable, and cardiovascular parameter (HR, SBP, DBP, or RSA) as a dependent variable. Extraversion (NEO-FFI), subjective stress, and physiological stress were measured in 166 undergraduate students randomly assigned to undergo moderate (n=82) or high-intensity (n=84) social stress (a public speaking task with different levels of social evaluation). All participants underwent continuous physiological monitoring while facing two consecutive stress exposures distributed across five laboratory phases: baseline, stress exposure 1, post-stress 1, stress exposure 2, post-stress 2. Results indicated that under moderate-intensity social stress, participants higher on extraversion exhibited lesser HR reactivity to stress than participants lower on extraversion, while under high-intensity social stress, they exhibited greater HR, SBP, DBP and RSA reactivity. Under both moderate- and high-intensity social stress, participants higher on extraversion exhibited pronounced SBP and DBP response adaptation to repeated stress, and showed either better degree of HR recovery or greater amount of SBP and DBP recovery after stress. These findings suggest that individuals higher on extraversion exhibit physiological flexibility to cope with social challenges and benefit from adaptive cardiovascular responses. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Generalized Unsafety Theory of Stress: Unsafe Environments and Conditions, and the Default Stress Response

    Directory of Open Access Journals (Sweden)

    Jos F. Brosschot

    2018-03-01

    Full Text Available Prolonged physiological stress responses form an important risk factor for disease. According to neurobiological and evolution-theoretical insights the stress response is a default response that is always “on” but inhibited by the prefrontal cortex when safety is perceived. Based on these insights the Generalized Unsafety Theory of Stress (GUTS states that prolonged stress responses are due to generalized and largely unconsciously perceived unsafety rather than stressors. This novel perspective necessitates a reconstruction of current stress theory, which we address in this paper. We discuss a variety of very common situations without stressors but with prolonged stress responses, that are not, or not likely to be caused by stressors, including loneliness, low social status, adult life after prenatal or early life adversity, lack of a natural environment, and less fit bodily states such as obesity or fatigue. We argue that in these situations the default stress response may be chronically disinhibited due to unconsciously perceived generalized unsafety. Also, in chronic stress situations such as work stress, the prolonged stress response may be mainly caused by perceived unsafety in stressor-free contexts. Thus, GUTS identifies and explains far more stress-related physiological activity that is responsible for disease and mortality than current stress theories.

  9. Generalized Unsafety Theory of Stress: Unsafe Environments and Conditions, and the Default Stress Response.

    Science.gov (United States)

    Brosschot, Jos F; Verkuil, Bart; Thayer, Julian F

    2018-03-07

    Prolonged physiological stress responses form an important risk factor for disease. According to neurobiological and evolution-theoretical insights the stress response is a default response that is always "on" but inhibited by the prefrontal cortex when safety is perceived. Based on these insights the Generalized Unsafety Theory of Stress (GUTS) states that prolonged stress responses are due to generalized and largely unconsciously perceived unsafety rather than stressors. This novel perspective necessitates a reconstruction of current stress theory, which we address in this paper. We discuss a variety of very common situations without stressors but with prolonged stress responses, that are not, or not likely to be caused by stressors, including loneliness, low social status, adult life after prenatal or early life adversity, lack of a natural environment, and less fit bodily states such as obesity or fatigue. We argue that in these situations the default stress response may be chronically disinhibited due to unconsciously perceived generalized unsafety. Also, in chronic stress situations such as work stress, the prolonged stress response may be mainly caused by perceived unsafety in stressor-free contexts. Thus, GUTS identifies and explains far more stress-related physiological activity that is responsible for disease and mortality than current stress theories.

  10. Melatonin protects against taurolithocholic-induced oxidative stress in rat liver.

    Science.gov (United States)

    Fuentes-Broto, Lorena; Miana-Mena, Francisco J; Piedrafita, Eduardo; Berzosa, César; Martínez-Ballarín, Enrique; García-Gil, Francisco A; Reiter, Russel J; García, Joaquín J

    2010-08-01

    Cholestasis, encountered in a variety of clinical disorders, is characterized by intracellular accumulation of toxic bile acids in the liver. Furthermore, oxidative stress plays an important role in the pathogenesis of bile acids. Taurolithocholic acid (TLC) was revealed in previous studies as the most pro-oxidative bile acid. Melatonin, a well-known antioxidant, is a safe and widely used therapeutic agent. Herein, we investigated the hepatoprotective role of melatonin on lipid and protein oxidation induced by TLC alone and in combination with FeCl(3) and ascorbic acid in rat liver homogenates and hepatic membranes. The lipid peroxidation products, malondialdehyde and 4-hydroxyalkenals (MDA + 4-HDA), and carbonyl levels were quantified as indices of oxidative damage to hepatic lipids and proteins, respectively. In the current study, the rise in MDA + 4-HDA levels induced by TLC was inhibited by melatonin in a concentration-dependent manner in both liver homogenates and in hepatic membranes. Melatonin also had protective effects against structural damage to proteins induced by TLC in membranes. These results suggest that the indoleamine melatonin may potentially act as a protective agent in the therapy of those diseases that involve bile acid toxicity. Published 2010 Wiley-Liss, Inc.

  11. CHANGES IN SERUM ENZYMES LEVELS ASSOCIATED WITH LIVER FUNCTIONS IN STRESSED MARWARI GOAT

    Directory of Open Access Journals (Sweden)

    Kataria N.

    2011-03-01

    Full Text Available Serum enzyme levels were determined in goats of Marwari breed belonging to farmers’ stock of arid tract of Rajasthan state, India. The animals were grouped into healthy and stressed comprising of gastrointestinal parasiticised, pneumonia affected, and drought affected. The serum enzymes determined were sorbitol dehydrogenase, malate dehydrogenase, glucose-6-phosphate dehydrogenase, glutamate dehydrogenase, ornithine carbamoyl transferase, gamma-glutamayl transferase, 5’nucleotidase, glucose-6-phosphatase, arginase, and aldolase. In stressed group the mean values of all the enzymes increased significantly (p≤0.05 as compared to respective healthy mean value. All the enzymes showed highest values in the gastrointestinal parasiticised animals and least values in the animals having pneumonia. In gastrointestinal parasiticised animals maximum change was observed in G-6-Pase activity and minimum change was observed in malate dehydrogenase mean value. It was concluded that Increased activity of all the serum enzymes was due to modulation of liver functions directly or indirectly.

  12. Contradictory Immune Response in Post Liver Transplantation Hepatitis B and C

    Directory of Open Access Journals (Sweden)

    Akinobu Takaki

    2014-01-01

    Full Text Available Hepatitis B and C often progress to decompensated liver cirrhosis requiring orthotopic liver transplantation (OLT. After OLT, hepatitis B recurrence is clinically controlled with a combination of hepatitis B immunoglobulin (HBIG and nucleos(tide analogues. Another approach is to induce self-producing anti-hepatitis B virus (HBV antibodies using a HBV envelope antigen vaccine. Patients who had not been HBV carriers such as acutely infected liver failure or who received liver from HBV self-limited donor are good candidate. For chronic HBV carrier patients, a successful response can only be achieved in selected patients such as those treated with experimentally reduced immunosuppression protocols or received an anti-HBV adaptive memory carrying donor liver. Hepatitis C virus (HCV reinfects transplanted livers at a rate of >90%. HCV reinfected patients show different severities of hepatitis, from mild and slowly progressing to severe and rapidly progressing, possibly resulting from different adaptive immune responses. More than half the patients require interferon treatment, although the success rate is low and carries risks for leukocytopenia and rejection. Managing the immune response has an important role in controlling recurrent hepatitis C. This study aimed to review the adaptive immune response in post-OLT hepatitis B and C.

  13. The relationship between beginning teachers' stress causes, stress responses, teaching behaviour and attrition

    NARCIS (Netherlands)

    Harmsen, Ruth; Lorenz, Michelle; Maulana, Ridwan; van Veen, Klaas

    2018-01-01

    In this study, the relationships between beginning teachers’ perceived stress causes, stress responses, observed teaching behaviour and attrition is investigated employing structural equation modelling (SEM). A total of 143 BTs were surveyed using the Questionnaire on the Experience and Evaluation

  14. Stress

    Science.gov (United States)

    ... can be life-saving. But chronic stress can cause both physical and mental harm. There are at least three different types of stress: Routine stress related to the pressures of work, family, and other daily responsibilities Stress brought about ...

  15. Oxidative stress-mediated mouse liver lesions caused by Clonorchis sinensis infection.

    Science.gov (United States)

    Maeng, Sejung; Lee, Hye Won; Bashir, Qudsia; Kim, Tae Im; Hong, Sung-Jong; Lee, Tae Jin; Sohn, Woon-Mok; Na, Byoung-Kuk; Kim, Tong-Soo; Pak, Jhang Ho

    2016-03-01

    Clonorchis sinensis is a high-risk pathogenic helminth that strongly provokes inflammation, epithelial hyperplasia, periductal fibrosis, and even cholangiocarcinoma in chronically infected individuals. Chronic inflammation is associated with an increased risk of various cancers due to the disruption of redox homeostasis. Accordingly, the present study was conducted to examine the time course relationship between histopathological changes and the appearance of oxidative stress markers, including lipid peroxidation, enzymes involved in lipid peroxidation, and mutagenic DNA adducts in the livers of mice infected with C. sinensis, as well as proinflammatory cytokines in infected mouse sera. Histopathological phenotypes such as bile duct epithelial hyperplasia, periductal fibrosis, edema and inflammatory infiltration increased in infected livers in a time-dependent manner. Intense immunoreactivity of lipid peroxidation products (4-hydroxy-2-nonenal; malondialdehyde), cyclooxygenase-2, 5-lipoxygenase and 8-oxo-7,8-dihydro-2'-deoxyguanosine were concomitantly observed in these injured regions. We also found elevated expressions of cyclooxygenase-2 and 5-lipoxygenase in C. sinensis excretory-secretory product-treated cholangiocarcinoma cells. Moreover, the levels of proinflammatory cytokines such as TNF-α, ILβ-1 and IL-6 were differentially upregulated in infected sera. With regard to oxidative stress-mediated carcinogenesis, our findings suggest that C. sinensis infestation may disrupt host redox homeostasis, creating a damaging environment that favors the development of advanced hepatobiliary diseases such as clonorchiasis-associated cholangiocarcinoma. Copyright © 2015 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  16. Molecular Mechanisms of Liver Injury and Hepatocarcinogenesis: Focusing on the Role of Stress-Activated MAPK

    Directory of Open Access Journals (Sweden)

    Hayato Nakagawa

    2012-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the third most common cause of cancer mortality. Short-term prognosis of patients with HCC has improved recently due to advances in early diagnosis and treatment, but long-term prognosis is still unsatisfactory. Therefore, obtaining a further understanding of the molecular carcinogenic mechanisms and the unique pathogenic biology of HCC is important. The most characteristic process in hepatocarcinogenesis is underlying chronic liver injury, which leads to repeated cycles of hepatocyte death, inflammation, and compensatory proliferation and subsequently provides a mitogenic and mutagenic environment leading to the development of HCC. Recent in vivo studies have shown that the stress-activated mitogen-activated protein kinase (MAPK cascade converging on c-Jun NH2-terminal kinase (JNK and p38 plays a central role in these processes, and it has attracted considerable attention as a therapeutic target. However, JNK and p38 have complex functions and a wide range of cellular effects. In addition, crosstalk with each other and the nuclear factor-kappaB pathway further complicate these functions. A full understanding is essential to bring these observations into clinical settings. In this paper, we discuss the latest findings regarding the mechanisms of liver injury and hepatocarcinogenesis focusing on the role of the stress-activated MAPK pathway.

  17. Influence of sex and developmental stage on acute hepatotoxic and inflammatory responses to liver procarcinogens in the mouse

    International Nuclear Information System (INIS)

    Hanna, Daniel; Riedmaier, Ariane Emami; Sugamori, Kim S.; Grant, Denis M.

    2016-01-01

    The incidence of liver cancer is higher in men than in women. This sex difference is also observed in murine tumor induction models that result in the appearance of liver tumors in adult mice following their exposure on postnatal days 8 and/or 15 to carcinogens such as 4-aminobiphenyl (ABP) or diethylnitrosamine (DEN). Previous studies performed in adult mice showed that acute hepatotoxic and inflammatory responses to high-dose DEN exposure were greater in males than in females, leading to the suggestion that these responses could account for the sex difference in tumor development. We also recently observed that female but not male mice exposed postnatally to ABP had slightly increased expression of the antioxidant defense genes Nqo1 and Ggt1, which are regulated by the oxidative stress response protein nuclear factor erythroid 2-related factor 2 (NRF2), while expression of Hmox1 was increased in both sexes. The goal of the present study was therefore to compare selected acute hepatotoxic, inflammatory and oxidative stress defense responses to ABP, DEN, or the prototype hepatotoxicant carbon tetrachloride (CCl 4 ), in male and female mice exposed to these chemicals either postnatally or as adults. Exposure of adult mice to ABP, DEN or CCl 4 produced a 2-fold greater acute elevation in serum levels of the hepatotoxicity biomarker alanine aminotransferase (ALT) in males than in females, while levels of the inflammatory biomarker interleukin-6 (IL-6) showed no sex difference. However, treatment of immature mice with either ABP or DEN using standard tumor-inducing postnatal exposure protocols produced no increase in serum ALT or IL-6 levels in either males or females, while CCl 4 produced a 40-fold ALT elevation but with no sex difference. Basal expression of the NRF2-responsive gene Nqo1 was higher in adult females than in males, but there was no sex difference in basal expression of Ggt1 or Hmox1. Sexually immature animals showed no sex difference in basal

  18. The physiological stress response and oxidative stress biomarkers in rainbow trout and brook trout from selenium-impacted streams in a coal mining region

    Energy Technology Data Exchange (ETDEWEB)

    Miller, L.L.; Rasmussen, J.B.; Palace, V.P.; Hontela, A. [University of Lethbridge, Lethbridge, AB (Canada). Dept. of Biological Science

    2009-11-15

    Selenium (Se) is an essential element that can be toxic at concentrations slightly greater than those required for homeostasis. The main chronic toxic effects of Se in fish are teratogenic deformities, but Se can also activate the physiological stress response and redox cycle with reduced glutathione causing oxidative damage. Rainbow trout, Oncorhynchus mykiss, appear to be more sensitive to Se than brook trout, Salvelinus fontinalis. The objective of this study was to compare the physiological stress response (plasma cortisol, glucose, triiodothyronine, thyroxine, gill Na+/K+ ATPase, cortisol secretory capacity, K and liver somatic index) and oxidative stress biomarkers (liver GSH, GPx, lipid peroxidation, vitamin A and vitamin E) in rainbow trout (RNTR) and brook trout (BKTR) collected from reference and Se-exposed streams. The physiological stress response was not impaired (cortisol secretory capacity unchanged); although there were species differences in plasma cortisol and plasma glucose levels. Liver GSH, GPx and vitamin levels were higher in RNTR than BKTR, but lipid peroxidation levels were not different. The elevated GSH reserves may make RNTR more sensitive to Se-induced lipid peroxidation, but this may be offset by the RNTR's higher antioxidant (GPx and vitamin) levels. Species-specific biochemical differences may mediate differences in Se sensitivity and be used in aquatic Se risk assessments.

  19. Thymoquinone restores liver fibrosis and improves oxidative stress status in a lipopolysaccharide-induced inflammation model in rats

    Directory of Open Access Journals (Sweden)

    Fereshteh Asgharzadeh

    2017-10-01

    Full Text Available Objective: Liver fibrosis is the primary sign of chronic liver injury induced by various causes. Thymoquinone (TQ is the major ingredient of Nigella sativa with several beneficial effects on the body. In the present study, we aimed to investigate the effect of TQ on liver fibrosis in a lipopolysaccharide (LPS-induced inflammation in male rats. Materials and methods: Fifty male Wistar rats were randomly divided into five groups (n=10 in each group as follow: (1 control; (2 LPS (1 mg/kg/day; i.p; (3 LPS+TQ 2 mg/kg/day (i.p (LPs+TQ2; (4 LPS+TQ 5 mg/kg/day (LPS+TQ5; (5 LPS+ TQ 10 mg/kg/day (LPS+ TQ10. After three weeks, blood samples were taken for evaluation of liver function tests. Then, the livers were harvested for histological evaluation of fibrosis and collagen content and measurement of oxidative stress markers including malondialdehyde (MDA, total thiol groups, superoxide dismutase (SOD and catalase activity in tissue homogenates. Results: LPS group showed higher levels of fibrosis and collagen content stained by Masson’s trichrome in liver tissue with impaired liver function test and increased oxidative stress markers (p

  20. Inhibitory Effects of Verrucarin A on Tunicamycin-Induced ER Stress in FaO Rat Liver Cells

    Directory of Open Access Journals (Sweden)

    Eun Young Bae

    2015-05-01

    Full Text Available Endoplasmic reticulum (ER stress is linked with development and maintenance of cancer, and serves as a therapeutic target for treatment of cancer. Verrucarin A, isolated from the broth of Fusarium sp. F060190, showed potential inhibitory activity on tunicamycin-induced ER stress in FaO rat liver cells. In addition, the compound decreased tunicamycin-induced GRP78 promoter activity in a dose dependent manner without inducing significant inhibition of luciferase activity and cell growth for 6 and 12 h. Moreover, the compound decreased the expression of GRP78, CHOP, XBP-1, and suppressed XBP-1, and reduced phosphorylation of IRE1α in FaO rat liver cells. This evidence suggests for the first time that verrucarin A inhibited tunicamycin-induced ER stress in FaO rat liver cells.

  1. Proteomic analysis of cold stress responses in tobacco seedlings ...

    African Journals Online (AJOL)

    Cold stress is one of the major abiotic stresses limiting the productivity and the geographical distribution of many important crops. To gain a better understanding of cold stress responses in tobacco (Nicotiana tabacum), we carried out a comparative proteomic analysis. Five-week-old tobacco seedlings were treated at 4°C ...

  2. gender and school types as factors responsible for job stress

    African Journals Online (AJOL)

    Emeka Egbochuku

    public Universities should be looked into so that all factors responsible for stress might be .... universities in Malaysia, university academic staffs faced more problems .... adjustment with different coping styles. .... in college students: The role of rumination and stress. ... International Journal of Stress Management, 8, 285–29.

  3. Carvedilol suppresses circulating and hepatic IL-6 responsible for hepatocarcinogenesis of chronically damaged liver in rats

    International Nuclear Information System (INIS)

    Balaha, Mohamed; Kandeel, Samah; Barakat, Waleed

    2016-01-01

    Carvedilol is an anti-oxidant non-selective β-blocker used for reduction of portal blood pressure, prophylaxis of esophageal varices development and bleeding in chronic liver diseases. Recently, it exhibited potent anti-inflammatory, anti-fibrotic, anti-proliferative and anti-carcinogenic effects. In the present study, we evaluated the possible suppressive effect of carvedilol on circulating and hepatic IL-6 levels responsible for hepatocarcinogenesis in a rat model of hepatic cirrhosis. Besides, its effect on hepatic STAT-3 levels, function tests, oxidative stress markers, and hydroxyproline content, hepatic tissue histopathological changes and immunohistochemical expression of E & N-cadherin. Nine-week-old male Wistar rats injected intraperitoneal by 1 ml/kg 10% CCL 4 in olive oil three times/week (every other day) for 12 weeks to induce hepatic cirrhosis. Carvedilol (10 mg/kg/day suspended in 0.5% CMC orally), silymarin (50 mg/kg/day suspended in 0.5% CMC orally) or combination of both used to treat hepatic cirrhosis from 15th to 84th day. Our data showed that carvedilol and silymarin co-treatment each alone or in combination efficiently reduced the elevated serum IL-6, ALT, AST, ALP and BIL, hepatic IL-6, STAT-3, MDA levels and hydroxyproline content. In addition, it elevated the reduced serum ALB level, hepatic CAT activity and GSH level. Meanwhile, it apparently restored the normal hepatic architecture, collagen distribution and immunohistochemical E & N-cadherin expression. Furthermore, carvedilol was superior to silymarin in improving MDA level. Moreover, the combination of carvedilol and silymarin showed an upper hand in amelioration of the CCL 4 induced hepatotoxicity than each alone. Therefore, carvedilol could be promising in prevention of hepatocarcinogenesis in chronic hepatic injuries. - Highlights: • Chronic liver damage ends into hepatocellular carcinoma in 5% of patients. • Persistent elevation of IL-6 induces hepatocarcinogenesis in chronic

  4. Carvedilol suppresses circulating and hepatic IL-6 responsible for hepatocarcinogenesis of chronically damaged liver in rats

    Energy Technology Data Exchange (ETDEWEB)

    Balaha, Mohamed, E-mail: Mohamed.Balaha@Med.Tanta.Edu.Eg [Pharmacology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta (Egypt); Kandeel, Samah [Histology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta (Egypt); Barakat, Waleed [Pharmacology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta (Egypt)

    2016-11-15

    Carvedilol is an anti-oxidant non-selective β-blocker used for reduction of portal blood pressure, prophylaxis of esophageal varices development and bleeding in chronic liver diseases. Recently, it exhibited potent anti-inflammatory, anti-fibrotic, anti-proliferative and anti-carcinogenic effects. In the present study, we evaluated the possible suppressive effect of carvedilol on circulating and hepatic IL-6 levels responsible for hepatocarcinogenesis in a rat model of hepatic cirrhosis. Besides, its effect on hepatic STAT-3 levels, function tests, oxidative stress markers, and hydroxyproline content, hepatic tissue histopathological changes and immunohistochemical expression of E & N-cadherin. Nine-week-old male Wistar rats injected intraperitoneal by 1 ml/kg 10% CCL{sub 4} in olive oil three times/week (every other day) for 12 weeks to induce hepatic cirrhosis. Carvedilol (10 mg/kg/day suspended in 0.5% CMC orally), silymarin (50 mg/kg/day suspended in 0.5% CMC orally) or combination of both used to treat hepatic cirrhosis from 15th to 84th day. Our data showed that carvedilol and silymarin co-treatment each alone or in combination efficiently reduced the elevated serum IL-6, ALT, AST, ALP and BIL, hepatic IL-6, STAT-3, MDA levels and hydroxyproline content. In addition, it elevated the reduced serum ALB level, hepatic CAT activity and GSH level. Meanwhile, it apparently restored the normal hepatic architecture, collagen distribution and immunohistochemical E & N-cadherin expression. Furthermore, carvedilol was superior to silymarin in improving MDA level. Moreover, the combination of carvedilol and silymarin showed an upper hand in amelioration of the CCL{sub 4} induced hepatotoxicity than each alone. Therefore, carvedilol could be promising in prevention of hepatocarcinogenesis in chronic hepatic injuries. - Highlights: • Chronic liver damage ends into hepatocellular carcinoma in 5% of patients. • Persistent elevation of IL-6 induces hepatocarcinogenesis

  5. Autophagy response in the liver of pigeon exposed to avermectin.

    Science.gov (United States)

    Wang, Xian-Song; Liu, Ci; Khoso, Pervez Ahmed; Zheng, Weijia; Li, Ming; Li, Shu

    2017-05-01

    Pesticide residues are an important aspect of environmental pollution. Environmental avermectin residues have produced adverse effects in organisms. Many pesticides exert their toxic effects via the mechanism of autophagy. The purpose of this study was to examine the changes in autophagy levels and in autophagy-related genes, including LC3, Beclin 1, Dynein, ATG5, TORC1, and TORC2, resulting from exposure to subchronic levels of AVM in liver tissue in the king pigeon model. We observed abundant autophagic vacuoles with extensively degraded organelles, autophagosomal vacuoles, secondary lysosomes, and double-membrane structures in the liver. The expression levels of the autophagy-related genes LC3-I, LC3-II, Beclin 1, ATG5, and Dynein were up-regulated; however, TORC1 and TORC2 expression levels were down-regulated. These changes occurred in a concentration-dependent manner after AVM exposure for 30, 60, and 90 days in pigeons. Taken together, these results suggested that AVM increased the autophagic flux and that upregulation of autophagy might be closely related to the hepatotoxicity of AVM in birds.

  6. Associations between circadian and stress response cortisol in children.

    Science.gov (United States)

    Simons, Sterre S H; Cillessen, Antonius H N; de Weerth, Carolina

    2017-01-01

    Hypothalamic-pituitary-adrenal (HPA) axis functioning is characterized by the baseline production of cortisol following a circadian rhythm, as well as by the superimposed production of cortisol in response to a stressor. However, it is relatively unknown whether the basal cortisol circadian rhythm is associated with the cortisol stress response in children. Since alterations in cortisol stress responses have been associated with mental and physical health, this study investigated whether the cortisol circadian rhythm is associated with cortisol stress responses in 6-year-old children. To this end, 149 normally developing children (M age  = 6.09 years; 70 girls) participated in an innovative social evaluative stress test that effectively provoked increases in cortisol. To determine the cortisol stress response, six cortisol saliva samples were collected and two cortisol stress response indices were calculated: total stress cortisol and cortisol stress reactivity. To determine children's cortisol circadian rhythm eight cortisol circadian samples were collected during two days. Total diurnal cortisol and diurnal cortisol decline scores were calculated as indices of the cortisol circadian rhythm. Hierarchical regression analyses indicated that higher total diurnal cortisol as well as a smaller diurnal cortisol decline, were both uniquely associated with higher total stress cortisol. No associations were found between the cortisol circadian rhythm indices and cortisol stress reactivity. Possible explanations for the patterns found are links with children's self-regulatory capacities and parenting quality.

  7. Approaches to modeling the development of physiological stress responsivity.

    Science.gov (United States)

    Hinnant, J Benjamin; Philbrook, Lauren E; Erath, Stephen A; El-Sheikh, Mona

    2018-05-01

    Influential biopsychosocial theories have proposed that some developmental periods in the lifespan are potential pivot points or opportunities for recalibration of stress response systems. To date, however, there have been few longitudinal studies of physiological stress responsivity and no studies comparing change in physiological stress responsivity across developmental periods. Our goals were to (a) address conceptual and methodological issues in studying the development of physiological stress responsivity within and between individuals, and (b) provide an exemplar for evaluating development of responsivity to stress in the parasympathetic nervous system, comparing respiratory sinus arrhythmia (RSA) responsivity from middle to late childhood with middle to late adolescence. We propose the use of latent growth modeling of stress responsivity that includes time-varying covariates to account for conceptual and methodological issues in the measurement of physiological stress responsivity. Such models allow researchers to address key aspects of developmental sensitivity including within-individual variability, mean level change over time, and between-individual variability over time. In an empirical example, we found significant between-individual variability over time in RSA responsivity to stress during middle to late childhood but not during middle to late adolescence, suggesting that childhood may be a period of greater developmental sensitivity at the between-individual level. © 2017 Society for Psychophysiological Research.

  8. The stress response system of proteins: Implications for bioreactor scaleup

    Science.gov (United States)

    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.

  9. Adaptive Responses to Thermal Stress in Mammals

    OpenAIRE

    Yasser Lenis Sanin; Angélica María Zuluaga Cabrera; Ariel Marcel Tarazona Morales

    2015-01-01

    The environment animals have to cope with is a combination of natural factors such as temperature. Extreme changes in these factors can alter homeostasis, which can lead to thermal stress. This stress can be due to either high temperatures or low temperatures. Energy transference for thermoregulation in homoeothermic animals occurs through several mechanisms: conduction, convection, radiation and evaporation. When animals are subjected to thermal stress, physiological mechanisms are activated...

  10. Proteomic studies of drought stress response in Fabaceae

    Directory of Open Access Journals (Sweden)

    Tanja ZADRAŽNIK

    2015-11-01

    Full Text Available Drought stress is a serious threat to crop production that influences plant growth and development and subsequently causes reduced quantity and quality of the yield. Plant stress induces changes in cell metabolism, which includes differential expression of proteins. Proteomics offer a powerful approach to analyse proteins involved in drought stress response of plants. Analyses of changes in protein abundance of legumes under drought stress are very important, as legumes play an important role in human and animal diet and are often exposed to drought. The presented results of proteomic studies of selected legumes enable better understanding of molecular mechanisms of drought stress response. The study of drought stress response of plants with proteomic approach may contribute to the development of potential drought-response markers and to the development of drought-tolerant cultivars of different legume crop species.

  11. Psychophysiological responses to stress after stress management training in patients with rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Sabine J M de Brouwer

    Full Text Available BACKGROUND: Stress management interventions may prove useful in preventing the detrimental effects of stress on health. This study assessed the effects of a stress management intervention on the psychophysiological response to stress in patients with rheumatoid arthritis (RA. METHODS: Seventy-four patients with RA, who were randomly assigned to either a control group or a group that received short-term stress management training, performed a standardized psychosocial stress task (Trier Social Stress Test; TSST 1 week after the stress management training and at a 9-week follow-up. Psychological and physical functioning, and the acute psychophysiological response to the stress test were assessed. RESULTS: Patients in the intervention group showed significantly lower psychological distress levels of anxiety after the training than did the controls. While there were no between-group differences in stress-induced tension levels, and autonomic (α-amylase or endocrine (cortisol responses to the stress test 1 week after the intervention, levels of stress-induced tension and cortisol were significantly lower in the intervention group at the 9-week follow-up. Overall, the response to the intervention was particularly evident in a subgroup of patients with a psychological risk profile. CONCLUSION: A relatively short stress management intervention can improve psychological functioning and influences the psychophysiological response to stress in patients with RA, particularly those psychologically at risk. These findings might help understand how stress can affect health and the role of individual differences in stress responsiveness. TRIAL REGISTRATION: TrialRegister.nl NTR1193.

  12. Transcriptome Responses to Combinations of Stresses in Arabidopsis

    DEFF Research Database (Denmark)

    Rasmussen, Simon; Barah, Pankaj; Suarez-Rodriguez, Maria Cristina

    2013-01-01

    In Arabidopsis, the response of the majority of the genes cannot be predicted from single stress experiments and only a small fraction of the genes have potential antagonistic responses, indicating that plants have evolved to cope with combinations of stresses and therefore may be bred to endure...

  13. Perceived stress at work is associated with attenuated DHEA-S response during acute psychosocial stress.

    Science.gov (United States)

    Lennartsson, Anna-Karin; Theorell, Töres; Kushnir, Mark M; Bergquist, Jonas; Jonsdottir, Ingibjörg H

    2013-09-01

    Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) have been suggested to play a protective role during acute psychosocial stress, because they act as antagonists to the effects of the stress hormone cortisol. This study aims to investigate whether prolonged psychosocial stress, measured as perceived stress at work during the past week, is related to the capacity to produce DHEA and DHEA-S during acute psychosocial stress. It also aims to investigate whether prolonged perceived stress affects the balance between production of cortisol and DHEA-S during acute psychosocial stress. Thirty-six healthy subjects (19 men and 17 women, mean age 37 years, SD 5 years), were included. Perceived stress at work during the past week was measured by using the Stress-Energy (SE) Questionnaire. The participants were divided into three groups based on their mean scores; Low stress, Medium stress and High stress. The participants underwent the Trier Social Stress Test (TSST) and blood samples were collected before, directly after the stress test, and after 30 min of recovery. General Linear Models were used to investigate if the Medium stress group and the High stress group differ regarding stress response compared to the Low stress group. Higher perceived stress at work was associated with attenuated DHEA-S response during acute psychosocial stress. Furthermore, the ratio between the cortisol production and the DHEA-S production during the acute stress test were higher in individuals reporting higher perceived stress at work compared to individuals reporting low perceived stress at work. There was no statistical difference in DHEA response between the groups. This study shows that prolonged stress, measured as perceived stress at work during the past week, seems to negatively affect the capacity to produce DHEA-S during acute stress. Given the protective functions of DHEA-S, attenuated DHEA-S production during acute stress may lead to higher risk for adverse

  14. The temporal dynamics of the stress response

    NARCIS (Netherlands)

    Koolhaas, J.M.; Meerlo, P; de Boer, S.F.; Strubbe, J.H.; Bohus, B.G J

    1997-01-01

    This paper summarises the available evidence that failure of defense mechanisms in (semi)-natural social groups of animals may lead to serious forms of stress pathology. Hence the study of social stress may provide animal models with a high face validity. However, most of the animal models of human

  15. Sublethal toxicity of quinalphos on oxidative stress and antioxidant responses in a freshwater fish Cyprinus carpio.

    Science.gov (United States)

    Hemalatha, Devan; Amala, Antony; Rangasamy, Basuvannan; Nataraj, Bojan; Ramesh, Mathan

    2016-11-01

    Extensive use of quinalphos, an organophosphorus pesticide, is likely to reach the aquatic environment and thereby posing a health concern for aquatic organisms. Oxidative stress and antioxidant responses may be good indicators of pesticide contamination in aquatic organisms. The data on quinalphos induced oxidative stress and antioxidant responses in carps are scanty. This study is aimed to assess the two sublethal concentrations of quinalphos (1.09 and 2.18 μL L -1 ) on oxidative stress and antioxidant responses of Cyprinus carpio for a period of 20 days. In liver, the malondialdehyde level was found to be significantly increased in both the concentrations. The results of the antioxidant parameters obtained show a significant increase in superoxide dismutase, catalase, and glutathione-S-transferase activity in liver of fish. These results demonstrate that environmentally relevant levels of the insecticide quinalphos can cause oxidative damage and increase the antioxidant scavenging capacity in C. carpio. This may reflect the potential role of these parameters as useful biomarkers for the assessment of pesticide contamination. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1399-1406, 2016. © 2015 Wiley Periodicals, Inc.

  16. Comparison of isolated and concomitant liver injuries: is hepatic trauma entirely responsible for the outcome?

    Science.gov (United States)

    Yazici, P; Aydin, U; Sozbilen, M

    2010-01-01

    This study was undertaken to examine both isolated and concomitant liver injuries to clarify the role of liver trauma on outcome. This retrospective study was a review of all abdominal trauma patients who presented with liver injuries, with or without concomitant injury at Ege University School of Medicine over a 3-year period. Presentation, injury grade, management, and outcomes were analyzed. Patients with isolated hepatic injury (Group A) were compared with patients who had concomitant hepatic injury (liver and spleen/small bowel) (Group B). Significance was set at 95% confidence intervals. Of 368 patients, 80 (21%) presented with liver injury. Of these, the aetiology was as follows: 53 (66.2%) blunt injury, 19 (23%) penetrating injury, and 8 (10%) gun shot trauma. There were 38 patients in Group A and 42 in Group B. Of these 42 patients, 19 were diagnosed with serious types of injury ; eight thoracic, three open long bone fracture, one intra-cardiac, one intracranial. Six additional patients were observed with injuries to large abdominal vessels. Eleven patients (28.9%) with isolated hepatic injury were managed non-operatively. Mortality, intensive care unit and hospital length of stay, and transfusion requirements were significantly higher in Group B. Only the number of transfused blood units and the grade of liver injury were found to be effective on outcome whereas stepwise regression analysis revealed that injury type (penetrating) and blood transfusion were predictive for mortality. This study highlighted that although isolated liver injury results in good outcome with non-operative management, concomitant injuries to the liver lead to a higher failure and mortality rate. However, liver injury itself is rarely responsible for death.

  17. Investigating hsp Gene Expression in Liver of Channa striatus under Heat Stress for Understanding the Upper Thermal Acclimation

    Directory of Open Access Journals (Sweden)

    Gopal Krishna Purohit

    2014-01-01

    Full Text Available Changes in hsp gene expression profiles in murrel Channa striatus experimentally exposed to temperature stress (36°C for 4, 15, and 30 days were investigated; fish collected from aquaculture ponds and maintained in laboratory at the pond temperature (25 ± 1°C served as control. Channa collected from a hot spring runoff (36°C was included in the study to examine the hsp profiles beyond 30 days of exposure. Gene expression analyses of a battery of hsps in liver tissues were carried out by quantitative RT-PCR and protein expressions were analyzed by immunoblotting. hsps could be grouped into three clusters based on similarity in response to heat stress: hsp70, hsp78, and hsp60, whose transcript level continued to increase with duration of exposure; hsp90 and hsp110 that increased to a much higher level and then decreased; hsp27 and hsp47 that did not significantly vary as compared to control. The results suggest that Hsp70, Hsp78, and Hsp60 are involved in thermal acclimation and long term survival at high temperature. Fish living in the hot spring runoff appears to continuously express hsps that can be approximated by long term induction of hsps in farmed fish if temperature of their environment is raised to 36°C.

  18. Psychological and hormonal stress response patterns during a blood donation.

    Science.gov (United States)

    Hoogerwerf, M D; Veldhuizen, I J T; Merz, E-M; de Kort, W L A M; Frings-Dresen, M H W; Sluiter, J K

    2017-11-01

    Donating blood has been associated with increased stress responses, with scarce evidence indicating that levels of psychological and hormonal stress are higher pre-donation than post-donation. We investigated whether a blood donation induces psychological and/or hormonal stress during the course of a blood donation, and whether responses differed between men and women, first-time and experienced donors and donors with high or low non-acute stress. In 363 donors, psychological (donation-stress and arousal) and hormonal (cortisol) stress were measured by questionnaire and salivary sample at seven key moments during a routine donation. Non-acute stress was assessed by a questionnaire. Repeated measurement analyses were performed, using the last measurement (leaving the donation center) as reference value. Levels of donation-stress, arousal and cortisol were significantly higher during donation than when leaving the donation center. When compared with men, women reported higher levels of donation-stress and cortisol in the first part of the visit. When compared with first-time donors, experienced donors reported lower levels of donation-stress during the first part of the visit, and higher levels of arousal but less reactivity throughout the visit. When compared to donors high on non-acute stress, donors low on non-acute stress reported lower levels of donation-stress during the first part of the visit, and showed less cortisol reactivity throughout the visit. Donating blood influences psychological and hormonal stress response patterns. The response patterns differ between women and men, first-time and experienced donors and between donors high and low on non-acute stress. © 2017 International Society of Blood Transfusion.

  19. Phosphate-dependent root system architecture responses to salt stress

    KAUST Repository

    Kawa, Dorota; Julkowska, Magdalena; Montero Sommerfeld, Hector; Horst, Anneliek ter; Haring, Michel A; Testerink, Christa

    2016-01-01

    Nutrient availability and salinity of the soil affect growth and development of plant roots. Here, we describe how phosphate availability affects root system architecture (RSA) of Arabidopsis and how phosphate levels modulate responses of the root to salt stress. Phosphate (Pi) starvation reduced main root length and increased the number of lateral roots of Arabidopsis Col-0 seedlings. In combination with salt, low Pi dampened the inhibiting effect of mild salt stress (75mM) on all measured RSA components. At higher NaCl concentrations, the Pi deprivation response prevailed over the salt stress only for lateral root elongation. The Pi deprivation response of lateral roots appeared to be oppositely affected by abscisic acid (ABA) signaling compared to the salt stress response. Natural variation in the response to the combination treatment of salt and Pi starvation within 330 Arabidopsis accessions could be grouped into four response patterns. When exposed to double stress, in general lateral roots prioritized responses to salt, while the effect on main root traits was additive. Interestingly, these patterns were not identical for all accessions studied and multiple strategies to integrate the signals from Pi deprivation and salinity were identified. By Genome Wide Association Mapping (GWAS) 13 genomic loci were identified as putative factors integrating responses to salt stress and Pi starvation. From our experiments, we conclude that Pi starvation interferes with salt responses mainly at the level of lateral roots and that large natural variation exists in the available genetic repertoire of accessions to handle the combination of stresses.

  20. Phosphate-dependent root system architecture responses to salt stress

    KAUST Repository

    Kawa, Dorota

    2016-05-20

    Nutrient availability and salinity of the soil affect growth and development of plant roots. Here, we describe how phosphate availability affects root system architecture (RSA) of Arabidopsis and how phosphate levels modulate responses of the root to salt stress. Phosphate (Pi) starvation reduced main root length and increased the number of lateral roots of Arabidopsis Col-0 seedlings. In combination with salt, low Pi dampened the inhibiting effect of mild salt stress (75mM) on all measured RSA components. At higher NaCl concentrations, the Pi deprivation response prevailed over the salt stress only for lateral root elongation. The Pi deprivation response of lateral roots appeared to be oppositely affected by abscisic acid (ABA) signaling compared to the salt stress response. Natural variation in the response to the combination treatment of salt and Pi starvation within 330 Arabidopsis accessions could be grouped into four response patterns. When exposed to double stress, in general lateral roots prioritized responses to salt, while the effect on main root traits was additive. Interestingly, these patterns were not identical for all accessions studied and multiple strategies to integrate the signals from Pi deprivation and salinity were identified. By Genome Wide Association Mapping (GWAS) 13 genomic loci were identified as putative factors integrating responses to salt stress and Pi starvation. From our experiments, we conclude that Pi starvation interferes with salt responses mainly at the level of lateral roots and that large natural variation exists in the available genetic repertoire of accessions to handle the combination of stresses.

  1. Reperfusion does not induce oxidative stress but sustained endoplasmic reticulum stress in livers of rats subjected to traumatic-hemorrhagic shock.

    Science.gov (United States)

    Duvigneau, Johanna Catharina; Kozlov, Andrey V; Zifko, Clara; Postl, Astrid; Hartl, Romana T; Miller, Ingrid; Gille, Lars; Staniek, Katrin; Moldzio, Rudolf; Gregor, Wolfgang; Haindl, Susanne; Behling, Tricia; Redl, Heinz; Bahrami, Soheyl

    2010-03-01

    Oxidative stress is believed to accompany reperfusion and to mediate dysfunction of the liver after traumatic-hemorrhagic shock (THS). Recently, endoplasmic reticulum (ER) stress has been suggested as an additional factor. This study investigated whether reperfusion after THS leads to increased oxidative and/or ER stress in the liver. In a rat model, including laparotomy, bleeding until decompensation, followed by inadequate or adequate reperfusion phase, three time points were investigated: 40 min, 3 h, and 18 h after shock. The reactive oxygen and nitrogen species and its scavenging capacity (superoxide dismutase 2), the nitrotyrosine formation in proteins, and the lipid peroxidation together with the status of endogenous antioxidants (alpha-tocopherylquinone-alpha-tocopherol ratio) were investigated as markers for oxidative or nitrosylative stress. Mitochondrial function and cytochrome P450 isoform 1A1 activity were analyzed as representatives for hepatocyte function. Activation of the inositol-requiring enzyme 1/X-box binding protein pathway and up-regulation of the 78-kDa glucose-regulated protein were recorded as ER stress markers. Plasma levels of alanine aminotransferase and Bax/Bcl-XL messenger RNA (mRNA) ratio were used as indicators for hepatocyte damage and apoptosis induction. Oxidative or nitrosylative stress markers or representatives of hepatocyte function were unchanged during and short after reperfusion (40 min, 3 h after shock). In contrast, ER stress markers were elevated and paralleled those of hepatocyte damage. Incidence for sustained ER stress and subsequent apoptosis induction were found at 18 h after shock. Thus, THS or reperfusion induces early and persistent ER stress of the liver, independent of oxidative or nitrosylative stress. Although ER stress was not associated with depressed hepatocyte function, it may act as an early trigger of protracted cell death, thereby contributing to delayed organ failure after THS.

  2. Induction of time-dependent oxidative stress and related transcriptional effects of perfluorododecanoic acid in zebrafish liver

    Energy Technology Data Exchange (ETDEWEB)

    Liu Yang [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Beijing 100101 (China); Graduate School of the Chinese Academy of Sciences, Beijing 100080 (China); Wang Jianshe; Wei Yanhong; Zhang Hongxia; Xu Muqi [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Beijing 100101 (China); Dai Jiayin [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Beijing 100101 (China)], E-mail: daijy@ioz.ac.cn

    2008-09-29

    The effects of acute perfluorododecanoic acid (PFDoA) exposure on the induction of oxidative stress and alteration of mitochondrial gene expression were studied in the livers of female zebrafish (Danio rerio). Female zebrafish were exposed to PFDoA via a single intraperitoneal injection (0, 20, 40, or 80 {mu}g PFDoA/g body weight) and were then sacrificed 48 h, 96 h, or seven days post-PFDoA administration. PFDoA-treated fish exhibited histopathological liver damage, including swollen hepatocytes, vacuolar degeneration, and nuclei pycnosis. Glutathione (GSH) content and catalase (CAT) activity decreased significantly at 48 h post-injection while superoxide dismutase (SOD) activity was initially decreased at 48 h post-injection but was then elevated by seven days post-injection. The activity of glutathione peroxidase (GPx) increased at 48 h and seven days compared to control fish, although the increased level at seven days post-injection was decreased compared to the level at 48 h post-injection. Lipid peroxidation levels were increased at seven days post-injection, while no apparent induction was observed at 48 h or 96 h post-injection. The mRNA expression of medium-chain fatty acid dehydrogenase (MCAD) was induced, while the transcriptional expression of liver fatty acid binding protein (L-FABP), peroxisome proliferating activating receptor {alpha} (PPAR{alpha}), carnitine palmitoyl-transferase I (CPT-I), uncoupling protein 2 (UCP-2), and Bcl-2 were significantly inhibited. Furthermore, the transcriptional expression of peroxisomal fatty acyl-CoA oxidase (ACOX), very long-chain acyl-CoA dehydrogenase (VLCAD), long-chain acyl-CoA dehydrogenase (LCAD) did not exhibit significant changes following PFDoA treatment. No significant changes were noted in the transcriptional expression of genes involved in mitochondrial respiratory chain and ATP synthesis, including cytochrome c oxidase subunit I (COXI), NADH dehydrogenase subunit I (NDI), and ATP synthase F0 subunit 6

  3. Induction of time-dependent oxidative stress and related transcriptional effects of perfluorododecanoic acid in zebrafish liver

    International Nuclear Information System (INIS)

    Liu Yang; Wang Jianshe; Wei Yanhong; Zhang Hongxia; Xu Muqi; Dai Jiayin

    2008-01-01

    The effects of acute perfluorododecanoic acid (PFDoA) exposure on the induction of oxidative stress and alteration of mitochondrial gene expression were studied in the livers of female zebrafish (Danio rerio). Female zebrafish were exposed to PFDoA via a single intraperitoneal injection (0, 20, 40, or 80 μg PFDoA/g body weight) and were then sacrificed 48 h, 96 h, or seven days post-PFDoA administration. PFDoA-treated fish exhibited histopathological liver damage, including swollen hepatocytes, vacuolar degeneration, and nuclei pycnosis. Glutathione (GSH) content and catalase (CAT) activity decreased significantly at 48 h post-injection while superoxide dismutase (SOD) activity was initially decreased at 48 h post-injection but was then elevated by seven days post-injection. The activity of glutathione peroxidase (GPx) increased at 48 h and seven days compared to control fish, although the increased level at seven days post-injection was decreased compared to the level at 48 h post-injection. Lipid peroxidation levels were increased at seven days post-injection, while no apparent induction was observed at 48 h or 96 h post-injection. The mRNA expression of medium-chain fatty acid dehydrogenase (MCAD) was induced, while the transcriptional expression of liver fatty acid binding protein (L-FABP), peroxisome proliferating activating receptor α (PPARα), carnitine palmitoyl-transferase I (CPT-I), uncoupling protein 2 (UCP-2), and Bcl-2 were significantly inhibited. Furthermore, the transcriptional expression of peroxisomal fatty acyl-CoA oxidase (ACOX), very long-chain acyl-CoA dehydrogenase (VLCAD), long-chain acyl-CoA dehydrogenase (LCAD) did not exhibit significant changes following PFDoA treatment. No significant changes were noted in the transcriptional expression of genes involved in mitochondrial respiratory chain and ATP synthesis, including cytochrome c oxidase subunit I (COXI), NADH dehydrogenase subunit I (NDI), and ATP synthase F0 subunit 6 (ATPo6). These

  4. Response inhibition and cognitive appraisal in clients with acute stress disorder and posttraumatic stress disorder.

    Science.gov (United States)

    Abolghasemi, Abass; Bakhshian, Fereshteh; Narimani, Mohammad

    2013-08-01

    The purpose of the present study was to compare response inhibition and cognitive appraisal in clients with acute stress disorder, clients with posttraumatic stress disorder, and normal individuals. This was a comparative study. The sample consisted of 40 clients with acute stress disorder, 40 patients with posttraumatic stress disorder, and 40 normal individuals from Mazandaran province selected through convenience sampling method. Data were collected using Composite International Diagnostic Interview, Stroop Color-Word Test, Posttraumatic Cognitions Inventory, and the Impact of Event Scale. Results showed that individuals with acute stress disorder are less able to inhibit inappropriate responses and have more impaired cognitive appraisals compared to those with posttraumatic stress disorder. Moreover, results showed that response inhibition and cognitive appraisal explain 75% of the variance in posttraumatic stress disorder symptoms and 38% of the variance in posttraumatic stress disorder symptoms. The findings suggest that response inhibition and cognitive appraisal are two variables that influence the severity of posttraumatic stress disorder and acute stress disorder symptoms. Also, these results have important implications for pathology, prevention, and treatment of posttraumatic stress disorder and acute stress disorder.

  5. Response Inhibition and Cognitive Appraisal in Clients with Acute Stress Disorder and Posttraumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Abass Abolghasemi

    2013-09-01

    Full Text Available Objective: The purpose of the present study was to compare response inhibition and cognitive appraisal in clients with acute stress disorder, clients with posttraumatic stress disorder, and normal individuals .Method:This was a comparative study. The sample consisted of 40 clients with acute stress disorder, 40 patients with posttraumatic stress disorder, and 40 normal individuals from Mazandaran province selected through convenience sampling method. Data were collected using Composite International Diagnostic Interview, Stroop Color-Word Test, Posttraumatic Cognitions Inventory, and the Impact of Event Scale. Results:Results showed that individuals with acute stress disorder are less able to inhibit inappropriate responses and have more impaired cognitive appraisals compared to those with posttraumatic stress disorder. Moreover, results showed that response inhibition and cognitive appraisal explain 75% of the variance in posttraumatic stress disorder symptoms and 38% of the variance in posttraumatic stress disorder symptoms .Conclusion:The findings suggest that response inhibition and cognitive appraisal are two variables that influence the severity of posttraumatic stress disorder and acute stress disorder symptoms. Also, these results have important implications for pathology, prevention, and treatment of posttraumatic stress disorder and acute stress disorder

  6. Oxidative stress/reactive metabolite gene expression signature in rat liver detects idiosyncratic hepatotoxicants

    Energy Technology Data Exchange (ETDEWEB)

    Leone, Angelique; Nie, Alex; Brandon Parker, J.; Sawant, Sharmilee; Piechta, Leigh-Anne; Kelley, Michael F., E-mail: mkelley2@its.jnj.com; Mark Kao, L.; Jim Proctor, S.; Verheyen, Geert; Johnson, Mark D.; Lord, Peter G.; McMillian, Michael K.

    2014-03-15

    Previously we reported a gene expression signature in rat liver for detecting a specific type of oxidative stress (OS) related to reactive metabolites (RM). High doses of the drugs disulfiram, ethinyl estradiol and nimesulide were used with another dozen paradigm OS/RM compounds, and three other drugs flutamide, phenacetin and sulindac were identified by this signature. In a second study, antiepileptic drugs were compared for covalent binding and their effects on OS/RM; felbamate, carbamazepine, and phenobarbital produced robust OS/RM gene expression. In the present study, liver RNA samples from drug-treated rats from more recent experiments were examined for statistical fit to the OS/RM signature. Of all 97 drugs examined, in addition to the nine drugs noted above, 19 more were identified as OS/RM-producing compounds—chlorpromazine, clozapine, cyproterone acetate, dantrolene, dipyridamole, glibenclamide, isoniazid, ketoconazole, methapyrilene, naltrexone, nifedipine, sulfamethoxazole, tamoxifen, coumarin, ritonavir, amitriptyline, valproic acid, enalapril, and chloramphenicol. Importantly, all of the OS/RM drugs listed above have been linked to idiosyncratic hepatotoxicity, excepting chloramphenicol, which does not have a package label for hepatotoxicity, but does have a black box warning for idiosyncratic bone marrow suppression. Most of these drugs are not acutely toxic in the rat. The OS/RM signature should be useful to avoid idiosyncratic hepatotoxicity of drug candidates. - Highlights: • 28 of 97 drugs gave a positive OS/RM gene expression signature in rat liver. • The specificity of the signature for human idiosyncratic hepatotoxicants was 98%. • The sensitivity of the signature for human idiosyncratic hepatotoxicants was 75%. • The signature can help eliminate hepatotoxicants from drug development.

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

    Science.gov (United States)

    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. © 2015 The Author The Plant Journal © 2015 John Wiley & Sons Ltd.

  8. Impairment of Akt activity by CYP2E1 mediated oxidative stress is involved in chronic ethanol-induced fatty liver

    Directory of Open Access Journals (Sweden)

    Tao Zeng

    2018-04-01

    Full Text Available Protein kinase B (PKB/Akt plays important roles in the regulation of lipid homeostasis, and impairment of Akt activity has been demonstrated to be involved in the development of non-alcoholic fatty liver disease (NAFLD. Previous studies suggest that cytochrome P4502E1 (CYP2E1 plays causal roles in the pathogenesis of alcoholic fatty liver (AFL. We hypothesized that Akt activity might be impaired due to CYP2E1-induced oxidative stress in chronic ethanol-induced hepatic steatosis. In this study, we found that chronic ethanol-induced hepatic steatosis was accompanied with reduced phosphorylation of Akt at Thr308 in mice liver. Chronic ethanol exposure had no effects on the protein levels of phosphatidylinositol 3 kinase (PI3K and phosphatase and tensin homologue deleted on chromosome ten (PTEN, and led to a slight decrease of phosphoinositide-dependent protein kinase 1 (PDK-1 protein level. Ethanol exposure resulted in increased levels of malondialdehyde (MDA and 4-hydroxynonenal (4-HNE-Akt adducts, which was significantly inhibited by chlormethiazole (CMZ, an efficient CYP2E1 inhibitor. Interestingly, N-acetyl-L-cysteine (NAC significantly attenuated chronic ethanol-induced hepatic fat accumulation and the decline of Akt phosphorylation at Thr308. In the in vitro studies, Akt phosphorylation was suppressed in CYP2E1-expressing HepG2 (CYP2E1-HepG2 cells compared with the negative control HepG2 (NC-HepG2 cells, and 4-HNE treatment led to significant decrease of Akt phosphorylation at Thr308 in wild type HepG2 cells. Lastly, pharmacological activation of Akt by insulin-like growth factor-1 (IGF-1 significantly alleviated chronic ethanol-induced fatty liver in mice. Collectively, these results indicate that CYP2E1-induced oxidative stress may be responsible for ethanol-induced suppression of Akt phosphorylation and pharmacological modulation of Akt in liver may be an effective strategy for the treatment of ethanol-induced fatty liver. Keywords

  9. Nrf2 the rescue: Effects of the antioxidative/electrophilic response on the liver

    International Nuclear Information System (INIS)

    Klaassen, Curtis D.; Reisman, Scott A.

    2010-01-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that positively regulates the basal and inducible expression of a large battery of cytoprotective genes. These gene products include proteins that catalyze reduction reactions (NAD(P)H:quinone oxidoreductase 1, Nqo1), conjugation reactions (glutathione-S-transferases, Gsts and UDP-glucuronosyltransferases, Ugts), as well as the efflux of potentially toxic xenobiotics and xenobiotic conjugates (multidrug resistance-associated proteins, Mrps). The significance of Nrf2 in the liver has been established, as livers of Nrf2-null mice are more susceptible to various oxidative/electrophilic stress-induced pathologies than wild-type mice. In contrast, both pharmacological and genetic models of hepatic Nrf2 activation are protective against oxidative/electrophilic stress. Furthermore, because certain Nrf2-target genes in the liver could affect the distribution, metabolism, and excretion of xenobiotics, the effects of Nrf2 on the kinetics of drugs and other xenobiotics should also be considered, with a special emphasis on metabolism and excretion. Therefore, this review highlights the research that has contributed to the understanding of the importance of Nrf2 in toxicodynamics and toxicokinetics, especially that which pertains to the liver.

  10. Stretching the Stress Boundary: Linking Air Pollution Health Effects to a Neurohormonal Stress Response

    Science.gov (United States)

    Inhaled pollutants produce effects in virtually all organ systems in our body and have been linked to chronic diseases including hypertension, atherosclerosis, Alzheimer’s and diabetes. A neurohormonal stress response (referred here as a systemic response produced by activation ...

  11. Aging increases the susceptibility of hepatic inflammation, liver fibrosis and aging in response to high-fat diet in mice.

    Science.gov (United States)

    Kim, In Hee; Xu, Jun; Liu, Xiao; Koyama, Yukinori; Ma, Hsiao-Yen; Diggle, Karin; You, Young-Hyun; Schilling, Jan M; Jeste, Dilip; Sharma, Kumar; Brenner, David A; Kisseleva, Tatiana

    2016-08-01

    We aimed to investigate whether aging increases the susceptibility of hepatic and renal inflammation or fibrosis in response to high-fat diet (HFD) and explore the underlying genetic alterations. Middle (10 months old) and old (20 months old) aged, male C57BL/6N mice were fed either a low-fat diet (4 % fat) or HFD (60 % fat) for 4 months. Young (3 months old) aged mice were included as control group. HFD-induced liver and kidney injuries were analyzed by serum and urine assay, histologic staining, immunohistochemistry, and reverse-transcription real-time quantitative polymerase chain reaction. Total RNA sequencing with next-generation technology was done with RNA extracted from liver tissues. With HFD feeding, aged was associated with higher serum alanine aminotransferase levels, marked infiltration of hepatic macrophages, and increased expression of inflammatory cytokines (MCP1, TNF-α, IL-1β, IL-6, IL-12, IL-17A). Importantly, aged mice showed more advanced hepatic fibrosis and increased expression of fibrogenic markers (Col-I-α1, αSMA, TGF-β1, TGF-β2, TGFβRII, PDGF, PDGFRβII, TIMP1) in response to HFD. Aged mice fed on HFD also showed increased oxidative stress and TLR4 expression. In the total RNA seq and gene ontology analysis of liver, old-aged HFD group showed significant up-regulation of genes linked to innate immune response, immune response, defense response, inflammatory response compared to middle-aged HFD group. Meanwhile, aging and HFD feeding showed significant increase in glomerular size and mesangial area, higher urine albumin/creatinine ratio, and advanced renal inflammation or fibrosis. However, the difference of HFD-induced renal injury between old-aged group and middle-aged group was not significant. The susceptibility of hepatic fibrosis as well as hepatic inflammation in response to HFD was significantly increased with aging. In addition, aging was associated with glomerular alterations and increased renal inflammation or

  12. Sarcoptic mange in dogs: Its effect on liver, oxidative stress, trace minerals and vitamins.

    Science.gov (United States)

    Beigh, S A; Soodan, J S; Bhat, A M

    2016-08-30

    The present study was aimed to determine the effect on liver, associated oxidative stress, trace element and vitamin alteration in dogs with sarcoptic mange. A total of 24 dogs with clinically established diagnosis of sarcoptic mange, divided into two groups, severely infested group (n=9) and mild/moderately infested group (n=15), according to the extent of skin lesions caused by sarcoptic mange and 6 dogs as control group were included in the present study. In comparison to healthy control hemoglobin, PCV, and TEC were significantly (Pdogs with sarcoptic mange however, significant increase in TLC along with neutrophilia and lymphopenia was observed only in severely infested dogs. The albumin, glucose and cholesterol were significantly (Pdogs when compared to other two groups. Malondialdehyde (MDA) levels were significantly (Pdogs with sarcoptic mange, with levels highest in severely infested groups. Activity of superoxide dismutase (SOD) (Psarcoptic infested dogs when compared with the healthy control group. Zinc and copper levels in dogs with sarcoptic mange were significantly (Psarcoptic infested dogs when compared to healthy control. From the present study, it was concluded that sarcoptic mange in dogs affects the liver and the infestation is associated with oxidant/anti-oxidant imbalance, significant alteration in trace elements and vitamins. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Baicalin Ameliorates Experimental Liver Cholestasis in Mice by Modulation of Oxidative Stress, Inflammation, and NRF2 Transcription Factor

    Directory of Open Access Journals (Sweden)

    Kezhen Shen

    2017-01-01

    Full Text Available Experimental cholestatic liver fibrosis was performed by bile duct ligation (BDL in mice, and significant liver injury was observed in 15 days. Administration of baicalin in mice significantly ameliorates liver fibrosis. Experimental cholestatic liver fibrosis was associated with induced gene expression of fibrotic markers such as collagen I, fibronectin, alpha smooth muscle actin (SMA, and connective tissue growth factor (CTGF; increased inflammatory cytokines (TNFα, MIP1α, IL1β, and MIP2; increased oxidative stress and reactive oxygen species- (ROS- inducing enzymes (NOX2 and iNOS; dysfunctional mitochondrial electron chain complexes; and apoptotic/necrotic cell death markers (DNA fragmentation, caspase 3 activity, and PARP activity. Baicalin administration on alternate day reduced fibrosis along with profibrotic gene expression, proinflammatory cytokines, oxidative stress, and cell death whereas improving the function of mitochondrial electron transport chain. We observed baicalin enhanced NRF2 activation by nuclear translocation and induced its target genes HO-1 and GCLM, thus enhancing antioxidant defense. Interplay of oxidative stress/inflammation and NRF2 were key players for baicalin-mediated protection. Stellate cell activation is crucial for initiation of fibrosis. Baicalin alleviated stellate cell activation and modulated TIMP1, SMA, collagen 1, and fibronectin in vitro. This study indicates that baicalin might be beneficial for reducing inflammation and fibrosis in liver injury models.

  14. Low-level shear stress promotes migration of liver cancer stem cells via the FAK-ERK1/2 signalling pathway.

    Science.gov (United States)

    Sun, Jinghui; Luo, Qing; Liu, Lingling; Song, Guanbin

    2018-07-28

    Cancer stem cells (CSCs) are a small subpopulation of tumour cells that have been proposed to be responsible for cancer initiation, chemotherapy resistance and cancer recurrence. Shear stress activated cellular signalling is involved in cellular migration, proliferation and differentiation. However, little is known about the effects of shear stress on the migration of liver cancer stem cells (LCSCs). Here, we studied the effects of shear stress that are generated from a parallel plated flow chamber system, on LCSC migration and the activation of focal adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2), using transwell assay and western blot, respectively. We found that 2 dyne/cm 2 shear stress loading for 6 h promotes LCSC migration and activation of the FAK and ERK1/2 signalling pathways, whereas treatment with the FAK phosphorylation inhibitor PF573228 or the ERK1/2 phosphorylation inhibitor PD98059 suppressed the shear stress-promoted migration, indicating the involvement of FAK and ERK1/2 activation in shear stress-induced LCSC migration. Additionally, atomic force microscopy (AFM) analysis showed that shear stress lowers LCSC stiffness via the FAK and ERK1/2 pathways, suggesting that the mechanism by which shear stress promotes LCSC migration might partially be responsible for the decrease in cell stiffness. Further experiments focused on the role of the actin cytoskeleton, demonstrating that the F-actin filaments in LCSCs are less well-defined after shear stress treatment, providing an explanation for the reduction in cell stiffness and the promotion of cell migration. Overall, our study demonstrates that shear stress promotes LCSC migration through the activation of the FAK-ERK1/2 signalling pathways, which further results in a reduction of organized actin and softer cell bodies. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Response of rocks to large stresses

    International Nuclear Information System (INIS)

    Schock, R.N.

    1976-01-01

    To predict the dimensions and characteristics of impact- and explosion-induced craters, one must know the equation of state of the rocks in which the crater is formed. Recent experimental data shed light upon inelastic processes that influence the stress/strain behavior of rocks. We examine these data with a view to developing models that could be used in predicting cratering phenomena. New data is presented on the volume behavior of two dissimilar rocks subjected to tensile stresses

  16. Pyrethroid insecticide lambda-cyhalothrin and its metabolites induce liver injury through the activation of oxidative stress and proinflammatory gene expression in rats following acute and subchronic exposure.

    Science.gov (United States)

    Aouey, Bakhta; Derbali, Mohamed; Chtourou, Yassine; Bouchard, Michèle; Khabir, Abdelmajid; Fetoui, Hamadi

    2017-02-01

    Lambda-cyhalothrin (LTC) [α-cyano-3-phenoxybenzyl-3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclo-propanecarboxylate] is a synthetic type II pyrethroid insecticide commonly used in residential and agricultural areas. The potential hepatotoxicity of pyrethroids remains unclear and could easily be assessed by measuring common clinical indicators of liver disease. To understand more about the potential risks for humans associated with LTC exposure, male adult rats were orally exposed to 6.2 and 31.1 mg/kg bw of LTC for 7, 30, 45, and 60 days. Histopathological changes and alterations of main parameters related to oxidative stress and inflammatory responses in the liver were evaluated. Further, lambda-cyhalothrin metabolites [3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropane carboxylic acid (CFMP), 4-hydroxyphenoxybenzoic acid (4-OH-3-PBA), and 3-phenoxybenzoic acid (3-PBA)] in the liver tissues were identified and quantified by ultra-high-performance liquid chromatography coupled to quadripole time-of-flight mass spectrometry (UHPLC-MS-Q-ToF). Results revealed that LTC exposure significantly increased markers of hepatic oxidative stress in a time-dependent and dose-dependent manner, and this was associated with an accumulation of CFMP and 3-PBA in the liver tissues. In addition, the levels of tumor necrosis factor-α (TNF-α) and interleukin (IL-6 and IL-1β) gene expressions were significantly increased in the liver of exposed rats compared to controls. Correlation analyses revealed that CFMP and 3-PBA metabolite levels in the liver tissues were significantly correlated with the indexes of oxidative stress, redox status, and inflammatory markers in rats exposed to lambda-cyhalothin. Overall, this study provided novel evidence that hepatic damage is likely due to increased oxidative stress and inflammation under the condition of acute and subchronic exposure to lambda-cyhalothrin and that LTC metabolites (CFMP and 3-PBA) could be used as

  17. Obesity, lipid profiles and oxidative stress in children after liver transplantation.

    Science.gov (United States)

    Czubkowski, Piotr; Wierzbicka, Aldona; Pawłowska, Joanna; Jankowska, Irena; Socha, Piotr

    2017-01-01

    In adult liver transplant recipients, coronary artery disease and congestive heart failure are significant cause of morbidity and mortality. This may be attributed to the long-term immunosuppressive treatment, mostly with calcineurin inhibitors and steroids, which in long-term may be associated with hyperlipidemia, oxidative stress and cardiovascular complications. Since such data for children is sparse, the aim of this study was to assess the lipid and oxidative stress markers after pediatric liver transplantation (LTx). We performed prospective analysis of 74 children, at the median age of 7.9 (2.8-11.6) years, 3.2 (1.2-4.3) years after LTx. We assessed the BMI Z-scores, cholesterol fractions (LDLc, HDLc, VLDLc), triglicerides, apolipoproteins (ApoAI, ApoB, ApoE), LCAT, insulin resistance by HOMA-IR and markers of oxidative stress and atherosclerosis: glutathione (GSH), glutathione peroxidase (GPx), asymmetrical dimethyl arginine (ADMA) and oxidized low-density lipoprotein (oxyLDL). At baseline, the results were compared with a healthy age-and-sex matched control group. After 3.1±0.3 year follow-up we repeated all investigations and compared them with the baseline results. At the baseline, we investigated 74 patients 3.2 (1.2-4.3) years after LTx, at the median age of 7.9 (2.8-11.6) years. The prevalence of overweight or obesity (BMI >85 th percentile) was 23% and was more common in girls (24% vs 20%). Fourteen patients had TCH >200 mg%, 9 patients had LDLc >130 mg% and TG were at normal levels in all patients. Compared to the controls, there were no significant differences in lipid profiles but we found decreased GSH (p95 th and >85 Th percentile was present in 8% and 14% respectively. ADMA and oxyLDL decreased, whilst GSH and GPx increased when compared to the baseline. There was also significant decrease in apoB and Lp(a). Children after LTx had normal lipid profiles when compared to controls, however there is a tendency for hypercholesterolemia and obesity

  18. Troxerutin protects against 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD{sup +}-depletion

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zi-Feng [School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, 101 Shanghai Road, Xuzhou 221116, Jiangsu Province (China); Zhang, Yan-qiu [School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Fan, Shao-Hua [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, 101 Shanghai Road, Xuzhou 221116, Jiangsu Province (China); Zhuang, Juan [School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Zheng, Yuan-Lin, E-mail: ylzheng@jsnu.edu.cn [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, 101 Shanghai Road, Xuzhou 221116, Jiangsu Province (China); Lu, Jun; Wu, Dong-Mei; Shan, Qun; Hu, Bin [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, 101 Shanghai Road, Xuzhou 221116, Jiangsu Province (China)

    2015-02-11

    Highlights: • BDE-47 promotes liver inflammation by triggering oxidative stress-induced NAD{sup +} depletion. • Troxerutin inhibits BDE-47-induced liver inflammation via its antioxidant properties. • Troxerutin restores NAD{sup +} level and consequently abates SirT1 loss. • Troxerutin represses acetylation of NF-κB p65 (K310) and H3K9. • Troxerutin is a candidate for prevention and therapy of BDE-47-induced hepatotoxicity. - Abstract: Emerging evidence indicates that 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) induces liver injury through enhanced ROS production and lymphocytic infiltration, which may promote a liver inflammatory response. Antioxidants have been reported to attenuate the cellular toxicity associated with polybrominated diphenyl ethers (PBDEs). In this study, we investigated the effect of troxerutin, a trihydroxyethylated derivative of the natural bioflavonoid rutin, on BDE-47-induced liver inflammation and explored the potential mechanisms underlying this effect. Our results showed that NAD{sup +}-depletion was involved in the oxidative stress-mediated liver injury in a BDE-47 treated mouse model, which was confirmed by Vitamin E treatment. Furthermore, our data revealed that troxerutin effectively alleviated liver inflammation by mitigating oxidative stress-mediated NAD{sup +}-depletion in BDE-47 treated mice. Consequently, troxerutin remarkably restored SirT1 protein expression and activity in the livers of BDE-47-treated mice. Mechanistically, troxerutin dramatically repressed the nuclear translocation of NF-κB p65 and the acetylation of NF-κB p65 (Lys 310) and Histone H3 (Lys9) to abate the transcription of inflammatory genes in BDE-47-treated mouse livers. These inhibitory effects of troxerutin were markedly blunted by EX527 (SirT1 inhibitor) treatment. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that troxerutin might be used in the prevention and therapy of BDE-47-induced

  19. The significance of translation regulation in the stress response

    OpenAIRE

    Picard, Flora; Loubière, Pascal; Girbal, Laurence; Bousquet, Muriel

    2013-01-01

    Background: The stress response in bacteria involves the multistage control of gene expression but is not entirely understood. To identify the translational response of bacteria in stress conditions and assess its contribution to the regulation of gene expression, the translational states of all mRNAs were compared under optimal growth condition and during nutrient (isoleucine) starvation. Results: A genome-scale study of the translational response to nutritional limitation was performed in t...

  20. Associations between circadian and stress response cortisol in children

    OpenAIRE

    Simons, S.S.H.; Cillessen, A.H.N.; Weerth, C. de

    2017-01-01

    Hypothalamic-pituitary-adrenal (HPA) axis functioning is characterized by the baseline production of cortisol following a circadian rhythm, as well as by the superimposed production of cortisol in response to a stressor. However, it is relatively unknown whether the basal cortisol circadian rhythm is associated with the cortisol stress response in children. Since alterations in cortisol stress responses have been associated with mental and physical health, this study investigated whether the ...

  1. Effects of acupuncture on the citrate and glucose metabolism in the liver under various types of stress

    International Nuclear Information System (INIS)

    Liao, Y.Y.; Seto, K.; Saito, H.; Kawakami, M.

    1980-01-01

    A study was made of the effect of acupuncture on citrate and glucose metabolism in the liver in terms of incorporation of 14 C-1, 5-citric acid and 14 C-u-glucose in some metabolites. The effect of acupuncture on citrate metabolism in the liver under control conditions was such as to increase production of G and reduce that of KB, FC and FFA. No effect of acupuncture on glucose metabolism in the liver under such conditions was observed. Both citrate and glucose metabolism were affected to a marked extent by immobilization stress or exposure to heat or cold. The deleterious effect of these types of stress was less prominent in animals receiving acupuncture at the Tsu-San-Li locus than in those treated otherwise or receiving no treatment

  2. Effects of acupuncture on the citrate and glucose metabolism in the liver under various types of stress

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Y.Y.; Seto, K.; Saito, H.; Kawakami, M.

    A study was made of the effect of acupuncture on citrate and glucose metabolism in the liver in terms of incorporation of /sup 14/C-1, 5-citric acid and /sup 14/C-u-glucose in some metabolites. The effect of acupuncture on citrate metabolism in the liver under control conditions was such as to increase production of G and reduce that of KB, FC and FFA. No effect of acupuncture on glucose metabolism in the liver under such conditions was observed. Both citrate and glucose metabolism were affected to a marked extent by immobilization stress or exposure to heat or cold. The deleterious effect of these types of stress was less prominent in animals receiving acupuncture at the Tsu-San-Li locus than in those treated otherwise or receiving no treatment.

  3. Predictors of responses to stress among families coping with poverty-related stress.

    Science.gov (United States)

    Santiago, Catherine DeCarlo; Etter, Erica Moran; Wadsworth, Martha E; Raviv, Tali

    2012-05-01

    This study tested how poverty-related stress (PRS), psychological distress, and responses to stress predicted future effortful coping and involuntary stress responses one year later. In addition, we explored age, sex, ethnicity, and parental influences on responses to stress over time. Hierarchical linear modeling analyses conducted with 98 low-income families (300 family members: 136 adults, 82 school-aged children, 82 adolescents) revealed that primary control coping, secondary control coping, disengagement, involuntary engagement, and involuntary disengagement each significantly predicted future use of that response. Primary and secondary control coping also predicted less maladaptive future responses to stress, while involuntary responses to stress undermined the development of adaptive responding. Age, sex, and interactions among PRS and prior coping were also found to predict certain responses to stress. In addition, child subgroup analyses demonstrate the importance of parental modeling of coping and involuntary stress responses, and warmth/nurturance and monitoring practices. Results are discussed with regard to the implications for preventive interventions with families in poverty.

  4. Metformin prevents ischemia reperfusion-induced oxidative stress in the fatty liver by attenuation of reactive oxygen species formation

    Czech Academy of Sciences Publication Activity Database

    Cahová, M.; Páleníčková, E.; Danková, H.; Sticová, E.; Burian, M.; Drahota, Zdeněk; Červinková, Z.; Kučera, O.; Gladkova, Ch.; Stopka, Pavel; Křížová, Jana; Papáčková, Z.; Oliyarnyk, O.; Kazdová, L.

    2015-01-01

    Roč. 309, č. 2 (2015), G100-G111 ISSN 0193-1857 R&D Projects: GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 ; RVO:61388980 Keywords : metformin * oxidative stress * mitochondrial respiration * liver injury * 31P MR spectroscopy Subject RIV: EB - Genetics ; Molecular Biology; CA - Inorganic Chemistry (UACH-T) Impact factor: 3.297, year: 2015

  5. Functional role of monocytes and macrophages for the inflammatory response in acute liver injury

    Directory of Open Access Journals (Sweden)

    Henning W Zimmermann

    2012-10-01

    Full Text Available Different etiologies such as drug toxicity, acute viral hepatitis B or acetaminophen poisoning can cause acute liver injury (ALI or even acute liver failure (ALF. Excessive cell death of hepatocytes in the liver is known to result in a strong hepatic inflammation. Experimental murine models of liver injury highlighted the importance of hepatic macrophages, so-called Kupffer cells, for initiating and driving this inflammatory response by releasing proinflammatory cytokines and chemokines including tumor necrosis factor (TNF, interleukin-6 (IL-6, IL-1-beta or monocyte chemoattractant protein 1 (MCP-1, CCL2 as well as activating other non-parenchymal liver cells, e.g. endothelial or hepatic stellate cells (HSC. Many of these proinflammatory mediators can trigger hepatocytic cell death pathways, e.g. via caspase activation, but also activate protective signaling pathways, e.g. via nuclear factor kappa B (NF-kB. Recent studies in mice demonstrated that these macrophage actions largely depend on the recruitment of monocytes into the liver, namely of the inflammatory Ly6c+ (Gr1+ monocyte subset as precursors of tissue macrophages. The chemokine receptor CCR2 and its ligand MCP-1/CCL2 promote monocyte subset infiltration upon liver injury. In contrast, the chemokine receptor CX3CR1 and its ligand fractalkine (CX3CL1 are important negative regulators of monocyte infiltration by controlling their survival and differentiation into functionally diverse macrophage subsets upon injury. The recently identified cellular and molecular pathways for monocyte subset recruitment, macrophage differentiation and interactions with other hepatic cell types in the injured liver may therefore represent interesting novel targets for future therapeutic approaches in ALF.

  6. Salinity-dependent nickel accumulation and oxidative stress responses in the euryhaline killifish (Fundulus heteroclitus).

    Science.gov (United States)

    Blewett, Tamzin A; Wood, Chris M

    2015-02-01

    The mechanisms of nickel (Ni) toxicity in marine fish remain unclear, although evidence from freshwater (FW) fish suggests that Ni can act as a pro-oxidant. This study investigated the oxidative stress effects of Ni on the euryhaline killifish (Fundulus heteroclitus) as a function of salinity. Killifish were exposed to sublethal levels (5, 10, and 20 mg L(-1)) of waterborne Ni for 96 h in FW (0 ppt) and 100 % saltwater (SW) (35 ppt). In general, SW was protective against both Ni accumulation and indicators of oxidative stress [protein carbonyl formation and catalase (CAT) activity]. This effect was most pronounced at the highest Ni exposure level. For example, FW intestine showed increased Ni accumulation relative to SW intestine at 20 mg Ni L(-1), and this was accompanied by significantly greater protein carbonylation and CAT activity in this tissue. There were exceptions, however, in that although liver of FW killifish at the highest exposure concentration showed greater Ni accumulation relative to SW liver, levels of CAT activity were greatly decreased. This may relate to tissue- and salinity-specific differences in oxidative stress responses. The results of the present study suggest (1) that there was Ni-induced oxidative stress in killifish, (2) that the effects of salinity depend on differences in the physiology of the fish in FW versus SW, and (3) that increased levels of cations (sodium, calcium, potassium, and magnesium) and anions (SO4 and Cl) in SW are likely protective against Ni accumulation in tissues exposed to the aquatic environment.

  7. Hormonal modulation of the heat shock response: insights from fish with divergent cortisol stress responses

    DEFF Research Database (Denmark)

    LeBlanc, Sacha; Höglund, Erik; Gilmour, Kathleen M.

    2012-01-01

    shock response, we capitalized on two lines of rainbow trout specifically bred for their high (HR) and low (LR) cortisol response to stress. We predicted that LR fish, with a low cortisol but high catecholamine response to stress, would induce higher levels of HSPs after acute heat stress than HR trout....... We found that HR fish have significantly higher increases in both catecholamines and cortisol compared with LR fish, and LR fish had no appreciable stress hormone response to heat shock. This unexpected finding prevented further interpretation of the hormonal modulation of the heat shock response...

  8. RNA-seq analysis of early hepatic response to handling and confinement stress in rainbow trout.

    Directory of Open Access Journals (Sweden)

    Sixin Liu

    Full Text Available Fish under intensive rearing conditions experience various stressors which have negative impacts on survival, growth, reproduction and fillet quality. Identifying and characterizing the molecular mechanisms underlying stress responses will facilitate the development of strategies that aim to improve animal welfare and aquaculture production efficiency. In this study, we used RNA-seq to identify transcripts which are differentially expressed in the rainbow trout liver in response to handling and confinement stress. These stressors were selected due to their relevance in aquaculture production. Total RNA was extracted from the livers of individual fish in five tanks having eight fish each, including three tanks of fish subjected to a 3 hour handling and confinement stress and two control tanks. Equal amount of total RNA of six individual fish was pooled by tank to create five RNA-seq libraries which were sequenced in one lane of Illumina HiSeq 2000. Three sequencing runs were conducted to obtain a total of 491,570,566 reads which were mapped onto the previously generated stress reference transcriptome to identify 316 differentially expressed transcripts (DETs. Twenty one DETs were selected for qPCR to validate the RNA-seq approach. The fold changes in gene expression identified by RNA-seq and qPCR were highly correlated (R(2 = 0.88. Several gene ontology terms including transcription factor activity and biological process such as glucose metabolic process were enriched among these DETs. Pathways involved in response to handling and confinement stress were implicated by mapping the DETs to reference pathways in the KEGG database.Raw RNA-seq reads have been submitted to the NCBI Short Read Archive under accession number SRP022881.All customized scripts described in this paper are available from Dr. Guangtu Gao or the corresponding author.

  9. Z α-1 antitrypsin deficiency and the endoplasmic reticulum stress response.

    LENUS (Irish Health Repository)

    Greene, Catherine M

    2010-10-06

    The serine proteinase inhibitor α-1 antitrypsin (AAT) is produced principally by the liver at the rate of 2 g\\/d. It is secreted into the circulation and provides an antiprotease protective screen throughout the body but most importantly in the lung, where it can neutralise the activity of the serine protease neutrophil elastase. Mutations leading to deficiency in AAT are associated with liver and lung disease. The most notable is the Z AAT mutation, which encodes a misfolded variant of the AAT protein in which the glutamic acid at position 342 is replaced by a lysine. More than 95% of all individuals with AAT deficiency carry at least one Z allele. ZAAT protein is not secreted effectively and accumulates intracellularly in the endoplasmic reticulum (ER) of hepatocytes and other AAT-producing cells. This results in a loss of function associated with decreased circulating and intrapulmonary levels of AAT. However, the misfolded protein acquires a toxic gain of function that impacts on the ER. A major function of the ER is to ensure correct protein folding. ZAAT interferes with this function and promotes ER stress responses and inflammation. Here the signalling pathways activated during ER stress in response to accumulation of ZAAT are described and therapeutic strategies that can potentially relieve ER stress are discussed.

  10. Plant Core Environmental Stress Response Genes Are Systemically Coordinated during Abiotic Stresses

    Directory of Open Access Journals (Sweden)

    Kenneth W. Berendzen

    2013-04-01

    Full Text Available Studying plant stress responses is an important issue in a world threatened by global warming. Unfortunately, comparative analyses are hampered by varying experimental setups. In contrast, the AtGenExpress abiotic stress experiment displays intercomparability. Importantly, six of the nine stresses (wounding, genotoxic, oxidative, UV-B light, osmotic and salt can be examined for their capacity to generate systemic signals between the shoot and root, which might be essential to regain homeostasis in Arabidopsis thaliana. We classified the systemic responses into two groups: genes that are regulated in the non-treated tissue only are defined as type I responsive and, accordingly, genes that react in both tissues are termed type II responsive. Analysis of type I and II systemic responses suggest distinct functionalities, but also significant overlap between different stresses. Comparison with salicylic acid (SA and methyl-jasmonate (MeJA responsive genes implies that MeJA is involved in the systemic stress response. Certain genes are predominantly responding in only one of the categories, e.g., WRKY genes respond mainly non-systemically. Instead, genes of the plant core environmental stress response (PCESR, e.g., ZAT10, ZAT12, ERD9 or MES9, are part of different response types. Moreover, several PCESR genes switch between the categories in a stress-specific manner.

  11. Pomegranate protects liver against cecal ligation and puncture-induced oxidative stress and inflammation in rats through TLR4/NF-κB pathway inhibition.

    Science.gov (United States)

    Makled, Mirhan N; El-Awady, Mohammed S; Abdelaziz, Rania R; Atwan, Nadia; Guns, Emma T; Gameil, Nariman M; Shehab El-Din, Ahmed B; Ammar, Elsayed M

    2016-04-01

    Acute liver injury secondary to sepsis is a major challenge in intensive care unit. This study was designed to investigate potential protective effects of pomegranate against sepsis-induced acute liver injury in rats and possible underlying mechanisms. Pomegranate was orally given (800mg/kg/day) for two weeks before sepsis induction by cecal ligation and puncture (CLP). Pomegranate improved survival and attenuated liver inflammatory response, likely related to downregulation of mRNA expression of toll like recptor-4, reduced nuclear translocation and DNA binding activity of proinflammatory transcription factor NF-κB subunit p65, decreased mRNA and protein expression of tumor necrosis factor-alpha and reduction in myeloperoxidase activity and mRNA expression. Pomegranate also decreased CLP-induced oxidative stress as reflected by decreased malondialdehyde content, and increased reduced glutathione level and superoxide dismutase activity. These results confirm the antiinflammatory and antioxidant effects of pomegranate in CLP-induced acute liver injury mediated through inhibiting TLR4/NF-κB pathway, lipid peroxidation and neutrophil infiltration. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Breviscapine ameliorates CCl4‑induced liver injury in mice through inhibiting inflammatory apoptotic response and ROS generation.

    Science.gov (United States)

    Liu, Yu; Wen, Pei-Hao; Zhang, Xin-Xue; Dai, Yang; He, Qiang

    2018-05-02

    Acute liver injury is characterized by fibrosis, inflammation and apoptosis, leading to liver failure, cirrhosis or cancer and affecting the clinical outcome in the long term. However, no effective therapeutic strategy is currently available. Breviscapine, a mixture of flavonoid glycosides, has been reported to have multiple biological functions. The present study aimed to investigate the effects of breviscapine on acute liver injury induced by CCl4 in mice. C57BL/6 mice were subjected to intraperitoneal injection with CCl4 for 8 weeks with or without breviscapine (15 or 30 mg/kg). Mice treated with CCl4 developed acute liver injury, as evidenced by histological analysis, Masson trichrome and Sirius Red staining, accompanied with elevated levels of alanine aminotransferase and aspartate aminotransferase. Furthermore, increases in pro‑inflammatory cytokines, chemokines and apoptotic factors, including caspase‑3 and poly(ADP ribose) polymerase‑2 (PARP‑2), were observed. Breviscapine treatment significantly and dose‑dependently reduced collagen deposition and the fibrotic area. Inflammatory cytokines were downregulated by breviscapine through inactivating Toll‑like receptor 4/nuclear factor-κB signaling pathways. In addition, co‑administration of breviscapine with CCl4 decreased the apoptotic response by enhancing B‑cell lymphoma-2 (Bcl‑2) levels, while reducing Bcl‑2‑associated X protein, apoptotic protease activating factor 1, caspase‑3 and PARP activity. Furthermore, CCl4‑induced oxidative stress was blocked by breviscapine through improving anti‑oxidants and impeding mitogen‑activated protein kinase pathways. The present study highlighted that breviscapine exhibited liver‑protective effects against acute hepatic injury induced by CCl4 via suppressing inflammation and apoptosis.

  13. Stress Generation and Adolescent Depression: Contribution of Interpersonal Stress Responses

    Science.gov (United States)

    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…

  14. Seasonal variations of cellular stress response of the gilthead sea bream (Sparus aurata).

    Science.gov (United States)

    Feidantsis, Konstantinos; Antonopoulou, Efthimia; Lazou, Antigone; Pörtner, Hans O; Michaelidis, Basile

    2013-07-01

    The present study aimed to investigate the seasonal cellular stress response in vital organs, like the heart, the liver, the whole blood and the skeletal (red and white) muscles of the Mediterranean fish Sparus aurata during a 1-year acclimatization period in the field, in two examined depths (0-2 m and 10-12 m). Processes studied included heat shock protein expression and protein kinase activation. Molecular responses were addressed through the expression of Hsp70 and Hsp90, the phosphorylation of stress-activated protein kinases and particularly p38 mitogen-activated protein kinase (p38 MAPK), the extracellular signal-regulated kinases (ERK-1/2) and c-Jun N-terminal kinases (JNK1/2/3). The induction of Hsp70 and Hsp90 and the phosphorylation of p38 MAPK, JNKs and ERKs in the examined five tissues of the gilthead sea bream indicated a cellular stress response under the prism of a seasonal pattern which was characterized by distinct tissue specificity. Specifically, Hsp induction and MAPK activation occurred before peak summer water temperatures, with no further increases in their levels despite increases in water temperatures. Moreover, although water temperature did not vary significantly with depth of immersion, significant effects of depth on cellular stress response were observed, probably caused by different light regime. The expression and the activation of these certain proteins can be used as tools to define the extreme thermal limits of the gilthead sea bream.

  15. Oxidative stress response after laparoscopic versus conventional sigmoid resection

    DEFF Research Database (Denmark)

    Madsen, Michael Tvilling; Kücükakin, Bülent; Lykkesfeldt, Jens

    2012-01-01

    Surgery is accompanied by a surgical stress response, which results in increased morbidity and mortality. Oxidative stress is a part of the surgical stress response. Minimally invasive laparoscopic surgery may result in reduced oxidative stress compared with open surgery. Nineteen patients...... scheduled for sigmoid resection were randomly allocated to open or laparoscopic sigmoid resection in a double-blind, prospective clinical trial. Three biochemical markers of oxidative stress (malondialdehyde, ascorbic acid, and dehydroascorbic acid) were measured at 6 different time points (preoperatively......, 1 h, 6 h, 24 h, 48 h, and 72 h postoperatively). There were no statistical significant differences between laparoscopic and open surgery for any of the 3 oxidative stress parameters. Malondialdehyde was reduced 1 hour postoperatively (P...

  16. Plant transcriptomics and responses to environmental stress

    Indian Academy of Sciences (India)

    Atta-ur-Rehman School of Applied Biosciences, National University of Sciences and Technology, H-12 Campus, Islamabad 25000, Pakistan; Stress Physiology Lab Department of Botany, Jiwaji University, Gwalior 474 011, India; Centre for Environmental Research, Near East University, 33010, Lefkosha, Turkish Republic ...

  17. The relationship between personality and the response to acute psychological stress

    NARCIS (Netherlands)

    Xin, Yuanyuan; Wu, Jianhui; Yao, Zhuxi; Guan, Qing; Aleman, Andre; Luo, Yuejia

    2017-01-01

    The present study examined the relationship between personality traits and the response to acute psychological stress induced by a standardized laboratory stress induction procedure (the Trier Social Stress Test, TSST). The stress response was measured with a combination of cardiovascular

  18. Cell Wall Metabolism in Response to Abiotic Stress

    Science.gov (United States)

    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

  19. Branched-Chain Amino Acid Supplementation Reduces Oxidative Stress and Prolongs Survival in Rats with Advanced Liver Cirrhosis

    Science.gov (United States)

    Mifuji-Moroka, Rumi; Hara, Nagisa; Miyachi, Hirohide; Sugimoto, Ryosuke; Tanaka, Hideaki; Fujita, Naoki; Gabazza, Esteban C.; Takei, Yoshiyuki

    2013-01-01

    Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (PBCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver. PMID:23936183

  20. Branched-chain amino acid supplementation reduces oxidative stress and prolongs survival in rats with advanced liver cirrhosis.

    Directory of Open Access Journals (Sweden)

    Motoh Iwasa

    Full Text Available Long-term supplementation with branched-chain amino acids (BCAA is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05. The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver.

  1. Stevia Prevents Acute and Chronic Liver Injury Induced by Carbon Tetrachloride by Blocking Oxidative Stress through Nrf2 Upregulation

    Science.gov (United States)

    Ramos-Tovar, Erika; Hernández-Aquino, Erika; Casas-Grajales, Sael; Buendia-Montaño, Laura D.; Tsutsumi, Víctor

    2018-01-01

    The effect of stevia on liver cirrhosis has not been previously investigated. In the present study, the antioxidant and anti-inflammatory properties of stevia leaves were studied in male Wistar rats with carbon tetrachloride- (CCl4-) induced acute and chronic liver damage. Acute and chronic liver damage induced oxidative stress, necrosis, and cholestasis, which were significantly ameliorated by stevia. Chronic CCl4 treatment resulted in liver cirrhosis, as evidenced by nodules of hepatocytes surrounded by thick bands of collagen and distortion of the hepatic architecture, and stevia significantly prevented these alterations. Subsequently, the underlying mechanism of action of the plant was analyzed. Our study for the first time shows that stevia upregulated Nrf2, thereby counteracting oxidative stress, and prevented necrosis and cholestasis through modulation of the main proinflammatory cytokines via NF-κB inhibition. These multitarget mechanisms led to the prevention of experimental cirrhosis. Given the reasonable safety profile of stevia, our results indicated that it may be useful for the clinical treatment of acute and chronic liver diseases. PMID:29849889

  2. Review of Signal Crosstalk in Plant Stress Responses

    Science.gov (United States)

    This book was prepared to summarize the current understanding of the dynamics of plant response to biotic and abiotic stresses. The preface of the book sets the stage for the contents of the different chapters by outlining that plants defend themselves from various environmental stresses through a v...

  3. Cellular stress responses for monitoring and modulating ageing

    DEFF Research Database (Denmark)

    Demirovic, Dino; Schnebert, Sylvianne; Nizard, Carine

    2013-01-01

    biochemical methods, detecting one or more proteins exclusively involved in the specific stress response pathways. The results indicate that the ageing phenotype is a result of an ineffective probability for cells to respond to stress. http://dx.doi.org/10.1016/j.freeradbiomed.2013.08.023...

  4. Personality, Stressful Life Events, and Treatment Response in Major Depression

    Science.gov (United States)

    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…

  5. Psychological and hormonal stress response patterns during a blood donation

    NARCIS (Netherlands)

    Hoogerwerf, M. D.; Veldhuizen, I. J. T.; Merz, E.-M.; de Kort, W. L. A. M.; Frings-Dresen, M. H. W.; Sluiter, J. K.

    2017-01-01

    Background and ObjectivesDonating blood has been associated with increased stress responses, with scarce evidence indicating that levels of psychological and hormonal stress are higher pre-donation than post-donation. We investigated whether a blood donation induces psychological and/or hormonal

  6. Differentiating anticipatory from reactive cortisol responses to psychosocial stress

    NARCIS (Netherlands)

    Engert, V.; Efanov, S.I.; Duchesne, A.; Vogel, S.; Corbo, V.; Pruessner, J.C.

    2013-01-01

    Most psychosocial stress studies assess the overall cortisol response without further identifying the temporal dynamics within hormone levels. It has been shown, however, that the amplitude of anticipatory cortisol stress levels has a unique predictive value for psychological health. So far, no

  7. Plant responsiveness to root-root communication of stress cues.

    Science.gov (United States)

    Falik, Omer; Mordoch, Yonat; Ben-Natan, Daniel; Vanunu, Miriam; Goldstein, Oron; Novoplansky, Ariel

    2012-07-01

    Phenotypic plasticity is based on the organism's ability to perceive, integrate and respond to multiple signals and cues informative of environmental opportunities and perils. A growing body of evidence demonstrates that plants are able to adapt to imminent threats by perceiving cues emitted from their damaged neighbours. Here, the hypothesis was tested that unstressed plants are able to perceive and respond to stress cues emitted from their drought- and osmotically stressed neighbours and to induce stress responses in additional unstressed plants. Split-root Pisum sativum, Cynodon dactylon, Digitaria sanguinalis and Stenotaphrum secundatum plants were subjected to osmotic stress or drought while sharing one of their rooting volumes with an unstressed neighbour, which in turn shared its other rooting volume with additional unstressed neighbours. Following the kinetics of stomatal aperture allowed testing for stress responses in both the stressed plants and their unstressed neighbours. In both P. sativum plants and the three wild clonal grasses, infliction of osmotic stress or drought caused stomatal closure in both the stressed plants and in their unstressed neighbours. While both continuous osmotic stress and drought induced prolonged stomatal closure and limited acclimation in stressed plants, their unstressed neighbours habituated to the stress cues and opened their stomata 3-24 h after the beginning of stress induction. The results demonstrate a novel type of plant communication, by which plants might be able to increase their readiness to probable future osmotic and drought stresses. Further work is underway to decipher the identity and mode of operation of the involved communication vectors and to assess the potential ecological costs and benefits of emitting and perceiving drought and osmotic stress cues under various ecological scenarios.

  8. Understanding the Posttranscriptional Regulation of Plant Responses to Abiotic Stress

    KAUST Repository

    Alshareef, Sahar

    2017-01-01

    Constitutive and alternative splicing of pre-mRNAs from multiexonic genes controls the diversity of the proteome; these precisely regulated processes also fine-tune responses to cues related to growth, development, and biotic and abiotic stresses

  9. Psychological distress, cortisol stress response and subclinical coronary calcification

    NARCIS (Netherlands)

    Seldenrijk, A.; Hamer, M.; Lahiri, A.; Penninx, B.W.J.H.; Steptoe, A.

    2012-01-01

    Objectives: Poor mental health has been associated with coronary heart disease (CHD). One hypothesized underlying mechanism is hypothalamus pituitary adrenal axis dysfunction. We examined the associations between psychological distress, cortisol response to laboratory-induced mental stress and

  10. Plant natriuretic peptides are apoplastic and paracrine stress response molecules

    KAUST Repository

    Wang, Yuhua; Gehring, Christoph A; Irving, Helen R.

    2011-01-01

    plant stress responses and that, much like in animals, peptide signaling molecules can create diverse and modular signals essential for growth, development and defense under rapidly changing environmental conditions. © 2011 The Author.

  11. Stress responses during ageing: molecular pathways regulating protein homeostasis.

    Science.gov (United States)

    Kyriakakis, Emmanouil; Princz, Andrea; Tavernarakis, Nektarios

    2015-01-01

    The ageing process is characterized by deterioration of physiological function accompanied by frailty and ageing-associated diseases. The most broadly and well-studied pathways influencing ageing are the insulin/insulin-like growth factor 1 signaling pathway and the dietary restriction pathway. Recent studies in diverse organisms have also delineated emerging pathways, which collectively or independently contribute to ageing. Among them the proteostatic-stress-response networks, inextricably affect normal ageing by maintaining or restoring protein homeostasis to preserve proper cellular and organismal function. In this chapter, we survey the involvement of heat stress and endoplasmic reticulum stress responses in the regulation of longevity, placing emphasis on the cross talk between different response mechanisms and their systemic effects. We further discuss novel insights relevant to the molecular pathways mediating these stress responses that may facilitate the development of innovative interventions targeting age-related pathologies such as diabetes, cancer, cardiovascular and neurodegenerative diseases.

  12. Herboxidiene triggers splicing repression and abiotic stress responses in plants

    KAUST Repository

    Alshareef, Sahar; Ling, Yu; Butt, Haroon; Mariappan, Kiruthiga G.; Benhamed, Moussa; Mahfouz, Magdy M.

    2017-01-01

    Constitutive and alternative splicing of pre-mRNAs from multiexonic genes controls the diversity of the proteome; these precisely regulated processes also fine-tune responses to cues related to growth, development, and stresses. Small

  13. Partial deletion of argininosuccinate synthase protects from pyrazole plus lipopolysaccharide-induced liver injury by decreasing nitrosative stress

    Science.gov (United States)

    Lu, Yongke; Leung, Tung Ming; Ward, Stephen C.

    2012-01-01

    Argininosuccinate synthase (ASS) is the rate-limiting enzyme in the urea cycle. Along with nitric oxide synthase (NOS)-2, ASS endows cells with the l-citrulline/nitric oxide (NO·) salvage pathway to continually supply l-arginine from l-citrulline for sustained NO· generation. Because of the relevant role of NOS in liver injury, we hypothesized that downregulation of ASS could decrease the availability of intracellular substrate for NO· synthesis by NOS-2 and, hence, decrease liver damage. Previous work demonstrated that pyrazole plus LPS caused significant liver injury involving NO· generation and formation of 3-nitrotyrosine protein adducts; thus, wild-type (WT) and Ass+/− mice (Ass−/− mice are lethal) were treated with pyrazole plus LPS, and markers of nitrosative stress, as well as liver injury, were analyzed. Partial ablation of Ass protected from pyrazole plus LPS-induced liver injury by decreasing nitrosative stress and hepatic and circulating TNFα. Moreover, apoptosis was prevented, since pyrazole plus LPS-treated Ass+/− mice showed decreased phosphorylation of JNK; increased MAPK phosphatase-1, which is known to deactivate JNK signaling; and lower cleaved caspase-3 than treated WT mice, and this was accompanied by less TdT-mediated dUTP nick end labeling-positive staining. Lastly, hepatic neutrophil accumulation was almost absent in pyrazole plus LPS-treated Ass+/− compared with WT mice. Partial Ass ablation prevents pyrazole plus LPS-mediated liver injury by reducing nitrosative stress, TNFα, apoptosis, and neutrophil infiltration. PMID:22052013

  14. ABA signaling in stress-response and seed development.

    Science.gov (United States)

    Nakashima, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2013-07-01

    KEY MESSAGE : We review the recent progress on ABA signaling, especially ABA signaling for ABA-dependent gene expression, including the AREB/ABF regulon, SnRK2 protein kinase, 2C-type protein phosphatases and ABA receptors. Drought negatively impacts plant growth and the productivity of crops. Drought causes osmotic stress to organisms, and the osmotic stress causes dehydration in plant cells. Abscisic acid (ABA) is produced under osmotic stress conditions, and it plays an important role in the stress response and tolerance of plants. ABA regulates many genes under osmotic stress conditions. It also regulates gene expression during seed development and germination. The ABA-responsive element (ABRE) is the major cis-element for ABA-responsive gene expression. ABRE-binding protein (AREB)/ABRE-binding factor (ABF) transcription factors (TFs) regulate ABRE-dependent gene expression. Other TFs are also involved in ABA-responsive gene expression. SNF1-related protein kinases 2 are the key regulators of ABA signaling including the AREB/ABF regulon. Recently, ABA receptors and group A 2C-type protein phosphatases were shown to govern the ABA signaling pathway. Moreover, recent studies have suggested that there are interactions between the major ABA signaling pathway and other signaling factors in stress-response and seed development. The control of the expression of ABA signaling factors may improve tolerance to environmental stresses.

  15. Effects of Delta-tocotrienol Supplementation on Liver Enzymes, Inflammation, Oxidative stress and Hepatic Steatosis in Patients with Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Pervez, Muhammad Amjad; Khan, Dishad Ahmet; Ijaz, Aamir; Khan, Shamrez

    2018-03-01

    Non-alcoholic fatty liver disease (NAFLD) is a growing public health problem worldwide and is associated with increased morbidity and mortality. Currently, there is no definitive treatment for this disease. δ-Tocotrienol has potent anti-inflammatory and antioxidant properties and may reduce liver injury in NAFLD. The present study aims to evaluate the efficacy and safety of δ-tocotrienol in the treatment of NAFLD. The present study was a randomized, double-blind, placebo-controlled pilot study conducted in patients aged > 20 years, belonging to both sexes, having ultrasound-proven fatty liver disease, having a fatty liver index (FLI) of ≥ 60, and persistent elevation of alanine transaminase. A total of 71 patients were assigned to receive either oral δ-tocotrienol (n=35, 300 mg twice daily) or placebo (n=36) for 12 weeks. At the baseline and at the end of the study, clinical and biochemical parameters, including lipid profile, liver function tests, high-sensitivity C-reactive protein (hs-CRP), and malondialdehyde (MDA) were measured. Body mass index and FLI were calculated, and ultrasound grading of hepatic steatosis was performed. Out of 71 enrolled patients, 64 patients, 31 in the δ-tocotrienol group and 33 in the placebo group, completed the study. After 12 weeks of supplementation, δ-tocotrienol showed greater efficacy than placebo by decreasing serum aminotransferases, hs-CRP, MDA, and FLI score (phepatic steatosis on ultrasound examination. No adverse effects were reported. δ-Tocotrienol was safe, and it effectively improved aminotransferase levels and inflammatory and oxidative stress markers in patients with NAFLD. Large-scale randomized clinical trials are warranted to further support these findings.

  16. Extra virgin olive oil reduces liver oxidative stress and tissue depletion of long-chain polyunsaturated fatty acids produced by a high saturated fat diet in mice

    Energy Technology Data Exchange (ETDEWEB)

    Valenzuela, B.R.; Hernandez Rodas, M.C.; Espinosa, A.; Rincon Cervera, M.A.; Romero, N.; Barrera Vazquez, C.; Marambio, M.; Vivero, J.; Valenzuela, B.A.

    2016-07-01

    Long-chain polyunsaturated fatty acids (LCPUFA) which are synthesized mainly in the liver have relevant functions in the organism. A diet high in fat (HFD) generates an increase in the levels of fat and induces oxidative stress (lipo-peroxidation) in the liver, along with a reduction in tissue n-3 and n-6 LCPUFA. Extra virgin olive oil (EVOO) is rich in anti-oxidants (polyphenols and tocopherols) which help to prevent the development of oxidative stress. This study evaluated the role of EVOO in preventing the induction of fat deposition and oxidative stress in the liver and in the depletion of LCPUFA in the liver, erythrocytes and brain generated by a HFD in C57BL/6J mice. Four experimental groups (n = 10/group) were fed a control diet (CD) or a HFD for 12 weeks and were respectively supplemented with EVOO (100 mg/day). The group fed HFD showed a significant increase (p < 0.05) in fat accumulation and oxidative stress in the liver, accompanied by a reduction in the levels of n-3 and n-6 LCPUFA in the liver, erythrocytes and brain. Supplementation with EVOO mitigated the increase in fat and oxidative stress produced by HFD in the liver, along with a normalization of LCPUFA levels in the liver, erythrocytes and brain. It is proposed that EVOO supplementation protects against fat accumulation, and oxidative stress and normalizes n-3 and n-6 LCPUFA depletion induced in mice fed a HFD. (Author)

  17. Plant Responses to Abiotic Stress Regulated by Histone Deacetylases

    Directory of Open Access Journals (Sweden)

    Ming Luo

    2017-12-01

    Full Text Available In eukaryotic cells, histone acetylation and deacetylation play an important role in the regulation of gene expression. Histone acetylation levels are modulated by histone acetyltransferases and histone deacetylases (HDACs. Recent studies indicate that HDACs play essential roles in the regulation of gene expression in plant response to environmental stress. In this review, we discussed the recent advance regarding the plant HDACs and their functions in the regulation of abiotic stress responses. The role of HDACs in autophagy was also discussed.

  18. Stress Response and Artemisinin Resistance in Malaria Parasite

    Science.gov (United States)

    2017-07-01

    AWARD NUMBER: W81XWH-16-1-0241 TITLE: Stress Response and Artemisinin Resistance in Malaria Parasite PRINCIPAL INVESTIGATOR: Juan C. Pizarro...SUBTITLE Stress Response and Artemisinin Resistance in Malaria Parasite 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0241 5c. PROGRAM ELEMENT...13. SUPPLEMENTARY NOTES 14. ABSTRACT In malaria , drug resistance is a major treat to disease control efforts. Unfortunately, there is a significant

  19. When does stress help or harm? The effects of stress controllability and subjective stress response on stroop performance.

    Science.gov (United States)

    Henderson, Roselinde K; Snyder, Hannah R; Gupta, Tina; Banich, Marie T

    2012-01-01

    The ability to engage in goal-directed behavior despite exposure to stress is critical to resilience. Questions of how stress can impair or improve behavioral functioning are important in diverse settings, from athletic competitions to academic testing. Previous research suggests that controllability is a key factor in the impact of stress on behavior: learning how to control stressors buffers people from the negative effects of stress on subsequent cognitively demanding tasks. In addition, research suggests that the impact of stress on cognitive functioning depends on an individual's response to stressors: moderate responses to stress can lead to improved performance while extreme (high or low) responses can lead to impaired performance. The present studies tested the hypothesis that (1) learning to behaviorally control stressors leads to improved performance on a test of general executive functioning, the color-word Stroop, and that (2) this improvement emerges specifically for people who report moderate (subjective) responses to stress. Experiment 1: Stroop performance, measured before and after a stress manipulation, was compared across groups of undergraduate participants (n = 109). People who learned to control a noise stressor and received accurate performance feedback demonstrated reduced Stroop interference compared with people exposed to uncontrollable noise stress and feedback indicating an exaggerated rate of failure. In the group who learned behavioral control, those who reported moderate levels of stress showed the greatest reduction in Stroop interference. In contrast, in the group exposed to uncontrollable events, self-reported stress failed to predict performance. Experiment 2: In a second sample (n = 90), we specifically investigated the role of controllability by keeping the rate of failure feedback constant across groups. In the group who learned behavioral control, those who reported moderate levels of stress showed the greatest Stroop

  20. Context and strain-dependent behavioral response to stress

    Directory of Open Access Journals (Sweden)

    Baum Amber E

    2008-06-01

    Full Text Available Abstract 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.

  1. Responses to Fiscal Stress: A Comparative Analysis

    Science.gov (United States)

    2013-12-01

    of “a significant decline in market share by the middle of the 20th century as travelers and shippers turned increasingly to airlines, trucks, and...1995). Intercity passenger rail: Financial and operating conditions threaten Amtrak’s long-term viability (GAO-95-71). Washington, DC: U.S...I. (1980). Retrenchment and flexibility in public organizations. Fiscal Stress and Public Policy, 159–178. Scheinberg, P. F. (1998). Intercity

  2. Radiation and Heat Stress Impact on Plasma Levels of Thyroid Hormones, Lipid Fractions, Glucose and Liver Glycogen in rats

    International Nuclear Information System (INIS)

    Abdel-Fattah, K.I.; Abou-Safi, H.M.

    2003-01-01

    Since Egypt is classified as a hot country, the present work has been directed to study the combined effect of heat stress and gamma radiation exposure on blood thyroid hormonal levels and some other parameters. Four groups of rats were served as: control, whole-body gamma irradiated (6Gy), exposed to ambient heat stress (38 C-40 C) and a group exposed to heat stress and irradiation. Four time intervals 1, 3, 5 and 7 days were determined for heat stress or exposure to heat followed by irradiation. Blood samples and liver specimens were taken at the end of each time interval in the third group and after one hour of irradiation in the second and fourth groups. To detect the radiation effects after the different periods of heat stress, plasma levels of thyroid hormones (T3 and T4), lipid fractions (triglycerides, total cholesterol, HDL- and LDL-cholesterol), glucose and liver glycogen content were determined. The results revealed that exposure to heat and ionizing radiation leads to a decrease in the levels of thyroid hormones, which was mostly pronounced in the T3 levels. Plasma glucose levels showed significant elevations in both, the heat-stressed group and the heat-treated then irradiated group. While, liver glycogen content exhibited similar elevations only during the 1st, 3 rd and 5 th days of heating followed by irradiation treatment as compared to the heat stressed group. Yet, it showed significant declines in comparison with both control and irradiated groups. Enormous increments in all determined plasma lipid fractions were induced by heat stress and / or gamma radiation

  3. Association Between Insulin Resistance and Oxidative Stress Parameters in Obese Adolescents with Non-Alcoholic Fatty Liver Disease

    OpenAIRE

    Pirgon, ?zg?r; Bilgin, H?seyin; ?ekmez, Ferhat; Kurku, H?seyin; D?ndar, Bumin Nuri

    2013-01-01

    Objective: Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in children. The aim of this study was to investigate the associations of oxidative stress with insulin resistance and metabolic risk factors in obese adolescents with NAFLD. Methods: Forty-six obese adolescents (23 girls and 23 boys, mean age: 12.8?2.2 years) and 29 control subjects (15 girls and 14 boys, mean age: 12.7?2.7 years) were enrolled in the study. The obese subjects were d...

  4. Stress and Bronchodilator Response in Children with Asthma.

    Science.gov (United States)

    Brehm, John M; Ramratnam, Sima K; Tse, Sze Man; Croteau-Chonka, Damien C; Pino-Yanes, Maria; Rosas-Salazar, Christian; Litonjua, Augusto A; Raby, Benjamin A; Boutaoui, Nadia; Han, Yueh-Ying; Chen, Wei; Forno, Erick; Marsland, Anna L; Nugent, Nicole R; Eng, Celeste; Colón-Semidey, Angel; Alvarez, María; Acosta-Pérez, Edna; Spear, Melissa L; Martinez, Fernando D; Avila, Lydiana; Weiss, Scott T; Soto-Quiros, Manuel; Ober, Carole; Nicolae, Dan L; Barnes, Kathleen C; Lemanske, Robert F; Strunk, Robert C; Liu, Andrew; London, Stephanie J; Gilliland, Frank; Sleiman, Patrick; March, Michael; Hakonarson, Hakon; Duan, Qing Ling; Kolls, Jay K; Fritz, Gregory K; Hu, Donglei; Fani, Negar; Stevens, Jennifer S; Almli, Lynn M; Burchard, Esteban G; Shin, Jaemin; McQuaid, Elizabeth L; Ressler, Kerry; Canino, Glorisa; Celedón, Juan C

    2015-07-01

    Stress is associated with asthma morbidity in Puerto Ricans (PRs), who have reduced bronchodilator response (BDR). To examine whether stress and/or a gene regulating anxiety (ADCYAP1R1) is associated with BDR in PR and non-PR children with asthma. This was a cross-sectional study of stress and BDR (percent change in FEV1 after BD) in 234 PRs ages 9-14 years with asthma. We assessed child stress using the Checklist of Children's Distress Symptoms, and maternal stress using the Perceived Stress Scale. Replication analyses were conducted in two cohorts. Polymorphisms in ADCYAP1R1 were genotyped in our study and six replication studies. Multivariable models of stress and BDR were adjusted for age, sex, income, environmental tobacco smoke, and use of inhaled corticosteroids. High child stress was associated with reduced BDR in three cohorts. PR children who were highly stressed (upper quartile, Checklist of Children's Distress Symptoms) and whose mothers had high stress (upper quartile, Perceived Stress Scale) had a BDR that was 10.2% (95% confidence interval, 6.1-14.2%) lower than children who had neither high stress nor a highly stressed mother. A polymorphism in ADCYAP1R1 (rs34548976) was associated with reduced BDR. This single-nucleotide polymorphism is associated with reduced expression of the gene for the β2-adrenergic receptor (ADRB2) in CD4(+) lymphocytes of subjects with asthma, and it affects brain connectivity of the amygdala and the insula (a biomarker of anxiety). High child stress and an ADCYAP1R1 single-nucleotide polymorphism are associated with reduced BDR in children with asthma. This is likely caused by down-regulation of ADRB2 in highly stressed children.

  5. Effect of previous exposure to hbv on liver histology and treatment response in chc patients

    International Nuclear Information System (INIS)

    Khan, H.A.

    2015-01-01

    Objective: To analyze the influence of previous exposure to HBV on liver histology and treatment outcomes in chronic hepatitis C (CHC) patients. Study Design: Case control study. Place and Duration of Study: Rawalian Liver Clinic, Department of Medicine, Holy Family Hospital, Rawalpindi, from January 2011 to December 2012. Methodology: Medical records of CHC patients attending the Rawalian Liver Clinic were retrospectively analyzed. Virological and treatment responses along with histological changes were compared between cases (anti-HBc positive) and controls (anti-HBc negative). Significance was determined through chi-square test at p < 0.05. Results: Among the 592 CHC patients, 254 (42.9%) had serological evidence of a positive anti-HBc (cases) and 338 (57.1%), patients had negative anti-HBc (controls). No significant difference was found between ETR, SVR and treatment responses (n=220) between the two groups. Out of 65 patients whose liver biopsy data was available, cases were more likely to respond in the absence of fibrosis (63.2%, (n=24) vs. 36.8%, (n=14), p=0.001). The controls responded more in the presence of fibrosis (100% (n=9) vs. 0, p=0.001). There was no significant effect of anti-HBc positivity on grades of inflammation and consequent treatment response (p=0.14). Conclusion: There are a significant number of CHC patients with markers of previous HBV infection in Pakistani population. Previous HBV (anti-HBc positive) does not seem to have an adverse effect on liver histology and treatment responses in HBV infection. (author)

  6. Interaction between nanoparticles generated by zinc chloride treatment and oxidative responses in rat liver

    Directory of Open Access Journals (Sweden)

    Azzouz I

    2013-12-01

    Full Text Available Inès Azzouz, Hamdi Trabelsi, Amel Hanini, Soumaya Ferchichi, Olfa Tebourbi, Mohsen Sakly, Hafedh AbdelmelekLaboratory of Integrative Physiology, Faculty of Sciences of Bizerte, Carthage University, TunisiaAbstract: The aim of the present study was to investigate the interaction of zinc chloride (3 mg/kg, intraperitoneally [ip] in rat liver in terms of the biosynthesis of nanoparticles. Zinc treatment increased zinc content in rat liver. Analysis of fluorescence revealed the presence of red fluorescence in the liver following zinc treatment. Interestingly, the co-exposure to zinc (3 mg/kg, ip and selenium (0.20 mg/L, per os [by mouth] led to a higher intensity of red fluorescence compared to zinc-treated rats. In addition, X-ray diffraction measurements carried out on liver fractions of zinc-treated rats point to the biosynthesis of zinc sulfide and/or selenide nanocomplexes at nearly 51.60 nm in size. Moreover, co-exposure led to nanocomplexes of about 72.60 nm in size. The interaction of zinc with other mineral elements (S, Se generates several nanocomplexes, such as ZnS and/or ZnSe. The nanocomplex ZnX could interact directly with enzyme activity or indirectly by the disruption of mineral elements' bioavailability in cells. Subacute zinc or selenium treatment decreased malondialdehyde levels, indicating a drop in lipid peroxidation. In addition, antioxidant enzyme assays showed that treatment with zinc or co-treatment with zinc and selenium increased the activities of glutathione peroxidase, catalase, and superoxide dismutase. Consequently, zinc complexation with sulfur and/or selenium at nanoscale level could enhance antioxidative responses, which is correlated to the ratio of number of ZnX nanoparticles (X=sulfur or X=selenium to malondialdehyde level in rat liver.Keywords: nanocomplexes biosynthesis, antioxidative responses, X-ray diffraction, fluorescence microscopy, liver

  7. Recent Molecular Advances on Downstream Plant Responses to Abiotic Stress

    Directory of Open Access Journals (Sweden)

    Cláudia Regina Batista de Souza

    2012-07-01

    Full Text Available Abiotic stresses such as extremes of temperature and pH, high salinity and drought, comprise some of the major factors causing extensive losses to crop production worldwide. Understanding how plants respond and adapt at cellular and molecular levels to continuous environmental changes is a pre-requisite for the generation of resistant or tolerant plants to abiotic stresses. In this review we aimed to present the recent advances on mechanisms of downstream plant responses to abiotic stresses and the use of stress-related genes in the development of genetically engineered crops.

  8. Heart rate variability response to mental arithmetic stress in patients with schizophrenia Autonomic response to stress in schizophrenia

    NARCIS (Netherlands)

    Castro, Mariana N.; Vigo, Daniel E.; Weidema, Hylke; Fahrer, Rodolfo D.; Chu, Elvina M.; De Achaval, Delfina; Nogues, Martin; Leiguarda, Ramon C.; Cardinali, Daniel P.; Guinjoan, Salvador N.

    Background: The vulnerability-stress hypothesis is an established model of schizophrenia symptom formation. We sought to characterise the pattern of the cardiac autonomic response to mental arithmetic stress in patients with stable schizophrenia. Methods: We performed heart rate variability (HRV)

  9. Comfort food is comforting to those most stressed: evidence of the chronic stress response network in high stress women.

    Science.gov (United States)

    Tomiyama, A Janet; Dallman, Mary F; Epel, Elissa S

    2011-11-01

    Chronically stressed rodents who are allowed to eat calorie-dense "comfort" food develop greater mesenteric fat, which in turn dampens hypothalamic-pituitary-adrenocortical (HPA) axis activity. We tested whether similar relations exist in humans, at least cross-sectionally. Fifty-nine healthy premenopausal women were exposed to a standard laboratory stressor to examine HPA response to acute stress and underwent diurnal saliva sampling for basal cortisol and response to dexamethasone administration. Based on perceived stress scores, women were divided into extreme quartiles of low versus high stress categories. We found as hypothesized that the high stress group had significantly greater BMI and sagittal diameter, and reported greater emotional eating. In response to acute lab stressor, the high stress group showed a blunted cortisol response, lower diurnal cortisol levels, and greater suppression in response to dexamethasone. These cross-sectional findings support the animal model, which suggests that long-term adaptation to chronic stress in the face of dense calories result in greater visceral fat accumulation (via ingestion of calorie-dense food), which in turn modulates HPA axis response, resulting in lower cortisol levels. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Modulation of immune responses in stress by Yoga

    Directory of Open Access Journals (Sweden)

    Arora Sarika

    2008-01-01

    Full Text Available 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.

  11. Sex differences in the stress response in SD rats.

    Science.gov (United States)

    Lu, Jing; Wu, Xue-Yan; Zhu, Qiong-Bin; Li, Jia; Shi, Li-Gen; Wu, Juan-Li; Zhang, Qi-Jun; Huang, Man-Li; Bao, Ai-Min

    2015-05-01

    Sex differences play an important role in depression, the basis of which is an excessive stress response. We aimed at revealing the neurobiological sex differences in the same study in acute- and chronically-stressed rats. Female Sprague-Dawley (SD) rats were randomly divided into 6 groups: chronic unpredictable mild stress (CUMS), acute foot shock (FS) and controls, animals in all 3 groups were sacrificed in proestrus or diestrus. Male SD rats were randomly divided into 3 groups: CUMS, FS and controls. Comparisons were made of behavioral changes in CUMS and control rats, plasma levels of corticosterone (CORT), testosterone (T) and estradiol (E2), and of the hypothalamic mRNA-expression of stress-related molecules, i.e. estrogen receptor α and β, androgen receptor, aromatase, mineralocorticoid receptor, glucocorticoid receptor, corticotropin-releasing hormone, arginine vasopressin and oxytocin. CUMS resulted in disordered estrus cycles, more behavioral and hypothalamic stress-related molecules changes and a stronger CORT response in female rats compared with male rats. Female rats also showed decreased E2 and T levels after FS and CUMS, while male FS rats showed increased E2 and male CUMS rats showed decreased T levels. Stress affects the behavioral, endocrine and the molecular response of the stress systems in the hypothalamus of SD rats in a clear sexual dimorphic way, which has parallels in human data on stress and depression. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Physiological stress response patterns during a blood donation.

    Science.gov (United States)

    Hoogerwerf, M D; Veldhuizen, I J T; Tarvainen, M P; Merz, E-M; Huis In 't Veld, E M J; de Kort, W L A M; Sluiter, J K; Frings-Dresen, M H W

    2018-03-24

    Donating blood is associated with increased psychological stress. This study investigates whether a blood donation induces physiological stress and if response patterns differ by gender, donation experience and non-acute stress. In 372 donors, physiological stress [blood pressure, pulse rate, pulse rate variability (PRV)] was measured at seven moments during routine donation. PRV was assessed using time domain [root mean square of successive differences (RMSSD)] and frequency domain [high frequency (HF) and low frequency (LF) power] parameters. Non-acute stress was assessed by questionnaire. Shape and significance of time course patterns were assessed by fitting multilevel models for each stress measure and comparing men and women, first-time and experienced donors, and donors with high and low levels of non-acute stress. Significant response patterns were found for all stress measures, where levels of systolic blood pressure (F(1,1315) = 24·2, P blood pressure (F(1,1326) = 50·9, P blood pressure/pulse rate in women; higher pulse rate in first-time donors; higher RMSSD at arrival and from screening until leaving in first-time donors; and higher LF and HF in first-time donors. This study shows an increase in physiological stress related to needle insertion, followed by a decrease when leaving the donation centre. Some group effects were also found. © 2018 International Society of Blood Transfusion.

  13. When does stress help or harm? The effects of stress controllability and subjective stress response on Stroop performance.

    Directory of Open Access Journals (Sweden)

    Roselinde Kaiser Henderson

    2012-06-01

    Full Text Available The ability to engage in goal-directed behavior despite exposure to stress is critical to resilience. Questions of how stress can impair or improve behavioral functioning are important in diverse settings, from athletic competitions to academic testing to clinical therapy. Previous research suggests that controllability is a key factor in the impact of stress on behavior: learning how to control stressors buffers people from the negative effects of stress on subsequent cognitively demanding tasks. In addition, research suggests that the impact of stress on cognitive functioning depends on an individual’s response to stressors: moderate responses to stress can lead to improved performance while extreme (high or low responses can lead to impaired performance. The present studies tested the hypothesis that 1 learning to behaviorally control stressors leads to improved performance on a test of general executive functioning, the color-word Stroop, and that 2 this improvement emerges specifically for people who report moderate (subjective responses to stress. Experiment 1: Stroop performance, measured before and after a stress manipulation, was compared across groups of undergraduate participants (n=109. People who learned to control a noise stressor and received accurate performance feedback demonstrated reduced Stroop interference compared with people exposed to uncontrollable noise stress and feedback indicating an exaggerated rate of failure. In the group who learned behavioral control, those who reported moderate levels of stress showed the greatest reduction in Stroop interference. In contrast, in the group exposed to uncontrollable events, self-reported stress failed to predict performance. Experiment 2: In a second sample (n=90, we specifically investigated the role of controllability by keeping the rate of failure feedback constant across groups. In the group who learned behavioral control, those who reported moderate levels of stress

  14. Critical-like features of stress response in frictional packings

    International Nuclear Information System (INIS)

    Cakir, Abdullah; Silbert, Leonardo E

    2015-01-01

    The mechanical response of static, unconfined, overcompressed face centred cubic, granular arrays is studied using large-scale, discrete element method simulations. Specifically, the stress response due to the application of a localised force perturbation—the Green function technique—is obtained in granular packings generated over several orders of magnitude in both the particle friction coefficient and the applied forcing. We observe crossover behaviour in the mechanical state of the system characterised by the changing nature of the resulting stress response. The transition between anisotropic and isotropic stress response exhibits critical-like features through the identification of a diverging length scale that distinguishes the spatial extent of anisotropic regions from those that display isotropic behaviour. A multidimensional phase diagram is constructed that parameterises the response of the system due to changing friction and force perturbations. (paper)

  15. Biochemical liver function test parameter levels in relation to treatment response in liver metastatic colorectal patients treated with FOLFOX4 with or without bevacizumab

    Directory of Open Access Journals (Sweden)

    Denić Kristina

    2016-01-01

    Full Text Available Introduction. Combined use of bevacizumab and conventional anticancer drugs leads to a significant improvement of treatment response in patients with metastatic colorectal carcinoma (CRC. Conventional treatment protocols exert undesired effects on the liver tissue. Hepatotoxic effects are manifested as a disturbance of liver function test parameters. The relation between clinical outcome and disorder of biochemical parameters has not been completely evaluated. Objective. The objective of our study was to examine whether clinical outcome in patients with liver metastatic CRC correlates with the level of liver function test parameters. Methods. The study included 96 patients with untreated liver metastatic CRC who received FOLFOX4 protocol with or without bevacizumab. Biochemical liver parameters were performed before and after the treatment completion. Treatment response was evaluated as disease regression, stable disease, and disease progression. The patients were divided into three groups according to the accomplished treatment response. Results. In the group of patients with disease regression the post-treatment levels of aspartate aminotransferase, alanine aminotransferase, and bilirubin were statistically significantly increased. In contrast to this, gamma-glutamyltransferase and protein post-treatment values were significantly lower in relation to initial values. In patients with stable disease, difference was found only in the level of proteins being lower after the treatment. In patients with disease progression, values of aspartate aminotransferase and bilirubin were significantly increased after completed treatment. Conclusion. Treatment responses are not completely associated with the level of liver function test parameters. The only parameter which correlated with treatment response is gamma-glutamyltransferase. Its decrease is accompanied with disease regression.

  16. In adenosine A2B knockouts acute treatment with inorganic nitrate improves glucose disposal, oxidative stress and AMPK signaling in the liver

    Directory of Open Access Journals (Sweden)

    Maria ePeleli

    2015-08-01

    Full Text Available Rationale: Accumulating studies suggest that nitric oxide (NO deficiency and oxidative stress are central pathological mechanisms in type 2 diabetes. Recent findings demonstrate therapeutic effects by boosting a nitrate-nitrite-NO pathway, an alternative pathway for NO formation. This study aimed at investigating the acute effects of inorganic nitrate on glucose and insulin signaling in adenosine A2B receptor knockout mice (A2B-/-, a genetic model of impaired metabolic regulation.Methods: Acute effects of nitrate treatment were investigated in aged wild-type (WT and A2B-/- mice. One hour after injection with nitrate or placebo, metabolic regulation was evaluated by glucose and insulin tolerance tests. NADPH oxidase-mediated superoxide production and AMPK phosphorylation were measured in livers obtained from non-treated or glucose-treated mice, with or without prior nitrate injection. Plasma was used to determine insulin resistance (HOMA-IR and NO signaling.Results: A2B-/- displayed increased body weight, reduced glucose clearance and attenuated overall insulin responses compared with age-matched WT. Nitrate treatment increased circulating levels of nitrate, nitrite and cGMP in A2B-/-, and improved glucose clearance. In WT mice, however, nitrate treatment did not influence glucose clearance. HOMA-IR increased following glucose injection in A2B-/-, but remained at basal levels in mice pretreated with nitrate. NADPH oxidase activity in livers from A2B-/-, but not WT mice, was reduced by nitrate. Livers from A2B-/- displayed reduced AMPK phosphorylation compared with WT mice, and this was increased by nitrate treatment. Injection with the anti-diabetic agent metformin induced similar therapeutic effects in the A2B-/- as observed with nitrate. Conclusion: The A2B-/- mouse is a genetic model of metabolic syndrome. Acute treatment with nitrate improved the metabolic profile, at least partly via reduction in oxidative stress and improved AMPK signaling

  17. Lipolysis Response to Endoplasmic Reticulum Stress in Adipose Cells*

    Science.gov (United States)

    Deng, Jingna; Liu, Shangxin; Zou, Liangqiang; Xu, Chong; Geng, Bin; Xu, Guoheng

    2012-01-01

    In obesity and diabetes, adipocytes show significant endoplasmic reticulum (ER) stress, which triggers a series of responses. This study aimed to investigate the lipolysis response to ER stress in rat adipocytes. Thapsigargin, tunicamycin, and brefeldin A, which induce ER stress through different pathways, efficiently activated a time-dependent lipolytic reaction. The lipolytic effect of ER stress occurred with elevated cAMP production and protein kinase A (PKA) activity. Inhibition of PKA reduced PKA phosphosubstrates and attenuated the lipolysis. Although both ERK1/2 and JNK are activated during ER stress, lipolysis is partially suppressed by inhibiting ERK1/2 but not JNK and p38 MAPK and PKC. Thus, ER stress induces lipolysis by activating cAMP/PKA and ERK1/2. In the downstream lipolytic cascade, phosphorylation of lipid droplet-associated protein perilipin was significantly promoted during ER stress but attenuated on PKA inhibition. Furthermore, ER stress stimuli did not alter the levels of hormone-sensitive lipase and adipose triglyceride lipase but caused Ser-563 and Ser-660 phosphorylation of hormone-sensitive lipase and moderately elevated its translocation from the cytosol to lipid droplets. Accompanying these changes, total activity of cellular lipases was promoted to confer the lipolysis. These findings suggest a novel pathway of the lipolysis response to ER stress in adipocytes. This lipolytic activation may be an adaptive response that regulates energy homeostasis but with sustained ER stress challenge could contribute to lipotoxicity, dyslipidemia, and insulin resistance because of persistently accelerated free fatty acid efflux from adipocytes to the bloodstream and other tissues. PMID:22223650

  18. Hypothalamic oxytocin mediates social buffering of the stress response.

    Science.gov (United States)

    Smith, Adam S; Wang, Zuoxin

    2014-08-15

    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. Female prairie voles (Microtus ochrogaster) were exposed to 1 hour immobilization stress and 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 female voles recovering alone with oxytocin or vehicle and female voles recovering with their male partner with a selective oxytocin receptor antagonist or vehicle. Group sizes varied from 6 to 8 voles (N = 98 total). We found that 1 hour immobilization increased anxiety-like behaviors and circulating levels of corticosterone, a stress hormone, in female prairie voles recovering alone but not the female prairie voles 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 of the hypothalamus. Intra-paraventricular nucleus oxytocin injections reduced behavioral and corticosterone responses to immobilization, whereas injections of an oxytocin receptor antagonist blocked the effects of the social buffering. Together, our data demonstrate that paraventricular nucleus oxytocin mediates the social buffering effects on the stress response and thus may be a target for treatment of stress-related disorders. Published by Society of Biological Psychiatry on behalf of Society of Biological Psychiatry.

  19. The surgical stress response: should it be prevented?

    DEFF Research Database (Denmark)

    Kehlet, H

    1991-01-01

    clinical trials have demonstrated a reduction in various aspects of postoperative morbidity by such a nociceptive blockade. Although a causal relationship has still to be demonstrated, these findings strongly argue the concept of "stress-free anesthesia and surgery" as an important instrument in improving......Postoperative complications such as myocardial infarction, pulmonary infection, thromboembolism and fatigue are probably related to increased demands, hypermetabolism, catabolism and other physiologic changes included in the global "surgical stress response." Strategies have been developed...... to suppress the detrimental components of the stress response so as to improve postoperative outcome. Of the various techniques to reduce the surgical stress response, afferent neural blockade with regional anesthesia to relieve pain is the most effective, although not optimal. Data from numerous controlled...

  20. Mini-review: Biofilm responses to oxidative stress.

    Science.gov (United States)

    Gambino, Michela; Cappitelli, Francesca

    2016-01-01

    Biofilms constitute the predominant microbial style of life in natural and engineered ecosystems. Facing harsh environmental conditions, microorganisms accumulate reactive oxygen species (ROS), potentially encountering a dangerous condition called oxidative stress. While high levels of oxidative stress are toxic, low levels act as a cue, triggering bacteria to activate effective scavenging mechanisms or to shift metabolic pathways. Although a complex and fragmentary picture results from current knowledge of the pathways activated in response to oxidative stress, three main responses are shown to be central: the existence of common regulators, the production of extracellular polymeric substances, and biofilm heterogeneity. An investigation into the mechanisms activated by biofilms in response to different oxidative stress levels could have important consequences from ecological and economic points of view, and could be exploited to propose alternative strategies to control microbial virulence and deterioration.

  1. The Yeast Environmental Stress Response Regulates Mutagenesis Induced by Proteotoxic Stress

    Science.gov (United States)

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

    2013-01-01

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

  2. Suitability of semi-automated tumor response assessment of liver metastases using a dedicated software package

    International Nuclear Information System (INIS)

    Kalkmann, Janine; Ladd, S.C.; Greiff, A. de; Forsting, M.; Stattaus, J.

    2010-01-01

    Purpose: to evaluate the suitability of semi-automated compared to manual tumor response assessment (TRA) of liver metastases. Materials and methods: in total, 32 patients with colorectal cancer and liver metastases were followed by an average of 2.8 contrast-enhanced CT scans. Two observers (O1, O2) measured the longest diameter (LD) of 269 liver metastases manually and semi-automatically using software installed as thin-client on a PACS workstation (LMS-Liver, MEDIAN Technologies). LD and TRA (''progressive'', ''stable'', ''partial remission'') were performed according to RECIST (Response Evaluation Criteria in Solid Tumors) and analyzed for between-method, interobserver and intraobserver variability. The time needed for evaluation was compared for both methods. Results: all measurements correlated excellently (r ≥ 0.96). Intraobserver (semi-automated), interobserver (manual) and between-method differences (by O1) in LD of 1.4 ± 2.6 mm, 1.9 ± 1.9 mm and 2.1 ± 2.0 mm, respectively, were not significant. Interobserver (semi-automated) and between-method (by O2) differences in LD of 3.0 ± 3.0 mm and 2.6 ± 2.0 mm, respectively, reflected a significant variability (p < 0.01). The interobserver agreement in manual and semi-automated TRA was 91.4%. The intraobserver agreement in semi-automated TRA was 84.5%. Between both methods a TRA agreement of 86.2% was obtained. Semi-automated evaluation (2.7 min) took slightly more time than manual evaluation (2.3 min). Conclusion: semi-automated and manual evaluation of liver metastases yield comparable results in response assessments and require comparable effort. (orig.)

  3. Energetic stress: The reciprocal relationship between energy availability and the stress response.

    Science.gov (United States)

    Harrell, C S; Gillespie, C F; Neigh, G N

    2016-11-01

    The worldwide epidemic of metabolic syndromes and the recognized burden of mental health disorders have driven increased research into the relationship between the two. A maladaptive stress response is implicated in both mental health disorders and metabolic disorders, implicating the hypothalamic-pituitary-adrenal (HPA) axis as a key mediator of this relationship. This review explores how an altered energetic state, such as hyper- or hypoglycemia, as may be manifested in obesity or diabetes, affects the stress response and the HPA axis in particular. We propose that changes in energetic state or energetic demands can result in "energetic stress" that can, if prolonged, lead to a dysfunctional stress response. In this review, we summarize the role of the hypothalamus in modulating energy homeostasis and then briefly discuss the relationship between metabolism and stress-induced activation of the HPA axis. Next, we examine seven mechanisms whereby energetic stress interacts with neuroendocrine stress response systems, including by glucocorticoid signaling both within and beyond the HPA axis; by nutrient-induced changes in glucocorticoid signaling; by impacting the sympathetic nervous system; through changes in other neuroendocrine factors; by inducing inflammatory changes; and by altering the gut-brain axis. Recognizing these effects of energetic stress can drive novel therapies and prevention strategies for mental health disorders, including dietary intervention, probiotics, and even fecal transplant. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Chronic stress affects immunologic but not cardiovascular responsiveness to acute psychological stress in humans

    NARCIS (Netherlands)

    Benschop, R. J.; Brosschot, J. F.; Godaert, G. L.; de Smet, M. B.; Geenen, R.; Olff, M.; Heijnen, C. J.; Ballieux, R. E.

    1994-01-01

    This study deals with the effect of chronic stress on physiological responsiveness to an acute psychological stressor in male high school teachers. Chronic stress was operationalized as the self-reported number of everyday problems. Twenty-seven subjects reporting extremely low or high numbers of

  5. Obesity challenges the hepatoprotective function of the integrated stress response to asparaginase exposure in mice.

    Science.gov (United States)

    Nikonorova, Inna A; Al-Baghdadi, Rana J T; Mirek, Emily T; Wang, Yongping; Goudie, Michael P; Wetstein, Berish B; Dixon, Joseph L; Hine, Christopher; Mitchell, James R; Adams, Christopher M; Wek, Ronald C; Anthony, Tracy G

    2017-04-21

    Obesity increases risk for liver toxicity by the anti-leukemic agent asparaginase, but the mechanism is unknown. Asparaginase activates the integrated stress response (ISR) via sensing amino acid depletion by the eukaryotic initiation factor 2 (eIF2) kinase GCN2. The goal of this work was to discern the impact of obesity, alone versus alongside genetic disruption of the ISR, on mechanisms of liver protection during chronic asparaginase exposure in mice. Following diet-induced obesity, biochemical analysis of livers revealed that asparaginase provoked hepatic steatosis that coincided with activation of another eIF2 kinase PKR-like endoplasmic reticulum kinase (PERK), a major ISR transducer to ER stress. Genetic loss of Gcn2 intensified hepatic PERK activation to asparaginase, yet surprisingly, mRNA levels of key ISR gene targets such as Atf5 and Trib3 failed to increase. Instead, mechanistic target of rapamycin complex 1 (mTORC1) signal transduction was unleashed, and this coincided with liver dysfunction reflected by a failure to maintain hydrogen sulfide production or apolipoprotein B100 (ApoB100) expression. In contrast, obese mice lacking hepatic activating transcription factor 4 ( Atf4 ) showed an exaggerated ISR and greater loss of endogenous hydrogen sulfide but normal inhibition of mTORC1 and maintenance of ApoB100 during asparaginase exposure. In both genetic mouse models, expression and phosphorylation of Sestrin2, an ATF4 gene target, was increased by asparaginase, suggesting mTORC1 inhibition during asparaginase exposure is not driven via eIF2-ATF4-Sestrin2. In conclusion, obesity promotes a maladaptive ISR during asparaginase exposure. GCN2 functions to repress mTORC1 activity and maintain ApoB100 protein levels independently of Atf4 expression, whereas hydrogen sulfide production is promoted via GCN2-ATF4 pathway. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Shanxi Aged Vinegar Protects against Alcohol-Induced Liver Injury via Activating Nrf2-Mediated Antioxidant and Inhibiting TLR4-Induced Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Ting Xia

    2018-06-01

    Full Text Available Shanxi aged vinegar (SAV is a typical fermented and antioxidant food, which has various health-promoting effects. This work aimed to explore the effects of SAV on alcohol-induced liver injury. A mice model of alcoholic liver injury was established to illuminate its potential mechanisms. All mice pretreated with SAV and then received an ethanol solution (50% w/v, 4.8 g/kg b.w.. The results showed that SAV ameliorated alcohol-induced histological changes and elevation of liver enzymes. SAV attenuated alcohol-induced oxidative stress by declining levels of hepatic oxidants, and restoring depletion of antioxidant enzyme activities in mice livers. Moreover, SAV alleviated alcohol-induced oxidative damage by activating nuclear factor erythroid-2-related factor 2 (Nrf2-mediated signal pathway. In addition, SAV prevented alcohol-induced inflammation by suppressing lipopolysaccharide (LPS level and activities of pro-inflammatory enzymes, and regulating inflammatory cytokines. SAV inhibited alcohol-induced inflammation through down-regulating the expression of Toll-like receptor 4 (TLR4-mediated inflammatory response. The findings provide crucial evidence for elucidating the hepatoprotective mechanisms of SAV and encourage the future application of SAV as a functional food for liver protection.

  7. Stress response and virulence in Vibrio anguillarum

    OpenAIRE

    Weber, Barbara

    2010-01-01

    Bacteria use quorum sensing, a cell to cell signaling mechanism mediated by small molecules that are produced by specific signal molecule synthases, to regulate gene expression in response to population density. In Vibrio anguillarum, the quorum-sensing phosphorelay channels information from three hybrid sensor kinases VanN, VanQ, CqsS that sense signal molecules produced by the synthases VanM, VanS and CqsA, onto the phosphotransferase VanU, to regulate activity of the response regulator Van...

  8. WRKY transcription factors in plant responses to stresses.

    Science.gov (United States)

    Jiang, Jingjing; Ma, Shenghui; Ye, Nenghui; Jiang, Ming; Cao, Jiashu; Zhang, Jianhua

    2017-02-01

    The WRKY gene family is among the largest families of transcription factors (TFs) in higher plants. By regulating the plant hormone signal transduction pathway, these TFs play critical roles in some plant processes in response to biotic and abiotic stress. Various bodies of research have demonstrated the important biological functions of WRKY TFs in plant response to different kinds of biotic and abiotic stresses and working mechanisms. However, very little summarization has been done to review their research progress. Not just important TFs function in plant response to biotic and abiotic stresses, WRKY also participates in carbohydrate synthesis, senescence, development, and secondary metabolites synthesis. WRKY proteins can bind to W-box (TGACC (A/T)) in the promoter of its target genes and activate or repress the expression of downstream genes to regulate their stress response. Moreover, WRKY proteins can interact with other TFs to regulate plant defensive responses. In the present review, we focus on the structural characteristics of WRKY TFs and the research progress on their functions in plant responses to a variety of stresses. © 2016 Institute of Botany, Chinese Academy of Sciences.

  9. Responses of neurons to extreme osmomechanical stress.

    Science.gov (United States)

    Wan, X; Harris, J A; Morris, C E

    1995-05-01

    Neurons are often regarded as fragile cells, easily destroyed by mechanical and osmotic insult. The results presented here demonstrate that this perception needs revision. Using extreme osmotic swelling, we show that molluscan neurons are astonishingly robust. In distilled water, a heterogeneous population of Lymnaea stagnalis CNS neurons swelled to several times their initial volume, yet had a ST50 (survival time for 50% of cells) > 60 min. Cells that were initially bigger survived longer. On return to normal medium, survivors were able, over the next 24 hr, to rearborize. Reversible membrane capacitance changes corresponding to about 0.7 muF/cm2 of apparent surface area accompanied neuronal swelling and shrinking in hypo- and hyperosmotic solutions; reversible changes in cell surface area evidently contributed to the neurons' ability to accommodate hydrostatic pressures then recover. The reversible membrane area/capacitance changes were not dependent on extracellular Ca2+. Neurons were monitored for potassium currents during direct mechanical inflation and during osmotically driven inflation. The latter but not the former stimulus routinely elicited small potassium currents, suggesting that tension increases activate the currents only if additional disruption of the cortex has occurred. Under stress in distilled water, a third of the neurons displayed a quite unexpected behavior: prolonged writhing of peripheral regions of the soma. This suggested that a plasma membrane-linked contractile machinery (presumably actomyosin) might contribute to the neurons' mechano-osmotic robustness by restricting water influx. Consistent with this possibility, 1 mM N-ethyl-maleimide, which inhibits myosin ATPase, decreased the ST50 to 18 min, rendered the survival time independent of initial size, and abolished writhing activity. For neurons, active mechanical resistance of the submembranous cortex, along with the mechanical compliance supplied by insertion or eversion of membrane

  10. Oxidative stress and hepatic stellate cell activation are key events in arsenic induced liver fibrosis in mice

    International Nuclear Information System (INIS)

    Ghatak, Subhadip; Biswas, Ayan; Dhali, Gopal Krishna; Chowdhury, Abhijit; Boyer, James L.; Santra, Amal

    2011-01-01

    Arsenic is an environmental toxicant and carcinogen. Exposure to arsenic is associated with development of liver fibrosis and portal hypertension through ill defined mechanisms. We evaluated hepatic fibrogenesis after long term arsenic exposure in a murine model. BALB/c mice were exposed to arsenic by daily gavages of 6 μg/gm body weight for 1 year and were evaluated for markers of hepatic oxidative stress and fibrosis, as well as pro-inflammatory, pro-apoptotic and pro-fibrogenic factors at 9 and 12 months. Hepatic NADPH oxidase activity progressively increased in arsenic exposure with concomitant development of hepatic oxidative stress. Hepatic steatosis with occasional collection of mononuclear inflammatory cells and mild portal fibrosis were the predominant liver lesion observed after 9 months of arsenic exposure, while at 12 months, the changes included mild hepatic steatosis, inflammation, necrosis and significant fibrosis in periportal areas. The pathologic changes in the liver were associated with markers of hepatic stellate cells (HSCs) activation, matrix reorganization and fibrosis including α-smooth muscle actin, transforming growth factor-β1, PDGF-Rβ, pro-inflammatory cytokines and enhanced expression of tissue inhibitor of metalloproteinase-1 and pro(α) collagen type I. Moreover, pro-apoptotic protein Bax was dominantly expressed and Bcl-2 was down-regulated along with increased number of TUNEL positive hepatocytes in liver of arsenic exposed mice. Furthermore, HSCs activation due to increased hepatic oxidative stress observed after in vivo arsenic exposure was recapitulated in co-culture model of isolated HSCs and hepatocytes exposed to arsenic. These findings have implications not only for the understanding of the pathology of arsenic related liver fibrosis but also for the design of preventive strategies in chronic arsenicosis.

  11. Systems responses to progressive water stress in durum wheat.

    Directory of Open Access Journals (Sweden)

    Dimah Z Habash

    Full Text Available Durum wheat is susceptible to terminal drought which can greatly decrease grain yield. Breeding to improve crop yield is hampered by inadequate knowledge of how the physiological and metabolic changes caused by drought are related to gene expression. To gain better insight into mechanisms defining resistance to water stress we studied the physiological and transcriptome responses of three durum breeding lines varying for yield stability under drought. Parents of a mapping population (Lahn x Cham1 and a recombinant inbred line (RIL2219 showed lowered flag leaf relative water content, water potential and photosynthesis when subjected to controlled water stress time transient experiments over a six-day period. RIL2219 lost less water and showed constitutively higher stomatal conductance, photosynthesis, transpiration, abscisic acid content and enhanced osmotic adjustment at equivalent leaf water compared to parents, thus defining a physiological strategy for high yield stability under water stress. Parallel analysis of the flag leaf transcriptome under stress uncovered global trends of early changes in regulatory pathways, reconfiguration of primary and secondary metabolism and lowered expression of transcripts in photosynthesis in all three lines. Differences in the number of genes, magnitude and profile of their expression response were also established amongst the lines with a high number belonging to regulatory pathways. In addition, we documented a large number of genes showing constitutive differences in leaf transcript expression between the genotypes at control non-stress conditions. Principal Coordinates Analysis uncovered a high level of structure in the transcriptome response to water stress in each wheat line suggesting genome-wide co-ordination of transcription. Utilising a systems-based approach of analysing the integrated wheat's response to water stress, in terms of biological robustness theory, the findings suggest that each durum

  12. The Effect of Music on the Human Stress Response

    Science.gov (United States)

    Thoma, Myriam V.; La Marca, Roberto; Brönnimann, Rebecca; Finkel, Linda; Ehlert, Ulrike; Nater, Urs M.

    2013-01-01

    Background Music listening has been suggested to beneficially impact health via stress-reducing effects. However, the existing literature presents itself with a limited number of investigations and with discrepancies in reported findings that may result from methodological shortcomings (e.g. small sample size, no valid stressor). It was the aim of the current study to address this gap in knowledge and overcome previous shortcomings by thoroughly examining music effects across endocrine, autonomic, cognitive, and emotional domains of the human stress response. Methods Sixty healthy female volunteers (mean age = 25 years) were exposed to a standardized psychosocial stress test after having been randomly assigned to one of three different conditions prior to the stress test: 1) relaxing music (‘Miserere’, Allegri) (RM), 2) sound of rippling water (SW), and 3) rest without acoustic stimulation (R). Salivary cortisol and salivary alpha-amylase (sAA), heart rate (HR), respiratory sinus arrhythmia (RSA), subjective stress perception and anxiety were repeatedly assessed in all subjects. We hypothesized that listening to RM prior to the stress test, compared to SW or R would result in a decreased stress response across all measured parameters. Results The three conditions significantly differed regarding cortisol response (p = 0.025) to the stressor, with highest concentrations in the RM and lowest in the SW condition. After the stressor, sAA (p=0.026) baseline values were reached considerably faster in the RM group than in the R group. HR and psychological measures did not significantly differ between groups. Conclusion Our findings indicate that music listening impacted the psychobiological stress system. Listening to music prior to a standardized stressor predominantly affected the autonomic nervous system (in terms of a faster recovery), and to a lesser degree the endocrine and psychological stress response. These findings may help better understanding the

  13. High calcium diet improves the liver oxidative stress and microsteatosis in adult obese rats that were overfed during lactation.

    Science.gov (United States)

    Conceição, E P S; Moura, E G; Soares, P N; Ai, X X; Figueiredo, M S; Oliveira, E; Lisboa, P C

    2016-06-01

    Obesity is related to diabetes, higher oxidative stress and nonalcoholic fatty liver disease, and dietetic therapies, for instance calcium-rich diet, can improve these dysfunctions. Rats raised in small litters (SL) had increased fat depots and insulin resistance at adulthood associated with higher liver oxidative stress and microsteatosis. Thus, we evaluated if dietary calcium can improve these changes. In PN3, litter size was adjusted to 3 pups (SL group) to induce overfeeding, while controls had 10 pups until weaning. At PN120, SL group was randomly divided into: rats fed with standard chow or fed with calcium supplementation (SL-Ca group, 10 g/kg chow) for 60 days. At PN180, dietary calcium normalized food consumption, visceral fat, plasma aspartate aminotransferase (AST) and glycaemia. Concerning oxidative balance, calcium restored both higher hepatic lipid peroxidation and protein carbonylation as well as higher plasma lipid peroxidation. Higher fatty acid synthase (FAS) content, steatosis and lower protein kinase B (Akt) in SL group were normalized by dietary calcium and SL-Ca rats had lower hepatic cholesterol. Thus, calcium supplementation improved the insulin sensitivity, redox balance and steatosis in the liver. Therefore, dietary calcium can be a promising therapy for liver disease in the metabolic syndrome. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Stress-related cortisol responsivity modulates prospective memory.

    Science.gov (United States)

    Glienke, K; Piefke, M

    2017-12-01

    It is known that there is inter-individual variation in behavioural and physiological stress reactions to the same stressor. The present study aimed to examine the impact of cortisol responsivity on performance in a complex real life-like prospective memory (PM) paradigm by a re-analysis of data published previously, with a focus on the taxonomy of cognitive dimensions of PM. Twenty-one male subjects were stressed with the Socially Evaluated Cold Pressor Test (SECPT) before the planning of intentions. Another group of 20 males underwent a control procedure. Salivary cortisol was measured to assess the intensity of the biological stress response. Additionally, participants rated the subjective experience of stress on a 5-point rating scale. Stressed participants were post-hoc differentiated in high (n = 11) and low cortisol responders (n = 10). Cortisol niveau differed significantly between the two groups, whereas subjective stress ratings did not. PM performance of low cortisol responders was stable across time and the PM performance of controls declined. High cortisol responders showed a nominally weaker PM retrieval across the early trails and significantly improved only on the last trial. The data demonstrate for the first time that participants with a low cortisol responsivity may benefit from stress exposure before the planning phase of PM. PM performance of high cortisol responders shows a more inconsistent pattern, which may be interpreted in the sense of a recency effect in PM retrieval. Alternatively, high cortisol responses may have a deteriorating effect on PM retrieval, which disappeared on the last trials of the task as a result of the decrease of cortisol levels across time. Importantly, the data also demonstrate that the intensity of cortisol responses does not necessarily correspond to the intensity of the mental experience of stress. © 2017 British Society for Neuroendocrinology.

  15. Exercise-Induced Oxidative Stress Responses in the Pediatric Population

    Directory of Open Access Journals (Sweden)

    Alexandra Avloniti

    2017-01-01

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

  16. Protective effects of Spirulina maxima on hyperlipidemia and oxidative-stress induced by lead acetate in the liver and kidney.

    Science.gov (United States)

    Ponce-Canchihuamán, Johny C; Pérez-Méndez, Oscar; Hernández-Muñoz, Rolando; Torres-Durán, Patricia V; Juárez-Oropeza, Marco A

    2010-03-31

    Oxidative damage has been proposed as a possible mechanism involved in lead toxicity, specially affecting the liver and kidney. Previous studies have shown the antioxidant effect of Spirulina maxima in several experimental models of oxidative stress. The current study was carried out to evaluate the antioxidant activity of Spirulina maxima against lead acetate-induced hyperlipidemia and oxidative damage in the liver and kidney of male rats. Control animals were fed on a standard diet and did not receive lead acetate (Control group). Experimental animals were fed on a standard laboratory diet with or without Spirulina maxima 5% in the standard laboratory diet and treated with three doses of lead acetate (25 mg each/weekly, intraperitoneal injection) (lead acetate with Spirulina, and lead acetate without Spirulina groups). The results showed that Spirulina maxima prevented the lead acetate-induced significant changes on plasma and liver lipid levels and on the antioxidant status of the liver and kidney. On the other hand, Spirulina maxima succeeded to improve the biochemical parameters of the liver and kidney towards the normal values of the Control group. It was concluded that Spirulina maxima has protective effects on lead acetate-induced damage, and that the effects are associated with the antioxidant effect of Spirulina.

  17. Intravital imaging of the immune responses during liver-stage malaria infection: An improved approach for fixing the liver.

    Science.gov (United States)

    Akbari, Masoud; Kimura, Kazumi; Houts, James T; Yui, Katsuyuki

    2016-10-01

    The host-parasite relationship is one of the main themes of modern parasitology. Recent revolutions in science, including the development of various fluorescent proteins/probes and two-photon microscopy, have made it possible to directly visualize and study the mechanisms underlying the interaction between the host and pathogen. Here, we describe our method of preparing and setting-up the liver for our experimental approach of using intravital imaging to examine the interaction between Plasmodium berghei ANKA and antigen-specific CD8 + T cells during the liver-stage of the infection in four dimensions. Since the liver is positioned near the diaphragm, neutralization of respiratory movements is critical during the imaging process. In addition, blood circulation and temperature can be affected by the surgical exposure due to the anatomy and tissue structure of the liver. To control respiration, we recommend anesthesia with isoflurane inhalation at 1% during the surgery. In addition, our protocol introduces a cushion of gauze around the liver to avoid external pressure on the liver during intravital imaging using an inverted microscope, which makes it possible to image the liver tissue for long periods with minimal reduction in the blood circulation and with minimal displacement and tissue damage. The key point of this method is to reduce respiratory movements and external pressure on the liver tissue during intravital imaging. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Oxidative stress impairs the heat stress response and delays unfolded protein recovery.

    Directory of Open Access Journals (Sweden)

    Masaaki Adachi

    2009-11-01

    Full Text Available Environmental changes, air pollution and ozone depletion are increasing oxidative stress, and global warming threatens health by heat stress. We now face a high risk of simultaneous exposure to heat and oxidative stress. However, there have been few studies investigating their combined adverse effects on cell viability.Pretreatment of hydrogen peroxide (H(2O(2 specifically and highly sensitized cells to heat stress, and enhanced loss of mitochondrial membrane potential. H(2O(2 exposure impaired the HSP40/HSP70 induction as heat shock response (HSR and the unfolded protein recovery, and enhanced eIF2alpha phosphorylation and/or XBP1 splicing, land marks of ER stress. These H(2O(2-mediated effects mimicked enhanced heat sensitivity in HSF1 knockdown or knockout cells. Importantly, thermal preconditioning blocked H(2O(2-mediated inhibitory effects on refolding activity and rescued HSF1 +/+ MEFs, but neither blocked the effects nor rescued HSF1 -/- MEFs. These data strongly suggest that inhibition of HSR and refolding activity is crucial for H(2O(2-mediated enhanced heat sensitivity.H(2O(2 blocks HSR and refolding activity under heat stress, thereby leading to insufficient quality control and enhancing ER stress. These uncontrolled stress responses may enhance cell death. Our data thus highlight oxidative stress as a crucial factor affecting heat tolerance.

  19. Differential gene expression in liver tissues of streptozotocin-induced diabetic rats in response to resveratrol treatment.

    Directory of Open Access Journals (Sweden)

    Gökhan Sadi

    Full Text Available This study was conducted to elucidate the genome-wide gene expression profile in streptozotocin induced diabetic rat liver tissues in response to resveratrol treatment and to establish differentially expressed transcription regulation networks with microarray technology. In addition to measure the expression levels of several antioxidant and detoxification genes, real-time quantitative polymerase chain reaction (qRT-PCR was also used to verify the microarray results. Moreover, gene and protein expressions as well as enzymatic activities of main antioxidant enzymes; superoxide dismutase (SOD-1 and SOD-2 and glutathione S-transferase (GST-Mu were analyzed. Diabetes altered 273 genes significantly and 90 of which were categorized functionally which suggested that genes in cellular catalytic activities, oxidation-reduction reactions, co-enzyme binding and terpenoid biosynthesis were dominated by up-regulated expression in diabetes. Whereas; genes responsible from cellular carbohydrate metabolism, regulation of transcription, cell signal transduction, calcium independent cell-to-cell adhesion and lipid catabolism were down-regulated. Resveratrol increased the expression of 186 and decreased the expression of 494 genes in control groups. While cellular and extracellular components, positive regulation of biological processes, biological response to stress and biotic stimulants, and immune response genes were up-regulated, genes responsible from proteins present in nucleus and nucleolus were mainly down-regulated. The enzyme assays showed a significant decrease in diabetic SOD-1 and GST-Mu activities. The qRT-PCR and Western-blot results demonstrated that decrease in activity is regulated at gene expression level as both mRNA and protein expressions were also suppressed. Resveratrol treatment normalized the GST activities towards the control values reflecting a post-translational effect. As a conclusion, global gene expression in the liver tissues is

  20. Developmental changes of the sensitivity of cardiac and liver mitochondrial permeability transition pore to calcium load and oxidative stress

    Czech Academy of Sciences Publication Activity Database

    Drahota, Zdeněk; Milerová, Marie; Endlicher, R.; Rychtrmoc, D.; Červinková, Z.; Ošťádal, Bohuslav

    2012-01-01

    Roč. 61, Suppl.1 (2012), S165-S172 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LL1204; GA ČR(CZ) GAP303/12/1162 Institutional support: RVO:67985823 Keywords : mitochondrial permeability transition pore * cardiac mitochondria * liver mitochondria * oxidative stress * calcium load * rat Subject RIV: ED - Physiology Impact factor: 1.531, year: 2012

  1. Lower liver stiffness in patients with sustained virological response 4 years after treatment for chronic hepatitis C

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Moessner, Belinda Klemmensen; Christensen, Peer Brehm

    2011-01-01

    Transient elastography (TE) is a noninvasive and well validated method for measurement of liver stiffness. The aim of this study was to use TE to evaluate whether patients with sustained virological response (SVR) have lower liver stiffness than patients with non-SVR after treatment for chronic...

  2. Reproduction elevates the corticosterone stress response in common fruit bats.

    Science.gov (United States)

    Klose, Stefan M; Smith, Carolynn L; Denzel, Andrea J; Kalko, Elisabeth K V

    2006-04-01

    Changes in reproductive state or the environment may affect the sensitivity of the hypothalamic-pituitary-andrenal (HPA) axis. However, little is known about the dynamics of the resulting corticosteroid stress response, in particular in tropical mammals. In this study, we address the modulation of corticosterone release in response to different reproductive conditions and seasonality in 326 free-living common fruit-eating bats (Artibeus jamaicensis) on Barro Colorado Island in Panama during dry and wet seasons. We present strong evidence that stress sensitivity is primarily modulated by reproductive condition. In reproductively active females, corticosterone increases were more rapid and reached higher levels, but also decreased significantly faster than in inactive females. The corticosterone response was weaker in reproducing males than in females and delayed compared to non-reproductive males. Testes volume in reproductively active males was negatively correlated with corticosterone concentrations. Our findings suggest differentiated dynamics in the corticosterone stress response between sexes, potentially reflecting conflicting ecological demands. In females, a strong acute corticosterone response may represent high stress- and risk-sensitivity that facilitates escape and thus helps to protect reproduction. In males, suppression during reproductive activity could reflect lowered stress sensitivity to avoid chronically elevated corticosterone levels in times of frequent aggressive and therefore costly inter-male encounters.

  3. A role for SR proteins in plant stress responses.

    Science.gov (United States)

    Duque, Paula

    2011-01-01

    Members of the SR (serine/arginine-rich) protein gene family are key players in the regulation of alternative splicing, an important means of generating proteome diversity and regulating gene expression. In plants, marked changes in alternative splicing are induced by a wide variety of abiotic stresses, suggesting a role for this highly versatile gene regulation mechanism in the response to environmental cues. In support of this notion, the expression of plant SR proteins is stress-regulated at multiple levels, with environmental signals controlling their own alternative splicing patterns, phosphorylation status and subcellular distribution. Most importantly, functional links between these RNA-binding proteins and plant stress tolerance are beginning to emerge, including a role in the regulation of abscisic acid (ABA) signaling. Future identification of the physiological mRNA targets of plant SR proteins holds much promise for the elucidation of the molecular mechanisms underlying their role in the response to abiotic stress.

  4. Proteomics analysis of alfalfa response to heat stress.

    Directory of Open Access Journals (Sweden)

    Weimin Li

    Full Text Available The proteome responses to heat stress have not been well understood. In this study, alfalfa (Medicago sativa L. cv. Huaiyin seedlings were exposed to 25 °C (control and 40 °C (heat stress in growth chambers, and leaves were collected at 24, 48 and 72 h after treatment, respectively. The morphological, physiological and proteomic processes were negatively affected under heat stress. Proteins were extracted and separated by two-dimensional polyacrylamide gel electrophoresis (2-DE, and differentially expressed protein spots were identified by mass spectrometry (MS. Totally, 81 differentially expressed proteins were identified successfully by MALDI-TOF/TOF. These proteins were categorized into nine classes: including metabolism, energy, protein synthesis, protein destination/storage, transporters, intracellular traffic, cell structure, signal transduction and disease/defence. Five proteins were further analyzed for mRNA levels. The results of the proteomics analyses provide a better understanding of the molecular basis of heat-stress responses in alfalfa.

  5. Regulation of cellulose synthesis in response to stress.

    Science.gov (United States)

    Kesten, Christopher; Menna, Alexandra; Sánchez-Rodríguez, Clara

    2017-12-01

    The cell wall is a complex polysaccharide network that provides stability and protection to the plant and is one of the first layers of biotic and abiotic stimuli perception. A controlled remodeling of the primary cell wall is essential for the plant to adapt its growth to environmental stresses. Cellulose, the main component of plant cell walls is synthesized by plasma membrane-localized cellulose synthases moving along cortical microtubule tracks. Recent advancements demonstrate a tight regulation of cellulose synthesis at the primary cell wall by phytohormone networks. Stress-induced perturbations at the cell wall that modify cellulose synthesis and microtubule arrangement activate similar phytohormone-based stress response pathways. The integration of stress perception at the primary cell wall and downstream responses are likely to be tightly regulated by phytohormone signaling pathways in the context of cellulose synthesis and microtubule arrangement. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Stress and fear responses in the teleost pallium

    DEFF Research Database (Denmark)

    Silva, Patricia Isabel da Mota E.; Martins, C.I.M.; Khan, Uniza Wahid

    2015-01-01

    Evolution has resulted in behavioural responses to threat which show extensive similarities between different animal species. The reaction to predator cues is one example of such prevailing responses, and functional homologies to mammalian limbic regions involved in threat-sensitive behaviour hav...... to chemical alarm cues, but this effect did not reach the level of statistical significance. Hence, limbic responses to stress and fear, akin to those seen in extant mammals, are also present in the teleost lineage...

  7. Effects of two aerobic exercise training protocols on parameters of oxidative stress in the blood and liver of obese rats.

    Science.gov (United States)

    Delwing-de Lima, Daniela; Ulbricht, Ariene Sampaio Souza Farias; Werlang-Coelho, Carla; Delwing-Dal Magro, Débora; Joaquim, Victor Hugo Antonio; Salamaia, Eloise Mariani; de Quevedo, Silvana Rodrigues; Desordi, Larissa

    2017-12-08

    We evaluated the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) protocols on the alterations in oxidative stress parameters caused by a high-fat diet (HFD), in the blood and liver of rats. The HFD enhanced thiobarbituric acid reactive substances (TBA-RS) and protein carbonyl content, while reducing total sulfhydryl content and catalase (CAT) and glutathione peroxidase (GSH-Px) activities in the blood. Both training protocols prevented an increase in TBA-RS and protein carbonyl content, and prevented a reduction in CAT. HIIT protocol enhanced SOD activity. In the liver, HFD didn't alter TBA-RS, total sulfhydryl content or SOD, but increased protein carbonyl content and CAT and decreased GSH-Px. The exercise protocols prevented the increase in protein carbonyl content and the MICT protocol prevented an alteration in CAT. In conclusion, HFD elicits oxidative stress in the blood and liver and both protocols prevented most of the alterations in the oxidative stress parameters.

  8. Liver-Specific Deletion of Protein-Tyrosine Phosphatase 1B (PTP1B) Improves Metabolic Syndrome and Attenuates Diet-Induced Endoplasmic Reticulum Stress

    Science.gov (United States)

    Delibegovic, Mirela; Zimmer, Derek; Kauffman, Caitlin; Rak, Kimberly; Hong, Eun-Gyoung; Cho, You-Ree; Kim, Jason K.; Kahn, Barbara B.; Neel, Benjamin G.; Bence, Kendra K.

    2009-01-01

    OBJECTIVE—The protein tyrosine phosphatase PTP1B is a negative regulator of insulin signaling; consequently, mice deficient in PTP1B are hypersensitive to insulin. Because PTP1B−/− mice have diminished fat stores, the extent to which PTP1B directly regulates glucose homeostasis is unclear. Previously, we showed that brain-specific PTP1B−/− mice are protected against high-fat diet–induced obesity and glucose intolerance, whereas muscle-specific PTP1B−/− mice have increased insulin sensitivity independent of changes in adiposity. Here we studied the role of liver PTP1B in glucose homeostasis and lipid metabolism. RESEARCH DESIGN AND METHODS—We analyzed body mass/adiposity, insulin sensitivity, glucose tolerance, and lipid metabolism in liver-specific PTP1B−/− and PTP1Bfl/fl control mice, fed a chow or high-fat diet. RESULTS—Compared with normal littermates, liver-specific PTP1B−/− mice exhibit improved glucose homeostasis and lipid profiles, independent of changes in adiposity. Liver-specific PTP1B−/− mice have increased hepatic insulin signaling, decreased expression of gluconeogenic genes PEPCK and G-6-Pase, enhanced insulin-induced suppression of hepatic glucose production, and improved glucose tolerance. Liver-specific PTP1B−/− mice exhibit decreased triglyceride and cholesterol levels and diminished expression of lipogenic genes SREBPs, FAS, and ACC. Liver-specific PTP1B deletion also protects against high-fat diet–induced endoplasmic reticulum stress response in vivo, as evidenced by decreased phosphorylation of p38MAPK, JNK, PERK, and eIF2α and lower expression of the transcription factors C/EBP homologous protein and spliced X box-binding protein 1. CONCLUSIONS—Liver PTP1B plays an important role in glucose and lipid metabolism, independent of alterations in adiposity. Inhibition of PTP1B in peripheral tissues may be useful for the treatment of metabolic syndrome and reduction of cardiovascular risk in addition to

  9. Hormonal contraception use alters stress responses and emotional memory

    OpenAIRE

    Nielsen, Shawn E.; Segal, Sabrina K.; Worden, Ian V.; Yim, Ilona S.; Cahill, Larry

    2012-01-01

    Emotionally arousing material is typically better remembered than neutral material. Since norepinephrine and cortisol interact to modulate emotional memory, sex-related influences on stress responses may be related to sex differences in emotional memory. Two groups of healthy women – one naturally cycling (NC women, N = 42) and one using hormonal contraceptives (HC women, N = 36) – viewed emotionally arousing and neutral images. Immediately after, they were assigned to Cold Pressor Stress (CP...

  10. Effects of Combined Anisodamine and Neostigmine Treatment on the Inflammatory Response and Liver Regeneration of Obstructive Jaundice Rats after Hepatectomy

    Directory of Open Access Journals (Sweden)

    Chong-Hui Li

    2014-01-01

    Full Text Available Background. Cholestasis is associated with high rates of morbidity and mortality in patients undergoing major liver resection. This study aimed to evaluate the effects of a combined anisodamine and neostigmine (Ani+Neo treatment on the inflammatory response and liver regeneration in rats with obstructive jaundice (OJ after partial hepatectomy. Materials and Methods. OJ was induced in the rats by bile duct ligation. After 7 days biliary drainage and partial hepatectomy were performed. These rats were assigned to a saline group or an Ani+Neo treatment group. The expressions of inflammatory mediators, liver regeneration, and liver damage were assessed at 48 h after hepatectomy. Results. The mRNA levels of TNF-α, IL-1β, IL-6, MCP-1, and MIP-1α, in the remnant livers, and the serum levels of TNF-α and IL-1β were substantially reduced in the Ani+Neo group compared with saline group (P<0.05. The Ani+Neo treatment obviously promoted liver regeneration as indicated by the liver weights and Ki-67 labeling index (P<0.05. The serum albumin and γ-GT levels and liver neutrophil infiltration also significantly improved in the Ani+Neo group (P<0.05 compared with the saline group. Conclusions. These results demonstrate that the combined anisodamine and neostigmine treatment is able to improve the liver regeneration in rats with OJ by substantially alleviating the inflammatory response.

  11. Sex differences in chronic stress responses and Alzheimer's disease.

    Science.gov (United States)

    Yan, Yan; Dominguez, Sky; Fisher, Daniel W; Dong, Hongxin

    2018-02-01

    Clinical studies indicate that Alzheimer's disease (AD) disproportionately affects women in both disease prevalence and severity, but the mechanisms underlying this sex divergence are unknown. Though some have suggested this difference in risk is a reflection of known differences in longevity between men and women, mounting clinical and preclinical evidence supports women also having intrinsic susceptibilities towards the disease. While a number of potential risk factors have been hypothesized to affect these differences in risks, none have been definitively verified. In this review, we discuss a novel hypothesis whereby women's susceptibility to chronic stress also mediates increased risk for AD. As stress is a risk factor for AD, and women are twice as likely to develop mood disorders where stress is a major etiology, it is possible that sex dimorphisms in stress responses contribute to the increase in women with AD. In line with this, sex divergence in biochemical responses to stress have been noted along the hypothalamic-pituitary-adrenal (HPA) axis and among known molecular effectors of AD, with crosstalk between these processes also being likely. In addition, activation of the cortical corticotrophin-releasing factor receptor 1 (CRF1) signaling pathway leads to distinct female-biased increases in molecules associated with AD pathogenesis. Therefore, the different biochemical responses to stress between women and men may represent an intrinsic, sex-dependent risk factor for AD.

  12. Hormonal contraception use alters stress responses and emotional memory.

    Science.gov (United States)

    Nielsen, Shawn E; Segal, Sabrina K; Worden, Ian V; Yim, Ilona S; Cahill, Larry

    2013-02-01

    Emotionally arousing material is typically better remembered than neutral material. Since norepinephrine and cortisol interact to modulate emotional memory, sex-related influences on stress responses may be related to sex differences in emotional memory. Two groups of healthy women - one naturally cycling (NC women, n=42) and one using hormonal contraceptives (HC women, n=36) - viewed emotionally arousing and neutral images. Immediately after, they were assigned to Cold Pressor Stress (CPS) or a control procedure. One week later, participants received a surprise free recall test. Saliva samples were collected and later assayed for salivary alpha-amylase (biomarker for norepinephrine) and cortisol. Compared to NC women, HC women exhibited significantly blunted stress hormone responses to the images and CPS. Recall of emotional images differed between HC and NC women depending on noradrenergic and cortisol responses. These findings may have important implications for understanding the neurobiology of emotional memory disorders, especially those that disproportionately affect women. Published by Elsevier B.V.

  13. Fagraea racemosa leaf extract inhibits oxidative stress-induced liver damage in Wistar rats

    Directory of Open Access Journals (Sweden)

    Eva Rachmi

    2012-07-01

    Full Text Available Latar belakang: Kemampuan hati mengatasi stres oksidatif dapat ditingkatkan dengan konsumsi antioksidan eksogen yang berasal dari alam. Penelitian ini ditujukan untuk mempelajari kemampuan hepatoprotektif dari ekstrak metanol  daun  Fagraea racemosa, dengan menggunakan CCL4 sebagai model sumber radikal bebas. Metode: Tiga kelompok perlakuan tikus Wistar  (enam ekor per  kelompok, masing-masing diberi dosis ekstrak berturut-turut 50, 100, 200 mg/kg bb per oral, sekali perhari selama 30 hari. CCl4 diinjeksikan intraperitoneal kepada ketiga kelompok , dua kali per minggu (1,5 ml/kg bb.  Sebagai pembanding, digunakan dua kelompok kontrol, yaitu kontrol normal dan kontrol CCl4.  Pada hari ke-30, tikus dibunuh dan hati diwarnai dengan hematoksilin-eosin. Perubahan histopatologi ditentukan berdasar derajat steatosis, degenerasi hidropik, dan inflamasi. Data dianalisis dengan Anova dan uji post hoc LSD (p≤0.05 menggunakan SPSS versi 13.0 Hasil: Hasil menunjukkan perbaikan derajat degenerasi hidropik dan inflamasi (p≤0,05 pada ketiga kelompok perlakuan bila dibanding dengan kelompok kontrol CCl4. Tetapi, derajat steatosis meningkat pada kelompok perlakuan dosis  50 dan 100 mg/kg bb, dan kemudian menurun secara bermakna pada perlakuan 200 mg/kg bb. Kesimpulan : Ekstrak methanol daun Fagraea racemosa  mampu melindungi hati dari radikal bebas yang dihasilkan dari CCl4. Hasil ini mengindikasikan bahwa Fagraea racemosa menjanjikan untuk dikembangkan sebagai suplemen antioksidan. (Health Science Indones 2011;2:46-51   Abstract Background: The ability of the liver in dealing with oxidative stress can be enhanced by consumption of exogenous antioxidants derived from nature. This study aimed to explore the hepatoprotective ability of Fagraea racemosa leaves methanolic extract against CCl4 exposure as a model of free radicals source. Methods: Three different doses (50, 100, 200 mg/kg bw were administered orally to three treatment groups of Wistar rats

  14. Coping as a mediator of the relationship between stress mindset and psychological stress response: a pilot study.

    Science.gov (United States)

    Horiuchi, Satoshi; Tsuda, Akira; Aoki, Shuntaro; Yoneda, Kenichiro; Sawaguchi, Yusuke

    2018-01-01

    Coping, the cognitive and behavioral effort required to manage the effects of stressors, is important in determining psychological stress responses (ie, the emotional, behavioral, and cognitive responses to stressors). Coping was classified into categories of emotional expression (eg, negative feelings and thoughts), emotional support seeking (eg, approaching loved ones to request encouragement), cognitive reinterpretation (eg, reframing a problem positively), and problem solving (eg, working to solve the problem). Stress mindset refers to the belief that stress has enhancing (stress-is-enhancing mindset) or debilitating consequences (stress-is-debilitating mindset). This study examined whether coping mediated the relationship between stress mindset and psychological stress responses. Psychological stress responses were conceptualized as depression-anxiety, irritability-anger, and helplessness. The following two hypotheses were tested: 1) a stronger stress-is-enhancing mindset is associated with less frequent use of emotional expression, emotional support seeking, and problem solving, which in turn is associated with lower levels of depression-anxiety, irritability-anger, and helplessness; 2) a stronger stress-is-debilitating mindset is associated with more frequent use of these coping strategies, which in turn is associated with higher levels of these psychological stress responses. The participants were 30 male and 94 female undergraduate and graduate students (mean age =20.4 years). Stress mindset, coping, and psychological stress responses were measured using self-report questionnaires. Six mediation analyses were performed with stress-is-enhancing mindset or stress-is-debilitating mindset as the independent variable, one of the psychological stress responses as the dependent variable, and the four coping strategies as mediators. Emotional expression partially mediated the relationship between a strong stress-is-debilitating mindset and higher irritability

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

    Directory of Open Access Journals (Sweden)

    Yuan Joshua S

    2008-08-01

    Full Text Available Abstract 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.

  16. Immune and stress responses in oysters with insights on adaptation.

    Science.gov (United States)

    Guo, Ximing; He, Yan; Zhang, Linlin; Lelong, Christophe; Jouaux, Aude

    2015-09-01

    Oysters are representative bivalve molluscs that are widely distributed in world oceans. As successful colonizers of estuaries and intertidal zones, oysters are remarkably resilient against harsh environmental conditions including wide fluctuations in temperature and salinity as well as prolonged air exposure. Oysters have no adaptive immunity but can thrive in microbe-rich estuaries as filter-feeders. These unique adaptations make oysters interesting models to study the evolution of host-defense systems. Recent advances in genomic studies including sequencing of the oyster genome have provided insights into oyster's immune and stress responses underlying their amazing resilience. Studies show that the oyster genomes are highly polymorphic and complex, which may be key to their resilience. The oyster genome has a large gene repertoire that is enriched for immune and stress response genes. Thousands of genes are involved in oyster's immune and stress responses, through complex interactions, with many gene families expanded showing high sequence, structural and functional diversity. The high diversity of immune receptors and effectors may provide oysters with enhanced specificity in immune recognition and response to cope with diverse pathogens in the absence of adaptive immunity. Some members of expanded immune gene families have diverged to function at different temperatures and salinities or assumed new roles in abiotic stress response. Most canonical innate immunity pathways are conserved in oysters and supported by a large number of diverse and often novel genes. The great diversity in immune and stress response genes exhibited by expanded gene families as well as high sequence and structural polymorphisms may be central to oyster's adaptation to highly stressful and widely changing environments. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Effect of childhood physical abuse on cortisol stress response.

    Science.gov (United States)

    Carpenter, Linda L; Shattuck, Thaddeus T; Tyrka, Audrey R; Geracioti, Thomas D; Price, Lawrence H

    2011-03-01

    Abuse and neglect are highly prevalent in children and have enduring neurobiological effects. Stressful early life environments perturb the hypothalamic-pituitary-adrenal (HPA) axis, which in turn may predispose to psychiatric disorders in adulthood. However, studies of childhood maltreatment and adult HPA function have not yet rigorously investigated the differential effects of maltreatment subtypes, including physical abuse. In this study, we sought to replicate our previous finding that childhood maltreatment was associated with attenuated cortisol responses to stress and determine whether the type of maltreatment was a determinant of the stress response. Salivary cortisol response to the Trier Social Stress Test (TSST) was examined in a non-clinical sample of women (n = 110). Subjects had no acute medical problems and were not seeking psychiatric treatment. Effects of five maltreatment types, as measured by the Childhood Trauma Questionnaire, on cortisol response to the TSST were investigated. To further examine the significant (p < 0.005) effect of one maltreatment type, women with childhood physical abuse (PA) (n = 20) were compared to those without past PA (n = 90). Women reporting childhood PA displayed a significantly blunted cortisol response to the TSST compared with subjects without PA, after controlling for estrogen use, age, other forms of maltreatment, and other potential confounds. There were no differences between PA and control groups with regard to physiological arousal during the stress challenge. In a non-clinical sample of women with minimal or no current psychopathology, physical abuse is associated with a blunted cortisol response to a psychosocial stress task.

  18. Peroxisome proliferator-activated receptor alpha acts as a mediator of endoplasmic reticulum stress-induced hepatocyte apoptosis in acute liver failure

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2016-07-01

    Full Text Available Peroxisome proliferator-activated receptor α (PPARα is a key regulator to ameliorate liver injury in cases of acute liver failure (ALF. However, its regulatory mechanisms remain largely undetermined. Endoplasmic reticulum stress (ER stress plays an important role in a number of liver diseases. This study aimed to investigate whether PPARα activation inhibits ER stress-induced hepatocyte apoptosis, thereby protecting against ALF. In a murine model of D-galactosamine (D-GalN- and lipopolysaccharide (LPS-induced ALF, Wy-14643 was administered to activate PPARα, and 4-phenylbutyric acid (4-PBA was administered to attenuate ER stress. PPARα activation ameliorated liver injury, because pre-administration of its specific inducer, Wy-14643, reduced the serum aminotransferase levels and preserved liver architecture compared with that of controls. The protective effect of PPARα activation resulted from the suppression of ER stress-induced hepatocyte apoptosis. Indeed, (1 PPARα activation decreased the expression of glucose-regulated protein 78 (Grp78, Grp94 and C/EBP-homologous protein (CHOP in vivo; (2 the liver protection by 4-PBA resulted from the induction of PPARα expression, as 4-PBA pre-treatment promoted upregulation of PPARα, and inhibition of PPARα by small interfering RNA (siRNA treatment reversed liver protection and increased hepatocyte apoptosis; (3 in vitro PPARα activation by Wy-14643 decreased hepatocyte apoptosis induced by severe ER stress, and PPARα inhibition by siRNA treatment decreased the hepatocyte survival induced by mild ER stress. Here, we demonstrate that PPARα activation contributes to liver protection and decreases hepatocyte apoptosis in ALF, particularly through regulating ER stress. Therefore, targeting PPARα could be a potential therapeutic strategy to ameliorate ALF.

  19. Quetiapine mitigates the ethanol-induced oxidative stress in brain tissue, but not in the liver, of the rat

    Directory of Open Access Journals (Sweden)

    Han JH

    2015-06-01

    Full Text Available Jin-hong Han,1,2 Hong-zhao Tian,2 Yang-yang Lian,1 Yi Yu,1 Cheng-biao Lu,2 Xin-min Li,3 Rui-ling Zhang,1 Haiyun Xu4 1The Second Affiliated Hospital of Xinxiang Medical University, 2School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 3Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada; 4The Mental Health Center, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: Quetiapine, an atypical antipsychotic, has been employed to treat alcoholic patients with comorbid psychopathology. It was shown to scavenge hydroxyl radicals and to protect cultured cells from noxious effects of oxidative stress, a pathophysiological mechanism involved in the toxicity of alcohol. This study compared the redox status of the liver and the brain regions of prefrontal cortex, hippocampus, and cerebellum of rats treated with or without ethanol and quetiapine. Ethanol administration for 1 week induced oxidative stress in the liver and decreased the activity of glutathione peroxidase and total antioxidant capacity (TAC there. Coadministration of quetiapine did not protect glutathione peroxidase and TAC in the liver against the noxious effect of ethanol, thus was unable to mitigate the ethanol-induced oxidative stress there. The ethanol-induced alteration in the redox status in the prefrontal cortex is mild, whereas the hippocampus and cerebellum are more susceptible to ethanol intoxication. For all the examined brain regions, coadministration of quetiapine exerted effective protection on the antioxidants catalase and total superoxide dismutase and on the TAC, thus completely blocking the ethanol-induced oxidative stress in these brain regions. These protective effects may explain the clinical observations that quetiapine reduced psychiatric symptoms intensity and maintained a good level of tolerability in chronic alcoholism with

  20. Growth and stress response mechanisms underlying post-feeding regenerative organ growth in the Burmese python.

    Science.gov (United States)

    Andrew, Audra L; Perry, Blair W; Card, Daren C; Schield, Drew R; Ruggiero, Robert P; McGaugh, Suzanne E; Choudhary, Amit; Secor, Stephen M; Castoe, Todd A

    2017-05-02

    Previous studies examining post-feeding organ regeneration in the Burmese python (Python molurus bivittatus) have identified thousands of genes that are significantly differentially regulated during this process. However, substantial gaps remain in our understanding of coherent mechanisms and specific growth pathways that underlie these rapid and extensive shifts in organ form and function. Here we addressed these gaps by comparing gene expression in the Burmese python heart, liver, kidney, and small intestine across pre- and post-feeding time points (fasted, one day post-feeding, and four days post-feeding), and by conducting detailed analyses of molecular pathways and predictions of upstream regulatory molecules across these organ systems. Identified enriched canonical pathways and upstream regulators indicate that while downstream transcriptional responses are fairly tissue specific, a suite of core pathways and upstream regulator molecules are shared among responsive tissues. Pathways such as mTOR signaling, PPAR/LXR/RXR signaling, and NRF2-mediated oxidative stress response are significantly differentially regulated in multiple tissues, indicative of cell growth and proliferation along with coordinated cell-protective stress responses. Upstream regulatory molecule analyses identify multiple growth factors, kinase receptors, and transmembrane receptors, both within individual organs and across separate tissues. Downstream transcription factors MYC and SREBF are induced in all tissues. These results suggest that largely divergent patterns of post-feeding gene regulation across tissues are mediated by a core set of higher-level signaling molecules. Consistent enrichment of the NRF2-mediated oxidative stress response indicates this pathway may be particularly important in mediating cellular stress during such extreme regenerative growth.

  1. Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion

    DEFF Research Database (Denmark)

    Santoni-Rugiu, Eric; Jelnes, Peter; Thorgeirsson, Snorri S

    2005-01-01

    created in the liver by a certain insult. This review will focus on molecular responses controlling activation and expansion of the hepatic progenitor cell niche, emphasizing similarities and differences in the microenvironments orchestrating regeneration by recruitment of progenitor cell populations...... cells, and recruited inflammatory cells as well as the variety of growth-modulating molecules produced and/or harboured by these elements. The cellular and molecular responses to different regenerative stimuli seem to depend on the injury inflicted and consequently on the molecular microenvironment...

  2. Social stress response in adolescents with bipolar disorder.

    Science.gov (United States)

    Casement, Melynda D; Goldstein, Tina R; Gratzmiller, Sarah M; Franzen, Peter L

    2018-05-01

    Theoretical models posit that stressors contribute to the onset and maintenance of bipolar disorder in adolescence through disruptions in stress physiology, but physiological response to stressors has not been evaluated in adolescents with bipolar illness. The present study tests the hypothesis that adolescents with bipolar disorder will have greater reactivity to a laboratory social stress task than healthy adolescents. Adolescents with bipolar illness (n = 27) and healthy adolescents (n = 28) completed a modified version of the Trier Social Stress Task. Stress response was assessed using high frequency heart rate variability (HF-HRV), heart rate (HR), mean arterial blood pressure (MAP), salivary cortisol, and subjective stress. Multilevel models were used to test for group differences in resting-state physiology, and stress reactivity and recovery. Adolescents with bipolar disorder had greater reactivity in HF-HRV (z = 3.32), but blunted reactivity in MAP (z = -3.08) and cortisol (z = -2.60), during the stressor compared to healthy adolescents. They also had lower resting HF-HRV (z = -3.49) and cortisol (z = -2.86), and higher resting HR (z = 3.56), than healthy adolescents. These results indicate that bipolar disorder is associated with disruptions in autonomic and endocrine response to stress during adolescence, including greater HF-HRV reactivity. Further research should evaluate whether these individual differences in stress physiology precede and predict the onset of mood episodes. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Eccentric-exercise induced inflammation attenuates the vascular responses to mental stress

    NARCIS (Netherlands)

    Paine, N.J.; Ring, C.; Aldred, S.; Bosch, J.A.; Wadley, A.J.; Veldhuijzen van Zanten, J.J.C.S.

    2013-01-01

    Mental stress has been identified as a trigger of myocardial infarction (MI), with inflammation and vascular responses to mental stress independently implicated as contributing factors. This study examined whether inflammation moderates the vascular responses to mental stress. Eighteen healthy male

  4. Respiratory Effects and Systemic Stress Response Following ...

    Science.gov (United States)

    Previous studies have demonstrated that exposure to the pulmonary irritant ozone causes myriad systemic metabolic and pulmonary effects attributed to sympathetic and hypothalamus-pituitary-adrenal (HPA) axis activation, which are exacerbated in metabolically impaired models. We examined respiratory and systemic effects following exposure to a sensory irritant acrolein to elucidate the systemic and pulmonary consequences in healthy and diabetic rat models. Male Wistar and Goto Kakizaki (GK) rats, a nonobese type II diabetic Wistar-derived model, were exposed by inhalation to 0, 2, or 4 ppm acrolein, 4 h/d for 1 or 2 days. Exposure at 4 ppm significantly increased pulmonary and nasal inflammation in both strains with vascular protein leakage occurring only in the nose. Acrolein exposure (4 ppm) also caused metabolic impairment by inducing hyperglycemia and glucose intolerance (GK > Wistar). Serum total cholesterol (GKs only), low-density lipoprotein (LDL) cholesterol (both strains), and free fatty acids (GK > Wistar) levels increased; however, no acrolein-induced changes were noted in branched-chain amino acid or insulin levels. These responses corresponded with a significant increase in corticosterone and modest but insignificant increases in adrenaline in both strains, suggesting activation of the HPA axis. Collectively, these data demonstrate that acrolein exposure has a profound effect on nasal and pulmonary inflammation, as well as glucose and lipid metabolis

  5. Response of Saccharomyces cerevisiae to cadmium stress

    International Nuclear Information System (INIS)

    Moreira, Luciana Mara Costa; Ribeiro, Frederico Haddad; Neves, Maria Jose; Porto, Barbara Abranches Araujo; Amaral, Angela M.; Menezes, Maria Angela B.C.; Rosa, Carlos Augusto

    2009-01-01

    The intensification of industrial activity has been greatly contributing with the increase of heavy metals in the environment. Among these heavy metals, cadmium becomes a serious pervasive environmental pollutant. The cadmium is a heavy metal with no biological function, very toxic and carcinogenic at low concentrations. The toxicity of cadmium and several other metals can be mainly attributed to the multiplicity of coordination complexes and clusters that they can form. Some aspects of the cellular response to cadmium were extensively investigated in the yeast Saccharomyces cerevisiae. The primary site of interaction between many toxic metals and microbial cells is the plasma membrane. Plasma-membrane permeabilisation has been reported in a variety of microorganisms following cadmium exposure, and is considered one mechanism of cadmium toxicity in the yeast. In this work, using the yeast strain S. cerevisiae W303-WT, we have investigated the relationships between Cd uptake and release of cellular metal ions (K + and Na + ) using neutron activation technique. The neutron activation was an easy, rapid and suitable technique for doing these metal determinations on yeast cells; was observed the change in morphology of the strains during the process of Cd accumulation, these alterations were observed by Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) during incorporation of cadmium. (author)

  6. Response of Saccharomyces cerevisiae to cadmium stress

    Energy Technology Data Exchange (ETDEWEB)

    Moreira, Luciana Mara Costa; Ribeiro, Frederico Haddad; Neves, Maria Jose [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Lab. de Radiobiologia], e-mail: luamatu@uol.com.br; Porto, Barbara Abranches Araujo; Amaral, Angela M.; Menezes, Maria Angela B.C. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Lab. de Ativacao Neutronica], e-mail: menezes@cdtn.br; Rosa, Carlos Augusto [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Microbiologia], e-mail: carlrosa@icb.ufmg

    2009-07-01

    The intensification of industrial activity has been greatly contributing with the increase of heavy metals in the environment. Among these heavy metals, cadmium becomes a serious pervasive environmental pollutant. The cadmium is a heavy metal with no biological function, very toxic and carcinogenic at low concentrations. The toxicity of cadmium and several other metals can be mainly attributed to the multiplicity of coordination complexes and clusters that they can form. Some aspects of the cellular response to cadmium were extensively investigated in the yeast Saccharomyces cerevisiae. The primary site of interaction between many toxic metals and microbial cells is the plasma membrane. Plasma-membrane permeabilisation has been reported in a variety of microorganisms following cadmium exposure, and is considered one mechanism of cadmium toxicity in the yeast. In this work, using the yeast strain S. cerevisiae W303-WT, we have investigated the relationships between Cd uptake and release of cellular metal ions (K{sup +} and Na{sup +}) using neutron activation technique. The neutron activation was an easy, rapid and suitable technique for doing these metal determinations on yeast cells; was observed the change in morphology of the strains during the process of Cd accumulation, these alterations were observed by Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) during incorporation of cadmium. (author)

  7. Psychological stress during exercise: immunoendocrine and oxidative responses.

    Science.gov (United States)

    Huang, Chun-Jung; Webb, Heather E; Evans, Ronald K; McCleod, Kelly A; Tangsilsat, Supatchara E; Kamimori, Gary H; Acevedo, Edmund O

    2010-12-01

    The purpose of this study was to examine the changes in catecholamines (epinephrine [EPI] and norepinephrine [NE]), interleukin-2 (IL-2) and a biomarker of oxidative stress (8-isoprostane) in healthy individuals who were exposed to a dual challenge (physical and psychological stress). Furthermore, this study also examined the possible relationships between catecholamines (NE and EPI) and 8-isoprostane and between IL-2 and 8-isoprostane following a combined physical and psychological challenge. Seven healthy male subjects completed two experimental conditions. The exercise-alone condition (EAC) consisted of cycling at 60% VO(2max) for 37 min, while the dual-stress condition (DSC) included 20 min of a mental challenge while cycling. DSC showed greater EPI and 8-isoprostane levels (significant condition by time interaction). NE and IL-2 revealed significant change across time in both conditions. In addition, following dual stress, EPI area-under-the-curve (AUC) demonstrated a positive correlation with NE AUC and IL-2 AUC. NE AUC was positively correlated with IL-2 AUC and peak 8-isoprostane, and peak IL-2 was positively correlated with peak 8-isoprostane in response to a dual stress. The potential explanation for elevated oxidative stress during dual stress may be through the effects of the release of catecholamines and IL-2. These findings may further provide the potential explanation that dual stress alters physiological homeostasis in many occupations including firefighting, military operations and law enforcement. A greater understanding of these responses to stress can assist in finding strategies (e.g. exercise training) to overcome the inherent psychobiological challenges associated with physically and mentally demanding professions.

  8. Heat indicators of oxidative stress, inflammation and metal transport show dependence of cadmium pollution history in the liver of female zebrafish.

    Science.gov (United States)

    Zhu, Qing-Ling; Guo, Sai-Nan; Yuan, Shuang-Shuang; Lv, Zhen-Ming; Zheng, Jia-Lang; Xia, Hu

    2017-10-01

    Environmental stressors such as high temperature and metal exposure may occur sequentially, simultaneously, previously in aquatic ecosystems. However, information about whether responses to high temperature depend on Cd exposure history is still unknown in fish. Zebrafish were exposed to 0 (group 1), 2.5 (group 2) and 5μg/L (group 3) cadmium (Cd) for 10 weeks, and then each group was subjected to Cd-free water maintained at 26°C and 32°C for 7days respectively. 26 indicators were used to compare differences between 26°C and 32°C in the liver of female zebrafish, including 5 biochemical indicators (activity of Cu/Zn-SOD, CAT and iNOS; LPO; MT protein), 8 molecular indicators of oxidative stress (mRNA levels of Nrf2, Cu/Zn-SOD, CAT, HSF1, HSF2, HSP70, MTF-1 and MT), 5 molecular indicators of inflammation (mRNA levels of IL-6, IL-1β, TNF-α, iNOS and NF-κB), 8 molecular indicators of metal transport (mRNA levels of, ZnT1, ZnT5, ZIP8, ZIP10, ATP7A, ATP7B and CTR1). All biochemical indicators were unchanged in group 1 and changed in group 2 and 3. Contrarily, differences were observed in almost all of molecular indicators of inflammation and metal transport in group 1, about half in group 2, and few in group 3. We also found that all molecular indicators of oxidative stress in group 2 and fewer in group 1 and 3 were significantly affected by heat. Our data indicated that heat indicators of oxidative stress, inflammation and metal transport showed dependence of previous cadmium exposure in the liver of zebrafish, emphasizing metal pollution history should be carefully considered when evaluating heat stress in fish. Copyright © 2017. Published by Elsevier B.V.

  9. Shark Cartilage Attenuates Oxidative Stress in the liver of Guinea Pigs Exposed to Carbon Tetrachloride and/or Gamma Irradiation

    International Nuclear Information System (INIS)

    Ibrahim, N.K.; Abd El Aziz, N.

    2009-01-01

    There is overwhelming evidence to indicate that oxidative stress is involved in the pathogenesis of several diseases. Carbon tetrachloride (CCl 4 ) and ionizing radiations are environmental pollutants well known to induce free radicals formation and oxidative stress. The objective of this work was to evaluate the effect of shark cartilage administration on CCl 4 and/or gamma radiation-induced oxidative damage in the liver. CCl 4 (1 ml/kg body wt) was subcutaneously administered to guinea pigs twice a week for four weeks. Gamma irradiation (RAD) was applied by whole body exposure of guinea pigs to 1.0 Gy/week up to a total dose of 4.0 Gy. Shark cartilage (ShC) was given to animals at a concentration of 1.0 g/kg body wt daily, one week before exposure to CCl 4 and/or gamma irradiation and during the experimental period. Animals sacrificed at the end of the experimental period showed that administration of shark cartilage has significantly attenuated the increase in liver malonaldehyde (MDA) observed in CCl 4 and/or irradiated guinea pigs. Furthermore, shark cartilage treatment has significantly increased the activity of antioxidant enzymes: superoxide dismutase (SOD) and catalase (CAT) and the content of reduced glutathione (GSH). The amelioration of oxidative stress induced in liver tissues of CCL 4 and/or irradiated guinea pigs treated with shark cartilage was associated with significant improvement in the activity of serum alanine amino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), as well as, bilirubin, albumin, and iron contents. It could be concluded that shark cartilage might protect liver tissues from oxidative injury induced by environmental pro-oxidants pollutants via modulating the antioxidant status and decreasing the process of lipid peroxidation

  10. Stretching the stress boundary: Linking air pollution health effects to a neurohormonal stress response.

    Science.gov (United States)

    Kodavanti, Urmila P

    2016-12-01

    Inhaled pollutants produce effects in virtually all organ systems in our body and have been linked to chronic diseases including hypertension, atherosclerosis, Alzheimer's and diabetes. A neurohormonal stress response (referred to here as a systemic response produced by activation of the sympathetic nervous system and hypothalamus-pituitary-adrenal (HPA)-axis) has been implicated in a variety of psychological and physical stresses, which involves immune and metabolic homeostatic mechanisms affecting all organs in the body. In this review, we provide new evidence for the involvement of this well-characterized neurohormonal stress response in mediating systemic and pulmonary effects of a prototypic air pollutant - ozone. A plethora of systemic metabolic and immune effects are induced in animals exposed to inhaled pollutants, which could result from increased circulating stress hormones. The release of adrenal-derived stress hormones in response to ozone exposure not only mediates systemic immune and metabolic responses, but by doing so, also modulates pulmonary injury and inflammation. With recurring pollutant exposures, these effects can contribute to multi-organ chronic conditions associated with air pollution. This review will cover, 1) the potential mechanisms by which air pollutants can initiate the relay of signals from respiratory tract to brain through trigeminal and vagus nerves, and activate stress responsive regions including hypothalamus; and 2) the contribution of sympathetic and HPA-axis activation in mediating systemic homeostatic metabolic and immune effects of ozone in various organs. The potential contribution of chronic environmental stress in cardiovascular, neurological, reproductive and metabolic diseases, and the knowledge gaps are also discussed. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. Published by Elsevier B.V.

  11. Response to stress in Drosophila is mediated by gender, age and stress paradigm.

    Science.gov (United States)

    Neckameyer, Wendi S; Nieto-Romero, Andres R

    2015-01-01

    All living organisms must maintain equilibrium in response to internal and external challenges within their environment. Changes in neural plasticity (alterations in neuronal populations, dendritic remodeling, and synaptic turnover) are critical components of the homeostatic response to stress, which has been strongly implicated in the onset of affective disorders. However, stress is differentially perceived depending on the type of stress and its context, as well as genetic background, age and sex; therefore, an individual's maintenance of neuronal homeostasis must differ depending upon these variables. We established Drosophila as a model to analyze homeostatic responses to stress. Sexually immature and mature females and males from an isogenic wild-type strain raised under controlled environmental conditions were exposed to four reproducible and high-throughput translatable stressors to facilitate the analysis of a large number of animals for direct comparisons. These animals were assessed in an open-field arena, in a light-dark box, and in a forced swim test, as well as for sensitivity to the sedative effects of ethanol. These studies establish that immature and mature females and males represent behaviorally distinct populations under control conditions as well as after exposure to different stressors. Therefore, the neural substrates mediating the stress response must be differentially expressed depending upon the hormonal status of the brain. In addition, an adaptive response to a given stressor in one paradigm was not predictive for outcomes in other paradigms.

  12. Stress effects on mood, HPA axis, and autonomic response: comparison of three psychosocial stress paradigms.

    Directory of Open Access Journals (Sweden)

    Grace E Giles

    Full Text Available Extensive experimental psychology research has attempted to parse the complex relationship between psychosocial stress, mood, cognitive performance, and physiological changes. To do so, it is necessary to have effective, validated methods to experimentally induce psychosocial stress. The Trier Social Stress Test (TSST is the most commonly used method of experimentally inducing psychosocial stress, but it is resource intensive. Less resource intense psychosocial stress tasks include the Socially Evaluative Cold Pressor Task (SECPT and a computerized mental arithmetic task (MAT. These tasks effectively produce a physiological and psychological stress response and have the benefits of requiring fewer experimenters and affording data collection from multiple participants simultaneously. The objective of this study was to compare the magnitude and duration of these three experimental psychosocial stress induction paradigms. On each of four separate days, participants completed either a control non-stressful task or one of the three experimental stressors: the TSST, SECPT, or MAT. We measured mood, working memory performance, salivary cortisol and alpha-amylase (AA, and heart rate. The TSST and SECPT exerted the most robust effects on mood and physiological measures. TSST effects were generally evident immediately post-stress as well as 10- and 20-minutes after stress cessation, whereas SECPT effects were generally limited to the duration of the stressor. The stress duration is a key determinant when planning a study that utilizes an experimental stressor, as researchers may be interested in collecting dependent measures prior to stress cessation. In this way, the TSST would allow the investigator a longer window to administer tasks of interest.

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

    Science.gov (United States)

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

    2018-05-01

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

  14. Modulation of ASK1 expression during overexpression of Trx and HSP70 in stressed fish liver mitochondria.

    Science.gov (United States)

    Padmini, Ekambaram; Vijaya Geetha, Bose

    2009-09-01

    Mitochondrial heat shock protein 70 (mtHSP70) is found to play a primary role in cellular defense against physiological stress like exposure to environmental contaminants and helpful in the maintenance of cellular homeostasis by promoting the cell survival. In the present investigation, the environmental-stress-induced increase in mtHSP70 levels along with the quantification of apoptosis signal regulating kinase 1 (ASK1) and thioredoxin (Trx) were measured in the liver mitochondria of grey mullets (Mugil cephalus) collected from the polluted Ennore estuary and the unpolluted Kovalam estuary for a period of 2 years. The results showed elevated lipid peroxide (LPO) and decreased total antioxidant capacity along with the decrease in mitochondrial viability percentage. Mitochondrial HSP70, ASK1, and Trx levels were increased under this stress condition. A 42% increase in LPO levels and 18% decrease in mitochondrial survivality were observed in the polluted-site fish liver mitochondria when compared to the results of unpolluted estuary. We also report that, under observed oxidative stress condition in Ennore fish samples, the ASK1 levels are only moderately elevated (13% increase). This may be due to mitochondrial-HSP70-induced adaptive tolerance signaling for the activation of Trx (22% increase) which suppresses the ASK1 expression thereby promoting the cell survival that leads to the maintenance of the cellular homeostasis.

  15. Physiological responses of genotypes soybean to simulated drought stress

    Directory of Open Access Journals (Sweden)

    Eleonóra Krivosudská

    2016-12-01

    Full Text Available The objective of this research was to investigate possible genetic variation in the sensitivity of soybean cultivars for nitrogen fixation rates in response to soil drying. The work confirmed that the selected physiological characteristics (RWC, osmotic potential, stress index and created nodules on roots are good evaluating parameters for the determination of water stress in plant. In the floricultural year 2014 an experiment with four genetic resources of soybean was launched. Sowing of Maverick (USA, Drina (HRV, Nigra (SVK and Polanka (CZK genotypes was carried out in the containers of 15 l capacity. This stress had a negative impact on the physiological parameters. By comparing the RWC values, the decrease was more significant at the end of dehydration, which was monitored in Maverick and Drina genotypes using the Nitrazon inoculants and water stress effect. Inoculated stressed Nigra and Polanka genotypes have kept higher water content till the end of dehydration period. Also the proline accumulation was monitored during the water stress, whilst higher content of free proline reached of Maverick. More remarkable decrease of osmotic potential was again registered in a foreign Drina and Maverick genotypes in the inoculated variations. Nigra and Polanka genotypes responses not so significant in the given conditions.

  16. Drought Stress Responses of Sunflower Germplasm Developed after Wide Hybridization

    Directory of Open Access Journals (Sweden)

    Roumiana Dimova Vassilevska-Ivanova

    2016-10-01

    Full Text Available Response of sunflower germplasms viz. cultivated sunflower H. annuus and two breeding lines H. annuus x T. rotundifolia and H. annuus x V. encelioides developed after wide hybridization were used for identification of drought tolerant sunflower genotypes at the seedling growth stage. Three water stress levels of zero (control, -0.4, and -0.8 MPa were developed using polyethyleneglycol-6000 (PEG-6000. Physiological and biochemical stress determining parameters such as root and shoots length, fresh weight, antioxidant enzyme activities (superoxide dismutase (SOD, catalase (CAT, guaiacol peroxidase (GPO, ascorbate peroxidase (APX and antioxidant metabolite content (total antioxidant capacity, total phenols and total flavonoids content were compared between seedlings of all three genotypes. Results revealed that sunflower genotypes have similar responses at two osmotic potentials for shoot and root length and fresh weight. The data also showed that drought stresss could induce oxidative stress, as indicated by the increase level of ascorbate peroxidase and guaiacol peroxidase at -04 MPa in H. annuus cv 1114. Although the activity of ascorbate peroxidase and guaiacol peroxidase was differentially influenced by drought, the changes of antioxidant enzyme activities such as catalase, superoxide dismutase, guaiacol peroxidase, and ascorbate peroxidase subjected to drought stress follow a similar pattern in both breeding lines, indicating that similar defense systems might be involved in the oxidative stress injury in sunflowers. Increase in content of phenols and flavonoids were detected for all three genotypes under stress, which showed that these were major antioxidant metabolites in scavenging cellular H2O2.

  17. Increased risk of nonalcoholic fatty liver disease with occupational stress in Chinese policemen: A 4-year cohort study.

    Science.gov (United States)

    Li, Chen; Xing, Jing-Jing; Shan, An-Qi; Leng, Ling; Liu, Jin-Chuan; Yue, Song; Yu, Hao; Chen, Xi; Tian, Feng-Shi; Tang, Nai-Jun

    2016-11-01

    Nonalcoholic fatty liver disease (NAFLD) and occupational stress have been recognized as major public health concerns. We aimed to explore whether occupational stress was associated with NAFLD in a police population.A total of 6559 male police officers were recruited for this prospective study in April 2007. Among them, 2367 eligible subjects participated in follow-up from 2008 to 2011. NAFLD was diagnosed based on standard criteria. Occupational stress was evaluated by Occupational Stress Inventory-Revised scores.The incidence of NAFLD was 31.2% in the entire police. After adjusting for traditional risk factors, moderate occupational stress (MOS), high occupational stress (HOS), and high personal strain (HPS) were risk factors (MOS: hazard ratio [HR] = 1.237, 95% confidence interval [CI] = 1.049-1.460; HOS: HR = 1.727, 95% CI = 1.405-2.124; HPS: HR = 3.602, 95% CI = 1.912-6.787); and low occupational stress (LOS) and low personal strain (LPS) were protective factors (LOS: HR = 0.366, 95% CI = 0.173-0.776; LPS: HR = 0.490, 95% CI = 0.262-0.919) for NAFLD in the entire police cohort. HOS and HPS remained robust among traffic police.HOS and HPS were independent predictors for the development of NAFLD in a Chinese police population. Additional future prospective investigations are warranted to validate our findings.

  18. Cortisol stress response in post-traumatic stress disorder, panic disorder, and major depressive disorder patients.

    Science.gov (United States)

    Wichmann, Susann; Kirschbaum, Clemens; Böhme, Carsten; Petrowski, Katja

    2017-09-01

    Previous research has focussed extensively on the distinction of HPA-axis functioning between patient groups and healthy volunteers, with relatively little emphasis on a direct comparison of patient groups. The current study's aim was to analyse differences in the cortisol stress response as a function of primary diagnosis of panic disorder (PD), post-traumatic stress disorder (PTSD), and major depressive disorder (MDD). A total of n=30 PD (mean age±SD: 36.07±12.56), n=23 PTSD (41.22±10.17), n=18 MDD patients (39.00±14.93) and n=47 healthy control (HC) individuals (35.51±13.15) participated in this study. All the study participants were female. The Trier Social Stress Test (TSST) was used for reliable laboratory stress induction. Blood sampling accompanied the TSST for cortisol and ACTH assessment. Panic-related, PTSD-specific questionnaires and the Beck Depression Inventory II were handed out for the characterisation of the study groups. Repeated measure ANCOVAs were conducted to test for main effects of time or group and for interaction effects. Regression analyses were conducted to take comorbid depression into account. 26.7% of the PD patients, 43.5% of the PTSD patients, 72.2% of the MDD patients and 80.6% of the HC participants showed a cortisol stress response upon the TSST. ANCOVA revealed a cortisol hypo-responsiveness both in PD and PTSD patients, while no significant group differences were seen in the ACTH concentrations. Additional analyses showed no impact of comorbid depressiveness on the cortisol stress response. MDD patients did not differ in the hormonal stress response neither compared to the HC participants nor to the PD and PTSD patients. Our main findings provide evidence of a dissociation between the cortisol and ACTH concentrations in response to the TSST in PTSD and in PD patients, independent of comorbid depression. Our results further support overall research findings of a cortisol hypo-responsiveness in PD patients. A hypo-response

  19. Deep Transcriptomic Analysis of Black Rockfish (Sebastes schlegelii) Provides New Insights on Responses to Acute Temperature Stress.

    Science.gov (United States)

    Lyu, Likang; Wen, Haishen; Li, Yun; Li, Jifang; Zhao, Ji; Zhang, Simin; Song, Min; Wang, Xiaojie

    2018-06-14

    In the present study, we conducted an RNA-Seq analysis to characterize the genes and pathways involved in acute thermal and cold stress responses in the liver of black rockfish, a viviparous teleost that has the ability to cope with a wide range of temperature changes. A total of 584 annotated differentially expressed genes (DEGs) were identified in all three comparisons (HT vs NT, HT vs LT and LT vs NT). Based on an enrichment analysis, DEGs with a potential role in stress accommodation were classified into several categories, including protein folding, metabolism, immune response, signal transduction, molecule transport, membrane, and cell proliferation/apoptosis. Considering that thermal stress has a greater effect than cold stress in black rockfish, 24 shared DEGs in the intersection of the HT vs LT and HT vs NT groups were enriched in 2 oxidation-related gene ontology (GO) terms. Nine important heat-stress-reducing pathways were significantly identified and classified into 3 classes: immune and infectious diseases, organismal immune system and endocrine system. Eight DEGs (early growth response protein 1, bile salt export pump, abcb11, hsp70a, rtp3, 1,25-dihydroxyvitamin d(3) 24-hydroxylase, apoa4, transcription factor jun-b-like and an uncharacterized gene) were observed among all three comparisons, strongly implying their potentially important roles in temperature stress responses.

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

    Directory of Open Access Journals (Sweden)

    Yuanyuan Zhang

    2014-06-01

    Full Text Available 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.

  1. Oxidative and ER stress-dependent ASK1 activation in steatotic hepatocytes and Kupffer cells sensitizes mice fatty liver to ischemia/reperfusion injury.

    Science.gov (United States)

    Imarisio, Chiara; Alchera, Elisa; Bangalore Revanna, Chandrashekar; Valente, Guido; Follenzi, Antonia; Trisolini, Elena; Boldorini, Renzo; Carini, Rita

    2017-11-01

    Steatosis intensifies hepatic ischemia/reperfusion (I/R) injury increasing hepatocyte damage and hepatic inflammation. This study evaluates if this process is associated to a differential response of steatotic hepatocytes (HP) and Kupffer cells (KC) to I/R injury and investigates the molecular mechanisms involved. Control or steatotic (treated with 50 μmol palmitic acid, PA) mouse HP or KC were exposed to hypoxia/reoxygenation (H/R). C57BL/6 mice fed 9 week with control or High Fat diet underwent to partial hepatic IR. PA increased H/R damage of HP and further activated the ASK1-JNK axis stimulated by ER stress during H/R. PA also induced the production of oxidant species (OS), and OS prevention nullified the capacity of PA to increase H/R damage and ASK1/JNK stimulation. ASK1 inhibition prevented JNK activation and entirely protected HP damage. In KC, PA directly activated ER stress, ASK1 and p38 MAPK and increased H/R damage. However, in contrast to HP, ASK1 inhibition further increased H/R damage by preventing p38 MAPK activation. In mice liver, steatosis induced the expression of activated ASK1 in only KC, whereas I/R exposure of steatotic liver activated ASK1 expression also in HP. "In vivo", ASK1 inhibition prevented ASK1, JNK and p38 MAPK activation and protected I/R damage and expression of inflammatory markers. Lipids-induced ASK1 stimulation differentially affects HP and KC by promoting cytotoxic or protective signals. ASK1 increases H/R damage of HP by stimulating JNK and protects KC activating p38MAPK. These data support the potentiality of the therapeutic employment of ASK1 inhibitors that can antagonize the damaging effects of I/R upon fatty liver surgery by the contextual reduction of HP death and of KC-mediated reactions. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Patterns of Sympathetic Responses Induced by Different Stress Tasks

    Science.gov (United States)

    Fechir, M; Schlereth, T; Purat, T; Kritzmann, S; Geber, C; Eberle, T; Gamer, M; Birklein, F

    2008-01-01

    Stress tasks are used to induce sympathetic nervous system (SNS) arousal. However, the efficacy and the patterns of SNS activation have not been systematically compared between different tasks. Therefore, we analyzed SNS activation during the following stress tasks: Presentation of negative, positive, and – as a control – neutral affective pictures, Color-Word interference test (CWT), mental arithmetic under time limit, singing a song aloud, and giving a spontaneous talk. We examined 11 healthy subjects and recorded the following SNS parameters: Activation of emotional sweating by quantitative sudometry, skin vasoconstriction by laser-Doppler flowmetry, heart rate by ECG, blood pressure by determination of pulse wave transit time (PWTT), and electromyographic (EMG) activity of the trapezius muscle. Moreover, subjective stress ratings were acquired for each task using a visual analog scale. All tasks were felt significantly stressful when compared to viewing neutral pictures. However, SNS activation was not reliable: Affective pictures did not induce a significant SNS response; singing, giving a talk and mental arithmetic selectively increased heart rate and emotional sweating. Only the CWT globally activated the SNS. Regarding all tasks, induction of emotional sweating, increase of heart rate and blood pressure significantly correlated with subjective stress ratings, in contrast to EMG and skin vasoconstriction. Our results show that the activation of the SNS widely varies depending on the stress task. Different stress tasks differently activate the SNS, which is an important finding when considering sympathetic reactions - in clinical situations and in research. PMID:19018304

  3. Differential effects of exposure to parasites and bacteria on stress response in turbot Scophthalmus maximus simultaneously stressed by low water depth.

    Science.gov (United States)

    Rodríguez-Quiroga, J J; Otero-Rodiño, C; Suárez, P; Nieto, T P; García Estévez, J M; San Juan, F; Soengas, J L

    2017-07-01

    The stress response of turbot Scophthalmus maximus was evaluated in fish maintained 8 days under different water depths, normal (NWD, 30 cm depth, total water volume 40 l) or low (LWD, 5 cm depth, total water volume 10 l), in the additional presence of infection-infestation of two pathogens of this species. This was caused by intraperitoneal injection of sublethal doses of the bacterium Aeromonas salmonicida subsp. salmonicida or the parasite Philasterides dicentrarchi (Ciliophora:Scuticociliatida). The LWD conditions were stressful for fish, causing increased levels of cortisol in plasma, decreased levels of glycogen in liver and nicotinamide adenine dinucleotide phosphate (NADP) and increased activities of G6Pase and GSase. The presence of bacteria or parasites in fish under NWD resulted in increased cortisol levels in plasma whereas in liver, changes were of minor importance including decreased levels of lactate and GSase activity. The simultaneous presence of bacteria and parasites in fish under NWD resulted a sharp increase in the levels of cortisol in plasma and decreased levels of glucose. Decreased levels of glycogen and lactate and activities of GSase and glutathione reductase (GR), as well as increased activities of glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and levels of nicotinamide adenine dinucleotide phosphate (NADPH) occurred in the same fish in liver. Finally, the presence of pathogens in S. maximus under stressful conditions elicited by LWD resulted in synergistic actions of both type of stressors in cortisol levels. In liver, the presence of bacteria or parasites induced a synergistic action on several variables such as decreased activities of G6Pase and GSase as well as increased levels of NADP and NADPH and increased activities of GPase, G6PDH and 6PGDH. © 2017 The Fisheries Society of the British Isles.

  4. Possible role of Arthrospira platensis in reversing oxidative stress-mediated liver damage in rats exposed to lead.

    Science.gov (United States)

    Khalil, Samah R; Elhady, Walaa M; Elewa, Yaser H A; Abd El-Hameed, Noura E; Ali, Sozan A

    2018-01-01

    Environmental pollutants, particularly metallic elements, mobilized and released into the environment, eventually accumulate in the food chain and thus pose a serious threat to human and animal health. In the present study, the role of Arthrospira (Spirulina platensis; SP) as a protector against oxidative stress-mediated liver damage induced by an exposure to lead acetate (LA; as a metallic pollutant) was assessed. To achieve this aim, rats were orally administered with 300 mg/kg bw SP for 15 days, before and concurrently with an intraperitoneal injection of 50 mg/kg bw LA (6 injections throughout 15 days). As a result, co-administration of SP with LA reduced the amount of lead that accumulated in both blood and liver tissue of the exposed rats and minimized the increased levels of lipid peroxidation, protein oxidation, DNA oxidative damage, and liver enzyme endpoints. In addition, because of SP administration, the levels of depleted biomarkers of antioxidant status and total antioxidant capacity in LA-exposed rats improved. Moreover, SP protected the liver tissue against the changes caused by LA exposure and also decreased the reactivity of HSP70 in the cytoplasm of hepatocytes. Collectively, our data suggest that SP has a potential use as a food supplement in the regions highly polluted with heavy metals such as lead. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Toxicity of thallium on isolated rat liver mitochondria: the role of oxidative stress and MPT pore opening.

    Science.gov (United States)

    Eskandari, M R; Mashayekhi, Vida; Aslani, Majid; Hosseini, Mir-Jamal

    2015-02-01

    Thallium(I) is a highly toxic heavy metal; however, up to now, its mechanisms are poorly understood. The authors' previous studies showed that this compound could induce reactive oxygen species (ROS) formation, reduced glutathione (GSH) oxidation, membrane lipid peroxidation, and mitochondrial membrane potential (MMP) collapse in isolated rat hepatocyte. Because the liver is the storage site of thallium, it seems that the liver mitochondria are one of the important targets for hepatotoxicity. In this investigation, the effects of thallium on mitochondria were studied to investigate its mechanisms of toxicity. Mitochondria were isolated from rat liver and incubated with different concentrations of thallium (25-200 µM). Thallium(I)-treated mitochondria showed a marked elevation in oxidative stress parameters accompanied by MMP collapse when compared with the control group. These results showed that different concentrations of thallium (25-200 µM) induced a significant (P thallium(I)-induced liver toxicity is a result of the disruptive effect of this metal on the mitochondrial respiratory complexes (I, II, and IV), which are the obvious causes of metal-induced ROS formation and ATP depletion. The latter two events, in turn, trigger cell death signaling via opening of mitochondrial permeability transition pore and cytochrome c expulsion. © 2013 Wiley Periodicals, Inc.

  6. Effect of Fenugreek (Trigonella Foenum-Graecum) Supplementation on Radiation-Induced Oxidative Stress in Liver and Kidney of Rats

    Energy Technology Data Exchange (ETDEWEB)

    EI-Tawil, G A [Radiation Biology Department, National Centre for Radiation Research and Technology (NCRRT), Atomic Energy Authority, Cairo (Egypt)

    2009-07-01

    Whole body exposure to ionizing radiation provokes oxidative damage, organ dysfunction and metabolic disturbances. Fenugreek (Trigonella foenumgraecum L. Leguminosae), one of the oldest medicinal plants rich in polyphenolic compounds is known to possess antioxidant properties. The present study was designed to determine the possible protective effect of fenugreek, against {gamma}-radiation-induced oxidative stress in liver and kidney tissues of rats. In parallel, the alteration in the activity of serum alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as markers of liver function, creatinine and urea levels as markers of kidney function. In addition, serum glucose and insulin levels were determined as markers for carbohydrate metabolism. Irradiated rats were whole body exposed to 3.5 Gy (Acute dose) {gamma}-radiations. Fenugreek-treated irradiated rats received 1g fenugreek seed powder/kg body weight/day, by gavages, during 7 days before irradiation. Animals were sacrificed on the 1 sl day after irradiation. The results obtained demonstrated that exposure to ionizing radiation induced significant decreases in SOD and CAT activities and GSH content associated to significant increase of TBARS levels in liver and kidney. Fenugreek treatment has significantly attenuated radiation-induced oxidative stress in both tissues, which was substantiated by the significant amelioration of serum ALP, AST and ALT activities, creatinine, urea, glucose, and insulin levels. It could be concluded that fenugreek would protect from oxidative damage and metabolic disturbances induced by ionizing irradiation.

  7. Effect of Fenugreek (Trigonella Foenum-Graecum) Supplementation on Radiation-Induced Oxidative Stress in Liver and Kidney of Rats

    International Nuclear Information System (INIS)

    EI-Tawil, G.A.

    2009-01-01

    Whole body exposure to ionizing radiation provokes oxidative damage, organ dysfunction and metabolic disturbances. Fenugreek (Trigonella foenumgraecum L. Leguminosae), one of the oldest medicinal plants rich in polyphenolic compounds is known to possess antioxidant properties. The present study was designed to determine the possible protective effect of fenugreek, against γ-radiation-induced oxidative stress in liver and kidney tissues of rats. In parallel, the alteration in the activity of serum alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as markers of liver function, creatinine and urea levels as markers of kidney function. In addition, serum glucose and insulin levels were determined as markers for carbohydrate metabolism. Irradiated rats were whole body exposed to 3.5 Gy (Acute dose) γ-radiations. Fenugreek-treated irradiated rats received 1g fenugreek seed powder/kg body weight/day, by gavages, during 7 days before irradiation. Animals were sacrificed on the 1 sl day after irradiation. The results obtained demonstrated that exposure to ionizing radiation induced significant decreases in SOD and CAT activities and GSH content associated to significant increase of TBARS levels in liver and kidney. Fenugreek treatment has significantly attenuated radiation-induced oxidative stress in both tissues, which was substantiated by the significant amelioration of serum ALP, AST and ALT activities, creatinine, urea, glucose, and insulin levels. It could be concluded that fenugreek would protect from oxidative damage and metabolic disturbances induced by ionizing irradiation

  8. Enterovirus Control of Translation and RNA Granule Stress Responses.

    Science.gov (United States)

    Lloyd, Richard E

    2016-03-30

    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.

  9. Eye surface temperature detects stress response in budgerigars (Melopsittacus undulatus).

    Science.gov (United States)

    Ikkatai, Yuko; Watanabe, Shigeru

    2015-08-05

    Previous studies have suggested that stressors not only increase body core temperature but also body surface temperature in many animals. However, it remains unclear whether surface temperature could be used as an alternative to directly measure body core temperature, particularly in birds. We investigated whether surface temperature is perceived as a stress response in budgerigars. Budgerigars have been used as popular animal models to investigate various neural mechanisms such as visual perception, vocal learning, and imitation. Developing a new technique to understand the basic physiological mechanism would help neuroscience researchers. First, we found that cloacal temperature correlated with eye surface temperature. Second, eye surface temperature increased after handling stress. Our findings suggest that eye surface temperature is closely related to cloacal temperature and that the stress response can be measured by eye surface temperature in budgerigars.

  10. [Regulation of heat shock gene expression in response to stress].

    Science.gov (United States)

    Garbuz, D G

    2017-01-01

    Heat shock (HS) genes, or stress genes, code for a number of proteins that collectively form the most ancient and universal stress defense system. The system determines the cell capability of adaptation to various adverse factors and performs a variety of auxiliary functions in normal physiological conditions. Common stress factors, such as higher temperatures, hypoxia, heavy metals, and others, suppress transcription and translation for the majority of genes, while HS genes are upregulated. Transcription of HS genes is controlled by transcription factors of the HS factor (HSF) family. Certain HSFs are activated on exposure to higher temperatures or other adverse factors to ensure stress-induced HS gene expression, while other HSFs are specifically activated at particular developmental stages. The regulation of the main mammalian stress-inducible factor HSF1 and Drosophila melanogaster HSF includes many components, such as a variety of early warning signals indicative of abnormal cell activity (e.g., increases in intracellular ceramide, cytosolic calcium ions, or partly denatured proteins); protein kinases, which phosphorylate HSFs at various Ser residues; acetyltransferases; and regulatory proteins, such as SUMO and HSBP1. Transcription factors other than HSFs are also involved in activating HS gene transcription; the set includes D. melanogaster GAF, mammalian Sp1 and NF-Y, and other factors. Transcription of several stress genes coding for molecular chaperones of the glucose-regulated protein (GRP) family is predominantly regulated by another stress-detecting system, which is known as the unfolded protein response (UPR) system and is activated in response to massive protein misfolding in the endoplasmic reticulum and mitochondrial matrix. A translational fine tuning of HS protein expression occurs via changing the phosphorylation status of several proteins involved in translation initiation. In addition, specific signal sequences in the 5'-UTRs of some HS

  11. Role of the peroxisome proliferator-activated receptor α (PPARα) in responses to trichloroethylene and metabolites, trichloroacetate and dichloroacetate in mouse liver

    International Nuclear Information System (INIS)

    Laughter, Ashley R.; Dunn, Corrie S.; Swanson, Cynthia L.; Howroyd, Paul; Cattley, Russell C.; Christopher Corton, J.

    2004-01-01

    Trichloroethylene (TCE) is an industrial solvent and a widespread environmental contaminant. Induction of liver cancer in mice by TCE is thought to be mediated by two carcinogenic metabolites, dichloroacetate (DCA) and trichloroacetate (TCA). TCE is considered to be a relatively weak peroxisome proliferator (PP), a group of rodent hepatocarcinogens that cause adaptive responses in liver through the PP-activated receptor alpha (PPARα). The objectives of this study were to determine whether effects of TCE, TCA and DCA in the liver associated with carcinogenesis are mediated by PPARα. Male wild-type and PPARα-null mice were given TCE by gavage for 3 days or 3 weeks; TCA or DCA were given in the drinking water for 1 week. Increases in relative liver and kidney weights by TCE were dependent on PPARα whereas liver weight increases by DCA were PPARα-independent. Dose-dependent increases in hepatocyte proliferation observed in wild-type mice after TCE exposure as determined by BrdU-labeling of hepatocytes were PPARα-dependent. Transcript profiling using macroarrays containing ∼1200 genes showed that 93% (40 out of 43) of all expression changes observed in wild-type mice upon TCE exposure were dependent on PPARα and included known targets of PP (Cyp4a12, epidermal growth factor receptor) and additional genes involved in cell growth. Increases in enzymes that catalyze β- and ω-oxidation of fatty acids were dependent on PPARα after exposure to TCE, TCA or DCA. TCE altered a unique set of genes in the livers of PPARα-null mice compared to wild-type mice including those that respond to different forms of stress. These data support the hypothesis that PPARα plays a dominant role in mediating the effects associated with hepatocarcinogenesis upon TCE exposure

  12. Protective Effect of Argan and Olive Oils against LPS-Induced Oxidative Stress and Inflammation in Mice Livers

    Directory of Open Access Journals (Sweden)

    Soufiane El Kamouni

    2017-10-01

    Full Text Available Sepsis causes severe dysregulation of organ functions, via the development of oxidative stress and inflammation. These pathophysiological mechanisms are mimicked in mice injected with bacterial lipopolysaccharide (LPS. Here, protective properties of argan oil against LPS-induced oxidative stress and inflammation are explored in the murine model. Mice received standard chow, supplemented with argan oil (AO or olive oil (OO for 25 days, before septic shock was provoked with a single intraperitoneal injection of LPS, 16 hours prior to animal sacrifice. In addition to a rise in oxidative stress and inflammatory markers, injected LPS also caused hepatotoxicity, accompanied by hyperglycemia, hypercholesterolemia and hyperuremia. These LPS-associated toxic effects were blunted by AO pretreatment, as corroborated by normal plasma parameters and cell stress markers (glutathione: GSH and antioxidant enzymology (catalase, CAT; superoxide dismutase, SOD and glutathione peroxidase, GPx. Hematoxylin–eosin staining revealed that AO can protect against acute liver injury, maintaining a normal status, which is pointed out by absent or reduced LPS-induced hepatic damage markers (i.e., alanine aminotransferase (ALT and aspartate transaminase (AST. Our work also indicated that AO displayed anti-inflammatory activity, due to down-regulations of genes encoding pro-inflammatory cytokines Interleukin-6 (IL-6 and Tumor Necrosis Factor-α (TNF-α and in up-regulations of the expression of anti-inflammatory genes encoding Interleukin-4 (IL-4 and Interleukin-10 (IL-10. OO provided animals with similar, though less extensive, protective changes. Collectively our work adds compelling evidence to the protective mechanisms of AO against LPS-induced liver injury and hence therapeutic potentialities, in regard to the management of human sepsis. Activations of IL-4/Peroxisome Proliferator-Activated Receptors (IL-4/PPARs signaling and, under LPS, an anti-inflammatory IL-10/Liver

  13. CENTRAL AMYGDALOID INVOLVEMENT IN NEUROENDOCRINE CORRELATES OF CONDITIONED STRESS RESPONSES

    NARCIS (Netherlands)

    ROOZENDAAL, B; KOOLHAAS, JM; BOHUS, B

    The purpose of this study was to examine the effects of bilateral electrolytic lesions of the central nucleus of the amygdala (CEA) in comparison with sham lesions on neuroendocrine responses during conditioned emotional stress in male Wistar rats. Lesions in the CEA, made either before or after the

  14. Physiological response of heat stressed broiler chickens to ...

    African Journals Online (AJOL)

    Effect of supplementing the drinking water of broilers reared under natural heat stress with ammonium chloride (NH4Cl), sodium bicarbonate (NaHCO3), calcium chloride (CaCl2) and ascorbic acid (AA) on physiological response was investigated. A 200, one-day Arbor acre chicks were randomly allotted to five treatments in ...

  15. Oxidative stress response pathways: Fission yeast as archetype

    DEFF Research Database (Denmark)

    Papadakis, Manos A.; Workman, Christopher

    2015-01-01

    Schizosaccharomyces pombe is a popular model eukaryotic organism to study diverse aspects of mammalian biology, including responses to cellular stress triggered by redox imbalances within its compartments. The review considers the current knowledge on the signaling pathways that govern the transc...

  16. Physiological responses of food animals to road transportation stress

    African Journals Online (AJOL)

    STORAGESEVER

    2009-12-29

    Dec 29, 2009 ... transportation are numerous and the responses of the animal to them are complex, non-specific and ..... at 3 h after a 6 h journey in male Japanese goats. During ..... animals are subjected to concomitant action of transport- tation and heat stress .... those measured in moving vehicles (Warriss et al., 1993).

  17. Variability salt stress response analysis of Tunisian natural ...

    African Journals Online (AJOL)

    We evaluated the responses to salt stress of 106 Medicago truncatula lines from 11 Tunisian natural populations collected from areas that varied in soil composition, salinity and water availability. Five references lines were also included in this study. Plants were cultivated in two treatments (0 and 50 mM of NaCl) during a ...

  18. Long-term salt stress responsive growth, carbohydrate metabolism ...

    African Journals Online (AJOL)

    We investigated the long-term responses of tobacco tissues to salt stress, with a particular interest for growth parameters, proline (Pro) accumulation, and carbohydrate metabolism. Exposure of 17-day-old tobacco plants to 0.2 M NaCl was followed by a higher decrease in dry matter in roots than shoots with a decrease of ...

  19. Differential response to water deficit stress in alfalfa ( Medicago ...

    African Journals Online (AJOL)

    The present study was fixed as objective to compare the response to water deficit (33% of field capacity, FC) stress of eight cultivars of Medicago sativa, originating from the Mediterranean basin. Comparison was performed on some key parameters such as growth, relative water content, leaf water potential, MDA tissue ...

  20. Modulation of the immune response by emotional stress

    NARCIS (Netherlands)

    Croiset, G; Heijnen, C J; Veldhuis, H D; de Wied, D; Ballieux, R E

    1987-01-01

    The influence of mild, emotional stress was investigated for its effect on the immune system by subjecting rats to the one-trial-learning passive avoidance test. The reactivity of the immune system was tested by determining the proliferative response after mitogenic stimulation in vitro as well as

  1. Association between neuroticism and amygdala responsivity emerges under stressful conditions

    NARCIS (Netherlands)

    Everaerd, Daphne; Klumpers, Floris; van Wingen, Guido; Tendolkar, Indira; Fernández, Guillén

    2015-01-01

    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

  2. Carica Papaya Seed Extract Enhances Cellular Response to Stress ...

    African Journals Online (AJOL)

    Therefore, the present study was carried out to investigate the role of Carica papaya seed (CPS) extract that contains, Benzyl Isothiocyanates, one of the inducers of phase II enzymes in the regulation of cellular stress. The cellular responses were observed in U937 cells (human monocyte/macrophage cell line) at the ...

  3. Physiological and biochemical responses to low temperature stress ...

    African Journals Online (AJOL)

    Cuttings of three hybrid clones of P. ussuriensis × P. deltoides were exposed to different low temperatures (cold and freezing) for 24 h, or consecutive low temperatures (5°C, 0 to 120 h), to determine physiological and biochemical responses to cold stress in these woody plants. Soluble sugar and protein contents increased ...

  4. Cyclooxygenase inhibitors and the exercise-induced stress response

    African Journals Online (AJOL)

    steroidal anti-inflammatory drug (NSAID) naproxen, and of the coxib, rofecoxib, on the exercise-induced stress response. Design. Eight subjects (age 20.9 ± 1.1 years, weight 70.4 ± 3.9 kg, height 170.9 ± 6.7 cm, body surface area 1.82 ± 0.09 m2, ...

  5. Flow stress asymmetry and cyclic stress--strain response in a BCC Ti--V alloy

    International Nuclear Information System (INIS)

    Koss, D.A.; Wojcik, C.C.

    1976-01-01

    The cyclic stress-strain response of relatively stable bcc β-phase Ti--40 percent V alloy single crystals was studied. Flow stress asymmetry found in the alloy is attributed to the fact that screw dislocations, when gliding on a (211) plane, are more mobile in the twinning direction than in the antitwinning direction. Thus the flow stress of the crystal is greater when it is sheared in the antitwinning direction than in the twinning direction (the latter case results when crystals of the 100 orientation are stressed in tension and those of the 110 orientation are stressed in compression). Such behavior can be a result of the core of a screw dislocation being asymmetric under stress which causes the flow stress asymmetry observed. It should be noted that screw dislocations dominate the low temperature deformation structure of Ti-40V, which strongly suggests deformation is controlled by screw dislocation motion. The observation in Mo that the microyield stress is independent of crystal orientation could be a result of edge dislocation motion controlling microyield in that instance and this observation would not be inconsistent with screw dislocation motion controlling the macroscopic (epsilon/sub p/ greater than 0.05 percent) deformation measured here

  6. Moving through the Stressed Genome: Emerging Regulatory Roles for Transposons in Plant Stress Response.

    Science.gov (United States)

    Negi, Pooja; Rai, Archana N; Suprasanna, Penna

    2016-01-01

    The recognition of a positive correlation between organism genome size with its transposable element (TE) content, represents a key discovery of the field of genome biology. Considerable evidence accumulated since then suggests the involvement of TEs in genome structure, evolution and function. The global genome reorganization brought about by transposon activity might play an adaptive/regulatory role in the host response to environmental challenges, reminiscent of McClintock's original 'Controlling Element' hypothesis. This regulatory aspect of TEs is also garnering support in light of the recent evidences, which project TEs as "distributed genomic control modules." According to this view, TEs are capable of actively reprogramming host genes circuits and ultimately fine-tuning the host response to specific environmental stimuli. Moreover, the stress-induced changes in epigenetic status of TE activity may allow TEs to propagate their stress responsive elements to host genes; the resulting genome fluidity can permit phenotypic plasticity and adaptation to stress. Given their predominating presence in the plant genomes, nested organization in the genic regions and potential regulatory role in stress response, TEs hold unexplored potential for crop improvement programs. This review intends to present the current information about the roles played by TEs in plant genome organization, evolution, and function and highlight the regulatory mechanisms in plant stress responses. We will also briefly discuss the connection between TE activity, host epigenetic response and phenotypic plasticity as a critical link for traversing the translational bridge from a purely basic study of TEs, to the applied field of stress adaptation and crop improvement.

  7. Moving through the Stressed Genome: Emerging Regulatory Roles for Transposons in Plant Stress Response

    Science.gov (United States)

    Negi, Pooja; Rai, Archana N.; Suprasanna, Penna

    2016-01-01

    The recognition of a positive correlation between organism genome size with its transposable element (TE) content, represents a key discovery of the field of genome biology. Considerable evidence accumulated since then suggests the involvement of TEs in genome structure, evolution and function. The global genome reorganization brought about by transposon activity might play an adaptive/regulatory role in the host response to environmental challenges, reminiscent of McClintock's original ‘Controlling Element’ hypothesis. This regulatory aspect of TEs is also garnering support in light of the recent evidences, which project TEs as “distributed genomic control modules.” According to this view, TEs are capable of actively reprogramming host genes circuits and ultimately fine-tuning the host response to specific environmental stimuli. Moreover, the stress-induced changes in epigenetic status of TE activity may allow TEs to propagate their stress responsive elements to host genes; the resulting genome fluidity can permit phenotypic plasticity and adaptation to stress. Given their predominating presence in the plant genomes, nested organization in the genic regions and potential regulatory role in stress response, TEs hold unexplored potential for crop improvement programs. This review intends to present the current information about the roles played by TEs in plant genome organization, evolution, and function and highlight the regulatory mechanisms in plant stress responses. We will also briefly discuss the connection between TE activity, host epigenetic response and phenotypic plasticity as a critical link for traversing the translational bridge from a purely basic study of TEs, to the applied field of stress adaptation and crop improvement. PMID:27777577

  8. Associations Between Paternal Responsiveness and Stress Responsiveness in the Biparental California Mouse, Peromyscus californicus

    OpenAIRE

    Chauke, Miyetani

    2012-01-01

    The mechanistic basis of paternal behavior in mammals is poorly understood. Assuming there are parallels between the factors mediating maternal and paternal behavior, it can be expected that the onset of paternal behavior is facilitated by reductions in stress responsiveness, as occurs in females of several mammalian species. This dissertation describes studies investigating the role of stress responsiveness in the expression of paternal behavior in biparental, monogamous California mice (Per...

  9. Liver protein expression in young pigs in response to a high-fat diet and diet restriction

    DEFF Research Database (Denmark)

    Sejersen, Henrik; Sørensen, Martin Tang; Larsen, Torben

    2013-01-01

    We investigated the liver response in young pigs to a high-fat diet (containing 25% animal fat) and diet restriction (equivalent to 60% of maintenance) using differential proteome analysis. The objective was to investigate whether young pigs can be used to model the liver response in adolescents...... to a high-fat diet and diet restriction-induced BW loss. The high-fat diet increased (P high-fat diet had normal glucose tolerance and liver lipid content despite a general increase (P ...-density lipoprotein decreased (P high-fat diet in young pigs is similar to that of humans in terms of increased fatty acid oxidation whereas the liver response to diet restriction is similar to humans...

  10. Early life adversity influences stress response association with smoking relapse.

    Science.gov (United States)

    al'Absi, Mustafa; Lemieux, Andrine; Westra, Ruth; Allen, Sharon

    2017-11-01

    We examined the hypothesis that stress-related blunting of cortisol in smokers is particularly pronounced in those with a history of severe life adversity. The two aims of this study were first to examine hormonal, craving, and withdrawal symptoms during ad libitum smoking and after the first 24 h of abstinence in smokers who experienced high or low levels of adversity. Second, we sought to examine the relationship between adversity and hypothalamic-pituitary-adrenal (HPA) hormones to predict relapse during the first month of a smoking cessation attempt. Hormonal and self-report measures were collected from 103 smokers (49 women) during ad libitum smoking and after the first 24 h of abstinence. HPA hormones were measured during baseline rest and in response to acute stress in both conditions. All smokers were interested in smoking cessation, and we prospectively used stress response measures to predict relapse during the first 4 weeks of the smoking cessation attempt. The results showed that high adversity was associated with higher distress and smoking withdrawal symptoms. High level of early life adversity was associated with elevated HPA activity, which was found in both salivary and plasma cortisol. Enhanced adrenocorticotropic hormone (ACTH) stress response was evident in high-adversity but not in low-adversity relapsers. This study demonstrated that early life adversity is associated with stress-related HPA responses. The study also demonstrated that, among smokers who experienced a high level of life adversity, heightened ACTH and cortisol responses were linked with increased risk for smoking relapse.

  11. Stress, Roles and Responsibilities of Single Mothers in Malaysia

    Directory of Open Access Journals (Sweden)

    Mohd Hashim Intan Hashimah

    2015-01-01

    Full Text Available Life as a single mother is often associated with great demands and many challenges. This study examines how a group of single mothers in Malaysia views sources of stress and challenges in their lives. It also investigates perceived roles and responsibilities of single mothers. Three hundred single mothers from all over Malaysia were interviewed in this study. Single mothers reported relatively low level of stress that was mostly related to financial (insufficient pay and day-to-day living. They had fairly low stress on issues related to romantic partner and romantic relationships. They however reported extensive roles and responsibilities. Single mothers reported feeling responsible across various domains of life including for their own health and well-being and also for the health and wellbeing of their family and friends. They reported high level of coping and particularly oriented towards solving the problems. They also reported general satisfaction over life. Correlation analysis indicated significant positive relationships between roles and responsibilities and life satisfaction and coping in which coping was associated with higher level of roles and responsibilities and life satisfaction. There was also a negative correlation between stress and life satisfaction in which more stress was associated with lower life satisfaction. Findings indicated a substantial nurturing role of single mothers and provided important policy and practice implications that highlights the important to study and continuously improve quality of life for these women. Finally, this study highlights the important to continuously study and support, important but marginalized groups in society such as single mothers.

  12. Elevation of liver endoplasmic reticulum stress in a modified choline-deficient l-amino acid-defined diet-fed non-alcoholic steatohepatitis mouse model.

    Science.gov (United States)

    Muraki, Yo; Makita, Yukimasa; Yamasaki, Midori; Amano, Yuichiro; Matsuo, Takanori

    2017-05-06

    Endoplasmic reticulum (ER) stress caused by accumulation of misfolded proteins is observed in several kinds of diseases. Since ER stress is reported to be involved in the progression of non-alcoholic steatohepatitis (NASH), highly sensitive and simple measurement methods are required for research into developing novel therapy for NASH. To investigate the involvement of ER stress in NASH pathogenesis in a mouse model, an assay for liver ER stress was developed using ER stress activated indicator-luciferase (ERAI-Luc) mice. To establish the assay method for detection of ER stress in the liver, tunicamycin (TM) (0.3 mg/kg i. p.) was administered to ERAI-Luc mice, and the luciferase activity was measured in ex vivo and in vivo. To evaluate ER stress in the NASH model, ERAI-Luc mice were fed a modified choline-deficient l-amino acid-defined (mCDAA) diet for 14 weeks. After measurement of ER stress by luminescence imaging, levels of liver lipids and pro-fibrotic and pro-inflammatory gene expression were measured as NASH-related indexes. In non-invasive whole-body imaging, TM elevated luciferase activity in the liver, induced by activation of ER stress. The highest luminescence in the liver was confirmed by ex vivo imaging of isolated tissues. In parallel with progression of NASH, elevated luminescence induced by ER stress in liver was observed in mCDAA diet-fed ERAI-Luc mice. Luciferase activity was significantly and positively correlated to levels of triglyceride and free cholesterol in the liver, as well as to the mRNA expression of type 1 collagen α1 chain and tumor necrosis factor α. These data indicated that the use of ERAI-Luc mice was effective in the detection of ER stress in the liver. Moreover, the NASH model using ERAI-Luc mice can be a useful tool to clarify the role of ER stress in pathogenesis of NASH and to evaluate effects of drugs targeted against ER stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Yeast signaling pathways in the oxidative stress response

    Energy Technology Data Exchange (ETDEWEB)

    Ikner, Aminah [Section of Microbiology, Division of Biological Sciences, University of California, Davis, CA 95616 (United States); Shiozaki, Kazuhiro [Section of Microbiology, Division of Biological Sciences, University of California, Davis, CA 95616 (United States)]. E-mail: kshiozaki@ucdavis.edu

    2005-01-06

    Oxidative stress that generates the reactive oxygen species (ROS) is one of the major causes of DNA damage and mutations. The 'DNA damage checkpoint' that arrests cell cycle and repairs damaged DNA has been a focus of recent studies, and the genetically amenable model systems provided by yeasts have been playing a leading role in the eukaryotic checkpoint research. However, means to eliminate ROS are likely to be as important as the DNA repair mechanisms in order to suppress mutations in the chromosomal DNA, and yeasts also serve as excellent models to understand how eukaryotes combat oxidative stress. In this article, we present an overview of the signaling pathways that sense oxidative stress and induce expression of various anti-oxidant genes in the budding yeast Saccharomyces cerevisiae, the fission yeast Schizosaccharomyces pombe and the pathogenic yeast Candida albicans. Three conserved signaling modules have been identified in the oxidative stress response of these diverse yeast species: the stress-responsive MAP kinase cascade, the multistep phosphorelay and the AP-1-like transcription factor. The structure and function of these signaling modules are discussed.

  14. Yeast signaling pathways in the oxidative stress response

    International Nuclear Information System (INIS)

    Ikner, Aminah; Shiozaki, Kazuhiro

    2005-01-01

    Oxidative stress that generates the reactive oxygen species (ROS) is one of the major causes of DNA damage and mutations. The 'DNA damage checkpoint' that arrests cell cycle and repairs damaged DNA has been a focus of recent studies, and the genetically amenable model systems provided by yeasts have been playing a leading role in the eukaryotic checkpoint research. However, means to eliminate ROS are likely to be as important as the DNA repair mechanisms in order to suppress mutations in the chromosomal DNA, and yeasts also serve as excellent models to understand how eukaryotes combat oxidative stress. In this article, we present an overview of the signaling pathways that sense oxidative stress and induce expression of various anti-oxidant genes in the budding yeast Saccharomyces cerevisiae, the fission yeast Schizosaccharomyces pombe and the pathogenic yeast Candida albicans. Three conserved signaling modules have been identified in the oxidative stress response of these diverse yeast species: the stress-responsive MAP kinase cascade, the multistep phosphorelay and the AP-1-like transcription factor. The structure and function of these signaling modules are discussed

  15. Understanding the Posttranscriptional Regulation of Plant Responses to Abiotic Stress

    KAUST Repository

    AlShareef, Sahar A.

    2017-06-01

    Constitutive and alternative splicing of pre-mRNAs from multiexonic genes controls the diversity of the proteome; these precisely regulated processes also fine-tune responses to cues related to growth, development, and biotic and abiotic stresses. Recent work showed that AS is pervasive across plant species, with more than 60% of intron-containing genes producing different isoforms. Mammalian cell-based assays have discovered various AS small-molecule inhibitors that perturb splicing and thereby provide invaluable tools for use as chemical probes to uncover the molecular underpinnings of splicing regulation and as potential anticancer compounds. Here, I show that the macrolide Pladienolide B (PB) and herboxidiene (GEX1A) inhibits both constitutive and alternative splicing, mimics an abiotic stress signal, and activates the abscisic acid (ABA) pathway in plants. Moreover, PB and GEX1A activate genome-wide transcriptional patterns involved in abiotic stress responses in plants. PB and GEX1A treatment triggered the ABA signaling pathway, activated ABA-inducible promoters, and led to stomatal closure. Interestingly, PB and GEX1A elicited similar cellular changes, including alterations in the patterns of transcription and splicing, suggesting that these compounds might target the same spliceosome complex in plant cells. This work establishes PB and GEX1A as potent splicing inhibitors in plants that can be used to probe the assembly, dynamics, and molecular functions of the spliceosome and to study the interplay between splicing stress and abiotic stresses, as well as having potential biotechnological applications.

  16. Transactional Associations between Youths' Responses to Peer Stress and Depression: The Moderating Roles of Sex and Stress Exposure

    Science.gov (United States)

    Agoston, Anna M.; Rudolph, Karen D.

    2011-01-01

    This study examined transactional associations between responses to peer stress and depression in youth. Specifically, it tested the hypotheses that (a) depression would predict fewer effortful responses and more involuntary, dysregulated responses to peer stress over time; and (b) fewer adaptive and more maladaptive responses would predict…

  17. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

    Science.gov (United States)

    Woodman, Andrew G; Mah, Richard; Keddie, Danae; Noble, Ronan M N; Panahi, Sareh; Gragasin, Ferrante S; Lemieux, Hélène; Bourque, Stephane L

    2018-06-01

    Prenatal iron deficiency alters fetal developmental trajectories, which results in persistent changes in organ function. Here, we studied the effects of prenatal iron deficiency on fetal kidney and liver mitochondrial function. Pregnant Sprague-Dawley rats were fed partially or fully iron-restricted diets to induce a state of moderate or severe iron deficiency alongside iron-replete control rats. We assessed mitochondrial function via high-resolution respirometry and reactive oxygen species generation via fluorescence microscopy on gestational d 21. Hemoglobin levels were reduced in dams in the moderate (-31%) and severe groups (-54%) compared with controls, which was accompanied by 55% reductions in fetal hemoglobin levels in both moderate and severe groups versus controls. Male iron-deficient kidneys exhibited globally reduced mitochondrial content and respiration, as well as increased cytosolic superoxide and decreased NO. Female iron-deficient kidneys exhibited complex II down-regulation and increased mitochondrial oxidative stress. Male iron-deficient livers exhibited reduced complex IV respiration and increased cytosolic superoxide, whereas female liver tissues exhibited no alteration in oxidant levels or mitochondrial function. These findings indicate that prenatal iron deficiency causes changes in mitochondrial content and function as well as oxidant status in a sex- and organ-dependent manner, which may be an important mechanism that underlies the programming of cardiovascular disease.-Woodman, A. G., Mah, R., Keddie, D., Noble, R. M. N., Panahi, S., Gragasin, F. S., Lemieux, H., Bourque, S. L. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

  18. [Change in histone proteins in rat liver chromatin during exposure of the animal to functional stress].

    Science.gov (United States)

    Panin, L E; Svechnikova, I G; Maianskaia, N N

    1996-01-01

    Pattern of rat liver histones at intensive physical exercises with preliminary injection of lysosomotropic drugs was studied by method of electrophoresis in PAAG. Elevation of the acetylated forms of histone H4 was revealed. The increased proteolysis of lysine-rich histones (H1, H2A, H2B) was shown in swimming rats previously stimulated by prodigiosan. The possible role of lysosomal proteinases of liver cells in mechanism of chromatine activation is discussed.

  19. Aging augments renal vasoconstrictor response to orthostatic stress in humans.

    Science.gov (United States)

    Clark, Christine M; Monahan, Kevin D; Drew, Rachel C

    2015-12-15

    The ability of the human body to maintain arterial blood pressure (BP) during orthostatic stress is determined by several reflex neural mechanisms. Renal vasoconstriction progressively increases during graded elevations in lower body negative pressure (LBNP). This sympathetically mediated response redistributes blood flow to the systemic circulation to maintain BP. However, how healthy aging affects the renal vasoconstrictor response to LBNP is unknown. Therefore, 10 young (25 ± 1 yr; means ± SE) and 10 older (66 ± 2 yr) subjects underwent graded LBNP (-15 and -30 mmHg) while beat-to-beat renal blood flow velocity (RBFV; Doppler ultrasound), arterial BP (Finometer), and heart rate (HR; electrocardiogram) were recorded. Renal vascular resistance (RVR), an index of renal vasoconstriction, was calculated as mean BP/RBFV. All baseline cardiovascular variables were similar between groups, except diastolic BP was higher in older subjects (P aging augments the renal vasoconstrictor response to orthostatic stress in humans. Copyright © 2015 the American Physiological Society.

  20. CT Perfusion for Early Response Evaluation of Radiofrequency Ablation of Focal Liver Lesions: First Experience

    Energy Technology Data Exchange (ETDEWEB)

    Marquez, Herman P., E-mail: hermanpaulo.marquezmasquiaran@usz.ch; Puippe, Gilbert; Mathew, Rishi Philip; Alkadhi, Hatem; Pfammatter, Thomas; Fischer, Michael A. [University Hospital Zurich, Department of Diagnostic and Interventional Radiology, Institute of Diagnostic and Interventional Radiology (Switzerland)

    2017-01-15

    PurposeTo investigate the value of perfusion CT (P-CT) for early assessment of treatment response in patients undergoing radiofrequency ablation (RFA) of focal liver lesions.Methods and Materials20 consecutive patients (14 men; mean age 64 ± 14) undergoing P-CT within 24 h after RFA of liver metastases (n = 10) or HCC (n = 10) were retrospectively included. Two readers determined arterial liver perfusion (ALP, mL/min/100 mL), portal liver perfusion (PLP, mL/min/100 mL), and hepatic perfusion index (HPI, %) in all post-RFA lesions by placing a volume of interest in the necrotic central (CZ), the transition (TZ), and the surrounding parenchymal (PZ) zone. Patients were classified into complete responders (no residual tumor) and incomplete responders (residual/progressive tumor) using imaging follow-up with contrast-enhanced CT or MRI after a mean of 57 ± 30 days. Prediction of treatment response was evaluated using the area under the curve (AUC) from receiver operating characteristic analysis.ResultsMean ALP/PLP/HPI of both readers were 4.8/15.4/61.2 for the CZ, 9.9/16.8/66.3 for the TZ and 20.7/29.0/61.8 for the PZ. Interreader agreement of HPI was fair for the CZ (intraclass coefficient 0.713), good for the TZ (0.813), and excellent for the PZ (0.920). For both readers, there were significant differences in HPI of the CZ and TZ between responders and nonresponders (both, P < 0.05). HPI of the TZ showed the highest AUC (0.911) for prediction of residual tumor, suggesting a cut-off value of 76 %.ConclusionIncreased HPI of the transition zone assessed with P-CT after RFA might serve as an early quantitative biomarker for residual tumor in patients with focal liver lesions.

  1. Transgenerational stress memory is not a general response in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Ales Pecinka

    Full Text Available Adverse conditions can trigger DNA damage as well as DNA repair responses in plants. A variety of stress factors are known to stimulate homologous recombination, the most accurate repair pathway, by increasing the concentration of necessary enzymatic components and the frequency of events. This effect has been reported to last into subsequent generations not exposed to the stress. To establish a basis for a genetic analysis of this transgenerational stress memory, a broad range of treatments was tested for quantitative effects on homologous recombination in the progeny. Several Arabidopsis lines, transgenic for well-established recombination traps, were exposed to 10 different physical and chemical stress treatments, and scored for the number of somatic homologous recombination (SHR events in the treated generation as well as in the two subsequent generations that were not treated. These numbers were related to the expression level of genes involved in homologous recombination and repair. SHR was enhanced after the majority of treatments, confirming previous data and adding new effective stress types, especially interference with chromatin. Compounds that directly modify DNA stimulated SHR to values exceeding previously described induction rates, concomitant with an induction of genes involved in SHR. In spite of the significant stimulation in the stressed generations, the two subsequent non-treated generations only showed a low and stochastic increase in SHR that did not correlate with the degree of stimulation in the parental plants. Transcripts coding for SHR enzymes generally returned to pre-treatment levels in the progeny. Thus, transgenerational effects on SHR frequency are not a general response to abiotic stress in Arabidopsis and may require special conditions.

  2. The relationship between personality and the response to acute psychological stress.

    Science.gov (United States)

    Xin, Yuanyuan; Wu, Jianhui; Yao, Zhuxi; Guan, Qing; Aleman, André; Luo, Yuejia

    2017-12-04

    The present study examined the relationship between personality traits and the response to acute psychological stress induced by a standardized laboratory stress induction procedure (the Trier Social Stress Test, TSST). The stress response was measured with a combination of cardiovascular reactivity, hypothalamic-pituitary-adrenal axis reactivity, and subjective affect (including positive affect, negative affect and subjective controllability) in healthy individuals. The Generalized Estimating Equations (GEE) approach was applied to account for the relationship between personality traits and stress responses. Results suggested that higher neuroticism predicted lower heart rate stress reactivity, lower cortisol stress response, more decline of positive affect and lower subjective controllability. Individuals higher in extraversion showed smaller cortisol activation to stress and less increase of negative affect. In addition, higher openness score was associated with lower cortisol stress response. These findings elucidate that neuroticism, extraversion and openness are important variables associated with the stress response and different dimensions of personality trait are associated with different aspects of the stress response.

  3. Dysregulation of the DNA Damage Response and KMT2A Rearrangement in Fetal Liver Hematopoietic Cells.

    Directory of Open Access Journals (Sweden)

    Mai Nanya

    Full Text Available Etoposide, a topoisomerase 2 (TOP2 inhibitor, is associated with the development of KMT2A (MLL-rearranged infant leukemia. An epidemiological study suggested that in utero exposure to TOP2 inhibitors may be involved in generation of KMT2A (MLL rearrangement. The present study examined the mechanism underlying the development of KMT2A (MLL-rearranged infant leukemia in response to in utero exposure to etoposide in a mouse model. Fetal liver hematopoietic stem cells were more susceptible to etoposide than maternal bone marrow mononuclear cells. Etoposide-induced Kmt2a breakage was detected in fetal liver hematopoietic stem cells using a newly developed chromatin immunoprecipitation (ChIP assay. Assessment of etoposide-induced chromosomal translocation by next-generation RNA sequencing (RNA-seq identified several chimeric fusion messenger RNAs that were generated by etoposide treatment. However, Kmt2a (Mll-rearranged fusion mRNA was detected in Atm-knockout mice, which are defective in the DNA damage response, but not in wild-type mice. The present findings suggest that in utero exposure to TOP2 inhibitors induces Kmt2a rearrangement when the DNA damage response is defective.

  4. The Transcriptomic Responses of Pinus massoniana to Drought Stress

    Directory of Open Access Journals (Sweden)

    Mingfeng Du

    2018-06-01

    Full Text Available Masson pine (Pinus massoniana is a major fast-growing timber species planted in southern China, a region of seasonal drought. Using a drought-tolerance genotype of Masson pine, we conducted large-scale transcriptome sequencing using Illumina technology. This work aimed to evaluate the transcriptomic responses of Masson pine to different levels of drought stress. First, 3397, 1695 and 1550 unigenes with differential expression were identified by comparing plants subjected to light, moderate or severe drought with control plants. Second, several gene ontology (GO categories (oxidation-reduction and metabolism and Kyoto Encyclopedia of Genes and Genomes (KEGG pathways (plant hormone signal transduction and metabolic pathways were enriched, indicating that the expression levels of some genes in these enriched GO terms and pathways were altered under drought stress. Third, several transcription factors (TFs associated with circadian rhythms (HY5 and LHY, signal transduction (ERF, and defense responses (WRKY were identified, and these TFs may play key roles in adapting to drought stress. Drought also caused significant changes in the expression of certain functional genes linked to osmotic adjustment (P5CS, abscisic acid (ABA responses (NCED, PYL, PP2C and SnRK, and reactive oxygen species (ROS scavenging (GPX, GST and GSR. These transcriptomic results provide insight into the molecular mechanisms of drought stress adaptation in Masson pine.

  5. Cytokinin Cross-talking During Biotic and Abiotic Stress Responses

    Directory of Open Access Journals (Sweden)

    Jose Antonio O'Brien

    2013-11-01

    Full Text Available 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.

  6. Psychological stress during exercise: cardiorespiratory and hormonal responses.

    Science.gov (United States)

    Webb, Heather E; Weldy, Michael L; Fabianke-Kadue, Emily C; Orndorff, G R; Kamimori, Gary H; Acevedo, Edmund O

    2008-12-01

    The purpose of this study was to examine the cardiorespiratory (CR) and stress hormone responses to a combined physical and mental stress. Eight participants (VO2(max) = 41.24 +/- 6.20 ml kg(-1) min(-1)) completed two experimental conditions, a treatment condition including a 37 min ride at 60% of VO2(max) with participants responding to a computerized mental challenge dual stress condition (DSC) and a control condition of the same duration and intensity without the mental challenge exercise alone condition (EAC). Significant interactions across time were found for CR responses, with heart rate, ventilation, and respiration rate demonstrating higher increases in the DSC. Additionally, norepinephrine was significantly greater in the DSC at the end of the combined challenge. Furthermore, cortisol area-under-the-curve (AUC) was also significantly elevated during the DSC. These results demonstrate that a mental challenge during exercise can exacerbate the stress response, including the release of hormones that have been linked to negative health consequences (cardiovascular, metabolic, autoimmune illnesses).

  7. Molecular Responses of Groundnut (Arachis hypogea L. to Zinc Stress

    Directory of Open Access Journals (Sweden)

    A. John De Britto

    2013-08-01

    Full Text Available Heavy metals are important environmental pollutants and their toxicity is a problem of increasing significance for ecological, evolutionary and environmental reasons. The interference of germination related proteins by heavy metals has not been well documented at the proteomic and genomic level. In the current study, molecular responses of germinating groundnut seeds were investigated under Zinc stress. The SDS-PAGE showed the preliminary changes in the polypeptides patterns under Zinc stress. Restriction digestion banding pattern of EcoRI and Hind III enzymes showed distinct banding pattern in the treated plants.

  8. Electrical response of relaxing dielectrics compressed by arbitrary stress pulses

    International Nuclear Information System (INIS)

    Lysne, P.C.

    1983-01-01

    The theoretical problem of the electric response of biased dielectrics and piezoelectrics subjected to planar stress pulse loading is considered. The materials are taken to exhibit dielectric relaxation in the sense that changes in the polarization induced by electric fields do not occur instantaneously with changes in the fields. While this paper considers arbitrary stress pulse loading of the specimen, examples that are amenable to projectile impact techniques are considered in detail. They are shock reverberation, thin pulse, and ramp loading experiments. It is anticipated that these experiments will play a role in investigations of dielectric relaxation caused by shock induced damage in insulators

  9. Surgical stress response: does endoscopic surgery confer an advantage?

    DEFF Research Database (Denmark)

    Kehlet, H

    1999-01-01

    of postoperative pulmonary function and less hypoxemia with endoscopic operation. The slight modification of surgical stress responses by endoscopic surgery is in contrast to the common, though not universal, demonstration of less pain, shorter hospital stay, and less morbidity after endoscopic surgery...... operations where differences are more likely to be found. The clinical consequences of these findings in relation to all over surgical outcome remain to be defined, but effective pain treatment, stress reduction by other techniques, and provision of an active rehabilitation program with early mobilization...

  10. Transcriptomic analysis of salt stress responsive genes in Rhazya stricta.

    Directory of Open Access Journals (Sweden)

    Nahid H Hajrah

    Full Text Available Rhazya stricta is an evergreen shrub that is widely distributed across Western and South Asia, and like many other members of the Apocynaceae produces monoterpene indole alkaloids that have anti-cancer properties. This species is adapted to very harsh desert conditions making it an excellent system for studying tolerance to high temperatures and salinity. RNA-Seq analysis was performed on R. stricta exposed to severe salt stress (500 mM NaCl across four time intervals (0, 2, 12 and 24 h to examine mechanisms of salt tolerance. A large number of transcripts including genes encoding tetrapyrroles and pentatricopeptide repeat (PPR proteins were regulated only after 12 h of stress of seedlings grown in controlled greenhouse conditions. Mechanisms of salt tolerance in R. stricta may involve the upregulation of genes encoding chaperone protein Dnaj6, UDP-glucosyl transferase 85a2, protein transparent testa 12 and respiratory burst oxidase homolog protein b. Many of the highly-expressed genes act on protecting protein folding during salt stress and the production of flavonoids, key secondary metabolites in stress tolerance. Other regulated genes encode enzymes in the porphyrin and chlorophyll metabolic pathway with important roles during plant growth, photosynthesis, hormone signaling and abiotic responses. Heme biosynthesis in R. stricta leaves might add to the level of salt stress tolerance by maintaining appropriate levels of photosynthesis and normal plant growth as well as by the participation in reactive oxygen species (ROS production under stress. We speculate that the high expression levels of PPR genes may be dependent on expression levels of their targeted editing genes. Although the results of PPR gene family indicated regulation of a large number of transcripts under salt stress, PPR actions were independent of the salt stress because their RNA editing patterns were unchanged.

  11. Role of Interleukin-6 in the Radiation Response of Liver Tumors

    International Nuclear Information System (INIS)

    Chen, Miao-Fen; Hsieh, Ching-Chuan; Chen, Wen-Cheng; Lai, Chia-Hsuan

    2012-01-01

    Purpose: To investigate the role of interleukin (IL)-6 in biological sequelae and tumor regrowth after irradiation for hepatic malignancy, which are critical for the clinical radiation response of liver tumors. Methods and Materials: The Hepa 1-6 murine hepatocellular cancer cell line was used to examine the radiation response by clonogenic assays and tumor growth delay in vivo. After irradiation in a single dose of 6 Gy in vitro or 15 Gy in vivo, biological changes including cell death and tumor regrowth were examined by experimental manipulation of IL-6 signaling. The effects of blocking IL-6 were assessed by cells preincubated in the presence of IL-6–neutralizing antibody for 24 hours or stably transfected with IL-6–silencing vectors. The correlations among tumor responses, IL-6 levels, and myeloid-derived suppressor cells (MDSC) recruitment were examined using animal experiments. Results: Interleukin-6 expression was positively linked to irradiation and radiation resistance, as demonstrated by in vitro and in vivo experiments. Interleukin-6–silencing vectors induced more tumor inhibition and DNA damage after irradiation. When subjects were irradiated with a sublethal dose, the regrowth of irradiated tumors significantly correlated with IL-6 levels and MDSC recruitment in vivo. Furthermore, blocking of IL-6 could overcome irradiation-induced MDSC recruitment and tumor regrowth after treatment. Conclusion: These data demonstrate that IL-6 is important in determining the radiation response of liver tumor cells. Irradiation-induced IL-6 and the subsequent recruitment of MDSC could be responsible for tumor regrowth. Therefore, treatment with concurrent IL-6 inhibition could be a potential therapeutic strategy for increasing the radiation response of tumors.

  12. Coping as a mediator of the relationship between stress mindset and psychological stress response: a pilot study

    Directory of Open Access Journals (Sweden)

    Horiuchi S

    2018-03-01

    Full Text Available Satoshi Horiuchi,1 Akira Tsuda,2 Shuntaro Aoki,3,4 Kenichiro Yoneda,5 Yusuke Sawaguchi6 1Faculty of Social Welfare, Iwate Prefectural University, Iwate, 2Department of Psychology, Kurume University, Fukuoka, 3Research Fellow of Japan Society for the Promotion of Science, Tokyo, 4Graduate School of Psychological Science, Health Sciences University of Hokkaido, Hokkaido, 5Graduate School of Psychology, Kurume University, Fukuoka, 6Graduate School of Social Welfare, Iwate Prefectural University, Iwate, Japan Background: Coping, the cognitive and behavioral effort required to manage the effects of stressors, is important in determining psychological stress responses (ie, the emotional, behavioral, and cognitive responses to stressors. Coping was classified into categories of emotional expression (eg, negative feelings and thoughts, emotional support seeking (eg, approaching loved ones to request encouragement, cognitive reinterpretation (eg, reframing a problem positively, and problem solving (eg, working to solve the problem. Stress mindset refers to the belief that stress has enhancing (stress-is-enhancing mindset or debilitating consequences (stress-is-debilitating mindset. This study examined whether coping mediated the relationship between stress mindset and psychological stress responses. Psychological stress responses were conceptualized as depression-anxiety, irritability-anger, and helplessness. The following two hypotheses were tested: 1 a stronger stress-is-enhancing mindset is associated with less frequent use of emotional expression, emotional support seeking, and problem solving, which in turn is associated with lower levels of depression-anxiety, irritability-anger, and helplessness; 2 a stronger stress-is-debilitating mindset is associated with more frequent use of these coping strategies, which in turn is associated with higher levels of these psychological stress responses. Materials and methods: The participants were 30 male and

  13. Vitamin C deficiency in weanling guinea pigs: differential expression of oxidative stress and DNA repair in liver and brain

    DEFF Research Database (Denmark)

    Lykkesfeldt, Jens; Trueba, Gilberto Perez; Poulsen, Henrik E

    2007-01-01

    Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency...... incision repair (P = 0.014) were all increased, while protein oxidation decreased (P = 0.003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may...

  14. Transcriptome Analysis of Spartina pectinata in Response to Freezing Stress.

    Directory of Open Access Journals (Sweden)

    Gyoungju Nah

    Full Text Available Prairie cordgrass (Spartina pectinata, a perennial C4 grass native to the North American prairie, has several distinctive characteristics that potentially make it a model crop for production in stressful environments. However, little is known about the transcriptome dynamics of prairie cordgrass despite its unique freezing stress tolerance. Therefore, the purpose of this work was to explore the transcriptome dynamics of prairie cordgrass in response to freezing stress at -5°C for 5 min and 30 min. We used a RNA-sequencing method to assemble the S. pectinata leaf transcriptome and performed gene-expression profiling of the transcripts under freezing treatment. Six differentially expressed gene (DEG groups were categorized from the profiling. In addition, two major consecutive orders of gene expression were observed in response to freezing; the first being the acute up-regulation of genes involved in plasma membrane modification, calcium-mediated signaling, proteasome-related proteins, and transcription regulators (e.g., MYB and WRKY. The follow-up and second response was of genes involved in encoding the putative anti-freezing protein and the previously known DNA and cell-damage-repair proteins. Moreover, we identified the genes involved in epigenetic regulation and circadian-clock expression. Our results indicate that freezing response in S. pectinata reflects dynamic changes in rapid-time duration, as well as in metabolic, transcriptional, post-translational, and epigenetic regulation.

  15. Allelopathic Responses of Rice Seedlings under Some Different Stresses

    Directory of Open Access Journals (Sweden)

    Tran Dang Khanh

    2018-05-01

    Full Text Available The objective of this study was to evaluate the allelopathic responses of rice seedlings under submergence stress at different temperatures (10, 25, 32, and 37 °C. The results showed that a wide range of allelopathic responses of rice seedlings depended on varieties and stress conditions, with temperature was being a key factor. It showed that the extracts of rice seedlings induced significant suppression on lettuce and radish seedling germination, but had negligible allelopathic effects on growth of barnyardgrass, whilst the emergence and growth of natural weeds was stimulated. In contrast, the root exudates of Koshihikari rice seedlings (K32 at 32 °C reduced the number of total weeds by ≈60.0% and the total dry weight of weeds by 93.0%; i.e., to a greater extent than other root exudates. Among the 13 identified phenolic acids, p-hydroxybenzoic, vanillic, syringic, sinapic and benzoic acids—at concentrations of 0.360, 0.045, 3.052, 1.309 and 5.543 μg/mL might be involved in allelopathic responses of K32, inhibiting the growth of barnyardgrass and natural weeds. Findings of the present study may provide useful information on allelopathic responses of rice under environmental stresses and thus further understand of the competitive relationships between rice and weeds under natural conditions.

  16. Comparative cytotoxic response of nickel ferrite nanoparticles in human liver HepG2 and breast MFC-7 cancer cells.

    Science.gov (United States)

    Ahamed, Maqusood; Akhtar, Mohd Javed; Alhadlaq, Hisham A; Khan, M A Majeed; Alrokayan, Salman A

    2015-09-01

    Nickel ferrite nanoparticles (NPs) have received much attention for their potential applications in biomedical fields such as magnetic resonance imaging, drug delivery and cancer hyperthermia. However, little is known about the toxicity of nickel ferrite NPs at the cellular and molecular levels. In this study, we investigated the cytotoxic responses of nickel ferrite NPs in two different types of human cells (i.e., liver HepG2 and breast MCF-7). Nickel ferrite NPs induced dose-dependent cytotoxicity in both types of cells, which was demonstrated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT), neutral red uptake (NRU) and lactate dehydrogenase (LDH) assays. Nickel ferrite NPs were also found to induce oxidative stress, which was evident by the depletion of glutathione and the induction of reactive oxygen species (ROS) and lipid peroxidation. The mitochondrial membrane potential due to nickel ferrite NP exposure was also observed. The mRNA levels for the tumor suppressor gene p53 and the apoptotic genes bax, CASP3 and CASP9 were up-regulated, while the anti-apoptotic gene bcl-2 was down-regulated following nickel ferrite NP exposure. Furthermore, the activities of apoptotic enzymes (caspase-3 and caspase-9) were also higher in both types of cells treated with nickel ferrite NPs. Cytotoxicity induced by nickel ferrite was efficiently prevented by N-acetyl cysteine (ROS scavenger) treatment, which suggested that oxidative stress might be one of the possible mechanisms of nickel ferrite NP toxicity. We also observed that MCF-7 cells were slightly more susceptible to nickel ferrite NP exposure than HepG2 cells. This study warrants further investigation to explore the potential mechanisms of different cytotoxic responses of nickel ferrite NPs in different cell lines. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Evasion of Apoptosis as a Cellular Stress Response in Cancer

    Directory of Open Access Journals (Sweden)

    Simone Fulda

    2010-01-01

    Full Text Available One of the hallmarks of human cancers is the intrinsic or acquired resistance to apoptosis. Evasion of apoptosis can be part of a cellular stress response to ensure the cell's survival upon exposure to stressful stimuli. Apoptosis resistance may contribute to carcinogenesis, tumor progression, and also treatment resistance, since most current anticancer therapies including chemotherapy as well as radio- and immunotherapies primarily act by activating cell death pathways including apoptosis in cancer cells. Hence, a better understanding of the molecular mechanisms regarding how cellular stress stimuli trigger antiapoptotic mechanisms and how this contributes to tumor resistance to apoptotic cell death is expected to provide the basis for a rational approach to overcome apoptosis resistance mechanisms in cancers.

  18. Stress response in female veterans: an allostatic perspective.

    Science.gov (United States)

    Groër, Maureen Wimberly; Burns, Candace

    2009-01-01

    Women serving in the military face many sources of stress, such as separation from home and family, sexual harassment and assault, and deployment to traumatic war zones. Some women are vulnerable to the effects of these stressors, resulting in deleterious mental and physical health outcomes. Understanding these risks through the theoretical model of allostasis can help identify those who will be most vulnerable and help healthcare providers prevent some negative outcomes and improve rehabilitation for some women when they return stateside. Women may be more likely than men to present with mental health problems such as posttraumatic stress disorder and depression after military service. They also may be at increased risk, based on their war-zone stress response, for disparate illness such as medically unexplained illness, cancer, and heart disease. The need for care for these women is expected to increase as more women are deployed to conflicts.

  19. Fatty liver in hepatitis C patients post-sustained virological response with direct-acting antivirals

    Science.gov (United States)

    Noureddin, Mazen; Wong, Micaela M; Todo, Tsuyoshi; Lu, Shelly C; Sanyal, Arun J; Mena, Edward A

    2018-01-01

    AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals. METHODS Transient elastography with controlled attenuation parameter (CAP) was used to assess hepatic steatosis post-sustained virological response (SVR); the CAP technology was not available in the United States at study initiation. Liver stiffness/fibrosis was measured before and 47 wk after treatment completion. Patients with genotype 3 and patients with cirrhosis were excluded. RESULTS One hundred and one patients were included in the study. Post-SVR there were decreases from baseline in alanine aminotransferase (ALT) (63.1 to 17.8 U/L), aspartate aminotransferase (51.8 to 21.5 U/L) and fibrosis score (7.4 to 6.1 kPa) (P steatosis on CAP; of these, 6.25% had advanced fibrosis. Patients with steatosis had higher body mass index (29.0 vs 26.1 kg/m2), glucose (107.8 vs 96.6 mg/dL), ALT (20.4 vs 15.3 mg/dL), CAP score (296.3 vs 212.4 dB/m) and fibrosis score (7.0 vs 5.3 kPa); P steatosis had change in fibrosis score post-SVR (7.7 kPa vs 7.0 kPa and 7.0 kPa vs 5.3 kPa); alternatively, (P steatosis continued to have clinically significant stiffness (≥ 7 kPa). CONCLUSION Fatty liver is very common in hepatitis C virus (HCV) patients post-SVR. These patients continue to have elevated mean fibrosis score (≥ 7 kPa) compared to those without fatty liver; some have advanced fibrosis. Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR. PMID:29568207

  20. The role of stress mindset in shaping cognitive, emotional, and physiological responses to challenging and threatening stress.

    Science.gov (United States)

    Crum, Alia J; Akinola, Modupe; Martin, Ashley; Fath, Sean

    2017-07-01

    Prior research suggests that altering situation-specific evaluations of stress as challenging versus threatening can improve responses to stress. The aim of the current study was to explore whether cognitive, physiological and affective stress responses can be altered independent of situation-specific evaluations by changing individuals' mindsets about the nature of stress in general. Using a 2 × 2 design, we experimentally manipulated stress mindset using multi-media film clips orienting participants (N = 113) to either the enhancing or debilitating nature of stress. We also manipulated challenge and threat evaluations by providing positive or negative feedback to participants during a social stress test. Results revealed that under both threat and challenge stress evaluations, a stress-is-enhancing mindset produced sharper increases in anabolic ("growth") hormones relative to a stress-is-debilitating mindset. Furthermore, when the stress was evaluated as a challenge, a stress-is-enhancing mindset produced sharper increases in positive affect, heightened attentional bias towards positive stimuli, and greater cognitive flexibility, whereas a stress-is-debilitating mindset produced worse cognitive and affective outcomes. These findings advance stress management theory and practice by demonstrating that a short manipulation designed to generate a stress-is-enhancing mindset can improve responses to both challenging and threatening stress.

  1. In response to community violence: coping strategies and involuntary stress responses among Latino adolescents.

    Science.gov (United States)

    Epstein-Ngo, Quyen; Maurizi, Laura K; Bregman, Allyson; Ceballo, Rosario

    2013-01-01

    Among poor, urban adolescents, high rates of community violence are a pressing public health concern. This study relies on a contextual framework of stress and coping to investigate how coping strategies and involuntary stress responses may both mediate and moderate the relation between exposure to community violence and psychological well-being. Our sample consists of 223 ninth grade Latino adolescents from poor, urban families. In response to community violence, these adolescents reported using an array of coping strategies as well as experiencing a number of involuntary stress responses; the most frequent coping responses were turning to religion and seeking social support. Hierarchical regression analyses demonstrated that involuntary stress responses mediated the relations between both witnessing or being victimized by violence and poorer psychological functioning, while coping strategies moderated these relations. These findings suggest that the negative psychological effects of exposure to community violence may, in part, be explained by involuntary stress responses, while religious-based coping may serve as a protective factor.

  2. Children's biological responsivity to acute stress predicts concurrent cognitive performance.

    Science.gov (United States)

    Roos, Leslie E; Beauchamp, Kathryn G; Giuliano, Ryan; Zalewski, Maureen; Kim, Hyoun K; Fisher, Philip A

    2018-04-10

    Although prior research has characterized stress system reactivity (i.e. hypothalamic-pituitary-adrenal axis, HPAA; autonomic nervous system, ANS) in children, it has yet to examine the extent to which biological reactivity predicts concurrent goal-directed behavior. Here, we employed a stressor paradigm that allowed concurrent assessment of both stress system reactivity and performance on a speeded-response task to investigate the links between biological reactivity and cognitive function under stress. We further investigated gender as a moderator given previous research suggesting that the ANS may be particularly predictive of behavior in males due to gender differences in socialization. In a sociodemographically diverse sample of young children (N = 58, M age = 5.38 yrs; 44% male), individual differences in sociodemographic covariates (age, household income), HPAA (i.e. cortisol), and ANS (i.e. respiratory sinus arrhythmia, RSA, indexing the parasympathetic branch; pre-ejection period, PEP, indexing the sympathetic branch) function were assessed as predictors of cognitive performance under stress. We hypothesized that higher income, older age, and greater cortisol reactivity would be associated with better performance overall, and flexible ANS responsivity (i.e. RSA withdrawal, PEP shortening) would be predictive of performance for males. Overall, females performed better than males. Two-group SEM analyses suggest that, for males, greater RSA withdrawal to the stressor was associated with better performance, while for females, older age, higher income, and greater cortisol reactivity were associated with better performance. Results highlight the relevance of stress system reactivity to cognitive performance under stress. Future research is needed to further elucidate for whom and in what situations biological reactivity predicts goal-directed behavior.

  3. Mechanism Profiling of Hepatotoxicity Caused by Oxidative Stress Using Antioxidant Response Element Reporter Gene Assay Models and Big Data.

    Science.gov (United States)

    Kim, Marlene Thai; Huang, Ruili; Sedykh, Alexander; Wang, Wenyi; Xia, Menghang; Zhu, Hao

    2016-05-01

    Hepatotoxicity accounts for a substantial number of drugs being withdrawn from the market. Using traditional animal models to detect hepatotoxicity is expensive and time-consuming. Alternative in vitro methods, in particular cell-based high-throughput screening (HTS) studies, have provided the research community with a large amount of data from toxicity assays. Among the various assays used to screen potential toxicants is the antioxidant response element beta lactamase reporter gene assay (ARE-bla), which identifies chemicals that have the potential to induce oxidative stress and was used to test > 10,000 compounds from the Tox21 program. The ARE-bla computational model and HTS data from a big data source (PubChem) were used to profile environmental and pharmaceutical compounds with hepatotoxicity data. Quantitative structure-activity relationship (QSAR) models were developed based on ARE-bla data. The models predicted the potential oxidative stress response for known liver toxicants when no ARE-bla data were available. Liver toxicants were used as probe compounds to search PubChem Bioassay and generate a response profile, which contained thousands of bioassays (> 10 million data points). By ranking the in vitro-in vivo correlations (IVIVCs), the most relevant bioassay(s) related to hepatotoxicity were identified. The liver toxicants profile contained the ARE-bla and relevant PubChem assays. Potential toxicophores for well-known toxicants were created by identifying chemical features that existed only in compounds with high IVIVCs. Profiling chemical IVIVCs created an opportunity to fully explore the source-to-outcome continuum of modern experimental toxicology using cheminformatics approaches and big data sources. Kim MT, Huang R, Sedykh A, Wang W, Xia M, Zhu H. 2016. Mechanism profiling of hepatotoxicity caused by oxidative stress using antioxidant response element reporter gene assay models and big data. Environ Health Perspect 124:634-641;

  4. Short-term spatial memory responses in aged Japanese quail selected for divergent adrenocortical stress responsiveness.

    Science.gov (United States)

    Suhr, C L; Schmidt, J B; Treese, S T; Satterlee, D G

    2010-04-01

    Stress-induced glucocorticoids can dampen learning and spatial memory via neuronal damage to the hippocampus. Cognition losses can be transient (associated with acute stress episodes) or permanent as in aged individuals who show chronic glucocorticoid-induced accelerated brain aging and neurodegeneration (dementia). Thus, chronic versus acute stress effects on spatial memory responses of quail selected for reduced (low stress, LS) or exaggerated (high stress, HS) plasma corticosterone (B) response to brief restraint were assessed. Aged food-motivated male LS and HS quail were tested for 10 min in a feed-baited 8-arm radial arm maze (RAM) 1) at 255 d of age (quail who had experienced lifelong management stressors but who were otherwise never intentionally stressed; that is, chronically stressed birds), 2) on the next day post-acute stressor treatment (5 min of restraint), and 3) on the next day without treatment (acute stress recovery). The RAM tests used the win-shift procedure in which visited arms were not rebaited. Radial arm maze performance was measured by determination of the total number of arm choices made, the number of correct entries made into baited arms out of the first 8 choices, the time required to make a choice, and the number of pellets eaten. Line effects (P LS), and number of pellets eaten (HS RAM testing nor its interaction with line further influenced these variables. Thus, although selection for divergent plasma B responsiveness to an acute stressor was found to be associated with severe impairment of spatial memory in aged male HS compared with LS quail, the observed spatial memory impairments (HS > LS) could not be further altered by acute stressor treatment. Line differences in cognition may reflect lifelong management-induced stress episodes that periodically produce higher plasma B responses in HS than LS quail, which underlie HS quail memory deficits, or other etiologies, or both.

  5. Gene Expression Dynamics Accompanying the Sponge Thermal Stress Response.

    Science.gov (United States)

    Guzman, Christine; Conaco, Cecilia

    2016-01-01

    Marine sponges are important members of coral reef ecosystems. Thus, their responses to changes in ocean chemistry and environmental conditions, particularly to higher seawater temperatures, will have potential impacts on the future of these reefs. To better understand the sponge thermal stress response, we investigated gene expression dynamics in the shallow water sponge, Haliclona tubifera (order Haplosclerida, class Demospongiae), subjected to elevated temperature. Using high-throughput transcriptome sequencing, we show that these conditions result in the activation of various processes that interact to maintain cellular homeostasis. Short-term thermal stress resulted in the induction of heat shock proteins, antioxidants, and genes involved in signal transduction and innate immunity pathways. Prolonged exposure to thermal stress affected the expression of genes involved in cellular damage repair, apoptosis, signaling and transcription. Interestingly, exposure to sublethal temperatures may improve the ability of the sponge to mitigate cellular damage under more extreme stress conditions. These insights into the potential mechanisms of adaptation and resilience of sponges contribute to a better understanding of sponge conservation status and the prediction of ecosystem trajectories under future climate conditions.

  6. Herboxidiene triggers splicing repression and abiotic stress responses in plants

    KAUST Repository

    Alshareef, Sahar

    2017-03-27

    Background Constitutive and alternative splicing of pre-mRNAs from multiexonic genes controls the diversity of the proteome; these precisely regulated processes also fine-tune responses to cues related to growth, development, and stresses. Small-molecule inhibitors that perturb splicing provide invaluable tools for use as chemical probes to uncover the molecular underpinnings of splicing regulation and as potential anticancer compounds. Results Here, we show that herboxidiene (GEX1A) inhibits both constitutive and alternative splicing. Moreover, GEX1A activates genome-wide transcriptional patterns involved in abiotic stress responses in plants. GEX1A treatment -activated ABA-inducible promoters, and led to stomatal closure. Interestingly, GEX1A and pladienolide B (PB) elicited similar cellular changes, including alterations in the patterns of transcription and splicing, suggesting that these compounds might target the same spliceosome complex in plant cells. Conclusions Our study establishes GEX1A as a potent splicing inhibitor in plants that can be used to probe the assembly, dynamics, and molecular functions of the spliceosome and to study the interplay between splicing stress and abiotic stresses, as well as having potential biotechnological applications.

  7. Oxidative Stress Responses in the Human Fungal Pathogen, Candida albicans

    Science.gov (United States)

    da Silva Dantas, Alessandra; 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

  8. Osmotic stress response in the wine yeast Dekkera bruxellensis.

    Science.gov (United States)

    Galafassi, Silvia; Toscano, Marco; Vigentini, Ileana; Piškur, Jure; Compagno, Concetta

    2013-12-01

    Dekkera bruxellensis is mainly associated with lambic beer fermentation and wine production and may contribute in a positive or negative manner to the flavor development. This yeast is able to produce phenolic compounds, such as 4-ethylguaiacol and 4-ethylphenol which could spoil the wine, depending on their concentration. In this work we have investigated how this yeast responds when exposed to conditions causing osmotic stress, as high sorbitol or salt concentrations. We observed that osmotic stress determined the production and accumulation of intracellular glycerol, and the expression of NADH-dependent glycerol-3-phosphate dehydrogenase (GPD) activity was elevated. The involvement of the HOG MAPK pathway in response to this stress condition was also investigated. We show that in D. bruxellensis Hog1 protein is activated by phosphorylation under hyperosmotic conditions, highlighting the conserved role of HOG MAP kinase signaling pathway in the osmotic stress response. Gene Accession numbers in GenBank: DbHOG1: JX65361, DbSTL1: JX965362. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Hypothalamic and pituitary clusterin modulates neurohormonal responses to stress.

    Science.gov (United States)

    Shin, Mi-Seon; Chang, Hyukki; Namkoong, Churl; Kang, Gil Myoung; Kim, Hyun-Kyong; Gil, So Young; Yu, Ji Hee; Park, Kyeong Han; Kim, Min-Seon

    2013-01-01

    Clusterin is a sulfated glycoprotein abundantly expressed in the pituitary gland and hypothalamus of mammals. However, its physiological role in neuroendocrine function is largely unknown. In the present study, we investigated the effects of intracerebroventricular (ICV) administration of clusterin on plasma pituitary hormone levels in normal rats. Single ICV injection of clusterin provoked neurohormonal changes seen under acute stress condition: increased plasma adrenocorticotropic hormone (ACTH), corticosterone, GH and prolactin levels and decreased LH and FSH levels. Consistently, hypothalamic and pituitary clusterin expression levels were upregulated following a restraint stress, suggesting an involvement of endogenous clusterin in stress-induced neurohormonal changes. In the pituitary intermediate lobe, clusterin was coexpressed with proopiomelanocortin (POMC), a precursor of ACTH. Treatment of clusterin in POMC expressing AtT-20 pituitary cells increased basal and corticotropin-releasing hormone (CRH)-stimulated POMC promoter activities and intracellular cAMP levels. Furthermore, clusterin treatment triggered ACTH secretion from AtT-20 cells in a CRH-dependent manner, indicating that increased clusterin under stressful conditions may augment CRH-stimulated ACTH production and release. In summary, hypothalamic and pituitary clusterin may function as a modulator of neurohormonal responses under stressful conditions. © 2013 S. Karger AG, Basel.

  10. Behaviour and stress responses in horses with gastric ulceration

    DEFF Research Database (Denmark)

    Malmkvist, Jens; Poulsen, Janne Møller; Luthersson, Nanna

    2012-01-01

    Only little is known about behaviour and stress responses in horses with gastric ulceration, despite the high prevalence of this condition. Our objectives in the present study was to (i) describe the severity of gastric ulceration in horses, housed under relatively standardised conditions, and (ii......) to investigate whether horses with severe glandular gastric ulceration have increased baseline and response concentration of stress hormones and behave differently than control horses. We investigated stomachs of 96 horses at one stud, and compared an ulcer group (n = 30; with severe lesions in the glandular...... conclude that the prevalence of gastric ulcers was high, and our results suggest different factors affecting ulceration in the glandular versus the nonglandular region of the horse stomach. Obvious external signs (e.g. poor body condition) identifying ulcer horses were absent. Horses with severe glandular...

  11. Stress (Tako-Tsubo) Cardiomyopathy Following Radiofrequency Ablation of a Liver Tumor: A Case Report

    International Nuclear Information System (INIS)

    Joo, Ijin; Lee, Jeong Min; Han, Joon Koo; Choi, Byung Ihn; Park, Eun-Ah

    2011-01-01

    Stress cardiomyopathy is characterized by transient left ventricular dysfunction occurring in the absence of obstructive coronary disease. It is precipitated by acute emotional or physical stress. We present a case of stress cardiomyopathy which developed during hepatic radiofrequency ablation of hepatocellular carcinoma.

  12. Metabolic reprogramming by PCK1 promotes TCA cataplerosis, oxidative stress and apoptosis in liver cancer cells and suppresses hepatocellular carcinoma.

    Science.gov (United States)

    Liu, Meng-Xi; Jin, Lei; Sun, Si-Jia; Liu, Peng; Feng, Xu; Cheng, Zhou-Li; Liu, Wei-Ren; Guan, Kun-Liang; Shi, Ying-Hong; Yuan, Hai-Xin; Xiong, Yue

    2018-03-01

    Phosphoenolpyruvate carboxykinase (PEPCK or PCK) catalyzes the first rate-limiting step in hepatic gluconeogenesis pathway to maintain blood glucose levels. Mammalian cells express two PCK genes, encoding for a cytoplasmic (PCPEK-C or PCK1) and a mitochondrial (PEPCK-M or PCK2) isoforms, respectively. Increased expressions of both PCK genes are found in cancer of several organs, including colon, lung, and skin, and linked to increased anabolic metabolism and cell proliferation. Here, we report that the expressions of both PCK1 and PCK2 genes are downregulated in primary hepatocellular carcinoma (HCC) and low PCK expression was associated with poor prognosis in patients with HCC. Forced expression of either PCK1 or PCK2 in liver cancer cell lines results in severe apoptosis under the condition of glucose deprivation and suppressed liver tumorigenesis in mice. Mechanistically, we show that the pro-apoptotic effect of PCK1 requires its catalytic activity. We demonstrate that forced PCK1 expression in glucose-starved liver cancer cells induced TCA cataplerosis, leading to energy crisis and oxidative stress. Replenishing TCA intermediate α-ketoglutarate or inhibition of reactive oxygen species production blocked the cell death caused by PCK expression. Taken together, our data reveal that PCK1 is detrimental to malignant hepatocytes and suggest activating PCK1 expression as a potential treatment strategy for patients with HCC.

  13. Effect of nutritional status on oxidative stress in an ex vivo perfused rat liver.

    Science.gov (United States)

    Stadler, Michaela; Nuyens, Vincent; Seidel, Laurence; Albert, Adelin; Boogaerts, Jean G

    2005-11-01

    Normothermic ischemia-reperfusion is a determinant in liver injury occurring during surgical procedures, ischemic state, and multiple organ failure. The preexisting nutritional status of the liver might contribute to the extent of tissue injury and primary nonfunction. The aim of this study was to determine the role of starvation on hepatic ischemia-reperfusion injury in normal rat livers. Rats were randomly divided into two groups: one had free access to food, the other was fasted for 16 h. The portal vein was cannulated, and the liver was removed and perfused in a closed ex vivo system. Two modes of perfusion were applied in each series of rats, fed and fasting. In the ischemia-reperfusion mode, the experiment consisted of perfusion for 15 min, warm ischemia for 60 min, and reperfusion during 60 min. In the nonischemia mode, perfusion was maintained during the 135-min study period. Five rats were included in each experimental condition, yielding a total of 20 rats. Liver enzymes, potassium, glucose, lactate, free radicals, i.e., dienes and trienes, and cytochrome c were analyzed in perfusate samples. The proportion of glycogen in hepatocytes was determined in tissue biopsies. Transaminases, lactate dehydrogenase, potassium, and free radical concentrations were systematically higher in fasting rats in both conditions, with and without ischemia. Cytochrome c was higher after reperfusion in the fasting rats. Glucose and lactate concentrations were greater in the fed group. The glycogen content decreased in both groups during the experiment but was markedly lower in the fasting rats. In fed rats, liver injury was moderate, whereas hepatocytes integrity was notably impaired both after continuous perfusion and warm ischemia in fasting animals. Reduced glycogen store in hepatocytes may explain reduced tolerance.

  14. Interstitial brachytherapy for liver metastases and assessment of response by positron emission tomography: a case report

    Directory of Open Access Journals (Sweden)

    Goura Kishor Rath

    2010-10-01

    Full Text Available For liver metastases (LM, image guided percutaneous ablative procedures such as radiofrequency ablation (RFA, laser induced thermal therapy (LITT and trans-arterial chemo-embolisation (TACE are increasingly being used because they are relatively safer, less invasive and equally effective. CT scan guided interstitial brachytherapy (IBT with a single large dose of radiation by high dose rate (HDR brachytherapy is a novel technique of treating LM and has shown good results. Positron emission tomography (PET scan may provide better information for assessing the response toIBT procedures. We hereby report a case of LM that was treated by HDR IBT and PET scan was done in addition to CT scan for assessing the response.

  15. Compensatory responses induced by oxidative stress in Alzheimer disease

    Directory of Open Access Journals (Sweden)

    PAULA I MOREIRA

    2006-01-01

    Full Text Available Oxidative stress occurs early in the progression of Alzheimer disease, significantly before the development of the pathologic hallmarks, neurofibrillary tangles and senile plaques. In the first stage of development of the disease, amyloid-β deposition and hyperphosphorylated tau function as compensatory responses and downstream adaptations to ensure that neuronal cells do not succumb to oxidative damage. These findings suggest that Alzheimer disease is associated with a novel balance in oxidant homeostasis.

  16. A Unique ISR Program Determines Cellular Responses to Chronic Stress

    Czech Academy of Sciences Publication Activity Database

    Guan, B.J.; van Hoef, V.; Jobava, R.; Elroy-Stein, O.; Valášek, Leoš Shivaya; Cargnello, M.; Gao, X.H.; Krokowski, D.; Merrick, W.C.; Kimball, S.R.; Komar, A.A.; Koromilas, A.E.; Wynshaw-Boris, A.; Topisirovic, I.; Larsson, O.; Hatzoglou, M.

    2017-01-01

    Roč. 68, č. 5 (2017), s. 885-900 ISSN 1097-2765 R&D Projects: GA ČR(CZ) GA17-06238S EU Projects: Wellcome Trust(GB) 090812/B/09/A Institutional support: RVO:61388971 Keywords : UNFOLDED PROTEIN RESPONSE * EUKARYOTIC TRANSLATION INITIATION * ENDOPLASMIC-RETICULUM STRESS Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 14.714, year: 2016

  17. Epidermal stem cells response to radiative genotoxic stress

    International Nuclear Information System (INIS)

    Marie, Melanie

    2013-01-01

    Human skin is the first organ exposed to various environmental stresses, which requires the development by skin stem cells of specific mechanisms to protect themselves and to ensure tissue homeostasis. As stem cells are responsible for the maintenance of epidermis during individual lifetime, the preservation of genomic integrity in these cells is essential. My PhD aimed at exploring the mechanisms set up by epidermal stem cells in order to protect themselves from two genotoxic stresses, ionizing radiation (Gamma Rays) and ultraviolet radiation (UVB). To begin my PhD, I have taken part of the demonstration of protective mechanisms used by keratinocyte stem cells after ionizing radiation. It has been shown that these cells are able to rapidly repair most types of radiation-induced DNA damage. Furthermore, we demonstrated that this repair is activated by the fibroblast growth factor 2 (FGF2). In order to know if this protective mechanism is also operating in cutaneous carcinoma stem cells, we investigated the response to gamma Rays of carcinoma stem cells isolated from a human carcinoma cell line. As in normal keratinocyte stem cells, we demonstrated that cancer stem cells could rapidly repair radio-induced DNA damage. Furthermore, fibroblast growth factor 2 also mediates this repair, notably thanks to its nuclear isoforms. The second project of my PhD was to study human epidermal stem cells and progenitors responses to UVB radiation. Once cytometry and irradiation conditions were set up, the toxicity of UVB radiation has been evaluate in the primary cell model. We then characterized UVB photons effects on cell viability, proliferation and repair of DNA damage. This study allowed us to bring out that responses of stem cells and their progeny to UVB are different, notably at the level of part of their repair activity of DNA damage. Moreover, progenitors and stem cells transcriptomic responses after UVB irradiation have been study in order to analyze the global

  18. Effects of cerium dioxide nanoparticles in Oncorhynchus mykiss liver after an acute exposure: assessment of oxidative stress, genotoxicity and histological alterations

    Directory of Open Access Journals (Sweden)

    Ana Cristina Nunes

    2015-12-01

    Full Text Available At present cerium oxide nanoparticles (CeO2 NP have numerous applications ranging from industry to the household, leading to its wide distribution namely in the aquatic environment. The hereby study aimed to assess the toxic effects of CeO2 NPs in Oncorhynchus mykiss liver following an acute exposure (96h to three different concentrations (0.25, 2.5 and 25 mg/L in terms of the genotoxicity (comet assay, oxidative stress response (Catalase CAT; Glutathione S-Transferases GSTs; Thiobarbituric Acid Reactive Substances TBARS and histopathology. CeO2 NP exposure resulted in genotoxic damage in all exposure treatments, inhibition of CAT in the highest concentration and histopathological changes in all exposure concentrations with predominance of progressive and circulatory alterations. However TBARS and GSTs showed no significant differences comparatively to the control (unexposed group. The results suggest that CeO2 NP are able to cause genotoxicity, biochemical impairment and histological alterations in the liver of rainbow trout.

  19. Evolution and Stress Responses of Gossypium hirsutum SWEET Genes.

    Science.gov (United States)

    Li, Wei; Ren, Zhongying; Wang, Zhenyu; Sun, Kuan; Pei, Xiaoyu; Liu, Yangai; He, Kunlun; Zhang, Fei; Song, Chengxiang; Zhou, Xiaojian; Zhang, Wensheng; Ma, Xiongfeng; Yang, Daigang

    2018-03-08

    The SWEET (sugars will eventually be exported transporters) proteins are sugar efflux transporters containing the MtN3_saliva domain, which affects plant development as well as responses to biotic and abiotic stresses. These proteins have not been functionally characterized in the tetraploid cotton, Gossypium hirsutum , which is a widely cultivated cotton species. In this study, we comprehensively analyzed the cotton SWEET gene family. A total of 55 putative G. hirsutum SWEET genes were identified. The GhSWEET genes were classified into four clades based on a phylogenetic analysis and on the examination of gene structural features. Moreover, chromosomal localization and an analysis of homologous genes in Gossypium arboreum , Gossypium raimondii , and G. hirsutum suggested that a whole-genome duplication, several tandem duplications, and a polyploidy event contributed to the expansion of the cotton SWEET gene family, especially in Clade III and IV. Analyses of cis -acting regulatory elements in the promoter regions, expression profiles, and artificial selection revealed that the GhSWEET genes were likely involved in cotton developmental processes and responses to diverse stresses. These findings may clarify the evolution of G. hirsutum SWEET gene family and may provide a foundation for future functional studies of SWEET proteins regarding cotton development and responses to abiotic stresses.

  20. Leptin regulates dopamine responses to sustained stress in humans.

    Science.gov (United States)

    Burghardt, Paul R; Love, Tiffany M; Stohler, Christian S; Hodgkinson, Colin; Shen, Pei-Hong; Enoch, Mary-Anne; Goldman, David; Zubieta, Jon-Kar

    2012-10-31

    Neural systems that identify and respond to salient stimuli are critical for survival in a complex and changing environment. In addition, interindividual differences, including genetic variation and hormonal and metabolic status likely influence the behavioral strategies and neuronal responses to environmental challenges. Here, we examined the relationship between leptin allelic variation and plasma leptin levels with DAD2/3R availability in vivo as measured with [(11)C]raclopride PET at baseline and during a standardized pain stress challenge. Allelic variation in the leptin gene was associated with varying levels of dopamine release in response to the pain stressor, but not with baseline D2/3 receptor availability. Circulating leptin was also positively associated with stress-induced dopamine release. These results show that leptin serves as a regulator of neuronal function in humans and provides an etiological mechanism for differences in dopamine neurotransmission in response to salient stimuli as related to metabolic function. The capacity for leptin to influence stress-induced dopaminergic function is of importance for pathological states where dopamine is thought to play an integral role, such as mood, substance-use disorders, eating disorders, and obesity.

  1. Stress Transmission in Granular Packings: Localization and Cooperative Response

    Science.gov (United States)

    Ramola, Kabir

    We develop a framework for stress transmission in two dimensional granular media that respects vector force balance at the microscopic level. For a packing of grains interacting via pairwise contact forces, we introduce local gauge degrees of freedom that determine the response of the system to external perturbations. This allows us to construct unique force-balanced solutions that determine the change in contact forces as a response to external stress. By mapping this response to diffusion in the underlying contact network, we show that this naturally leads to spatial localization of forces. We present numerical evidence for stress localization using exact diagonalization studies of network Laplacians associated with soft disk packings. We use this formalism to characterize the deviation from elastic behaviour as the amount of disorder in the underlying network is varied. We discuss generalizations to systems with large friction between grains and other networks that display topological disorder. This work has been supported by NSF-DMR 1409093 and the W. M. Keck Foundation.

  2. Blockade of PD-1 Signaling Enhances Th2 Cell Responses and Aggravates Liver Immunopathology in Mice with Schistosomiasis japonica.

    Directory of Open Access Journals (Sweden)

    Sha Zhou

    2016-10-01

    Full Text Available More than 220 million people worldwide are chronically infected with schistosomes, causing severe disease or even death. The major pathological damage occurring in schistosomiasis is attributable to the granulomatous inflammatory response and liver fibrosis induced by schistosome eggs. The inflammatory response is tightly controlled and parallels immunosuppressive regulation, constantly maintaining immune homeostasis and limiting excessive immunopathologic damage in important host organs. It is well known that the activation of programmed death 1 (PD-1 signaling causes a significant suppression of T cell function. However, the roles of PD-1 signaling in modulating CD4+ T cell responses and immunopathology during schistosome infection, have yet to be defined.Here, we show that PD-1 is upregulated in CD4+ T cells in Schistosoma japonicum (S. japonicum-infected patients. We also show the upregulation of PD-1 expression in CD4+ T cells in the spleens, mesenteric lymph nodes, and livers of mice with S. japonicum infection. Finally, we found that the blockade of PD-1 signaling enhanced CD4+ T helper 2 (Th2 cell responses and led to more severe liver immunopathology in mice with S. japonicum infection, without a reduction of egg production or deposition in the host liver.Overall, our study suggests that PD-1 signaling is specifically induced to control Th2-associated inflammatory responses during schistosome infection and is beneficial to the development of PD-1-based control of liver immunopathology.

  3. Gene expression during different periods of the handling-stress response in Pampus argenteus

    Science.gov (United States)

    Sun, Peng; Tang, Baojun; Yin, Fei

    2017-11-01

    Common aquaculture practices subject fish to a variety of acute and chronic stressors. Such stressors are inherent in aquaculture production but can adversely affect survival, growth, immune response, reproductive capacity, and behavior. Understanding the biological mechanisms underlying stress responses helps with methods to alleviate the negative effects through better aquaculture practices, resulting in improved animal welfare and production efficiency. In the present study, transcriptome sequencing of liver and kidney was performed in silver pomfret (Pampus argenteus) subjected to handling stress versus controls. A total of 162.19 million clean reads were assembled to 30 339 unigenes. The quality of the assembly was high, with an N50 length of 2 472 bases. For function classification and pathway assignment, the unigenes were categorized into three GO (gene ontology) categories, twenty-six clusters of eggNOG (evolutionary genealogy of genes: non-supervised orthologous groups) function categories, and thirty-eight KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. Stress affected different functional groups of genes in the tissues studied. Differentially expressed genes were mainly involved in metabolic pathways (carbohydrate metabolism, lipid metabolism, amino-acid metabolism, uptake of cofactors and vitamins, and biosynthesis of other secondary metabolites), environmental information processing (signaling molecules and their interactions), organismal systems (endocrine system, digestive system), and disease (immune, neurodegenerative, endocrine and metabolic diseases). This is the first reported analysis of genome-wide transcriptome in P. argenteus, and the findings expand our understanding of the silver pomfret genome and gene expression in association with stress. The results will be useful to future analyses of functional genes and studies of healthy artificial breeding in P. argenteus and other related fish species.

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

    Science.gov (United States)

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

    2017-01-02

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

  5. Cortisol responses to naturalistic and laboratory stress in student teachers: comparison with a non-stress control day.

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    Wolfram, Maren; Bellingrath, Silja; Feuerhahn, Nicolas; Kudielka, Brigitte M

    2013-04-01

    Ambulatory assessments of hypothalamus-pituitary-adrenal axis responses to acute natural stressors yield evidence on stress regulation with high ecological validity. Sampling of salivary cortisol is a standard technique in this field. In 21 healthy student teachers, we assessed cortisol responses to a demonstration lesson. On a control day, sampling was repeated at analogous times. Additionally, the cortisol awakening response (CAR) was assessed on both days. Participants were also exposed to a laboratory stressor, the Trier Social Stress Test, and rated their individual levels of chronic work stress. In pre-to-post-stress assessment, cortisol levels declined after the lesson. However, post-stress cortisol levels were significantly higher compared with those on the control day. Also, the Trier Social Stress Test yielded higher cortisol responses when using the control day as reference baseline. Associations between the CAR and chronic stress measures were observed solely on the control day. There were no significant associations between cortisol responses to the natural and laboratory stressors. Our results indicate that a control day might be an important complement in laboratory but especially in ambulatory stress research. Furthermore, associations between chronic stress measures and the CAR might be obscured by acute stress exposure. Finally, responses to the laboratory stressor do not seem to mirror natural stress responses. Copyright © 2012 John Wiley & Sons, Ltd.

  6. Effect of bullfrog (Rana catesbeiana oil administered by gavage on the fatty acid composition and oxidative stress of mouse liver

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    L.P. Silva

    2004-10-01

    Full Text Available The aim of the present study was to investigate the effects of daily intragastric administration of bullfrog oil (oleic, linoleic and palmitoleic acid-rich oil, corresponding to 0.4% of body weight for four weeks, on fatty acid composition and oxidative stress (lipid peroxidation and catalase activity in mouse liver. The activities of aspartate aminotransferase (AST, alkaline phosphatase (ALP, alanine aminotransferase (ALT, and gamma-glutamyltransferase (GGT, biomarkers of tissue injury, were determined in liver homogenates and serum. The proportions of 18:2n-6, 20:4n-6, 20:5n-3, and 22:6n-3 (polyunsaturated fatty acids, from 37 to 60% in the total fatty acid content were increased in the liver of the bullfrog oil-treated group (P < 0.05 compared to control. At the same time, a significant decrease in the relative abundance of 14:0, 16:0, and 18:0 (saturated fatty acids, from 49 to 25% was observed. The hepatic content of thiobarbituric acid reactive substances (TBARS was increased from 2.3 ± 0.2 to 12.3 ± 0.3 nmol TBA-MDA/mg protein and catalase activity was increased from 840 ± 32 to 1110 ± 45 µmol reduced H2O2 min-1 mg protein-1 in the treated group. Bullfrog oil administration increased AST and ALP activities in the liver (from 234.10 ± 0.12 to 342.84 ± 0.13 and 9.38 ± 0.60 to 20.06 ± 0.27 U/g, respectively and in serum (from 95.41 ± 6.13 to 120.32 ± 3.15 and 234.75 ± 11.5 to 254.41 ± 2.73 U/l, respectively, suggesting that this treatment induced tissue damage. ALT activity was increased from 287.28 ± 0.29 to 315.98 ± 0.34 U/g in the liver but remained unchanged in serum, whereas the GGT activity was not affected by bullfrog oil treatment. Therefore, despite the interesting modulation of fatty acids by bullfrog oil, a possible therapeutic use requires care since some adverse effects were observed in liver.

  7. Protective Effect of γ-Irradiated Dried Powder of Artichoke Leaves against CCl4 Oxidative Stress Induced in Rat Liver

    International Nuclear Information System (INIS)

    Hamza, R.G.; El shahat, A.N.; Mekawey, H.M.S.

    2012-01-01

    Liver injuries are one of the most degenerative worldwide diseases and can lead to different complications. Artichoke (Cynara scolymus L.) is full of natural antioxidants and has hepato protective effect against liver toxicity. Gamma irradiation has been widely used as a first choice sterilization method of raw medicinal plants to be used in the phytotherapic industry worldwide .This study was designed to investigate the effect of dietary supplementation with γ- irradiated artichoke against carbon tetrachloride (CCl 4 )-induced oxidative stress and hepatotoxicity. The results of high performance liquid chromatography (HPLC) analysis of artichoke leaves indicated that the value of some of the main phenolic constituents was elevated under the effect of γ-irradiation (10 KGy). CCl 4 administration resulted in significant increase in the activity of serum alkaline phosphatase, gamma glutamyl transferase and transaminase in addition to an increase in the level of total bilirubine, malondialdehyde (MDA), glucose and the concentration of some lipid contents. Furthermore, CCl 4 administration reduced glutathione content, superoxides dismutase (SOD) and catalase (CAT) activity as well as a remarkable decrease in the level of insulin and high density lipoprotein-cholesterol was observed. In CCl 4 -treated rats dietary supplemented with either raw or γ-irradiated artichoke, a significant amelioration was observed on the adverse effects of the above mentioned parameters induced by CCl 4 administration. The present findings concluded that artichoke may be useful, as dietary supplement and possess phenolic compounds, for the prevention of oxidative stress-induced hepatotoxicity

  8. Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats

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    Oluwafemi O. Oguntibeju

    2016-01-01

    Full Text Available Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ- induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg aqueous solution was administered (daily orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC, ferric reducing antioxidant power (FRAP, catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue.

  9. The Mancozeb-containing carbamate fungicide tattoo induces mild oxidative stress in goldfish brain, liver, and kidney.

    Science.gov (United States)

    Atamaniuk, Tetiana M; Kubrak, Olga I; Husak, Viktor V; Storey, Kenneth B; Lushchak, Volodymyr I

    2014-11-01

    Tattoo belongs to the group of carbamate fungicides and contains Mancozeb (ethylene(bis)dithiocarbamate) as its main constituent. The toxicity of Mancozeb to living organisms, particularly fish, is not resolved. This work investigated the effects of 96 h of exposure to 3, 5, or 10 mg L(-1) of Tattoo (corresponding to 0.9, 1.5, or 3 mg L(-1) of Mancozeb) on the levels of oxidative stress markers and the antioxidant enzyme system of brain, liver, and kidney of goldfish, Carassius auratus). In liver, Tattoo exposure resulted in increased activities of superoxide dismutase (SOD) by 70%-79%, catalase by 23%-52% and glutathione peroxidase (GPx) by 49%. The content of protein carbonyls (CP) in liver was also enhanced by 92%-125% indicating extensive damage to proteins. Similar increases in CP levels (by 98%-111%) accompanied by reduced glucose-6-phosphate dehydrogenase activity (by 13%-15%) was observed in kidney of fish exposed to Tattoo; however, SOD activity increased by 37% in this tissue after treatment with 10 mg L(-1) Tattoo. In brain, a rise in lipid peroxide level (by 29%) took place after exposure to 10 mg L(-1) Tattoo and was accompanied by elevation of high-molecular mass thiols (by 14%). Tattoo exposure also resulted in a concentration-dependent decrease in glutathione reductase activity (by 26%-37%) in brain. The data collectively show that exposure of goldfish to 3-10 mg L(-1) of the carbamate fungicide Tattoo resulted in the development of mild oxidative stress and activation of antioxidant defense systems in goldfish tissues. Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.

  10. Association between insulin resistance and oxidative stress parameters in obese adolescents with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Pirgon, Özgür; Bilgin, Hüseyin; Çekmez, Ferhat; Kurku, Hüseyin; Dündar, Bumin Nuri

    2013-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in children. The aim of this study was to investigate the associations of oxidative stress with insulin resistance and metabolic risk factors in obese adolescents with NAFLD. Forty-six obese adolescents (23 girls and 23 boys, mean age: 12.8 ± 2.2 years) and 29 control subjects (15 girls and 14 boys, mean age: 12.7 ± 2.7 years) were enrolled in the study. The obese subjects were divided into two groups (NAFLD group and non-NAFLD group) based on the elevated alanine aminotransferase levels (>30 IU/L) and the presence or absence of liver steatosis detected by ultrasonography. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR) from fasting samples. Plasma total antioxidant status (TAS) and total oxidant status (TOS) level measurements (REL Assay Diagnostics) were done in all participants. The ratio of TOS to TAS was regarded as an oxidative stress index (OSI), an indicator of the degree of OS. Fasting insulin levels and HOMA-IR values in the NAFLD group were significantly higher than in the non-NAFLD and control groups. TAS measurements were decreased in both obese groups (NAFLD and non-NAFLD) in comparison with the control group. TOS and OSI measurements were higher in the NAFLD group than in the non-NAFLD and control groups. OSI was positively correlated with fasting insulin (r=0.67, p=0.01) and HOMA-IR (r=0.71, p=0.02) in the NAFLD obese group. In this cross-sectional study, elevated OS markers in obese adolescents with NAFLD were associated with insulin resistance. This data suggest that an antioxidant therapy might have a potential for treating NAFLD associated with insulin resistance.

  11. Lifelong Aerobic Exercise Reduces the Stress Response in Rats.

    Science.gov (United States)

    Pietrelli, A; Di Nardo, M; Masucci, A; Brusco, A; Basso, N; Matkovic, L

    2018-04-15

    The aim of this study was to analyze the effects of lifelong aerobic exercise (AE) on the adaptive response of the stress system in rats. It is well known that hypothalamic-pituitary-adrenal axis (HPA) activity differs when triggered by voluntary or forced exercise models. Male Wistar rats belonging to exercise (E) or control (C) groups were subjected to chronic AE, and two cutoff points were established at 8 (middle age) and 18 months (old age). Behavioral, biochemical and histopathological studies were performed on the main components/targets of the stress system. AE increased adrenal sensitivity (AS), brain corticosterone (CORT) and corticotropin-releasing factor (CRF), but had no effect on the thymus, adrenal glands (AGs) weight or plasma CORT. In addition, AE exerted no effect on the sympathetic tone, but significantly reduced anxiety-related behavior and emotionality. Aging decreased AS and deregulated neuroendocrine feedback, leading to an anxiogenic state which was mitigated by AE. Histopathological and morphometric analysis of AGs showed no alterations in middle-aged rats but adrenal vacuolization in approximately 20% old rats. In conclusion, lifelong AE did not produce adverse effects related to a chronic stress state. On the contrary, while AE upregulated some components of the HPA axis, it generated an adaptive response to cumulative changes, possibly through different compensatory and/or super compensatory mechanisms, modulated by age. The long-term practice of AE had a strong positive impact on stress resilience so that it could be recommended as a complementary therapy in stress and depression disease. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Slight hypercalcemia is not associated with positive responses in the Comet Assay in male rat liver.

    Science.gov (United States)

    Thiel, Anette; Hamel, Annie; Schaefer, Katrien; Cardoso, Renato; Beilstein, Paul

    2017-08-01

    Maintenance of physiological levels of intracellular and extracellular calcium is essential for life. Increased intracellular calcium levels are involved in cell death (apoptosis and necrosis) and are associated with positive responses in the Comet assay in vitro. In addition, high calcium and vitamin D intakes were reported to induce apoptosis in adipose tissue in obese mice and to increase DNA-migration in the Comet assay. To investigate increased serum concentration of calcium as a potential confounding factor in the regulatory Comet assay in vivo, we induced mild hypercalcemia in male Wistar rats by 3-day continuous intravenous infusion of calcium gluconate and performed the Comet assay in the liver in line with regulatory guidelines. The results of the study showed that mild increases in serum calcium concentration (up to 1.4 times above the concurrent control) and increased urinary calcium concentration (up to 27.8 times above the concurrent control) results in clinical signs like mild tremor, faster respiration rate and decreased activity in a few animals. However, under the conditions of the study, no increase in the %Tail DNA in the Comet assay and no indication of liver damage as determined by histopathological means were observed. Thus, mild increases in plasma calcium did not lead to positive results in a genotoxicity assessment by the Comet assay in the rat liver. This result is important as it confirms the reliability of this assay for regulatory evaluation of safety. Copyright © 2017 DSM Nutritional Products AG. Published by Elsevier B.V. All rights reserved.

  13. Global transcriptomic profiling demonstrates induction of oxidative stress and of compensatory cellular stress responses in brown trout exposed to glyphosate and Roundup.

    Science.gov (United States)

    Uren Webster, Tamsyn M; Santos, Eduarda M

    2015-01-31

    Glyphosate, the active ingredient in Roundup formulations, is the most widely used herbicide worldwide, and as a result contaminates surface waters and has been detected in food residues, drinking water and human urine, raising concerns for potential environmental and human health impacts. Research has shown that glyphosate and Roundup can induce a broad range of biological effects in exposed organisms, particularly via generation of oxidative stress. However, there has been no comprehensive investigation of the global molecular mechanisms of toxicity of glyphosate and Roundup for any species. We aimed to characterise and compare the global mechanisms of toxicity of glyphosate and Roundup in the liver of brown trout (Salmo trutta), an ecologically and economically important vertebrate species, using RNA-seq on an Illumina HiSeq 2500 platform. To do this, we exposed juvenile female brown trout to 0, 0.01, 0.5 and 10 mg/L of glyphosate and Roundup (glyphosate acid equivalent) for 14 days, and sequenced 6 replicate liver samples from each treatment. We assembled the brown trout transcriptome using an optimised de novo approach, and subsequent differential expression analysis identified a total of 1020 differentially-regulated transcripts across all treatments. These included transcripts encoding components of the antioxidant system, a number of stress-response proteins and pro-apoptotic signalling molecules. Functional analysis also revealed over-representation of pathways involved in regulating of cell-proliferation and turnover, and up-regulation of energy metabolism and other metabolic processes. These transcriptional changes are consistent with generation of oxidative stress and the widespread induction of compensatory cellular stress response pathways. The mechanisms of toxicity identified were similar across both glyphosate and Roundup treatments, including for environmentally relevant concentrations. The significant alterations in transcript expression observed

  14. Dose response relationship in anti-stress gene regulatory networks.

    Science.gov (United States)

    Zhang, Qiang; Andersen, Melvin E

    2007-03-02

    To maintain a stable intracellular environment, cells utilize complex and specialized defense systems against a variety of external perturbations, such as electrophilic stress, heat shock, and hypoxia, etc. Irrespective of the type of stress, many adaptive mechanisms contributing to cellular homeostasis appear to operate through gene regulatory networks that are organized into negative feedback loops. In general, the degree of deviation of the controlled variables, such as electrophiles, misfolded proteins, and O2, is first detected by specialized sensor molecules, then the signal is transduced to specific transcription factors. Transcription factors can regulate the expression of a suite of anti-stress genes, many of which encode enzymes functioning to counteract the perturbed variables. The objective of this study was to explore, using control theory and computational approaches, the theoretical basis that underlies the steady-state dose response relationship between cellular stressors and intracellular biochemical species (controlled variables, transcription factors, and gene products) in these gene regulatory networks. Our work indicated that the shape of dose response curves (linear, superlinear, or sublinear) depends on changes in the specific values of local response coefficients (gains) distributed in the feedback loop. Multimerization of anti-stress enzymes and transcription factors into homodimers, homotrimers, or even higher-order multimers, play a significant role in maintaining robust homeostasis. Moreover, our simulation noted that dose response curves for the controlled variables can transition sequentially through four distinct phases as stressor level increases: initial superlinear with lesser control, superlinear more highly controlled, linear uncontrolled, and sublinear catastrophic. Each phase relies on specific gain-changing events that come into play as stressor level increases. The low-dose region is intrinsically nonlinear, and depending on

  15. Dose response relationship in anti-stress gene regulatory networks.

    Directory of Open Access Journals (Sweden)

    Qiang Zhang

    2007-03-01

    Full Text Available To maintain a stable intracellular environment, cells utilize complex and specialized defense systems against a variety of external perturbations, such as electrophilic stress, heat shock, and hypoxia, etc. Irrespective of the type of stress, many adaptive mechanisms contributing to cellular homeostasis appear to operate through gene regulatory networks that are organized into negative feedback loops. In general, the degree of deviation of the controlled variables, such as electrophiles, misfolded proteins, and O2, is first detected by specialized sensor molecules, then the signal is transduced to specific transcription factors. Transcription factors can regulate the expression of a suite of anti-stress genes, many of which encode enzymes functioning to counteract the perturbed variables. The objective of this study was to explore, using control theory and computational approaches, the theoretical basis that underlies the steady-state dose response relationship between cellular stressors and intracellular biochemical species (controlled variables, transcription factors, and gene products in these gene regulatory networks. Our work indicated that the shape of dose response curves (linear, superlinear, or sublinear depends on changes in the specific values of local response coefficients (gains distributed in the feedback loop. Multimerization of anti-stress enzymes and transcription factors into homodimers, homotrimers, or even higher-order multimers, play a significant role in maintaining robust homeostasis. Moreover, our simulation noted that dose response curves for the controlled variables can transition sequentially through four distinct phases as stressor level increases: initial superlinear with lesser control, superlinear more highly controlled, linear uncontrolled, and sublinear catastrophic. Each phase relies on specific gain-changing events that come into play as stressor level increases. The low-dose region is intrinsically nonlinear

  16. Increased oxidative stress associated with the severity of the liver disease in various forms of hepatitis B virus infection.

    Science.gov (United States)

    Bolukbas, Cengiz; Bolukbas, Fusun Filiz; Horoz, Mehmet; Aslan, Mehmet; Celik, Hakim; Erel, Ozcan

    2005-10-31

    Oxidative stress can be defined as an increase in oxidants and/or a decrease in antioxidant capacity. There is limited information about the oxidative status in subjects with hepatitis B virus infection. We aimed to evaluate the oxidative status in patients with various clinical forms of chronic hepatitis B infection. Seventy-six patients with hepatitis B virus infection, in whom 33 with chronic hepatitis, 31 inactive carriers and 12 with cirrhosis, and 16 healthy subjects were enrolled. Total antioxidant response and total peroxide level measurement, and calculation of oxidative stress index were performed in all participants. Total antioxidant response was significantly lower in cirrhotics than inactive HbsAg carriers and controls (p = 0.008 and p = 0.008, respectively). Total peroxide level and oxidative stress index was significantly higher in cirrhotic (p Total antioxidant response was comparable in chronic hepatitis B subjects, inactive HbsAg carriers and controls (both, p > 0.05/6). Total peroxide level and oxidative stress index were also comparable in inactive HBsAg carriers and controls (both, p > 0.05/6). Serum alanine amino transferase level was positively correlated with total peroxide level and oxidative stress index only in chronic hepatitis B subjects (p = 0.002, r = 0.519 and p = 0.008, r = 0.453, respectively). Oxidative stress occurs secondarily to increased total lipid peroxidation and inadequate total antioxidant response and is related to severity of the disease and replication status of virus in hepatitis B infection.

  17. Phenobarbital induces cell cycle transcriptional responses in mouse liver humanized for constitutive androstane and pregnane x receptors.

    Science.gov (United States)

    Luisier, Raphaëlle; Lempiäinen, Harri; Scherbichler, Nina; Braeuning, Albert; Geissler, Miriam; Dubost, Valerie; Müller, Arne; Scheer, Nico; Chibout, Salah-Dine; Hara, Hisanori; Picard, Frank; Theil, Diethilde; Couttet, Philippe; Vitobello, Antonio; Grenet, Olivier; Grasl-Kraupp, Bettina; Ellinger-Ziegelbauer, Heidrun; Thomson, John P; Meehan, Richard R; Elcombe, Clifford R; Henderson, Colin J; Wolf, C Roland; Schwarz, Michael; Moulin, Pierre; Terranova, Rémi; Moggs, Jonathan G

    2014-06-01

    The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CAR(KO)-PXR(KO)), double humanized CAR and PXR (CAR(h)-PXR(h)), and wild-type C57BL/6 mice. Wild-type and CAR(h)-PXR(h) mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CAR(KO)-PXR(KO) mouse livers and largely reversible in wild-type and CAR(h)-PXR(h) mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CAR(h)-PXR(h) mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.

  18. Responses to reductive stress in the cardiovascular system.

    Science.gov (United States)

    Handy, Diane E; Loscalzo, Joseph

    2017-08-01

    There is a growing appreciation that reductive stress represents a disturbance in the redox state that is harmful to biological systems. On a cellular level, the presence of increased reducing equivalents and the lack of beneficial fluxes of reactive oxygen species can prevent growth factor-mediated signaling, promote mitochondrial dysfunction, increase apoptosis, and decrease cell survival. In this review, we highlight the importance of redox balance in maintaining cardiovascular homeostasis and consider the tenuous balance between oxidative and reductive stress. We explain the role of reductive stress in models of protein aggregation-induced cardiomyopathies, such as those caused by mutations in αB-crystallin. In addition, we discuss the role of NADPH oxidases in models of heart failure and ischemia-reperfusion to illustrate how oxidants may mediate the adaptive responses to injury. NADPH oxidase 4, a hydrogen peroxide generator, also has a major role in promoting vascular homeostasis through its regulation of vascular tone, angiogenic responses, and effects on atherogenesis. In contrast, the lack of antioxidant enzymes that reduce hydrogen peroxide, such as glutathione peroxidase 1, promotes vascular remodeling and is deleterious to endothelial function. Thus, we consider the role of oxidants as necessary signals to promote adaptive responses, such as the activation of Nrf2 and eNOS, and the stabilization of Hif1. In addition, we discuss the adaptive metabolic reprogramming in hypoxia that lead to a reductive state, and the subsequent cellular redistribution of reducing equivalents from NADH to other metabolites. Finally, we discuss the paradoxical ability of excess reducing equivalents to stimulate oxidative stress and promote injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Liver proteome response of largemouth bass (Micropterus salmoides) exposed to several environmental contaminants: Potential insights into biomarker development

    International Nuclear Information System (INIS)

    Sanchez, Brian C.; Ralston-Hooper, Kimberly J.; Kowalski, Kevin A.; Dorota Inerowicz, H.; Adamec, Jiri; Sepulveda, Maria S.

    2009-01-01

    Liver proteome response of largemouth bass (Micropterus salmoides) exposed to environmental contaminants was analyzed to identify novel biomarkers of exposure. Adult male bass were exposed to cadmium chloride (CdCl 2 ), atrazine, PCB 126, phenanthrene, or toxaphene via intraperitoneal injection with target body burdens of 0.00067, 3.0, 2.5, 50, and 100 μg/g, respectively. After a 96 h exposure, hepatic proteins were separated with two-dimensional gel electrophoresis and differentially expressed proteins (vs. controls) recognized and identified with MALDI-TOF/TOF mass spectrometry. We identified, 30, 18, eight, 19, and five proteins as differentially expressed within the CdCl 2 , atrazine, PCB 126, phenanthrene, and toxaphene treatments, respectively. Alterations were observed in the expression of proteins associated with cellular ion homeostasis (toxaphene), oxidative stress (phenanthrene, PCB 126), and energy production including glycolysis (CdCl 2 , atrazine) and ATP synthesis (atrazine). This work supports the further evaluation of several of these proteins as biomarkers of contaminant exposure in fish.

  20. Attenuation of the cortisol response to stress in female rainbow trout chronically exposed to dietary selenomethionine

    Energy Technology Data Exchange (ETDEWEB)

    Wiseman, Steve, E-mail: steve.wiseman@usask.ca [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Thomas, Jith K.; McPhee, Landon; Hursky, Olesya; Raine, Jason C. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Pietrock, Michael [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Giesy, John P. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong (Hong Kong); School of Biological Sciences, University of Hong Kong, Hong Kong (Hong Kong); Department of Zoology, Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States); State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing (China); Hecker, Markus [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); School of Environment and Sustainability, University of Saskatchewan, Saskatoon, SK, S7N 5CB (Canada); Janz, David M. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada)

    2011-10-15

    Highlights: Trout exposed to Se-Met had greater concentration of cortisol compared to controls. Transcript abundance of mc2r was greater in trout exposed to Se-Met. Trout exposed to Se-Met had a reduced cortisol response to a handling stressor. Cortisone concentration was greater in Se-Met exposed trout post-handling stressor. - Abstract: Selenomethionine (Se-Met) is the major dietary form of selenium (Se). While Se is a required nutrient, it can also influence the physiological stress response because it stimulates greater concentrations of cortisol in blood plasma of exposed fish. However, little is known about the effects of exposure to Se on the ability to cope with a secondary stressor. In the current study, female rainbow trout were exposed to an environmentally relevant dietary concentration (8.47 mg Se/kg dry mass (dm)) of Se-Met for 126 d, after which time fish were subjected to a 3-min handling stressor and sampled at 2 h and 24 h post-stressor exposure. Concentrations of cortisol, cortisone, glucose, and lactate in blood plasma and concentrations of glycogen and triglycerides in liver and muscle were determined. Abundances of transcripts of proteins involved in corticosteroidogenesis were determined using quantitative RT-PCR. Concentrations of cortisol were significantly greater in blood plasma of trout exposed to Se-Met, relative to control trout sampled prior to the handling stressor. A typical response of cortisol to the handling stressor was observed in the control trout. However, trout exposed to Se-Met were unable to mount a cortisol response to the handling stressor. Concentrations of cortisone, the inactive metabolite of cortisol, were significantly greater following the handling stressor in trout exposed to Se-Met. In trout exposed to Se-Met, transcript abundance of melanocortin 2 receptor (mc2r) and peripheral benzodiazepine receptor (pbr) were greater, which is consistent with the conclusion that synthesis of cortisol was greater. However