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At least 937 records · Page 52Linked to original sources
PubMed1994

Decrease of heat shock protein 27/28 with heat stress in HTLV-I-transformed cells.

We have previously reported an increase of human T-lymphotropic leukemia/lymphoma virus type I (HTLV-I) replication after heat treatment of MT-2 cells, an HTLV-I-transformed human lymphoid cell line. In this study, we investigated the effect of heat stress on the expression of Hsp27/28 in MT-2 cells. In contrast with previous studies of other cell types, a decrease of Hsp27/28 expression in MT-2 cells and an increase of Hsp70 family proteins in both MT-2 and uninfected lymphoid CEM cells were found following heat treatment at 42 degrees C. Furthermore, heat treatment resulted in an early rapid increase in the phosphorylated form of Hsp27/28 in both MT-2 and CEM cells. The results suggest that early post-translational phosphorylation of HSP27/28 could be a determinant of the ability of MT-2 cells to survive hyperthermia.

Blotting, Northern↗
PubMed2006

Rapid adaptive divergence of life-history traits in response to abiotic stress within a natural population of a parthenogenetic nematode.

Sexual reproduction is acknowledged to facilitate adaptation to novel environments while asexual eukaryotes are often regarded as having low adaptive potential. This view has been challenged in a number of studies, but the adaptive potential of asexual populations in the field is poorly documented. We investigated the response of natural populations of the parthenogenetic nematode Acrobeloides nanus to imposed divergent selective pressures. For this purpose, we employed a replicated evolution experiment in the field. After 20 years of evolution under abiotic stress and control conditions, life-history traits were assessed in reaction norm- and reciprocal transplant experiments. Both these experiments indicated adaptive divergence within the population of A. nanus. Namely, the transplant experiment demonstrated that in the stressed soil environment, body growth rate was more reduced in the nematodes originating from the control treatment. In the reaction norm experiment, survival and reproduction were higher under test conditions corresponding to the native environment of the nematodes. The differences in the analysed traits are discussed in the context of life-history theory. Overall, our results strongly support high adaptive potential of A. nanus and suggest that population structure and distribution of asexual species is shaped by local adaptation events.

Adaptation, Physiological↗
PubMed2006

Critical role of DNA checkpoints in mediating genotoxic-stress-induced filamentous growth in Candida albicans.

The polymorphic fungus Candida albicans switches from yeast to filamentous growth in response to a range of genotoxic insults, including inhibition of DNA synthesis by hydroxyurea (HU) or aphidicolin (AC), depletion of the ribonucleotide-reductase subunit Rnr2p, and DNA damage induced by methylmethane sulfonate (MMS) or UV light (UV). Deleting RAD53, which encodes a downstream effector kinase for both the DNA-replication and DNA-damage checkpoint pathways, completely abolished the filamentous growth caused by all the genotoxins tested. Deleting RAD9, which encodes a signal transducer of the DNA-damage checkpoint, specifically blocked the filamentous growth induced by MMS or UV but not that induced by HU or AC. Deleting MRC1, the counterpart of RAD9 in the DNA-replication checkpoint, impaired DNA synthesis and caused cell elongation even in the absence of external genotoxic insults. Together, the results indicate that the DNA-replication/damage checkpoints are critically required for the induction of filamentous growth by genotoxic stress. In addition, either of two mutations in the FHA1 domain of Rad53p, G65A, and N104A, nearly completely blocked the filamentous-growth response but had no significant deleterious effect on cell-cycle arrest. These results suggest that the FHA domain, known for its ability to bind phosphopeptides, has an important role in mediating genotoxic-stress-induced filamentous growth and that such growth is a specific, Rad53p-regulated cellular response in C. albicans.

Alleles↗
PubMed2003

High NaCl causes Mre11 to leave the nucleus, disrupting DNA damage signaling and repair.

High NaCl causes DNA double-strand breaks and cell cycle arrest, but the mechanism of its genotoxicity has been unclear. In this study, we describe a novel mechanism that contributes to this genotoxicity. The Mre11 exonuclease complex is a central component of DNA damage response. This complex assembles at sites of DNA damage, where it processes DNA ends for subsequent activation of repair and initiates cell cycle checkpoints. However, this does not occur with DNA damage caused by high NaCl. Rather, following high NaCl, Mre11 exits from the nucleus, DNA double-strand breaks accumulate in the S and G2 phases of the cell cycle, and DNA repair is inhibited. Furthermore, the exclusion of Mre11 from the nucleus by high NaCl persists following UV or ionizing radiation, also preventing DNA repair in response to those stresses, as evidenced by absence of H2AX phosphorylation at places of DNA damage and by impaired repair of damaged reporter plasmids. Activation of chk1 by phosphorylation on Ser345 generally is required for DNA damage-induced cell cycle arrest. However, chk1 does not become phosphorylated during high NaCl-induced cell cycle arrest. Also, high NaCl prevents ionizing and UV radiation-induced phosphorylation of chk1, but cell cycle arrest still occurs, indicating the existence of alternative mechanisms for the S and G2/M delays. DNA breaks that occur normally during processes such as DNA replication and transcription, as well as damages to DNA induced by genotoxic stresses, ordinarily are rapidly repaired. We propose that inhibition of this repair by high NaCl results in accumulation of DNA damage, accounting for the genotoxicity of high NaCl, and that cell cycle delay induced by high NaCl slows accumulation of DNA damage until the DNA damage-response network can be reactivated.

Animals↗
PubMed2006

Effects of affiliation arousal (hope of closeness) and affiliation stress (fear of rejection) on progesterone and cortisol.

Our prior research has suggested a connection between progesterone (PROG) and implicit affiliation motivation, the non-conscious drive for positive social contact. In particular, experimental arousal of affiliation motivation led to relative PROG increase in women and men [Schultheiss, O.C., Wirth, M.M., Stanton, S.J., 2004. Effects of affiliation and power motivation arousal on salivary progesterone and testosterone. Horm. Behav. 46(5), 592-599]. The present study aimed to (1) replicate this effect, (2) simultaneously assess cortisol (CORT) levels in this paradigm in order to rule out non-specific adrenal effects induced by affiliation arousal, and (3) examine effects on PROG and CORT of approach (hope for closeness, HOC) versus avoidance (fear of rejection, FOR) affiliation arousal. These motivational states were experimentally aroused in participants using film segments containing approach- or avoidance-oriented affiliation-related themes; a neutral film segment was used as a control condition. The film segments affected participants' implicit affiliation motivation and self-reported mood, demonstrating effectiveness of the manipulation. In the FOR condition, participants' CORT and PROG were increased post-film, consistent with the idea that fear of rejection is stressful. We did not replicate our prior finding of PROG increase following the HOC manipulation. However, relationships between PROG and implicit affiliation motivation were apparent across conditions. In particular, PROG co-varied positively with affiliation motivation, and baseline affiliation motivation positively predicted PROG increase in the FOR condition. As prior research implicates PROG in down-regulation of stress, we speculate that PROG release during stress may encourage affiliation for stress reduction purposes.

Adolescent↗
PubMed2005

Terminal differentiation into plasma cells initiates the replicative cycle of Epstein-Barr virus in vivo.

In this paper we demonstrate that the cells which initiate replication of Epstein-Barr virus (EBV) in the tonsils of healthy carriers are plasma cells (CD38hi, CD10-, CD19+, CD20lo, surface immunoglobulin negative, and cytoplasmic immunoglobulin positive). We further conclude that differentiation into plasma cells, and not the signals that induce differentiation, initiates viral replication. This was confirmed by in vitro studies showing that the promoter for BZLF1, the gene that begins viral replication, becomes active only after memory cells differentiate into plasma cells and is also active in plasma cell lines. This differs from the reactivation of BZLF1 in vitro, which occurs acutely and is associated with apoptosis and not with differentiation. We suggest that differentiation and acute stress represent two distinct pathways of EBV reactivation in vivo. The fraction of cells replicating the virus decreases as the cells progress through the lytic cycle such that only a tiny fraction actually release infectious virus. This may reflect abortive replication or elimination of cells by the cellular immune response. Consistent with the later conclusion, the cells did not down regulate major histocompatibility complex class I molecules, suggesting that this is not an immune evasion tactic used by EBV and that the cells remain vulnerable to cytotoxic-T-lymphocyte attack.

Antigens, CD20↗
PubMed2000

Plasmid-encoded MucB protein is a DNA polymerase (pol RI) specialized for lesion bypass in the presence of MucA', RecA, and SSB.

Replication through damaged sites in DNA requires in Escherichia coli the SOS stress-inducible DNA polymerase V (UmuC), which is specialized for lesion bypass. Homologs of the umuC gene were found on native conjugative plasmids, which often carry multiple antibiotic-resistant genes. MucB is a UmuC homolog present on plasmid R46, and its variant plasmid pKM101 has been introduced into Salmonella strains for use in the Ames test for mutagens. Using a translesion replication assay based on a gapped plasmid carrying a site-specific synthetic abasic site in the single-stranded DNA region, we show that MucB is a DNA polymerase, termed pol RI, which is specialized for lesion bypass. The activity of pol RI requires the plasmid-encoded MucA' protein and the E. coli RecA and single-strand DNA binding proteins. Elimination of any of the proteins from the reaction abolished lesion bypass and polymerase activity. The unprocessed MucA could not substitute for MucA' in the bypass reaction. The presence of a lesion bypass DNA polymerase on a native conjugative plasmid, which has a broad host range specificity and carries multiple antibiotic-resistant genes, raises the possibility that mutagenesis caused by pol RI plays a role in the spreading of antibiotic resistance among bacterial pathogens.

Bacterial Proteins↗
PubMed1984

Developmental time and adult longevity in two strains of Drosophila melanogaster in a constant low-stress environment.

This study examines the life spans of wild type flies (Sevelen strain, n = 2991) and post-replication DNA repair-deficient flies (mei-41D5, n = 1607) as members of age-synchronized birth cohorts and as members of full sibships. Flies were individually housed from the time they were laid as eggs until they died as imagoes; environmental conditions were constant throughout the life span of these virgins. In this minimal stress experiment, developmental time and imaginal longevity were negligibly correlated (r = -0.09 to -0.25), even though developmental time was canalized at different levels in both strains. Previous research involving environmental perturbations during the life span of Drosophila (e.g. temperature, diet, population density) has demonstrated significant strong correlations, mostly positive, between developmental time and adult longevity. We have demonstrated that the duration of development and aging are not coupled in the absence of such stresses. We therefore suggest that related changes in the duration of the pre-imaginal and the adult stages of the lifecycle of Drosophila may have evolved through adaptation to environmental stresses.

Animals↗
PubMed1994

Use of skin conductance changes during mental stress testing as an index of autonomic arousal in cardiovascular research.

Mental stress testing is used to study the cardiovascular changes caused by psychologic stress. To examine the effects of cardiac drugs on mental stress-induced changes, it is useful to attain a degree of arousal that can be replicated in serial studies. Skin conductance level, a cholinergically mediated index of arousal, was assessed for its stability in serial studies and under conditions of beta-blockade. In normal subjects, skin conductance increased in response to mental stress (p < 0.001) and was stable across three sessions. In patients with mild hypertension, skin conductance was elevated during mental stress during both placebo and nadolol therapy (p < 0.001). As expected, nadolol reduced baseline and stress-induced peak arterial pressure and heart rate but had no significant effect on skin conductance. Thus skin conductance level can serve as a stable and useful index of autonomic arousal in clinical trials, even in patients using beta-blocking medications.

Adult↗
PubMed2005

Regulation of TOP2 by various abiotic stresses including cold and salinity in pea and transgenic tobacco plants.

Although abiotic stress affects plant growth and development, demonstration of its direct effect on regulation of the components of the DNA replication machinery is largely unknown. In this work, we demonstrate that the expression of TOP2 (encoding topoisomerase II) is up-regulated by various abiotic stresses including salinity and low temperature, and phytohormones such as ABA (abscisic acid) and SA (salicylic acid). Transgenic studies with different deletion versions of the TOP2 promoter in tobacco define several promoter determinants responsible for specific abiotic stress responsiveness. Taken together, these results demonstrate a direct involvement of stress in the transcriptional regulation of TOP2.

Abscisic Acid↗
PubMed2004

Heat-shock protein 70 exerts opposing effects on Vpr-dependent and Vpr-independent HIV-1 replication in macrophages.

HIV-1 viral protein R (Vpr) shuttles between the nucleus and the cytoplasm and is believed to contribute to the process of nuclear translocation of the viral preintegration complex, thus facilitating HIV-1 replication in macrophages. In this report, we demonstrate that Hsp70, a heat-shock protein contributing to cellular stress responses, inhibits nuclear translocation of HIV-1 Vpr. In macrophages, Hsp70 is induced shortly after HIV-1 infection. Recombinant Hsp70 or a mild heat shock diminished replication of the wild-type HIV-1, suggesting that Hsp70 might function as an innate antiviral factor. Surprisingly, Hsp70 stimulated nuclear import and replication in macrophages of the Vpr-deficient HIV-1 construct. This finding suggests that Hsp70 and Vpr may function in a similar manner when expressed separately, but they neutralize each other's activity when present together. Consistent with this interpretation, Hsp70 coprecipitated with Vpr from HIV-1-infected cells.

Active Transport, Cell Nucleus↗
PubMed2004

Epstein-Barr virus lytic replication elicits ATM checkpoint signal transduction while providing an S-phase-like cellular environment.

When exposed to genotoxic stress, eukaryotic cells demonstrate a DNA damage response with delay or arrest of cell-cycle progression, providing time for DNA repair. Induction of the Epstein-Barr virus (EBV) lytic program elicited a cellular DNA damage response, with activation of the ataxia telangiectasia-mutated (ATM) signal transduction pathway. Activation of the ATM-Rad3-related (ATR) replication checkpoint pathway, in contrast, was minimal. The DNA damage sensor Mre11-Rad50-Nbs1 (MRN) complex and phosphorylated ATM were recruited and retained in viral replication compartments, recognizing newly synthesized viral DNAs as abnormal DNA structures. Phosphorylated p53 also became concentrated in replication compartments and physically interacted with viral BZLF1 protein. Despite the activation of ATM checkpoint signaling, p53-downstream signaling was blocked, with rather high S-phase CDK activity associated with progression of lytic infection. Therefore, although host cells activate ATM checkpoint signaling with response to the lytic viral DNA synthesis, the virus can skillfully evade this host checkpoint security system and actively promote an S-phase-like environment advantageous for viral lytic replication.

Ataxia Telangiectasia Mutated Proteins↗
PubMed1993

Model system for DNA replication of a plasmid DNA containing the autonomously replicating sequence from Saccharomyces cerevisiae.

A negatively supercoiled plasmid DNA containing autonomously replicating sequence (ARS) 1 from Saccharomyces cerevisiae was replicated with the proteins required for simian virus 40 DNA replication. The proteins included simian virus 40 large tumor antigen as a DNA helicase, DNA polymerase alpha.primase, and the multisubunit human single-stranded DNA-binding protein from HeLa cells; DNA gyrase from Escherichia coli, which relaxes positive but not negative supercoils, was included as a "swivelase." DNA replication started from the ARS region, proceeded bidirectionally with the synthesis of leading and lagging strands, and resulted in the synthesis of up to 10% of the input DNA in 1 h. The addition of HeLa DNA topoisomerase I, which relaxes both positive and negative supercoils, to this system inhibited DNA replication, suggesting that negative supercoiling of the template DNA is required for initiation. These results suggest that DNA replication starts from the ARS region where the DNA duplex is unwound by torsional stress; this unwound region can be recognized by a DNA helicase with the assistance of the multisubunit human single-stranded DNA-binding protein.

Base Sequence↗
PubMed1993

What we do not know about families with children who have developmental disabilities: Questionnaire on Resources and Stress as a case study.

A selective review of studies using the Questionnaire on Resources and Stress (QRS) was presented in order to highlight current problems and future directions for research about families who are rearing children with developmental disabilities. Three primary difficulties--definitional problems, multiple measures of the same construct that do not converge, and failure to replicate--were high-lighted, and recommendations for approaches to solving them were provided. These approaches include the separation of demands, stresses, and strains, perhaps by a variation of the multitrait-multimethod technique, and more extensive norming and programmatic replication.

Adaptation, Psychological↗
PubMed2000

Subcytotoxic H2O2 stress triggers a release of transforming growth factor-beta 1, which induces biomarkers of cellular senescence of human diploid fibroblasts.

Stress-induced premature senescence (SIPS) is induced 3 days after exposure of human diploid fibroblasts to subcytotoxic oxidative stress with H(2)O(2), with appearance of several biomarkers of replicative senescence. In this work, we show that transforming growth factor-beta1 (TGF-beta1) regulates the induction of several of these biomarkers in SIPS: cellular morphology, senescence-associated beta-galactosidase activity, increase in the steady-state level of fibronectin, apolipoprotein J, osteonectin, and SM22 mRNA. Indeed, the neutralization of TGF-beta1 or its receptor (TGF-beta RII) using specific antibodies decreases sharply the percentage of cells positive for the senescent-associated beta-galactosidase activity and displaying a senescent morphology. In the presence of each of these antibodies, the steady-state level of fibronectin, osteonectin, apolipoprotein J, and SM22 mRNA is no more increased at 72 h after stress. Results obtained on fibroblasts retrovirally transfected with the human papillomavirus E7 cDNA suggest that retinoblastoma protein (Rb) regulates the expression of TGF-beta1 in stressful conditions, leading to SIPS and overexpression of these four genes.

Cells, Cultured↗
PubMedDate not supplied

[Prevention of structural damage to myocardial DNA caused by emotionally painful stress by means of beta-adrenoreceptor and lipid peroxidation blockade].

Emotional-painful stress was accompanied by an increase in the rates of depolymerization and of repairatory replication of heart muscle DNA. When the repairatory replication of DNA was repressed by actinomycin D, the rate of its depolymerization was simultaneously increased. A beta-adrenoreceptor blocking agent inderal and an inhibitor of lipoperoxidation ionol prevented the DNA depolymerization and activation of the polymer synthesis under the stressory conditions. These data corroborate the hypothesis that stress favors an increase in content of catecholamines, increasing the rate of lipoperoxidation and producing free radicals responsible for impairment of heart muscle DNA. In ontogenesis the multiple damage-repair cycles in DNA apparently lead to accumulation of genetic errors, which may be among the reasons of senescense.

Acute Disease↗
PubMed2005

Stress-induced premature senescence in mononuclear cells from patients on long-term hemodialysis.

BACKGROUND: Repeatedly stimulated mononuclear cells may become senescent prematurely as a result of frequent activation-induced replication. In hemodialysis patients, mononuclear cells are activated repeatedly with each hemodialysis procedure. Characteristics of senescent mononuclear cells include telomere length shortening, increased p53 expression, CD14dim/CD16bright expression, and interleukin overproduction. METHODS: Peripheral mononuclear cells from 15 hemodialysis patients and 15 age-matched controls were evaluated. Telomere length was assessed by means of fluorescence in situ hybridization in flow cytometry. Expression of p53, CD14/CD16, and intracellular cytokine production (interleukin-1beta [IL-1beta], IL-6, and IL-4) was evaluated by means of flow cytometry using specific antibodies. RESULTS: Features of senescence were found in a subpopulation of mononuclear cells: (1) accelerated telomere shortening, (2) increased p53 expression, (3) CD14dim/CD16bright expression, and (4) cytokine overproduction (IL-1beta, IL-6, and IL-4). Telomere length shortening was present in 40% +/- 6% of cells from hemodialysis patients compared with less than 5% from age-matched controls. Percentage of cells with short telomeres correlated positively with serum C-reactive protein level, which reflects inflammation. p53 expression was increased in mononuclear cells from hemodialysis patients. Mononuclear cells from hemodialysis patients with decreased telomere length mainly showed the CD14dim/CD16bright phenotype; conversely, cells with normal telomeres presented the CD14bright/CD16dim phenotype. Finally, mononuclear cells from hemodialysis patients, but not controls, spontaneously produced the proinflammatory cytokines IL-1beta and IL-6. CONCLUSION: This study shows the presence of a prematurely senescent subpopulation of peripheral mononuclear cells in hemodialysis patients. These senescent cells probably result from repeated activation and may have a pathophysiological role in the chronic inflammation described in hemodialysis patients.

Adult↗