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At least 307 records · Page 17Linked to original sources
PubMed2006

Nucleolin inhibits Hdm2 by multiple pathways leading to p53 stabilization.

Nucleolin is a c-Myc-induced gene product with defined roles in ribosomal RNA processing and the inhibition of chromosomal DNA replication following stress. Here we find that changes in nucleolin protein levels in unstressed cells cause parallel changes in the amount of p53 protein. Alterations in p53 levels arise from nucleolin binding to the p53 antagonist Hdm2, resulting in the inhibition of both p53 ubiquitination and Hdm2 auto-ubiquitination. Nucleolin does not alter p53 ubiquitination by human papillomavirus E6, indicating that the effect is specific for Hdm2. Although the inhibition of ligase activity would be expected to stabilize Hdm2, we instead find that nucleolin also reduces Hdm2 protein levels, demonstrating that nucleolin inhibits Hdm2 using multiple mechanisms. Increases in nucleolin levels in unstressed cells led to higher expression of p21(cip1/waf1), a reduced rate of cellular proliferation, and an increase in apoptosis. Thus, nucleolin has a number of properties in common with the tumor suppressor ARF (alternate reading frame). We propose that nucleolin, like ARF, responds to hyperproliferative signals by upregulation of p53 through Hdm2 inhibition.

Blotting, Western↗
PubMed2002

Participation of the calcium/calmodulin-dependent kinases in hydrogen peroxide-induced Ikappa B phosphorylation in human T lymphocytes.

NF-kappaB is an important transcription factor that has a role in a variety of responses such as inflammation, oncogenesis, apoptosis, and viral replication. Oxidative stress is well known to induce the activation of NF-kappaB. Cells can be exposed to either endogenously produced oxidants or oxidants produced by surrounding cells. In addition, ischemia reperfusion and certain cancer therapies such as chemotherapy and photodynamic therapy are thought to result in oxygen radical production. Because of the important role that NF-kappaB has in multiple responses, it is critical to determine the mechanisms by which oxidative stress induces NF-kappaB activity. We report that the calmodulin antagonist W-7 and the calcium/calmodulin-dependent (CaM) kinase inhibitors KN-93 and K252a, can block oxidative stress-induced IkappaB phosphorylation in Jurkat T lymphocytes. Furthermore, KN-93 but not KN-92 can block hydrogen peroxide-induced Akt and IKK phosphorylation. In addition, we found that expression of a kinase-dead CaM-KIV construct in two cell lines inhibits IkappaB phosphorylation or degradation and that expression of CaM-KIV augments hydrogen peroxide-induced IkappaB phosphorylation and degradation. Although the CaM kinases appear to be required for this response, increases in intracellular calcium do not appear to be required. These results identify the CaM kinases as potential targets that can be used to minimize NF-kappaB activation in response to oxidative stress.

Benzylamines↗
PubMed2004

Delivery using herpes simplex virus: an overview.

The human herpesviruses represent excellent candidate viruses for several types of gene vector applications. As a class, they are large DNA viruses with the potential to accommodate large or multiple transgene cassettes, and they have evolved to persist in a lifelong nonintegrated latent state without causing disease in the immune-competent host. Among the herpesviruses, herpes simplex virus type 1 (HSV-1) is an attractive vehicle because in natural infection, the virus establishes latency in neurons, a state in which viral genomes may persist for the life of the host as intranuclear episomal elements. The natural lifelong persistence of latent genomes in trigeminal ganglia (TG) without the development of sensory loss or histologic damage to the ganglion attests to the effectiveness of these natural latency mechanisms. Although the wild-type virus may be reactivated from latency under the influence of a variety of stresses, completely replication defective viruses can be constructed that retain the ability to establish persistent quiescent genomes in neurons, but that are unable to subsequently reactivate in the nervous system. These persistent genomes are devoid of lytic gene expression, but retain the ability to express latency-associated transcripts (LATs).

Animals↗
PubMed2000

Telomere shortening in kidneys with age.

The histology and function of the kidney deteriorates with age and age-related diseases, but the mechanisms involved in renal aging are not known. In vitro studies suggest that telomere shortening is important in replicative senescence, and is accelerated by stresses that increase replication. This study explored the relationship between age and telomere length in surgical samples from 24 human kidneys, which were either histologically normal (17) or displayed histologic abnormalities (7). Telomere loss was assessed by two independent methods: Southern blotting of terminal restriction fragments (TRF) and slot blotting using telomere-specific probes. The results of these methods correlated with each other. The mean TRF length determined by Southern blotting in cortex was about 12 kb pairs (kbp) in infancy and was shorter in older kidneys. The slope of the regression line was about 0.029 kbp (0.24%, P = 0.023) per year. Telomere DNA loss in cortex by the slot blot method was 0.25% per year (P = 0.011). By both methods, the telomere loss in medulla was not significant and was less than in cortex. Comparisons of TRF length from 20 paired samples from cortex and medulla showed that TRF was greater in cortex than medulla, with the differences being greater in young kidneys and lessening with age due to telomere loss in cortex. These findings indicate that telomeres shorten in an age-dependent manner in the kidney, either due to developmental factors or aging, particularly in renal cortex.

Adult↗
PubMed1987

The role of the cytoskeleton in endothelial repair.

The injured endothelium undergoes rapid repair of areas of cell desquamation in order to maintain the structural integrity of the endothelial surface. Endothelial repair involves a series of processes which include endothelial cell spreading, translocation, and proliferation. These processes are well defined events which occur sequentially in time. Spreading and translocation are mediated by the cell cytoskeleton--F-actin microfilaments and microtubules and associated centrosomes. The regulation of these processes is complex and is likely due to soluble factors present at the site of injury which are released from activated endothelial cells, platelets, the subendothelial substratum, activated serum factors, and hemodynamic shear stress. Cell replication occurs in order to replace lost cells and maintain the appropriate cell density of the endothelial surface. The factors which regulate endothelial cell proliferation are currently under study.

Actin Cytoskeleton↗
PubMed2006

Replication and examination of research data on job stress and coworker social support with Internet and traditional samples.

PURPOSE: To replicate previous results about job stress and coworkers' support that were obtained from a Web-based American sample with a sample of Jordanian nurses using traditional methods. DESIGN AND METHODS: The convenience sample of 300 Jordanian staff nurses completed the pencil-and-paper version of a questionnaire that included the Nursing Stress Scale, the McCain and Marklin Social Integration Scale, and the demographic form. The sample of the replicated study consisted of 263 American staff nurses who were accessible over the Internet and completed the Web-based version of the questionnaire. Descriptive statistics, chi-square, t test, and Pearson product-moment correlations were used to analyze the data. RESULTS: The American and Jordanian samples differed significantly on all demographic variables. However, they had similar patterns of responses in regard to the association between job stress and social support from coworkers. CONCLUSIONS: The predicted comparability of findings with different methods and samples lends credence to the reliability and validity of Internet-based research.

Adult↗
PubMed2005

HtrA stress protein is involved in intramacrophagic replication of adherent and invasive Escherichia coli strain LF82 isolated from a patient with Crohn's disease.

Adherent and invasive Escherichia coli (AIEC) bacteria isolated from Crohn's disease patients are able to greatly replicate within macrophages without escaping from the phagosome and without inducing macrophage death. In the present study, evidence is provided that in AIEC strain LF82 the htrA gene encoding the stress protein HtrA is essential for intracellular replication within J774-A1 macrophages. Deletion of the htrA gene in strain LF82 induced increased sensitivity of the isogenic mutant to oxidative stress caused by hydrogen peroxide and a reduced rate of growth in an acid and nutrient-poor medium partly reproducing the microenvironment of the phagosome. In vitro experiments using an LF82 htrA gene promoter fusion with the lacZ gene revealed a 38-fold activation of the promoter in AIEC LF82 intramacrophagic bacteria. The CpxRA two-component signaling pathway was not involved in this activation. In addition, the activation of the LF82 htrA gene promoter was not observed in the nonpathogenic E. coli K-12 intramacrophagic bacteria, indicating that the AIEC LF82 genetic background is crucial for induction of htrA gene transcription during phagocytosis.

Cell Division↗
PubMed1999

[Replicative senescence as a model of aging: the role of oxidative stress and telomere shortening--an overview].

Replicative senescence is characterized by the irreversible loss of division potential of cultivated human and animal cells. Correlations between the replicative potential in vitro and the age of the donor or the maximal lifespan of the species suggest replicative senescence to be an appropriate model for aging. Telomeres of human somatic cells shorten with each cell division but are stabilized at constant length in tumors and immortal cells by the enzyme telomerase. The assumption of a causal role of telomere shortening for the limited lifespan of cells in vitro was borne out recently. We could demonstrate oxidative stress as a main reason for telomere shortening. Telomeres are sensors for oxidative damage in the genome. Telomeres shorten during in vivo aging as well; however, there are significant differences between individuals. Telomere erosion might play a major role for the aging of the immune system. Our data suggest that telomere shortening in vivo could reflect the cumulative amount of oxidative damage to the organism. It might be useful as a biomarker of aging.

Animals↗
PubMed1978

Dynamics of correlated genetic systems. IV. Multilocus effects of ethanol stress environments.

Four replicate populations of Drosophila melanogaster, two reared on medium supplemented with ethanol and two reared on standard medium, were electrophoretically monitored for 28 generations. During the first 12 generations, allelic, genotypic and gametic frequencies were determined for eight polymorphic enzymes: GOT, alpha-GPDH, MDH, ADH, TO, E6, Ec and ODH. Samples from generation 18 and 28 were electrophoretically typed for ADH and alpha-GPDH. In addition, samples from generation 27 were analyzed for the presence of inversion heterozygotes. The experimental results showed rapid gene-frequency divergence between control and treatment populations at the Adh locus in a direction consistent with the activity hierarchy of Adh genotypes. Gene-frequency divergence between control and treatment populations also occurred at the alpha-Gpdh locus, although the agreement among replicates appeared to have broken down by generation 28. No differential gene-frequency change occurred at any of the six remaining marker loci. Furthermore, values of linkage disequilibria among all linked pairs of genes were initially small and remained small throughout the course of the experiment. Taking these facts into account, it is argued that the gene-frequency response observed at ADH is most probably caused by selection at the Adh locus. The gene frequency response at alpha-Gpdh can also be be accounted for in terms of the effect of ethanol on energy metabolism, although other explanations cannot be excluded.

Alcohol Oxidoreductases↗
PubMed2002

Economic pressure in African American families: a replication and extension of the family stress model.

This study of 422 two-caregiver African American families, each with a 10-11-year-old focal child (54% girls), evaluated the applicability of the family stress model of economic hardship for understanding economic influences on child development in this population. The findings generally replicated earlier research with European American families. The results showed that economic hardship positively relates to economic pressure in families. Economic pressure was related to the emotional distress of caregivers, which in turn was associated with problems in the caregiver relationship. These problems were related to disrupted parenting practices, which predicted lower positive child adjustment and higher internalizing and externalizing symptoms. The results provide significant support for the family stress model of economic hardship and its generalizability to diverse populations.

Adult↗
PubMed2006

SMC1 inhibition results in FRA3B expression but has no effect on its delayed replication.

Cellular processes involved in fragile site expression have been investigated by studying the effect on the replication pattern of the commonest fragile site FRA3B of RNA interference (RNAi)-mediated sister maintenance chromosome 1 (SMC1) inhibition in normal human fibroblasts. Replication timing of FRA3B in G2 was studied by bromodeoxyuridine (BrdU) labeling for the final 2h of cell culture whereas in the S phase was investigated by a fluorescence in situ hybridization (FISH)-based approach through the analysis of clones spanning the FRA3B region. Results showed that FRA3B is normally late replicated even though it is not expressed in untreated cells. On the other hand, SMC1 inhibition leads to FRA3B expression even if the percent of late replicated cells is comparable to control cells. These results obtained by analysing the commonest fragile site suggest that SMC1 plays a role in protecting late replicating regions from stresses occurring in the final steps of genome replication and that delayed replication is necessary but not sufficient for inducing fragile site expression.

Acid Anhydride Hydrolases↗
PubMed2005

Mammalian SIRT1 limits replicative life span in response to chronic genotoxic stress.

The Saccharomyces cerevisiae chromatin silencing factor Sir2 suppresses genomic instability and extends replicative life span. In contrast, we find that mouse embryonic fibroblasts (MEFs) deficient for SIRT1, a mammalian Sir2 homolog, have dramatically increased resistance to replicative senescence. Extended replicative life span of SIRT1-deficient MEFs correlates with enhanced proliferative capacity under conditions of chronic, sublethal oxidative stress. In this context, SIRT1-deficient cells fail to normally upregulate either the p19(ARF) senescence regulator or its downstream target p53. However, upon acute DNA damage or oncogene expression, SIRT1-deficient cells show normal p19(ARF) induction and cell cycle arrest. Together, our findings demonstrate an unexpected SIRT1 function in promoting replicative senescence in response to chronic cellular stress and implicate p19(ARF) as a downstream effector in this pathway.

Animals↗
PubMed2005

Hepatitis C virus (HCV) constitutively activates STAT-3 via oxidative stress: role of STAT-3 in HCV replication.

The hepatitis C virus (HCV) causes chronic hepatitis, which often results in liver cirrhosis and hepatocellular carcinoma. We have previously shown that HCV nonstructural proteins induce activation of STAT-3 via oxidative stress and Ca2+ signaling (G. Gong, G. Waris, R. Tanveer, and A. Siddiqui, Proc. Natl. Acad. Sci. USA 98:9599-9604, 2001). In this study, we focus on the signaling pathway leading to STAT-3 activation in response to oxidative stress induced by HCV translation and replication activities. Here, we demonstrate the constitutive activation of STAT-3 in HCV replicon-expressing cells. The HCV-induced STAT-3 activation was inhibited in the presence of antioxidant (pyrrolidine dithiocarbamate) and Ca2+ chelators (BAPTA-AM and TMB-8). Previous studies have shown that maximum STAT-3 transactivation requires Ser727 phosphorylation in addition to tyrosine phosphorylation. Using a series of inhibitors and dominant negative mutants, we show that HCV-induced activation of STAT-3 is mediated by oxidative stress and influenced by the activation of cellular kinases, including p38 mitogen-activated protein kinase, JNK, JAK-2, and Src. Our results also suggest a potential role of STAT-3 in HCV RNA replication. We also observed the constitutive activation of STAT-3 in the liver biopsy of an HCV-infected patient. These studies provide an insight into the mechanisms by which HCV induces intracellular events relevant to liver pathogenesis associated with the viral infection.

Cell Line, Tumor↗
PubMedDate not supplied

[Suppression of replication and activation of DNA reparative synthesis in stress and prevention of these phenomena by preliminary adaptation].

Effects of preliminary adaptation to short-term stress or to regular hypoxia on disturbances of DNA biosynthesis were studied in liver and heart tissues under conditions of emotional-painful stress (EPS). EPS was found to induced activation of DNA reparative synthesis in heart and liver tissues and affected dissimilarly DNA replication in these tissues: activation of the reaction in heart and suppression in liver tissue. Adaptation to regular hypoxia limited distinctly the burst of DNA reparative synthesis in cells of both these tissues, reduced activation of the DNA replicative synthesis in heart and prevented the stress induced depression of DNA replication in hepatic cell nuclei and mitochondria. Mechanisms of the hepatoprotective effect of adaptation to hypoxia is discussed.

Adaptation, Physiological↗
PubMedDate not supplied

Child behaviour problems and partner mental health as correlates of stress in mothers and fathers of children with autism.

BACKGROUND: Previous research has suggested that the mothers and fathers of children with disabilities experience stress differently. Although there has been a great deal of research exploring how children affect parents, there have been many fewer studies of the interrelationships between mothers' and fathers' psychological well-being. METHODS: Eighteen married couples who were the parents of children with autism reported on their stress and their general mental health (i.e. anxiety and depression). Teachers rated the behaviour problems of the children with autism. RESULTS: Mothers and fathers did not differ in their levels of stress and depression, but mothers reported more anxiety than fathers. Partial correlation analyses revealed that child behaviour problems and fathers' mental health were associated with mothers' stress. However, neither child behaviour problems or mothers' mental health was associated with fathers' stress. CONCLUSIONS: Although requiring replication, the results suggest that stress in mothers of children with disabilities may be affected by the psychological health of other family members, whereas fathers' stress is affected more by other factors. Methodological and conceptual issues, and the practical implications of these results are discussed.

Adult↗
PubMed1992

Effects of the nursing Mutual Participation Model of Care on parental stress in the pediatric intensive care unit--a replication.

The pediatric intensive care unit (PICU) hospitalization of a child is stressful for parents. Helping parents to decrease their stress is warranted so that they can function in a vital role that is therapeutic to them and their critically ill child. Although many interventions have been recommended to help parents decrease their stress, only the Nursing Mutual Participation Model of Care (NMPMC) has been tested in the clinical setting. This article reports a study that expands on Curley's original work by investigating the effects of the NMPMC on parental stress when implemented by PICU staff nurses. Fifty-six parents participated in the study, which used a quasi-experimental design. Sequential sampling placed the first 31 subjects into the control group and the next 25 subjects in the experimental group. The experimental group received care from staff nurses instructed in the NMPMC. The dependent measure was the Parental Stressor Scale:Pediatric Intensive Care Unit (PSS:PICU) administered within 24 to 48 hours of PICU admission, every 48 hours thereafter, and 24 hours after PICU discharge. The results indicated that parents in the experimental group perceived less stress than the control group, specifically the stress related to alterations in parental role in the PICU setting. Implications for nursing care are discussed.

Adult↗
PubMed2004

Oxidative stress in NRTI-induced toxicity: evidence from clinical experience and experiments in vitro and in vivo.

This article reviews the relationship of oxidative stress with nucleoside reverse transcriptase inhibitor (NRTI)-induced toxicity and suggests how oxi-dative stress may participate in NRTI-mediated toxicity. NRTIs are pro-drugs that require intracellular phosphorylation to their 5' triphosphates by cellular kinases to inhibit viral and mitochondrial DNA (mtDNA) replication. NRTIs in highly active antiretroviral therapy have decreased morbidity and mortality, but side effects can be limiting after prolonged use. These side effects may be linked through mitochondrial dysfunction arising from altered mtDNA replication and oxidative stress via destruction of elements of mtDNA replication, decreased oxidative phosphorylation, and cellular function. Although oxidative stress is associated with NRTI therapy, there is still debate about whether it plays a direct role in NRTI-induced toxicity. The impact of oxidative stress on cardiovascular disease is likely to increase because patients with HIV infection are living longer as a result of effective antiretroviral therapy.

Animals↗