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At least 793 records · Page 44Linked to original sources
PubMed1990

Polyoma DNA replication dependent upon growth condition of SEWA sarcoma cells.

Extrachromosomal replication of viral DNA sequences has been observed in transformed as well as in normal cells following "stress"-inducing treatments. To explore the effect of growth conditions on the ability to support such replication, we analyzed SEWA sarcoma cells that grew subcutaneously or as ascites tumors in vivo as well as cell lines that were established from each of these tumors. The replicative form of polyoma DNA sequences was observed in SEWA tumors grown in ascites fluids but not in cells maintained as solid tumors. Polyoma DNA replication was found in ascites-derived cells that were adapted to grow in culture, only when the cultured cells are stimulated with UV irradiation. Immunoprecipitation of T antigens enabled detection of large T antigen only in the ascites-derived cells. The mechanisms that may regulate this phenomenon and the possible role large T may play in different growth conditions of SEWA cells are discussed.

Animals↗
PubMed2005

Proteomic analysis of the entomopathogenic nematode Steinernema feltiae IS-6 IJs under evaporative and osmotic stresses.

In order to improve the storage capability under desiccation of the widely sold biological insecticides based on entomopathogenic nematodes (EPNs), we need to understand how these organisms respond to desiccation stress. As part of our studies to achieve this, we studied survival and protein expression in infective juveniles of the EPN Steinernema feltiae IS-6 when exposed to evaporative (exposure to 97% relative humidity (RH) for 3 days, followed by a 1-day exposure to 85% RH) and osmotic (exposure to 24% glycerol for 8h) stresses. More than 400 protein spots that were detected by proteomic analysis showed reproducible abundance within replications. Of these, 10 spots and 7 spots showed detectable changes in abundance under evaporative and osmotic stress, respectively, compared to fully hydrated nematodes. Three spots exhibited a differential response pattern between evaporative and osmotic desiccation (one was down regulated and two were novel in evaporative desiccation). Peptide mass mapping with MALDI-TOF mass spectrometry (MS) identified 10 desiccation-response proteins, among which several are known to be stress responsive including heat shock protein 60, coenzyme q biosynthesis protein, inositol monophosphatase and fumarate lyase that were found in both stresses. Other identified proteins are known to be involved in the cell cycle regulation, regulation of gene transcription, organization of macromolecular structure and some currently have no known functions. Our results suggest that it is unlikely that improvement of desiccation tolerance in EPNs can be achieved through genetic transformation and addition of single genes and that selective breeding could be the best approach to generate desiccation resistant worms.

Adaptation, Physiological↗
PubMed2000

Stress response genes: the genes that make cancer metastasize.

Cancer is characterized by dysregulated growth control, overcoming of replicative senescence, and metastasis formation. The topology of cancer spread is mediated by a set of developmentally nonessential genes which are physiologically involved in stress responses, inflammation, wound healing, and neovascularization. The function of these gene products is extensively modified posttranscriptionally. In cancer, metastasis genes are dysregulated at the levels of expression or splicing. These genes constitute a unique group of cancer-related biomolecules.

Animals↗
PubMed2004

Replication and cytopathic effect of oncolytic vesicular stomatitis virus in hypoxic tumor cells in vitro and in vivo.

Tumor hypoxia presents an obstacle to the effectiveness of most antitumor therapies, including treatment with oncolytic viruses. In particular, an oncolytic virus must be resistant to the inhibition of DNA, RNA, and protein synthesis that occurs during hypoxic stress. Here we show that vesicular stomatitis virus (VSV), an oncolytic RNA virus, is capable of replication under hypoxic conditions. In cells undergoing hypoxic stress, VSV infection produced larger amounts of mRNA than under normoxic conditions. However, translation of these mRNAs was reduced at earlier times postinfection in hypoxia-adapted cells than in normoxic cells. At later times postinfection, VSV overcame a hypoxia-associated increase in alpha subunit of eukaryotic initiation factor 2 (eIF-2alpha) phosphorylation and initial suppression of viral protein synthesis in hypoxic cells to produce large amounts of viral protein. VSV infection caused the dephosphorylation of the translation initiation factor eIF-4E and inhibited host translation similarly under both normoxic and hypoxic conditions. VSV produced progeny virus to similar levels in hypoxic and normoxic cells and showed the ability to expand from an initial infection of 1% of hypoxic cells to spread through an entire population. In all cases, virus infection induced classical cytopathic effects and apoptotic cell death. When VSV was used to treat tumors established in nude mice, we found VSV replication in hypoxic areas of these tumors. This occurred whether the virus was administered intratumorally or intravenously. These results show for the first time that VSV has an inherent capacity for infecting and killing hypoxic cancer cells. This ability could represent a critical advantage over existing therapies in treating established tumors.

Animals↗
PubMed2000

Highly mutagenic replication by DNA polymerase V (UmuC) provides a mechanistic basis for SOS untargeted mutagenesis.

When challenged by DNA-damaging agents, Escherichia coli cells respond by inducing the SOS stress response, which leads to an increase in mutation frequency by two mechanisms: translesion replication, a process that causes mutations because of misinsertion opposite the lesions, and an inducible mutator activity, which acts at undamaged sites. Here we report that DNA polymerase V (pol V; UmuC), which previously has been shown to be a lesion-bypass DNA polymerase, was highly mutagenic during in vitro gap-filling replication of a gapped plasmid carrying the cro reporter gene. This reaction required, in addition to pol V, UmuD', RecA, and single-stranded DNA (ssDNA)-binding protein. pol V produced point mutations at a frequency of 2.1 x 10(-4) per nucleotide (2.1% per cro gene), 41-fold higher than DNA polymerase III holoenzyme. The mutational spectrum of pol V was dominated by transversions (53%), which were formed at a frequency of 1.3 x 10(-4) per nucleotide (1. 1% per cro gene), 74-fold higher than with pol III holoenzyme. The prevalence of transversions and the protein requirements of this system are similar to those of in vivo untargeted mutagenesis (SOS mutator activity). This finding suggests that replication by pol V, in the presence of UmuD', RecA, and ssDNA-binding protein, is the basis of chromosomal SOS untargeted mutagenesis.

ATP-Binding Cassette Transporters↗
PubMedDate not supplied

Stress management at the worksite for hypertension: compliance, cost-benefit, health care and hypertension-related variables.

The blood pressure-lowering effects of a group stress management program conducted with hypertensive employees at the worksite were assessed and replicated. Both systolic (SBP) and diastolic (DBP) blood pressure were significantly reduced from a baseline period to the end of a 10-week stress management training period (Group T1, N = 22). A control Group, T2 (N = 18), showed no significant SBP and DBP reduction over a comparable time period. When Group T2 was then given stress management training, the resulting SBP and DBP reductions were significant. When BP was recorded 3 years later, there were significant reductions for both SBP and DBP. Thirty percent of the subjects who had a medication regimen responded with BP judged to be a clinically significant reduction. The frequency of relaxation practice and the amount of BP reduction achieved during relaxation practice were significantly correlated with BP reduction after the stress management program. It was also found that the stress management program lowered health care costs and increased health supportive behavior.

Adult↗
PubMed2002

Stress-dependent nucleolin mobilization mediated by p53-nucleolin complex formation.

We recently discovered that heat shock causes nucleolin to relocalize from the nucleolus to the nucleoplasm, whereupon it binds replication protein A and inhibits DNA replication initiation. We report that nucleolin mobilization also occurs following exposure to ionizing radiation (IR) and treatment with camptothecin. Mobilization was selective in that another nucleolar marker, upstream binding factor, did not relocalize in response to IR. Nucleolin relocalization was dependent on p53 and stress, the latter initially stimulating nucleolin-p53 complex formation. Nucleolin relocalization and complex formation in vivo were independent of p53 transactivation but required the p53 C-terminal regulatory domain. Nucleolin and p53 also interact directly in vitro, with a similar requirement for p53 domains. These data indicate a novel p53-dependent mechanism in which cell stress mobilizes nucleolin for transient replication inhibition and DNA repair.

Active Transport, Cell Nucleus↗
PubMed2000

Modulation of HIV-1 replication by a novel RhoA effector activity.

The RhoA GTPase is involved in regulating actin cytoskeletal organization, gene expression, cell proliferation, and survival. We report here that p115-RhoGEF, a specific guanine nucleotide exchange factor (GEF) and activator of RhoA, modulates HIV-1 replication. Ectopic expression of p115-RhoGEF or Galpha13, which activates p115-RhoGEF activity, leads to inhibition of HIV-1 replication. RhoA activation is required and the inhibition affects HIV-1 gene expression. The RhoA effector activity in inhibiting HIV-1 replication is genetically separable from its activities in transformation of NIH3T3 cells, activation of serum response factor, and actin stress fiber formation. These findings reveal that the RhoA signal transduction pathway regulates HIV-1 replication and suggest that RhoA inhibits HIV-1 replication via a novel effector activity.

Amino Acid Sequence↗
PubMed2001

Workshop 1 (synthesis): steps towards increased effectiveness in water use--possibilities and replicability.

Inevitable increases in human needs and wants leading to mounting water stress necessitate that each unit of water is used as efficiently as possible. Excessive use of water cannot be accepted. Similarly, the least possible impact on water quality is a must. Yet, regional development and urgent social and environmental objectives may motivate an allocation of scarce water resources where the output is lower as compared to what could have been accomplished with an alternative allocation. In essence, the effective use of water presumes a broad and long-term perspective on societal development and environmental sustainability. Presentations illuminated that technical and institutional arrangements must be applied to reach an effective use. In practice, although not ncessarily in policy statements, technical arrangements continue to have a pivotal position in this regard.

Conservation of Natural Resources↗
PubMed2005

The stress-responsive chaperone alpha-crystallin 2 is required for pathogenesis of Mycobacterium tuberculosis.

Mycobacterium tuberculosis has two members of the alpha-crystallin (Acr) family of molecular chaperones. Expression of Acr1 is induced by exposure to hypoxia or nitric oxide and is associated with bacterial persistence in a non-replicating state. Expression of Acr2 is induced by heat shock, oxidative stress, and uptake by macrophages. We have shown that Acr2 continues to be expressed at a high level during both acute and chronic infection in the mouse model, with an increased ratio of acr2:acr1 mRNA in the persistent phase. Deletion of the acr2 gene resulted in a decrease in the resistance of M. tuberculosis to oxidative stress but did not impair growth in mouse bone marrow macrophages. There was no difference in bacterial load in mice infected with an acr2 deletion mutant, but a marked alteration in disease progression was evident from reduced weight loss over a prolonged infection. This correlated with reduced recruitment of T-cells and macrophages to the lungs of mice infected with the acr2 mutant and reduced immune-related pathology. These findings demonstrate that both alpha-crystallins contribute to persistent infection with M. tuberculosis and suggest that manipulation of acr expression can influence the host response to infection.

Animals↗
PubMed2005

Irreversible cellular senescence induced by prolonged exposure to H2O2 involves DNA-damage-and-repair genes and telomere shortening.

H2O2 has been the most commonly used inducer for stress-induced premature senescence (SIPS), which shares features of replicative senescence. However, there is still uncertainty whether SIPS and replicative senescence differ or utilize different pathways. 'Young' human diploid fibroblasts (HDFs), treated with prolonged low doses of hydrogen peroxide, led to irreversible cellular senescence. Cells exhibited senescent-morphological features, irreversible G1 cell cycle arrest and irreversible senescence-associated beta-galactosidase positivity. The appearance of these cellular senescence markers was accompanied by significant increases of p21, gadd45 expression and p53 binding activity, as well as a significant decline in DNA repair capability and accelerated telomere shortening. Our results suggest that multiple pathways might be involved in oxidative SIPS, including genes related to DNA-damage-and-repair and telomere shortening, and that SIPS shares the same mechanisms with replicative senescence in vivo. Our findings indicate that several aging theories can be merged together by a common mechanism of oxidative damage, and that the level of oxidative DNA-damage-and-repair capacity may be exploited as reliable markers of cell senescence.

Cell Cycle Proteins↗
PubMed1983

Suppressed lymphocyte blastogenic responses and enhanced in vitro growth of infectious bovine rhinotracheitis virus in stressed feeder calves.

Hereford steers were stressed on a large-animal treadmill operating at speeds of 1.8 to 2.2 m/s. Blood samples were collected from indwelling jugular catheters before, during, and after exercise. Peripheral blood lymphocytes from stressed calves at 5 and 30 minutes after exercise had less (P less than 0.01) mitogen-induced blastogenic responses when compared to pre- or 60-minute postexercise values. Serum from stressed calves incorporated into lymphocyte cultures from nonstressed steers resulted in less (P less than 0.01) lymphocyte blastogenic responses. Infectious bovine rhinotracheitis viral growth in bovine kidney cell cultures was enhanced 4-fold when cultured with serum from stressed calves. These data indicate that acute physical exertion may cause physiologic alterations in calves that modulate cellular immunity and viral replication.

Animals↗
PubMed2005

Xenobiotic stress induces hepatomegaly and liver tumors via the nuclear receptor constitutive androstane receptor.

The constitutive androstane receptor (CAR, NR1I3) is a central regulator of xenobiotic metabolism. CAR activation induces hepatic expression of detoxification enzymes and transporters and increases liver size. Here we show that CAR-mediated hepatomegaly is a transient, adaptive response to acute xenobiotic stress. In contrast, chronic CAR activation results in hepatocarcinogenesis. In both acute and chronic xenobiotic responses, hepatocyte DNA replication is increased and apoptosis is decreased. These effects are absent in CAR null mice, which are completely resistant to tumorigenic effects of chronic xenobiotic stress. In the acute response, direct up-regulation of Mdm2 expression by CAR contributes to both increased DNA replication and inhibition of p53-mediated apoptosis. These results demonstrate an essential role for CAR in regulating both liver homeostasis and tumorigenesis in response to xenobiotic stresses, and they also identify a specific molecular mechanism linking chronic environmental stress and tumor formation.

Animals↗
PubMed1997

Cell cycle checkpoints in bacteria.

When DNA replication is interrupted in bacteria, a specific inhibitor (SfiA), a component of the SOS system, is synthesised which transiently blocks cell division. This is the prototype, dispensable, cell cycle checkpoint, essential for maximal survival under a particular stress. In contrast, no process specifically signalling the termination of chromosomal replication to activate the subsequent division event, which might be termed an essential checkpoint, has yet been demonstrated. In E coli, a specific mechanism is apparently required to reactivate replication forks blocked by damage, but its molecular basis is unclear. Induction of the stringent response, mediated by RelA via the level of ppGpp, presumably to optimise macromolecular synthesis according to the availability of nutrients, activates a control system which inhibits DNA replication in both E coli and B subtilis. In E coli, this blocks new rounds of initiation at oriC, although the mechanism is not clear. Conversely, initiation is not blocked in B subtilis, but replication is blocked apparently at a number of distinct sites 100-200 kb downstream and either side of oriC. This nutrient-dependent replicating checkpoint specifically requires RTP, the chromosomal terminator protein, and new evidence indicates that specific RTP binding sites may be involved in this post-initiation control mechanism. A similar post-initiation control mechanism appears to block replication reversibly after premature initiation in B subtilis, indicating that this system may have a dual function, limiting replication in starvation conditions and as a mechanism to compensate for premature initiations.

Bacteria↗
PubMed2004

Expression of heat shock protein in broiler embryo tissues after acute cold or heat stress.

This study evaluated the expression of heat shock protein 70 kD (hsp70) in broiler chicken embryos subjected to cold (Experiment I) or high incubation temperature (Experiment II). In each experiment, fertile eggs were distributed in three incubators kept at 37.8 degrees C. At day 13 (D13), D16, and D19 of incubation, the embryos were subjected to acute cold (32 degrees C) or heat (40 degrees C) for 4-6 hr. Immediately after cold or heat exposure, samples from the liver, heart, breast muscle, brain, and lungs of 40 embryos were taken per age and treatment (control or stressed embryos). A tissue pool from 10 embryos was used as 1 replication. The levels of hsp70 in each tissue sample was quantified by Western blot analysis. The data were analyzed in a 3 x 2 factorial arrangement of treatments with four replications. hsp70 was detected in all embryo tissues, and the brain contained 2- to 5-times more hsp70 protein compared to the other tissues in either cold or heat stressed embryos. hsp70 increases were observed in the heart and breast muscle of cold stressed embryos at D16 and D19, respectively. Heat stressed embryos showed an increase of hsp70 in the heart at D13 and D19, and in the lung at D19 of incubation. Younger embryos had higher hsp70 synthesis than older embryos, irrespective of the type of thermal stressor. The results indicate that the expression of hsp70 in broiler chicken embryos is affected by cold and heat distress, and is tissue- and age-dependent.

Animals↗
PubMed2001

Replication protein A is sequentially phosphorylated during meiosis.

Phosphorylation of the cellular single-stranded DNA-binding protein, replication protein A (RPA), occurs during normal mitotic cell cycle progression and also in response to genotoxic stress. In budding yeast, these reactions require the ATM homolog Mec1, a central regulator of the DNA replication and DNA damage checkpoint responses. We now demonstrate that the middle subunit of yeast RPA (Rfa2) becomes phosphorylated in two discrete steps during meiosis. Primary Rfa2 phosphorylation occurs early in meiotic progression and is independent of DNA replication, recombination and Mec1. In contrast, secondary Rfa2 phosphorylation is activated upon initiation of recombination and requires Mec1. While the primary Rfa2 phosphoisomer is detectable throughout most of meiosis, the secondary Rfa2 phosphoisomer is only transiently generated and begins to disappear soon after recombination is complete. Extensive secondary Rfa2 phosphorylation is observed in a recombination mutant defective for the pachytene checkpoint, indicating that Mec1-dependent Rfa2 phosphorylation does not function to maintain meiotic delay in response to DNA double-strand breaks. Our results suggest that Mec1-dependent RPA phosphorylation could be involved in regulating recombination rather than cell cycle or meiotic progression.

DNA Replication↗
PubMed1993

Protection of human endothelial cells from oxidant injury by adenovirus-mediated transfer of the human catalase cDNA.

In a variety of disorders, endothelial cells are exposed to high levels of oxidants, generated within the cells and/or consequent to local inflammation. In the context of the sensitivity of endothelial cells to oxidant stress, particularly related to H2O2, we have designed a replication deficient recombinant adenovirus containing the human catalase cDNA (AdCL) to transfer the catalase cDNA to the endothelial cells, in order to augment intracellular anti-H2O2 protection. Human umbilical vein endothelial cells that were not infected or infected with control adenovirus maintained low levels of catalase mRNA. Endothelial cells infected with AdCL expressed AdCL-driven exogenous catalase mRNA, as early as 24 hr and at least for 7 days. Catalase protein levels were increased significantly over controls in cells infected with AdCL, as were catalase activity levels, with catalase activity correlated closely with levels of catalase protein. Importantly, when the endothelial cells were exposed to 500 microM H2O2, all the AdCL infected endothelial cells survived, compared to only 37% of the control cells. Thus, a recombinant adenovirus containing the human catalase cDNA is able to infect human endothelial cells in vitro and express high levels of functional intracellular catalase, protecting the cells against H2O2-mediated oxidant stress. These observations support the feasibility of the transfer of catalase cDNA to human endothelium to protect against oxidant injury.

Adenoviridae↗
PubMed1995

Responding to subliminal threat cues is related to trait anxiety and emotional vulnerability: a successful replication of Macleod and Hagan (1992)

Macleod and Hagan (1992) [Behaviour Research and Therapy, 30, 151-161] reported that threat-relevant interference on a masked Stroop task, where neutral and negative words cannot be consciously perceived, is positively correlated with trait anxiety and emotional vulnerability to stressful life events. Their findings were obtained from subjects who were currently stressed. The aim of the present study was to determine whether the Macleod and Hagan findings could be replicated in a sample that was not currently stressed. Using a sample of 32 volunteers, we found a significant correlation between trait anxiety and threat-relevant interference on a masked Stroop. Furthermore, it was found that the single best predictor of vulnerability to life stress was the interference on the masked Stroop. The findings of the present study correspond quite closely to those reported by Macleod and Hagan (1992).

Adult↗