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Oxidative Stress Response (oxidative + stress_response)
Selected AbstractsThe multicopper oxidase (CueO) and cell aggregation in Escherichia coliENVIRONMENTAL MICROBIOLOGY, Issue 8 2007Jai J. Tree Summary cueO encodes a periplasmic multicopper oxidase, which is known to be involved in copper homeostasis and protection against oxidative stress in Escherichia coli K12. Transcriptional profiling showed that expression of genes associated with motility was lowered in a cueO mutant while expression of genes associated with autoaggregation was elevated. Increased aggregation was correlated with increased expression of cell surface proteins antigen 43 and curli. Changes in gene expression caused by the deletion of cueO were essentially independent of SoxR and OxyR, the global regulators of oxidative stress response. [source] The Pseudomonas aeruginosa quinolone signal (PQS) has an iron-chelating activityENVIRONMENTAL MICROBIOLOGY, Issue 8 2006Florian Bredenbruch Summary Virulence factor production and the development of biofilms in Pseudomonas aeruginosa have been shown to be regulated by two hierarchically organized quorum-sensing systems activated by two types of small acyl-homoserine lactone signal molecules. Recently, a third type of bacterial signal molecule, the Pseudomonas quinolone signal (PQS), has been identified, which positively regulates a subset of genes dependent on the quorum-sensing systems. However, the molecular mechanism underlying PQS signalling has remained poorly understood. In this study the global transcriptional profile of P. aeruginosa in response to PQS revealed a marked upregulation of genes belonging to the tightly interdependent functional groups of the iron acquisition and the oxidative stress response. Remarkably, most of the differentially regulated genes, as well as the induction of rhlR, could be traced back to an iron-chelating effect of PQS. Our results amount to the elucidation of how PQS affects P. aeruginosa and have important implications for the understanding of the complex regulatory circuits involved in P. aeruginosa gene regulation. [source] Early transcriptional response of Saccharomyces cerevisiae to stress imposed by the herbicide 2,4-dichlorophenoxyacetic acidFEMS YEAST RESEARCH, Issue 2 2006Miguel Cacho Teixeira Abstract The global gene transcription pattern of the eukaryotic experimental model Saccharomyces cerevisiae in response to sudden aggression with the widely used herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was analysed. Under acute stress, 14% of the yeast transcripts suffered a greater than twofold change. The yeastract database was used to predict the transcription factors mediating the response registered in this microarray analysis. Most of the up-regulated genes in response to 2,4-D are known targets of Msn2p, Msn4p, Yap1p, Pdr1p, Pdr3p, Stp1p, Stp2p and Rpn4p. The major regulator of ribosomal protein genes, Sfp1p, is known to control 60% of the down-regulated genes, in particular many involved in the transcriptional and translational machinery and in cell division. The yeast response to the herbicide includes the increased expression of genes involved in the oxidative stress response, the recovery or degradation of damaged proteins, cell wall remodelling and multiple drug resistance. Although the protective role of TPO1 and PDR5 genes was confirmed, the majority of the responsive genes encoding multidrug resistance do not confer resistance to 2,4-D. The increased expression of genes involved in alternative carbon and nitrogen source metabolism, fatty acid ,-oxidation and autophagy was also registered, suggesting that acute herbicide stress leads to nutrient limitation. [source] Glutamine administration in patients undergoing cardiac surgery and the influence on blood glutathione levelsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2009J. M. ENGEL Background: Cardiac surgery with an extracorporeal circulation cardiopulmonary bypass (CPB) is characterized by an oxidative stress response. Glutathione (GSH) belongs to the major antioxidative defense. In metabolic stress, glutamine (GLN) may be the rate-limiting factor of GSH synthesis. Decreased GLN plasma levels were observed after various critical states. We evaluated, in patients undergoing open heart surgery with CPB, the effects of a peri-operative GLN supplementation on GSH in whole blood and assessed their influence on the Sequential Organ Failure Assessment score and the intensive care unit length of stay. Methods: In this prospective, randomized, double-blinded study, we included 60 patients (age older than 70 years, ejection fraction <40% or mitral valve replacement) undergoing an elective cardiac surgery with CPB. We randomly assigned each subject to receive an infusion with either GLN (0.5 g/kg/day, group 1) or an isonitrogeneous, isocaloric, isovolemic amino acids solution (group 2) or saline (group 3). Results: From the first post-operative day GLN plasma levels in group 1 were significantly increased compared with the other groups. With saline GSH the levels decreased significantly post-operatively compared with GLN. We observed a significant correlation between GLN delivery and GSH levels. Conclusions: A peri-operative high-dose GLN infusion increased plasma GLN concentrations and maintained the GSH levels after cardiac surgery with CPB. [source] Interaction of pyridostigmine and physical stress on antioxidant defense system in skeletal muscle of miceJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2001R. Jagannathan Abstract Pyridostigmine bromide (PB), a reversible anticholinesterase drug, had been used against possible nerve gas exposure during the Persian Gulf War. The Gulf War veterans used PB and they were under physical stress. This study investigated the delayed and interactive effects of pyridostigmine and physical stress on the antioxidant defense system in triceps muscle of mice. Male NIH Swiss mice were divided into four groups and treated as follows: sedentary control; pyridostigmine (1.2 mg kg,1 p.o.); exercise; and PB plus exercise. Mice were exercised for 10 weeks, but PB was administered daily during the 5th and 6th weeks. Mice were sacrificed 24 h after the last treatments and the triceps muscle was isolated and analyzed. There was a significant increase in total superoxide dismutase (CuZn-SOD + Mn-SOD) activity (141% of control) with PB plus exercise, suggesting that any influx of superoxide anions was scavenged efficiently. The Mn-SOD enzyme protein levels were reduced significantly (63% of control) by PB plus exercise. Catalase enzyme protein levels were increased significantly by exercise (132% of control) as well as by PB plus exercise (139% of control). Glutathione levels were increased significantly by exercise alone (123% of control). Pyridostigmine bromide plus exercise significantly increased the malondialdehyde concentration (124% of control) in the triceps muscle, indicating an oxidative stress response of the combination. The data indicate that a combination of PB ingestion and exercise training significantly altered the antioxidant enzyme activities, enzyme protein levels and lipid peroxidation, leading to oxidative injury. Physical stress amplified the delayed effects of PB in the skeletal muscle of mice. Copyright © 2001 John Wiley & Sons, Ltd. [source] Ethanol-induced alterations of the antioxidant defense system in rat kidneyJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 6 2006Diana Dinu Abstract We report here the effects of chronic ethanol consumption on the antioxidant defense system in rat kidney. Thirty-two male Wistar rats were randomly divided in two identical groups and were treated as follows: control group (water for fluid) and the ethanol-fed group (2 g/kg body weight/24 h). The animals were sacrificed after 10 weeks, and respectively 30 weeks of ethanol consumption, and the renal tissue was isolated and analyzed. Results revealed that kidney alcohol dehydrogenase activities increased significantly after ethanol administration, but the electrophoretic pattern of alcohol dehydrogenase isoforms was unmodified. The SDS polyacrylamidegel electrophoretic study of kidney proteins has revealed the appearance of two new protein bands after long-term ethanol consumption. The kidney reduced glutathione/oxidized glutathione ratio decreased, indicating an oxidative stress response due to ethanol ingestion. The malondialdehyde contents and xanthine oxidase activities were unchanged. The antioxidant enzymatic defense system showed a different response during the two periods of ethanol administration. After 10 weeks, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase were activated, while superoxide dismutase, glutathione transferase, and ,-glutamyltranspeptidase levels were stationary. After 30 weeks, superoxide dismutase and glutathione peroxidase activities were unmodified, but catalase, glutathione transferase, ,-glutamyltranspeptidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities were significantly increased. Remarkable changes have been registered after 30 weeks of ethanol administration for glutathione reductase and glucose-6-phosphate dehydrogenase activities, including an increase by 106 and 216' of control values, respectively. These results showed specific changes in rat kidney antioxidant system and glutathione status as a consequence of long-term ethanol administration. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:386-395, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20101 [source] Differential control of apoptosis by DJ-1 in prostate benign and cancer cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2004Yaacov Hod Abstract DJ-1 is a conserved protein reported to be involved in diverse cellular processes ranging from cellular transformation, control of protein,RNA interaction, oxidative stress response to control of male infertility, among several others. Mutations in the human gene have been shown to be associated with an autosomal recessive, early onset Parkinson's disease (PARK7). The present study examines the control of DJ-1 expression in prostatic benign hyperplasia (BPH-1) and cancer (PC-3) cell lines in which DJ-1 abundance differs significantly. We show that while BPH-1 cells exhibit low basal level of DJ-1 expression, stress-inducing agents such as H2O2 and mitomycin C markedly increase the intracellular level of the polypeptide. In contrast, DJ-1 expression is relatively high in PC-3 cells, and incubation with the same cytotoxic drugs does not modulate further the level of the polypeptide. In correlation with the expression of DJ-1, both cytotoxic agents activate the apoptotic pathway in the prostatic benign cells but not in PC-3 cells, which are resistant to their action. We further demonstrate that incubation of BPH-1 cells with TNF-related-apoptosis-inducing-ligand/Apo-2L (TRAIL) also enhances DJ-1 expression and that TRAIL and H2O2 act additively to stimulate DJ-1 accumulation but synergistically in the activation of the apoptotic pathway. Time-course analysis of DJ-1 stimulation shows that while DJ-1 level increases without significant lag in TRAIL-treated cells, there is a delay in H2O2 -treated cells, and that the increase in DJ-1 abundance precedes the activation of apoptosis. Unexpectedly, over-expression of DJ-1 de-sensitizes BPH-1 cells to the action of apoptotic-inducing agents. However, RNA-interference-mediated silencing of DJ-1 expression results in sensitization of PC-3 cells to TRAIL action. These results are consistent with a model in which DJ-1 is involved in the control of cell death in prostate cell lines. DJ-1 appears to play a differential role between cells expressing a low but inducible level of DJ-1 (e.g., BPH-1 cells) and those expressing a high but constitutive level of the polypeptide (e.g., PC-3 cells). © 2004 Wiley-Liss, Inc. [source] HIV-1 viral envelope glycoprotein gp120 produces oxidative stress and regulates the functional expression of multidrug resistance protein-1 (Mrp1) in glial cellsJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Patrick T. Ronaldson Abstract Brain human immunodeficiency virus type-1 (HIV-1) infection is associated with oxidative stress, which may lead to HIV-1 encephalitis, a chronic neurodegenerative condition. In vitro, oxidative stress can be induced in glial cells by exposure to HIV-1 envelope protein glycoprotein (gp120). Multidrug resistance proteins (Mrps) are known to efflux endogenous substrates (i.e. GSH and GSSG) involved in cellular defense against oxidative stress. Altered GSH/GSSG export may contribute to oxidative damage during HIV-1 encephalitis. At present, it is unknown if gp120 exposure can alter the functional expression of Mrp isoforms. Heat-shock protein 70, inducible nitric oxide synthase, intracellular GSSG, 2,,7,-dichlorofluorescein fluorescence, and extracellular nitrite were increased in primary cultures of rat astrocytes triggered with gp120, suggesting an oxidative stress response. RT-PCR and immunoblot analysis demonstrated increased Mrp1 mRNA (2.3-fold) and protein (2.2-fold), respectively, in gp120 treated astrocytes while Mrp4 mRNA or protein expression was not changed. Cellular retention of 2,,7,-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, an established Mrp substrate, was reduced (twofold) in gp120-treated astrocytes, suggesting increased Mrp-mediated transport. In addition, GSH and GSSG export were enhanced in gp120-triggered cells. These data suggest that gp120 can up-regulate Mrp1, but not Mrp4, functional expression in cultured astrocytes. Our observation of increased GSH/GSSG efflux in response to gp120 treatment implies that Mrp isoforms may be involved in regulating the oxidative stress response in glial cells. [source] Hypoxia-like effect of Cobalt Chromium alloy micro particles on fibroblasts in vitroJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 10 2010Bernadette K. Madathil Abstract Periprosthetic osteolysis leading to asceptic loosening remains the primary cause of failure of joint replacement. Although many inflammatory cell types have been implicated, the exact pathomechanisms of asceptic loosening have not been delineated. In the present study we have adopted a proteomic approach to elucidate the initial signals that are expressed to particulate material, using an in vitro cell culture system. Human lung fibroblasts MRC-5 were cultured with Cobalt Chromium (CoCr ASTM F-75, 1,7,µm) particles. Cells were harvested after 72,h incubation and total cellular proteins extracted for downstream analysis via 2D Gel Electrophoresis and tandem mass spectrometry using MALDI-TOF-TOF-MS. Thirteen protein spots showed greater than twofold increase, following 72,h incubation of fibroblast with CoCr particles. Four of these proteins were identified by tandem mass spectrometry. These were Annexin II, Pyruvate kinase, Triose phosphate isomerase, and N-myc downstream regulated gene 1 protein. Cobalt is a hypoxia mimicking agent and N-myc downstream regulated gene 1 protein, Triose phosphate isomerase, Pyruvate kinase, and Annexin II are important hypoxia regulated gene products that are found to be over expressed in cellular oxidative stress response. Our data indicates that exposure of fibroblast to CoCr alloy induces the transition of these cells into a hypoxia like state and oxidative stress even in normoxic culture conditions. The study reflects the possibility of the presence of a hypoxic environment in the periprosthetic tissue surrounding metallic implants. Published by Wiley Periodicals, Inc. J Orthop Res 28:1360,1367, 2010 [source] Comparative study of the physiological roles of three peroxidases (NADH peroxidase, Alkyl hydroperoxide reductase and Thiol peroxidase) in oxidative stress response, survival inside macrophages and virulence of Enterococcus faecalisMOLECULAR MICROBIOLOGY, Issue 5 2007Stephanie La Carbona Summary The opportunistic pathogen Enterococcus faecalis is well equipped with peroxidatic activities. It harbours three loci encoding a NADH peroxidase, an alkyl hydroperoxide reductase and a protein (EF2932) belonging to the AhpC/TSA family. We present results demonstrating that ef2932 does encode a thiol peroxidase (Tpx) and show that it is part of the regulon of the hydrogen peroxide regulator HypR. Characterization of unmarked deletion mutants showed that all three peroxidases are important for the defence against externally provided H2O2. Exposure to internal generated H2O2 by aerobic growth on glycerol, lactose, galactose or ribose showed that Npr was absolutely required for aerobic growth on glycerol and optimal growth on the other substrates. Growth on glycerol was also dependent on Ahp. Addition of catalase restored growth of the mutants, and therefore, extracellular H2O2 concentrations have been determined. This showed that the time point of growth arrest of the ,npr mutant correlated with the highest H2O2 concentration measured. Analysis of the survival of the different strains inside peritoneal macrophages revealed that Tpx was the most important antioxidant activity for protecting the cells against the hostile phagocyte environment. Finally, the ,tpx and the triple mutant showed attenuated virulence in a mouse peritonitis model. [source] A Rox1-independent hypoxic pathway in yeast.MOLECULAR MICROBIOLOGY, Issue 4 2000Antagonistic action of the repressor Ord, activator Yap1 for hypoxic expression of the SRP1/TIR1 gene Hypoxic SRP1/TIR1 gene expression depends on the absence of haem but is independent of Rox1-mediated repression. We have found a new hypoxic pathway involving an antagonistic interaction between the Ixr1/Ord1 repressor and the Yap1 factor, a transcriptional activator involved in oxidative stress response. Here, we show that Ord1 repressed SRP1 gene expression under normoxia and hypoxia, whereas Yap1 activated it. Ord1 and Yap1 have been shown to bind the SRP1 promoter in a region extending from ,299 to ,156 bp upstream of the start codon. A typical AP-1 responsive element lying from ,247 to ,240 bp allows Yap1 binding. Internal deletion of sequences within the SRP1 promoter were introduced. Two regions were characterized at positions ,299/,251 and ,218/,156 that, once removed, resulted in a constitutive expression of SRP1 in a wild-type strain under normoxic conditions. Deletion of both these two sequences allowed the bypass of YAP1 requirement in a ,yap1 strain, whereas these two internal deletions did not yield increased expression in a ,ord1 strain compared with the full-length promoter. Both a single ,ord1 mutant and a doubly disrupted ,yap1 ,ord1 strain yielded normoxic constitutive SRP1 expression and increased hypoxic SRP1 induction, thereby demonstrating that ord1 is epistatic to yap1. Thus, Yap1 is not directly involved in SRP1 induction by hypoxia, but is necessary to counteract the Ord1 effect. [source] Centella asiatica extract selectively decreases amyloid , levels in hippocampus of Alzheimer's disease animal modelPHYTOTHERAPY RESEARCH, Issue 1 2009Muralikrishnan Dhanasekaran Abstract PSAPP mice expressing the ,Swedish' amyloid precursor protein and the M146L presenilin 1 mutations are a well-characterized model for spontaneous amyloid , plaque formation. Centella asiatica has a long history of use in India as a memory enhancing drug in Ayurvedic literature. The study investigated whether Centella asiatica extract (CaE) can alter the amyloid pathology in PSAPP mice by administering CaE (2.5 or 5.0 g/kg/day) starting at 2 months of age prior to the onset of detectable amyloid deposition and continued for either 2 months or 8 months. A significant decrease in amyloid , 1,40 and 1,42 was detectable by ELISA following an 8 month treatment with 2.5 mg/kg of CaE. A reduction in Congo Red stained fibrillar amyloid plaques was detected with the 5.0 mg/kg CaE dose and long-term treatment regimen. It was also confirmed that CaE functions as an antioxidant in vitro, scavenging free radicals, reducing lipid peroxidation and protecting against DNA damage. The data indicate that CaE can impact the amyloid cascade altering amyloid , pathology in the brains of PSAPP mice and modulating components of the oxidative stress response that has been implicated in the neurodegenerative changes that occur with Alzheimer's disease. Copyright © 2008 John Wiley & Sons, Ltd. [source] Pseudomonas putida KT2440 responds specifically to chlorophenoxy herbicides and their initial metabolitesPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 11 2006Dirk Benndorf Dr. Abstract Pseudomonas putida,KT2440 is often used as a model to investigate toxicity mechanisms and adaptation to hazardous chemicals in bacteria. The objective of this paper was to test the impact of the chlorophenoxy herbicides 2,4-dichlorophenoxyacetic acid,(2,4-D) and 2-(2,4-dichlorophenoxy)propanoic acid,(DCPP) and their metabolites 2,4-dichlorophenol,(DCP) and 3,5-dichlorocatechol,(DCC), on protein expression patterns and physiological parameters. Both approaches showed that DCC has a different mode of action and induces different responses than DCPP, 2,4-D and DCP. DCC was the most toxic compound and was active as an uncoupler of oxidative phosphorylation. It repressed the synthesis of ferric uptake regulator (Fur)-dependent proteins, e.g. fumarase,C and L -ornithine N5-oxygenase, which are involved in oxidative stress response and iron uptake. DCPP, 2,4-D and DCP were less toxic than DCC. They disturbed oxidative phosphorylation to a lesser extent by a yet unknown mechanism. Furthermore, they repressed enzymes of energy-consuming biosynthetic pathways and induced membrane transporters for organic substrates. A TolC homologue component of multidrug resistance transporters was found to be induced, which is probably involved in the removal of lipophilic compounds from membranes. [source] Neuroproteomics and its applications in research on nicotine and other drugs of abusePROTEOMICS - CLINICAL APPLICATIONS, Issue 11 2007Ming D. Li Dr. Abstract The rapidly growing field of neuroproteomics is able to track changes in protein expression and protein modifications underlying various physiological conditions, including the neural diseases related to drug addiction. Thus, it presents great promise in characterizing protein function, biochemical pathways, and networks to understand the mechanisms underlying drug dependence. In this article, we first provide an overview of proteomics technologies and bioinformatics tools available to analyze proteomics data. Then we summarize the recent applications of proteomics to profile the protein expression pattern in animal or human brain tissues after the administration of nicotine, alcohol, amphetamine, butorphanol, cocaine, and morphine. By comparing the protein expression profiles in response to chronic nicotine exposure with those appearing in response to treatment with other drugs of abuse, we identified three biological processes that appears to be regulated by multiple drugs of abuse: energy metabolism, oxidative stress response, and protein degradation and modification. Such similarity indicates that despite the obvious differences among their chemical properties and the receptors with which they interact, different substances of abuse may cause some similar changes in cellular activities and biological processes in neurons. [source] An in vitro study on reproductive toxicology of Deltamethrin on rat spermatozoaANDROLOGIA, Issue 4 2010F. Ben Abdallah Summary Recent findings indicate that synthetic pyrethroid insecticide may induce toxic manifestations by enhancing the production of reactive oxygen species and disrupting the balance between pro-oxidants and antioxidants as a result of lipid peroxidation (LP) of cell membranes. The aim of the study was to examine the potency of Deltamethrin (Del) to induce oxidative stress response in rat spermatozoa in vitro. Spermatozoa were incubated with different concentrations (0, 10, 50, 100 and 200 ,m) of Del for 3 h at 37 °C. After that, sperm parameters (motility, viability and abnormal morphology), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) levels were determined. We found that in vitro exposure to Del caused a significant decline of sperm motility and viability and increase of abnormal sperm morphology, MDA, SOD and CAT levels at different concentrations of Del. This study demonstrated that Del caused deterioration in sperm motility and viability, and induction in LP, abnormal morphology of spermatozoa and antioxidants enzyme activities. [source] Hydrogen peroxide-induced oxidative stress responses in Desulfovibrio vulgaris HildenboroughENVIRONMENTAL MICROBIOLOGY, Issue 10 2010Aifen Zhou Summary To understand how sulphate-reducing bacteria respond to oxidative stresses, the responses of Desulfovibrio vulgaris Hildenborough to H2O2 -induced stresses were investigated with transcriptomic, proteomic and genetic approaches. H2O2 and induced chemical species (e.g. polysulfide, ROS) and redox potential shift increased the expressions of the genes involved in detoxification, thioredoxin-dependent reduction system, protein and DNA repair, and decreased those involved in sulfate reduction, lactate oxidation and protein synthesis. A gene coexpression network analysis revealed complicated network interactions among differentially expressed genes, and suggested possible importance of several hypothetical genes in H2O2 stress. Also, most of the genes in PerR and Fur regulons were highly induced, and the abundance of a Fur regulon protein increased. Mutant analysis suggested that PerR and Fur are functionally overlapped in response to stresses induced by H2O2 and reaction products, and the upregulation of thioredoxin-dependent reduction genes was independent of PerR or Fur. It appears that induction of those stress response genes could contribute to the increased resistance of deletion mutants to H2O2 -induced stresses. In addition, a conceptual cellular model of D. vulgaris responses to H2O2 stress was constructed to illustrate that this bacterium may employ a complicated molecular mechanism to defend against the H2O2 -induced stresses. [source] Methionine sulphoxide reductase is an important antioxidant enzyme in the gastric pathogen Helicobacter pyloriMOLECULAR MICROBIOLOGY, Issue 5 2004Praveen Alamuri Summary The ability of Helicobacter pylori to colonize the stomach requires that it combat oxidative stress responses imposed by the host. The role of methionine sulfoxide reductase (Msr), a methionine repair enzyme, in H. pylori stress resistance was evaluated by a mutant analysis approach. An msr mutant strain lacked immunologically detectable sulphoxide reductase protein and also showed no enzyme activity when provided with oxidized methionines as substrates. The mutant strain showed diminished growth compared to the parent strain in the presence of chemical oxidants, and showed rapid viability loss when exposed to oxidizing conditions. The stress resistance and enzyme activity could be recovered by complementing the mutant with a functional copy of the msr gene. Upon fractionation of parent strain and the complemented mutant cells into membranes and cytoplasmic proteins, most of the immunologically detectable Msr was localized to the membrane, and this fraction contained all of the Msr activity. Qualitative detection of the whole cell protein pattern using 2,4-dinitro phenyl hydrazine (DNPH) showed a far greater number of oxidized protein species in the mutant than in the parent strain when the cells were subjected to oxygen, peroxide or s-nitrosoglutathione (GSNO) induced stress. Importantly, no oxidized proteins were discerned in either strain upon incubation in anaerobic conditions. A mutant strain that synthesized a truncated Msr (corresponding to the MsrA domain) was slightly more resistant to oxidative stress than the msr strain. Mouse colonization studies showed Msr is an important colonization factor, especially for effective longer-term (14 and 21 days) colonization. Complementation of the mutant msr strain by chromosomal insertion of a functional gene restored mouse colonization ability. [source] Mechanisms of iron regulation in mycobacteria: role in physiology and virulenceMOLECULAR MICROBIOLOGY, Issue 6 2003G. Marcela Rodriguez Summary The role of iron in mycobacteria as in other bacteria goes beyond the need for this essential cofactor. Limitation of this metal triggers an extensive response aimed at increasing iron acquisition while coping with iron deficiency. In contrast, iron-rich environments prompt these prokaryotes to induce synthesis of iron storage molecules and to increase mechanisms of protection against iron-mediated oxidative damage. The response to changes in iron availability is strictly regulated in order to maintain sufficient but not excessive and potentially toxic levels of iron in the cell. This response is also linked to other important processes such as protection against oxidative stress and virulence. In bacteria, iron metabolism is regulated by controlling transcription of genes involved in iron uptake, transport and storage. In mycobacteria, this role is fulfilled by the iron- dependent regulator IdeR. IdeR is an essential protein in Mycobacterium tuberculosis, the causative agent of human tuberculosis. It functions as a repressor of iron acquisition genes, but is also an activator of iron storage genes and a positive regulator of oxidative stress responses. [source] In this issue: Biotechnology Journal 9/2010BIOTECHNOLOGY JOURNAL, Issue 9 2010Article first published online: 10 SEP 2010 Linking obesity and colorectal cancer Sung and Bae, Biotechnol. J. 2010, 5, 930,941 Obesity is known as one of the most closely related risk factors of colorectal cancer (CRC). However, due to the complicated nature of the diet, it has been very difficult to provide clear explanations and molecular mechanisms for the role of dietary components in carcinogenesis. Nutrigenomics has become a powerful tool to study the relationships between food components and genes. It includes nutrigenetics (dealing with genetic variations related to phenotypic changes in response to diet), nutritional epigenomics and nutritional transcriptomics/proteomics/metabolomics. This review summarizes data on genes, proteins and metabolites that are related to either obesity or CRC and candidate molecules that may link obesity and CRC. The application of bioinformatics helps to perform large-scale network analysis to study cause-effect relationships between dietary components and CRC in the future. Hepatoprotective effects of oleuropein Kim et al., Biotechnol. J. 2010, 5, 950,960 Oleuropein, an active constituent of olive leaf, has a variety of pharmacological activities associated with its capacity to scavenge reactive oxygen species and has a protective effect against non-alcoholic fatty liver disease (NAFLD) in vivo. To gain insights into the molecular mechanisms of its hepatoprotective action the group of Taesun Park (Seoul, Korea) fed mice with a high fat diet supplemented with oleuropein. Then, liver tissue was subjected to DNA microarray analysis. Oleuropein in high fat diet reduced the mRNA level of regulators of hepatic fatty acid uptake and transport. The expression of a number of genes involved in oxidative stress responses, detoxification of lipid peroxidation products and proinflammatory cytokine genes were reduced, while highly regulated transcription factors were implicated in the lipogenesis, inflammation, insulin resistance and fibrosis, underlying the multifactorial effect of oleuropein on NAFLD. Genetic variations in obesity and diabetes Varma et al., Biotechnol. J. 2010, 5, 942,949 Obesity is a state of metabolic deregulation and a leading cause for development of type 2 diabetes, which are complex polygenic diseases. Here, authors from the National Centre of Toxicological Research at the FDA (Jefferson, Arizona, USA) used a data mining approach to evaluate the role of carbohydrate metabolic pathway genes in the development of obesity and type 2 diabetes. Data from public databases were used to map the position of these genes to known quantitative trait loci (QTL) and to find sequence and structural genetic variants such as single nucleotide polymorphisms (SNPs). The results demonstrated that a majority of carbohydrate metabolic pathways genes are associated with QTL for obesity and many for type 2 diabetes. This data mining approach can establish a strategy for interpreting an individual's risk factor for disease development, instead of population attributable risks. [source] Hepatoprotective effect of oleuropein in mice: Mechanisms uncovered by gene expression profilingBIOTECHNOLOGY JOURNAL, Issue 9 2010Yunjung Kim Abstract Oleuropein, an active constituent of olive leaf, has a variety of pharmacological activities associated with its capacity to scavenge reactive oxygen species. Oleuropein is also reported to have protective effects against non-alcoholic fatty liver disease (NAFLD) in vivo. In this study, gene expression profiling of hepatic tissues was examined, and transcription factors (TFs) with target genes that were modulated by oleuropein were identified to gain insights into the molecular mechanisms for the hepatoprotective action of this compound. C57BL/6N mice were fed either a high-fat diet (HFD) or 0.03% oleuropein-supplemented HFD for 10 weeks, after which their livers were subjected to oligo DNA microarray analysis. The oleuropein with which the HFD was supplemented reduced the hepatic mRNA level of the genes that encoded the key regulators of the hepatic fatty acid uptake and transport. In addition, the oleuropein reduced the expression of a number of hepatic genes involved in the oxidative stress responses and detoxification of lipid peroxidation products and proinflammatory cytokine genes. The (putative) candidate TFs that bound to the promoters of the genes regulated at least threefold (both up and down) by oleuropein were implicated in the lipogenesis, inflammation, insulin resistance, fibrosis, and cell proliferation and differentiation, which implies that the mechanisms that underlie the beneficial effects of oleuropein on NAFLD may be multifactorial. [source] Neuropathology and Pathogenesis of Encephalitis following Amyloid , Immunization in Alzheimer's DiseaseBRAIN PATHOLOGY, Issue 1 2004Isidre Ferrer Immunizing transgenic PDAPP mice, which overexpress mutant APP and develop ,-amyloid deposition resembling plaques in Alzheimer's disease (AD), results in a decrease of amyloid burden when compared with non treated transgenic animals im-munization with amyloid , peptide has been initiated in a randomised pilot study in AD. Yet a minority of patients developed a neurological complication consistent with meningoencephalitis and one patient died; the trial has been stopped. Neuropathological examination in that patient showed meningoencephalitis and focal atypically low numbers of diffuse and neuritic plaques but not of vascular amyloid nor regression of tau pathology in neurofibrillary tangles and neuropil threads. The present neuropathological study reports the second case of menigoencephalitis following immunization with amyloid-, peptide in AD, and has been directed toward exploring mechanisms underlying decreased tau pathology in relation- with amyliod deposit regression, and possible molecular bases involved in the inflammatory response following immunization. Inflammatory infiltrates were composed of CD8+, CD3+, CD5+ and, rarely, CD7+ lymphocytes, whereas B lymphocytes and T cytotoxic cells CD16, CD57, TIA and graenzyme were negative. Characteristic neuropathological findings were focal depletion of diffuse and neuritic plaques, but not of amyloid angiopathy, and the presence of small numbers of extremely dense(collapsed) plaques surrounded by active microglia, and multinucleated giant cells filled with dense A,42and A,40, in addition to severe small cerebral blood Reduced amyloid burden was accompanied by low amyloid-associated oxidative stress responses (reduced superoxide dismutase-1:SOD-1 expression) and by local inhibition of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 kinase which are involved in tau phosphorylation. These results support the amyloid cascade of tau phosphorylation in AD regarding phosphorylation of tau in neurofibrillary tangles and ,-amyloid deposition in neuritic plaques, but not of tau in neurofibrillary tangles and threads. Furthermore, amyloid reduction was accompanied by increased expression of the PA28,/, inductor, and of LMP7, LMP2 and MECL1 subunits of the immunopro-teasome in microglial and inflammatory cells surrounding collapsed plaques, and in multinucleated giant cells.Immunoproteasome subunit expression was accompanied by local presentation of MHC class molecules. Release of antigenic peptides derived from ,-amyloid processing may enhance T-cell inflammatory responses accounting for the meningoencephalitis following amyloid-, peptide immunization [source] | ||||||||||||||||